Device, systems and methods for prevention of deep vein thrombosis

Abstract

To provide favorable devices, systems and methods for preventing deep vein thrombosis.SOLUTION: One embodiment provides a DVT prevention device comprising a cuff that fits over a patient's leg, an applanator coupled to an inside cuff surface, an expandable member (EM) coupled to the applanator, a pressure source fluidically coupled to the EM, and a controller for controlling inflation of the EM. When the EM is expanded, the EM applies a force to the applanator such that the force is transmitted by the applanator as a force to a leg surface which causes a DV under the cuff to be compressed so as to minimize a blood flow through the DV. The EM is then deflated, stopping DV compression and the blood flow resumes. The EM can be inflated in a cycle including pulsed inflation, inflation hold and relaxation. The cycles can be repeated and adjusted to achieve a desired increase of the flow / velocity in the DV.SELECTED DRAWING: Figure 2

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of priority to U.S. Provisional Application No. 62 / 541,784 (Attorney Docket No. 54800-703.101), filed August 7, 2017, the entire contents of which are incorporated herein in their entirety.

[0002] 1. FIELD OF THE INVENTION FIELD OF THE INVENTION Embodiments described herein relate to the prevention of blood clots in the vascular system. More particularly, embodiments of the present invention relate to devices, systems, and methods for the prevention of blood clots in the venous system. Even more particularly, embodiments of the present invention relate to devices, systems, and methods for the prevention of deep vein thrombosis, including in the legs and arms. [Background technology]

[0003] BACKGROUND OF THE INVENTION Deep vein thrombosis (DVT) is the formation of a blood clot (thrombus) in the deep veins of the body. While DVT is typically encountered in the lower extremities, it can occur in any venous structure. Clinically, DVT results in localized thrombophlebitis or pain, swelling, erythema, and warmth. When DVT embolizes into the pulmonary arterial circulation, it causes pulmonary embolism. Pulmonary embolism is the most dangerous complication of DVT and can lead to pulmonary infarction, heart failure, and sudden death. Physiologically, DVT results from a constellation of conditions known as Virchow's triad. Virchow's triad can be summarized as venous congestion, vessel wall injury, or hypercoagulability. The CDC estimates that DVT occurs in 200,000 to 600,000 people annually, with 60,000 to 100,000 deaths annually due to pulmonary embolism. Pulmonary embolism is cited as the most common, yet preventable, cause of death. The Surgeon General's Executive Report and the CDC report that the incidence and prevalence of DVT continues to increase, citing rates of 1 to 2 cases per 1,000 patients and as high as 1 per 100 in high-risk populations. The Centers for Medicare and Medicaid, along with the Surgeon General's Call to Action To Prevent DVTs and Pulmonary Embolism, consider DVT and pulmonary embolism "never events" and deny payment for prolonged hospitalizations resulting from DVT or pulmonary embolism.

[0004] The current approach to the management of DVT and pulmonary embolism can be summarized into three steps: prevention, diagnosis, and treatment. Prevention strategies can be divided into anticoagulant drugs and devices that attempt to recirculate venous blood. DVT is diagnosed using duplex ultrasound. An ultrasound technician evaluates each vein for compressibility and patency and then sends the images to a radiologist for interpretation. The majority of DVTs are never diagnosed because they occur outside of a hospital, either at home or in a nursing home. Treatment options for patients diagnosed with DVT include catheter-directed thrombolysis, anticoagulation therapy to prevent secondary clot formation, and IVC filter placement to prevent pulmonary embolism (PE) if the patient cannot be anticoagulated. In addition, various preventive measures are taken to reduce the relatively high risk of secondary DVT formation.

[0005] Although anticoagulant drugs have been shown to reduce the risk of DVT / PE, these drugs are associated with an increased risk of bleeding. The risk of bleeding increases significantly when these drugs are used in high-risk DVT patients, who are typically elderly, post-surgical, and cancer patients. Devices that attempt to recirculate venous blood are understood to function by increasing the velocity of blood in the common femoral vein, thereby preventing venous congestion.

[0006] Currently available devices for recirculating venous blood include continuous compression devices (SCDs) and compression stockings. However, both devices have significant drawbacks. In particular, SCDs require a large battery source and exert external pressure on the ankle, calf, or thigh veins. Typically, SCDs function on the tibial and peroneal veins, which are surrounded by two large muscles, the soleus and gastrocnemius. In healthy individuals, during locomotion, these large muscles compress the tibial veins, promoting venous return of blood. One-way venous valves in these patients ensure that venous blood flows against gravity, preventing backflow or pooling of blood. In immobile or bedridden patients, SCDs attempt to externally replicate this mechanism. To exert a sufficient force to compress the calf veins and promote venous blood flow, the SCD must work against the calf muscles, resulting in undesirable and excessive pressure on the lower extremities. This high pressure, in particular, can result in damage to venous valves and an increased risk of future DVT / PE. To exert the high pressure required to prevent DVT formation, these large, bulky devices typically incorporate a large battery pack and pressure-generating mechanism. This bulky structure makes it difficult for patients to ambulate and contributes to venous congestion, one of the components of Virchow's triad that promotes DVT formation.

[0007] Compression stockings are another approach to promoting venous return of blood. However, they are difficult to use and have poor compliance rates. Furthermore, studies have shown that compression stockings do not achieve a sufficient level of compression to prevent DVT / PE.

[0008] Therefore, due to the many shortcomings of current techniques for DVT prophylaxis, there is a need for improved devices and methods for the prevention of deep vein thrombosis and associated conditions such as pulmonary embolism. Summary of the Invention [Problem to be solved by the invention]

[0009] (Brief Description of the Invention) Various embodiments of the present invention provide devices, systems, and methods for the prevention of deep vein thrombosis (DVT) in appendages such as the arms and legs. Many embodiments provide devices, systems, and methods for the prevention of deep vein thrombosis in the veins of the legs, including, for example, the femoral, popliteal, and tibial veins. [Means for solving the problem]

[0010] Certain embodiments of DVT prevention devices provide a cuff-like device that fits over a patient's leg and include an applanation device that applies force to the surface of the leg, flattening or otherwise compressing the deep veins in the leg, including the popliteal vein, so that blood flow through the deep veins is substantially occluded. The force is then released, and blood flow resumes. The force is typically generated using an inflatable balloon attached to the applanation device, although other inflation devices are also contemplated. In a preferred embodiment, the cuff is configured to fit over the knee, and the applanation device is positioned over the cuff behind the knee to apply sufficient force to compress one or more of the distal common femoral vein, popliteal vein, posterior tibial vein, anterior tibial vein, and peroneal vein. Notably, more than 90% of DVTs occur in this area. However, it should be understood that cuff embodiments can be adapted to fit over any portion of the leg, such as the calf or upper thigh, as well as the arm. Additionally, although various embodiments refer to the popliteal vein as the vein compressed by the applanation device / DVT prevention device, it should be understood that various embodiments of the present invention contemplate compression of any vein, including any deep vein in the arm or leg, as well as superficial veins in the same or different locations.

[0011] In many embodiments of the present invention, the force from the applanation device is applied according to a pressure / inflation cycle, also known as a compression regimen. Typically, a compression regimen includes a pattern of restraining force pulses (also described herein as compression pulses or pressure pulses) that result in increased blood flow through the compressed veins for an extended period of time after the regimen is completed. In certain embodiments, including those in which a cuff is positioned over the knee, the compression regimen can be configured to generate direct intermittent compression and relaxation of the popliteal vein or other deep veins in the knee region. This causes cyclical opening and closing of the popliteal vein, which in turn results in increased venous circulation, total femoral venous velocity, which indirectly drains the veins of the lower leg.

[0012] The compression regimen can be repeated multiple times over a selected period of time, resulting in a prolonged (e.g., approximately 5-60 minutes) increase in venous blood flow and velocity through the compressed area of tissue, including the compressed deep vein. Using such a regimen, the average blood velocity / flow rate within one or more compressed deep veins can be increased by more than 100, 200, 300, 400%, or even more than 500% over an extended period of time. Particular embodiments of the device using such a regimen have demonstrated an average increase of 387% to 506% in blood velocity / flow rate within deep veins, such as the common femoral vein. As a result of such an increase in blood flow through the affected veins, the risk of thrombus formation is substantially reduced. Embodiments of the present invention are useful for preventing DVT in patients who are bedridden or have poor circulation, particularly poor venous circulation. Furthermore, embodiments of the present invention are particularly useful for preventing DVT in the deep veins of the legs, such as the femoral and popliteal veins, in patients who are hospitalized or otherwise bedridden for any length of time, and in patients who are immobile or sedentary for any length of time, such as those patients who must be wheelchair bound or otherwise take long airplane flights.

[0013] Embodiments of DVT prevention devices and associated methods of using the devices reduce a patient's risk of developing deep vein thrombosis (DVT) by greatly improving the flow rate and efficiency of peripheral and central venous return. The reasons behind this risk reduction are as follows: Blood congestion and venous pooling are well-known risk factors for the formation of DVT. Numerous conditions exist that can result in temporary or permanent immobility, predisposing a patient to the development of venous congestion and, subsequently, the formation of DVT or pulmonary embolism (PE) and / or other pulmonary embolic events (PEE). While arteries have muscular walls that can restrict and facilitate blood circulation, veins have a very thin muscle layer and, by themselves, are not very capable of promoting blood recirculation. However, veins contain one-way venous valves that facilitate unidirectional venous blood return to the heart. Venous valves are a critical component in the body's ability to recirculate blood against gravity. Recent studies have precisely delineated the anatomical locations of venous valves. Venous valves are most prevalent in the calf veins and upper leg veins. The deep veins of the calf and thigh are surrounded by large thigh and calf muscles, which provide an additional mechanism for venous return. Muscle contraction during walking exerts circumferential forces around the deep veins of the calf and thigh. This results in decreased venous congestion and increased venous blood velocity, thereby reducing the risk of DVT. To compress the veins of the calf and thigh, a continuous compression device (SCD) must exert a large force to penetrate the large muscles and reach the deep veins. These large forces often damage venous valves, leading to venous insufficiency and congestion. Damage to the venous valves prevents proper recirculation of venous blood, resulting in venous congestion. This promotes the formation of DVT and subsequent PEE. Injury to veins, including deep veins, can occur in either post-traumatic or post-operative conditions; however, the use of standard continuous compression devices, which primarily function on the leg, scapular, or femoral veins, can also result in venous valve injury, subsequently leading to venous valve insufficiency and venous congestion, resulting in DVT and PE.Anatomical studies have demonstrated that the popliteal venous valve is identified at or just distal to the adductor hiatus, where the vessels and nerves emerge from just below the adductor muscles. The adductor hiatus is located above the popliteal fossa within the posterior aspect of the distal thigh. Embodiments of the DVT prevention device reduce a patient's risk of developing DVT by increasing peripheral and central venous velocities and promoting efficient return of venous blood to the heart.

[0014] Compared to standard continuous compression devices (SCDS), embodiments of the DVT prevention device and associated method described herein offer many potential advantages. First, the device is lightweight, battery-powered, and does not require a large power source or large air pressure-generating device. This allows the device to be portable, allowing patients to ambulate while wearing the device. This also allows the device to be used comfortably outside of a hospital environment. Second, while standard continuous compression devices attempt to overcome muscle resistance and the depth of deep venous structures in the calf and thigh by increasing the force required to compress the venous structures, embodiments of the device and method described herein leverage anatomical knowledge to intermittently occlude the popliteal vein. Intermittent compression of the popliteal vein is preferable over deep venous structures in the calf and thigh because, as mentioned above, the popliteal vein is a superficial structure that requires much less force to intermittently compress. Additionally, as mentioned above, the anatomical location of the popliteal vein valve is immediately distal to the adductor hiatus, so the device does not damage the venous valve. Furthermore, because the popliteal vein is the major venous conduit between the calf veins and the deep thigh veins, intermittent compression of the popliteal vein also results in a buildup of back pressure in the calf veins, which results in indirect drainage of the calf and foot veins via the Venturi effect.

[0015] Third, while standard continuous compression devices function by generating graduated compression forces or intermittent forces on deep veins, device embodiments function by simultaneously using two different mechanisms to increase peripheral and central venous blood flow. In various embodiments, this can be achieved through the use of specific pressure or inflation cycles, from a balloon or other expansion device to an applanation device, to inflate and apply pressure to a treatment area behind a patient's knee or other selected treatment area, such as another area of the arm or leg. In certain embodiments, the pressure or inflation cycle includes a specific, complex intermittent compression, hold, and relaxation cycle, also known as a compression regimen. In contrast, traditional continuous compression devices generate graduated compression forces. According to one or more embodiments, the cycles can be tailored or otherwise adjusted to each patient's unique physiology (e.g., their hemodynamic parameters, history of DVT, etc.) to optimize the increase in venous flow rate and velocity within the patient's leg or other appendage area being treated with the DVT device.

[0016] One embodiment of the pressure cycle / compression regimen includes the following: First, variable intermittent compression of the popliteal vein is achieved by an inflatable balloon that is intermittently inflated and deflated. The balloon acts against an applanation device to apply force through the skin to the popliteal vein. The applanation device distributes all of the force of the balloon onto the popliteal vein instead of the surrounding tissue, which results in a sustained increase in the total femoral venous velocity.

[0017] Second, at the end of the variable intermittent compression period, the device holds the popliteal vein closed for a variable amount of time, generating backpressure within the leg and calf veins. When the device relaxes and the popliteal vein opens, the backpressure results in the forced evacuation of blood from the leg, calf, and popliteal veins. This results in a second mechanism by which peripheral and central venous blood velocity is also increased. This, in turn, results in elevated venous blood flow rates for approximately 5 to 60 minutes after the device is turned off, suggesting that the combination of both intermittent compression and generation is highly effective in generating increased venous circulation within the area compressed by the device.

[0018] Device embodiments are simple to use in that they fit easily over the knee, just like an elastic kneeband. They are automated, and in many embodiments, they may have Bluetooth or other wireless connectivity, allowing the user or physician to set device parameters to a specific user's individual attributes, including, for example, the user's knee size and muscle tone (which affects the pressure selected), hemodynamic condition, physical condition (e.g., bedridden vs. ambulatory), and activity profile. Fifth, device embodiments can be used with the user in a supine, semi-recumbent (seated with legs outstretched), seated, or standing position.

[0019] In a first aspect, the present invention provides a device for preventing deep vein thrombosis (DVT) in a patient, comprising: a cuff configured to fit over a patient's leg; an applanation device coupled to the inner surface of the cuff; an expandable member or other expansion device coupled to the applanation device; a pressure source fluidly or otherwise coupled to the expansion device; and a controller operably coupled to the pressure source to control expansion of the expandable member. When the balloon or other expandable member is expanded, it applies a force to the applanation device, which is transmitted as a force / pressure by the tissue-contacting surface of the applanation device to the surface of the leg, causing the deep vein to be flattened or otherwise compressed to minimize blood flow through the deep vein. When the expandable member is deflated, pressure applied to the leg from the applanation device is discontinued, and the vein expands with resumption of blood flow. As described herein, the expandable balloon is cyclically inflated and deflated according to a pressure cycle to enhance blood flow through the compressed vein.

[0020] The cuff is desirably sufficiently elastic to be placed over and positioned over a desired area of the user's leg, such as the knee area. Thus, the cuff may comprise various elastomers known in the art, such as silicone, polyurethane, etc. In additional or alternative embodiments, the cuff can be configured to be wrapped over and around the leg and then held in place by a fastening means such as VELCRO®.

[0021] An applanation device is configured to apply force to the outer surface of the leg, such as that behind the knee, to flatten or otherwise compress a selected vein and intermittently substantially stop blood flow through the leg. Thus, as used herein, the term "applanation device" refers to a device or structure for applying force from an external tissue surface of the body to flatten or otherwise compress a vein beneath the tissue surface, such as a deep vein. Applanation device embodiments will typically have a curved or other shaped tissue-contacting surface configured to apply sufficient force (per unit area) to the surface of the leg to compress a deep vein in the leg, such as the popliteal vein. The force may be in the range of approximately 0.5 to 10 pounds, and in specific embodiments, 1, 2, 3, 5, 6, 7, 8, and 9 pounds. Thus, applanation devices can be fabricated from a variety of materials having sufficient stiffness to apply the desired amount of force. Suitable materials include various thermosetting polymers and rigid metals. Typically, the tissue-contacting surface of an applanation device will have a semicircular shape to concentrate the force on the center of the leg or other area containing the selected deep vein. In the case of the popliteal vein, the applanation device diameter may be approximately 1 to 3 times the diameter of the popliteal vein to ensure that the vein is compressed. In related embodiments, the diameter of the tissue contact surface may also approximately correspond to the distance between the two major tendons on either side of the popliteal vein. In various embodiments, the applanation device may be custom-fit to the individual patient (e.g., based on these or other measurements, depending on the area to be treated). Such a custom fit may be achieved by custom fabrication using various methods known in polymer and machining technology, including, for example, one or more of molding, CMC machining, and 3D printing methods. Furthermore, the applanation device is desirably positioned on the cuff so that it is centered over the selected deep vein to be compressed. In this case, for the popliteal vein, this corresponds to the center of the back of the knee.

[0022] In various embodiments, the applanation device will typically include a base portion having a rectangular or square shape and a curved tissue-contacting portion attached to or integral with the base portion. As explained above, the tissue-contacting portion will typically have a semicircular or other convex shape, with the convex portion contacting the tissue. In many embodiments, the base portion of the applanation device is attached to a hinge plate that is attached either directly or indirectly to the cuff. The hinge plate includes a hinge element on one side that engages with a corresponding hinge element on the applanation device, allowing the applanation device to pivot up into the tissue when the balloon or other expandable member is inflated. The base portion of the hinge may have a recessed portion in its central area that has a contour approximating at least a portion of the balloon to hold the balloon in place when it is inflated. Additionally, desirably, as described below with respect to the support structure, the hinge plate is sufficiently rigid so that it does not deform significantly upon inflation of the balloon and functions mechanically in a manner similar to the support structure to prevent expansion of the cuff and direct the balloon inflation force to the applanation device and, in turn, to the underlying tissue compressed by the applanation device.

[0023] According to one or more embodiments, the DVT device may also include a support structure attached to the cuff and positioned between the cuff and the hinge plate. The support structure is mechanically constructed, for example, in terms of its shape and rigidity, to direct the force generated by the balloon or other expansion device inward onto the applanation device rather than dissipating it by causing the cuff to expand. Desirably, the support structure is made of a sufficiently rigid material, such as a thermosetting plastic, that does not deform when the balloon is inflated.

[0024] In certain embodiments, the support structure may have a flat surface or may have two portions: a recessed portion and a larger flat portion surrounding the recessed flat portion. Similar to a hinge plate, the recessed portion may have a contour corresponding to at least a portion of that of an inflated balloon to partially retain the balloon when inflated. The larger flat portion serves to distribute the force from the balloon expansion over a larger area of the cuff, reducing the pressure on the cuff and therefore the amount of cuff expansion resulting from the balloon expansion. This, in turn, reduces the dissipation of force from the balloon expansion by causing the cuff to expand or the VELCRO® constricting portion on the cuff to release. This, in turn, causes a greater amount of balloon expansion force to be transmitted to the applanation device, which in turn causes compression / flattening of selected deep veins directly below the applanation device, such as the popliteal vein. Such embodiments are particularly useful for elastic cuff embodiments or those using VELCRO® constricting portions that may become uncoiled due to the force from the expanding balloon. Additionally, the support structure flat portion desirably has a larger surface area than the upper hinge plate to provide additional mechanical resistance to forces from balloon expansion that tend to cause cuff expansion, as well as distribute those forces over a larger area of the cuff, thus reducing the amount and likelihood of cuff expansion.

[0025] The dilation device will typically correspond to various expandable balloons or other expandable members known in the medical device art, including balloon catheter art. According to various embodiments, the expandable balloon may be fabricated from one of various expandable balloon materials known in the medical art, including, for example, silicone, polyurethane, and copolymers thereof. In preferred embodiments, the expandable balloon or other expandable member is made from a relatively inflexible material, such as PET, polyethylene (e.g., HDPE), irradiated polyethylene, and other polymers and copolymers thereof, so that the balloon retains a fixed expanded shape and is capable of applying a force to the applanation device rather than continuing to expand outward beyond its expanded shape. In alternative or additional embodiments, the dilation device may comprise an electromechanically-based dilation device, including, for example, a piezoelectric-based device, a solenoid, an electric motor, or the like. For embodiments using an electromechanically-based device, no pressure source is required, simply by a power source, such as a portable battery, e.g., an alkaline or lithium-ion battery, known in the art.

[0026] The pressure source will typically correspond to a pump, such as a pneumatic or mechanical pump, selected and configured to generate sufficient pressure for the expandable member to apply sufficient compressive force from the applanation device to the target tissue surface to flatten / compress the selected deep vein beneath the tissue surface as described herein. The generated pressure may be in the range of approximately 0.5 to 20 atmospheres, and in specific embodiments, 2, 5, 7, 10, and 15 atmospheres. In various embodiments, the pressure source may correspond to a pneumatic or mechanical pump. In alternative or additional embodiments, the pressure source may correspond to a compressed gas source, including compressed air or an inert gas.

[0027] According to one or more embodiments, the pressure source may be directly connected to the balloon or expandable member. In additional or alternative embodiments, they may be indirectly connected using a valve fluidly coupled to at least one of the pressure source or expandable member. The valve is configured and positioned to control the pressure released from the pressure source to the balloon or other expandable member. Typically, the valve will be an external valve positioned between the pressure source and the expandable member, but may be positioned elsewhere relative to these elements as well. In other embodiments, the valve may be integral to one or both of the pressure source or balloon.

[0028] The valve may correspond to one or more control valves known in the art, including, for example, various electronically controlled valves, including solenoid valves. For the latter embodiment, the valve may be operably coupled to a controller such that the control device can send and receive signals to open the valve according to a specific time sequence and / or based on pressure measurements. In the latter embodiment, the device may also include a pressure sensor fluidly coupled to one or more of the pressure source and / or expandable member and operably coupled to the controller to send a signal corresponding to the measured pressure to the controller. The pressure sensor may correspond to various electronic and / or solid-state pressure sensors known in the art.

[0029] The controller is configured to control the inflation of the expandable balloon or other expandable member by controlling one or more of the pressure source and / or control valve embodiments described herein. According to various embodiments, the controller is configured to control the inflation of the expandable member to generate a selected pressure cycle and / or compression regimen described herein. In many embodiments, this can be achieved through the use of modules (typically software modules) containing sets of algorithmic electronic instructions for performing these tasks. The controller will typically correspond to a microprocessor, which may be off-the-shelf or incorporated into an ASIC. In other cases, the controller may correspond to a hardware device that may correspond to various analog devices, including various state devices.

[0030] In many embodiments, the DVT prevention device will also include an internal power source for powering one or more of the controller, pressure source, or electronic devices or components contained within the DVT prevention device. Suitable power sources include various electrochemical storage batteries, such as alkaline, lithium, or lithium-ion batteries, although other battery chemistries are also contemplated. The use of rechargeable batteries is also contemplated. In these and related embodiments, the device may be configured to be plugged into an external power source to power the device and recharge the battery. In various embodiments, the external power source may comprise a wall outlet or USB source, although other power sources are also contemplated. During use, embodiments employing an external power source allow for the conservation of battery power and a means for recharging the batteries and for replacing them. For embodiments using battery power, the use of circuitry and / or algorithms to detect the state of battery charge and alert the user is also contemplated.

[0031] In many embodiments, the DVT prevention device will also include a transmitter for wireless communication with an external device (e.g., a mobile phone), a network, or the cloud. Typically, the transmitter will comprise a small RF transmitter and will be operably coupled to at least the controller. The RF or other transmitter will be further configured to send and receive signals from external devices, such as a mobile phone, tablet device, or other similar device, allowing the DVT device, including the controller, to communicate wirelessly with these external devices. The RF transmitter may be connected to or integral with the controller. Typically, the transmitter and / or controller will be configured to communicate via the BLUETOOTH® protocol, although other wireless protocols known in the art are also contemplated. For BLUETOOTH® embodiments, the responder may comprise a BLUETOOTH® responder known in the art. In use, such wireless communication capabilities enable a user or physician to do one or more of the following: 1) custom program the DVT device for an individual user (e.g., to include specific pressure cycles), 2) receive data regarding device performance (e.g., number of pressure cycles implemented, pressure generated, compression hold time, battery life data, etc.), 3) share data with others (e.g., physicians) via the cloud or other network, and 4) reprogram the device as needed depending on changes in date or patient or mobility status. For example, in the latter case, the device could be specifically programmed with a unique compression regimen for an extended airline trip in which the user will be seated for an extended period of time (e.g., 3-14 hours).

[0032] In alternative or additional embodiments, the DVT prevention device may also include one or more of push buttons and the like, a display, and an audio alarm, one or more of which may be coupled to the controller. The push buttons can be configured to allow a user to 1) turn the device on and off, 2) select or adjust a compression regimen and / or pressure cycle, and 3) select or adjust a pressure level. The display can display various information, including the pressure level being used, information about the pressure cycle (e.g., a graph of pressure versus time, the particular cycle / pressure regimen selected and / or implemented, and the time remaining in the cycle), and information about the battery life. In various embodiments, the display can be a touch screen, allowing a user to input information and / or otherwise interact with the device and perform various functions, such as those described with respect to the push buttons. The audio alarm can be configured to alert the user to various events and / or information, including, for example, the start or end of a pressure cycle, the interruption of a pressure cycle, and alarms about the amount of battery charge and / or battery life. Still other information and events are contemplated. In various embodiments, the controller can also be configured to send information about the alarm event to an external device and / or via the cloud, which creates an audio alarm on the external device and / or creates an audio alarm via the cloud to a monitoring physician.

[0033] In a second aspect, the present invention provides a system for preventing deep vein thrombosis (DVT) comprising an embodiment of a DVT prevention device described herein and an external device, such as a mobile phone, tablet device, etc., configured to communicate with the DVT prevention device. In many embodiments, the external device and the DVT device are configured to communicate with each other using the BLUETOOTH® communication protocol; in such embodiments, each device will include a BLUETOOTH® transponder as known in the art.

[0034] The external device will typically include a software module for displaying and / or wirelessly adjusting one or more parameters of the balloon inflation process, including, for example, the set balloon inflation pressure, the actual balloon inflation pressure, the balloon inflation time, the interval between inflations, and the time remaining in the current balloon inflation or inflation cycle described herein, as well as related parameters and metrics. The display of the external device may also be configured to allow a user to select, view, or wirelessly change such parameters used by the DVT device. Thus, in use, the software module on the external device functions as a chimeric application, allowing the patient or physician to wirelessly view and control various parameters and metrics of the DVT device.

[0035] In another aspect, the present invention provides a method for preventing deep vein thrombosis and associated pulmonary embolic events (PEE). In one embodiment, the method includes placing an embodiment of a DVT prevention device described herein around a patient's limb, such as a leg, at risk of developing DVT due to poor circulation. In certain embodiments, the device is placed around the patient's knee to compress one or more of the popliteal, femoral, common femoral, or tibial veins. The device may be placed over or wrapped around the knee. A balloon or other expansion device is then expanded according to a pressure cycle or compression regimen. One embodiment of such a regimen or pressure cycle includes periods of intermittent balloon inflation and resulting intermittent application of compression force to tissues beneath the leg, followed by a period of balloon inflation and holding the constant applied compression force, followed by balloon deflation and relaxation of the compression force applied to the leg. The intermittent compression periods may, in some embodiments, correspond to a series of compression pulses with periods of relaxation between them. The pulses may have a selected duration, for example, within the range of 1 to 20 seconds, with specific embodiments of 5, 10, and 15 seconds. Longer durations are also contemplated. A cycle including a compression pulse, compression hold, and relaxation period can be repeated multiple times over a selected period. As shown in the Examples section, use of such a pressure cycle resulted in an average increase in peak blood velocity in the common femoral vein of approximately 388 to 506%, depending on whether the subject was sitting with their knees bent or lying down. The largest increase was obtained after the pressure hold period. After completion of the cycle, baseline peak velocity remained elevated for a period of 5 to 60 minutes, and two specific individual baseline levels remained elevated for 15 and 60 minutes, respectively, thus demonstrating the long-term effectiveness of the cycle in maintaining elevated levels of venous circulation in the tissue area compressed by the applanation device or in the leg or other limb.

[0036] In various embodiments, pressure cycle parameters, including one or more of balloon inflation pressure, pulse duration, duration between pulses, and hold time and pressure, can be selected and / or adjusted for an individual patient using the ultrasound imaging and blood velocity measurement approaches described in the Examples section. Additionally, these parameters can be adjusted by the patient or physician in response to changes in one or more of the patient's physical condition, activity level, or medications (e.g., anticoagulants or blood pressure medications) using the external device embodiments described herein. They can also be adjusted when the patient is expected to engage in extended periods of seated sitting with limited mobility, such as during an airplane flight or passenger seating.

[0037] In other aspects of the invention, embodiments of DVT prevention devices can be used to increase venous blood velocity and flow to produce one or more physiological benefits in addition to DVT and associated PE prevention. Such benefits may include, for example, increased venous return, increased cardiac output, or reduced lactate accumulation (e.g., in the leg, arm, or tissue site compressed by an embodiment of a DVT prevention device). In certain embodiments, the device and pressure regimen can be adapted to increase venous blood velocity and flow to increase venous return in patients suffering from venous insufficiency or related conditions. In other embodiments, the device and pressure regimen can be adapted to increase venous blood velocity and flow to increase cardiac output in patients suffering from one or more forms of heart failure, particularly left ventricular failure.

[0038] Embodiments of DVT prevention devices and regimens can also be configured to produce one or more of the physiological benefits described above, for example, to provide improved athletic performance by increasing cardiac output and / or reducing lactic acid accumulation and / or CO2 levels in exercising muscles. Improved athletic performance can include improved performance in running, swimming, weightlifting, or other aerobic or anaerobic exercise. In certain embodiments, pressure regimens can be adapted to produce increased venous velocity and blood flow rates tailored for improved performance in selected exercises or activities, such as running or cycling.

[0039] Further details of these and other embodiments of deep venous prevention devices, apparatus, and systems are more fully described below with reference to the accompanying figures. The present specification also provides, for example, the following items: (Item 1) 1. A device for preventing deep vein thrombosis (DVT) in a patient, the device comprising: a cuff configured to fit over the patient's leg; an applanation device coupled to an inner surface of the cuff, the applanation device having a tissue contacting surface with a curved shape, the tissue contacting surface configured to apply pressure to a surface of the leg and compress deep veins within the leg; a stretching device coupled to the applanation device for applying a force to the applanation device; Equipped with When the stretching device is expanded, it applies a force to the applanation device, which force is transmitted to the surface of the leg by the tissue contacting surface of the applanation device, causing the deep veins to be compressed and minimizing blood flow through the deep veins. (Item 2) Item 10. The DVT prevention device of item 1, wherein the cuff comprises an elastic or elastomeric material configured to stretch to fit over the patient's leg and then contract to hold the cuff in place. (Item 3) Item 10. The DVT prevention device according to item 1, wherein the cuff includes a fastening means that allows the cuff to be wrapped around the user's leg and then fastened to itself using the fastening means. (Item 4) Item 4. The DVT prevention device according to item 3, wherein the fastening means comprises first and second portions of the cuff, the first and second portions of the cuff comprising a VELCRO® hook and a VELCRO® fastener, respectively. (Item 5) Item 1, wherein the expansion device is an expandable member. (Item 6) Item 6. The DVT prevention device according to item 5, wherein the expandable member is an expandable balloon. (Item 7) Item 6. The DVT prevention device according to item 5, further comprising a pressure source fluidly coupled to the expandable member. (Item 8) 8. The DVT prevention device according to item 7, wherein the pressure source is a pump, a pneumatic pump, or a mechanical pump. (Item 9) 8. The DVT prevention device according to any one of items 5 or 7, further comprising a pressure sensor fluidly coupled to at least one of the expandable member or the pressure source to measure pressure within the expandable member. (Item 10) 8. The DVT prevention device according to any of items 5 or 7, further comprising a valve fluidly coupled to the expandable member for maintaining and / or releasing pressure within the expandable member. (Item 11) Item 10. The DVT prevention device of item 1, wherein the expansion device comprises an electrical device, a piezoelectric device, or a solenoid. (Item 12) Item 10. The DVT prevention device of item 1, further comprising a controller operably coupled to the expansion device, the controller configured to control expansion of the expansion device. (Item 13) Item 13. The DVT prevention device of item 12, wherein the controller includes a module for controlling the expansion of the expansion device. (Item 14) Item 13. The DVT prevention device according to item 12, further comprising a transmitter operably coupled to the controller for transmitting and receiving signals to an external device. (Item 15) Item 15. The DVT prevention device according to item 14, wherein the transmitter is an RF transmitter or a BLUETOOTH (registered trademark) transponder. (Item 16) Item 15. The DVT prevention device of item 14, wherein at least one of the transmitter or the controller is configured to use the BLUETOOTH (registered trademark) protocol to send and receive signals from the external device. (Item 17) Item 15. The DVT prevention device according to item 14, wherein the external device is a mobile phone or a tablet. (Item 18) Item 10. The DVT prevention device of item 1, further comprising a support structure coupled to the cuff and positioned between the cuff and the expansion device, the support structure configured to direct force generated by the expansion device inward onto the applanation device. (Item 19) Item 19. The DVT prevention device according to item 18, wherein the support structure has a stiffness configured to direct the force generated by the expansion device inward onto the applanation device. (Item 20) Item 1. The DVT prevention device according to item 1, wherein the cuff is configured to be positioned over the patient's knee, and the applanation device is positioned on the cuff and is positioned over the posterior aspect of the knee when the cuff is placed over the knee. (Item 21) Item 14. The DVT prevention device of item 1, wherein the device is configured to compress at least one of the femoral vein, the common femoral vein, the popliteal vein, or the tibial vein. (Item 22) 2. The DVT prevention device according to item 1, wherein the applanation device is configured to apply a force to the surface of the leg to substantially flatten the deep vein. (Item 23) Item 10. The DVT prevention device of item 1, wherein the device is configured to function when the patient is engaged in ambulatory activity. (Item 24) Item 24. The DVT prevention device according to Item 23, wherein the ambulatory activity is walking or running. (Item 25) 1. A device for preventing deep vein thrombosis (DVT) in a patient, the device comprising: a cuff configured to fit over the patient's leg; an applanation device coupled to an inner surface of the cuff, the applanation device having a tissue contacting surface with a curved shape, the tissue contacting surface configured to apply pressure to a surface of the leg and compress deep veins within the leg; an expandable member coupled to the applanation device for applying a force to the applanation device; a pressure source fluidly coupled to the expandable member for expanding the expandable member; a valve fluidly coupled to at least one of the expandable member or the pressure source; a controller operably coupled to at least one of the pressure source or the valve; Equipped with the controller is configured to control the expansion of the expandable member; When the expandable member is expanded, the expandable member applies a force to the applanation device, which force is transmitted to the surface of the leg by the tissue contacting surface of the applanation device, causing the deep veins to be compressed and minimizing blood flow through the deep veins. (Item 26) 26. The DVT prevention device of item 25, wherein the device is configured to compress at least one of the femoral vein, the common femoral vein, the popliteal vein, or the tibial vein. (Item 27) 26. The DVT prevention device according to item 25, further comprising a power source operably coupled to at least one of the controller or the pressure source. (Item 28) 28. The DVT prevention device according to item 27, wherein the power source is an electrochemical battery, a lithium battery, or a lithium-ion battery. (Item 29) 26. The DVT prevention device according to item 25, further comprising a transmitter operably coupled to the controller for transmitting and receiving signals to an external device. (Item 30) 30. The DVT prevention device according to item 29, wherein the external device is a mobile phone or a tablet device. (Item 31) 30. The DVT prevention device of item 29, wherein the transmitter is configured to use the BLUETOOTH® protocol to send and receive signals from the external device. (Item 32) Item 32. The DVT prevention device of item 31, wherein the transmitter comprises a BLUETOOTH® transponder. (Item 33) 30. The DVT prevention device of item 29, wherein the transmitter comprises an RF transmitter. (Item 34) 26. The DVT prevention device according to item 25, wherein the pressure source is a pump, a pneumatic pump, a mechanical pump, or a compressed gas source. (Item 35) 26. The DVT prevention device of claim 25, further comprising a pressure sensor fluidly coupled to at least one of the expandable member or the pressure source for measuring pressure within the expandable member or the pressure source. (Item 36) Item 26. The DVT prevention device of item 25, wherein the controller comprises at least one software module. (Item 37) Item 37. The DVT prevention device according to item 36, wherein the at least one software module includes a module for controlling the expansion of the expandable member. (Item 38) Item 38. The DVT prevention device according to item 37, wherein the inflation control module includes at least one of a pump driver or a valve driver. (Item 39) Item 37. The DVT prevention device of item 36, wherein the at least one software module includes a power control module for monitoring a battery charge level or charging a battery. (Item 40) Item 37. The DVT prevention device according to item 36, wherein the at least one software module includes a communication module for controlling wireless communication with an external device. (Item 41) Item 26. The DVT prevention device according to item 25, wherein the controller is configured to inflate the inflation device according to a cycle. (Item 42) Item 42. The DVT prevention device according to item 41, wherein the cycle comprises: i) a period of intermittent inflation; ii) a period of constant inflation; and iii) a relaxation period with little or no inflation. (Item 43) Item 43. The DVT prevention device of item 42, wherein the period of intermittent inflation comprises a series of pressure pulses to the inflation device. (Item 44) 1. A device for preventing deep vein thrombosis (DVT) in a patient, the device comprising: a cuff configured to fit over the patient's leg; an applanation device coupled to an inner surface of the cuff, the applanation device having a tissue contacting surface with a curved shape, the tissue contacting surface configured to apply pressure to a surface of the leg and compress deep veins within the leg; a stretching device coupled to the applanation device for applying a force to the applanation device, wherein when the stretching device is expanded, the stretching device applies a force to the applanation device, the force being transmitted to the surface of the leg by a tissue contacting surface of the applanation device, causing the deep vein to be compressed and minimizing blood flow through the deep vein; a controller operably coupled to the expansion device, the controller configured to control expansion of the expansion device; and a transmitter operably coupled to the controller for transmitting and receiving signals to an external device; A device comprising: (Item 45) 1. A system for the prevention of deep vein thrombosis in a patient, the system comprising: The DVT prevention device according to item 45, an external device configured to communicate with the DVT prevention device; A system comprising: (Item 46) Item 46. The DVT prevention system of item 45, wherein the external device includes a software module for wirelessly adjusting parameters associated with inflation of the expansion device. (Item 47) Item 47. The DVT prevention system according to item 46, wherein the parameter is at least one of inflation pressure, inflation time, or interval between inflations. (Item 48) Item 46. The DVT prevention system of item 45, wherein the external device comprises a mobile phone or tablet device. (Item 49) Item 46. The DVT prevention system of item 45, wherein the external device is configured to display parameters associated with inflation of the expansion device. (Item 50) Item 49. The DVT prevention system of item 49, wherein the external device is configured to allow a user to adjust the inflation parameters. (Item 51) Item 49. The DVT prevention system according to item 49, wherein the inflation parameter is at least one of inflation pressure, inflation time, or time remaining in an inflation cycle. (Item 52) 1. A method of preventing deep vein thrombosis (DVT) in a patient, the method comprising applying a force from an applanation device to a surface of the patient's leg to compress deep veins in the leg and minimize blood flow through the deep veins, the force being applied in compression cycles comprising: i) a pulse period comprising a series of force pulses with relaxation intervals between said pulses; ii) the holding period of the constant force, and iii) A relaxation period with little or no force applied Including, Upon completion of the cycle, the blood velocity in the compressed vein remains elevated by at least about 100% for an extended period of time compared to the blood velocity in the compressed vein prior to application of force. (Item 53) 53. The method of claim 52, wherein the force is applied from an applanation device. (Item 54) 53. The method of claim 52, wherein the applanation device is positioned on an inner surface of a cuff, the method further comprising positioning the cuff over a portion of the patient's leg such that the applanation device is positioned over the selected deep vein. (Item 55) 53. The method of claim 52, wherein the pulse duration is in the range of about 1 to 20 seconds. (Item 56) Item 53. The method according to item 52, wherein the relaxation interval is within the range of about 1 to 20 seconds. (Item 57) Item 53. The method according to item 52, wherein the holding period is within the range of about 1 to 5 minutes. (Item 58) Item 53. The method of item 52, wherein the series of force pulses comprises five pulses. (Item 59) 53. The method of claim 52, further comprising repeating the compression cycle. (Item 60) Item 61. The method of item 60, wherein the compression cycle is repeated at least twice. (Item 61) 53. The method of claim 52, wherein the deep vein is a femoral vein, a common femoral vein, a popliteal vein, a posterior tibial vein, an anterior tibial vein, or a peroneal vein. (Item 62) 53. The method of claim 52, wherein the extended period of time is at least about 15 minutes. (Item 63) 53. The method of claim 52, wherein the extended period is up to about 1 hour. (Item 64) 53. The method of claim 52, wherein the blood velocity is increased by at least about 200%. (Item 65) 53. The method of claim 52, wherein the blood velocity is increased by at least about 300%. (Item 66) Item 53. The method of claim 52, wherein the blood velocity is increased within the range of about 484 to 506%. (Item 67) Item 53. The method of claim 52, wherein the blood velocity is increased within the range of about 355 to 633%. (Item 68) 53. The method of claim 52, wherein the blood velocity is a peak velocity. (Item 69) 53. The method of claim 52, wherein the increase in blood velocity occurs when the patient's knee is flexed. (Item 70) Item 53. The method of item 52, wherein the increase in blood velocity occurs when the patient's knee is straight. (Item 71) 53. The method of item 52, wherein the occurrence of embolism caused by DVT is prevented. (Item 72) Item 72. The method according to item 71, wherein the occurrence of pulmonary embolism caused by DVT is prevented. (Item 73) 53. The method of claim 52, wherein the compression cycles are performed while the patient is engaged in ambulatory activity. (Item 74) Item 74. The method of item 73, wherein the ambulatory activity is walking or running. (Item 75) 53. The method of claim 52, wherein the applied force from the applanation device does not damage venous valves in the compressed vein. (Item 76) 53. The method of claim 52, wherein the applied force from the applanation device does not damage venous valves in the selected leg. (Item 77) 1. A method of preventing deep vein thrombosis (DVT) in a patient, the method comprising applying force from an applanation device to a surface of the patient's leg to compress deep veins in the leg and minimize blood flow through the deep veins; the force is applied in a series of force pulses with relaxation intervals between the pulses; Upon completion of the series of force pulses, blood velocity within the compressed vein is increased by approximately 281 to 483% compared to blood velocity within the compressed vein prior to application of force. (Item 78) 78. The method of claim 77, wherein the compression cycles are performed while the patient is engaged in ambulatory activity. (Item 79) 1. A method of preventing deep vein thrombosis (DVT) in a patient, the method comprising applying a force from an applanation device to a surface of the patient's leg to compress deep veins in the leg and minimize blood flow through the deep veins, the force being applied in compression cycles, the compression cycles comprising: i) a pulse period comprising a series of force pulses with relaxation intervals between said pulses; ii) the holding period of the constant force; and iii) A relaxation period with little or no force applied Including, Upon completion of the cycle, blood velocity within the compressed vein remains elevated for an extended period of time. (Item 80) 80. The method of claim 79, wherein the increase in blood velocity is at least about 100% compared to the blood velocity in the compressed vein prior to application of force. (Item 81) 80. The method of claim 79, wherein the extended period of time is at least about 15 minutes. (Item 82) 80. The method of claim 79, wherein the extended period is up to about 1 hour. (Item 83) 80. The method of claim 79, wherein the compression cycles are performed while the patient is engaged in ambulatory physical activity. (Item 84) 80. The method of claim 79, wherein the applied force from the applanation device does not damage venous valves in the compressed vein. (Item 85) 80. The method of claim 79, wherein the applied force from the applanation device does not damage venous valves in the selected leg. (Item 86) 1. A method of increasing blood flow within a patient's venous system, the method comprising applying a force from an applanation device to a surface of an appendage of the patient to compress at least one vein within the appendage and minimize blood flow through the at least one vein, the force being applied in compression cycles; The compression cycle comprises: i) a pulse period comprising a series of force pulses with relaxation intervals between said pulses; ii) the holding period of the constant force, and iii) A relaxation period with little or no force applied Including, Upon completion of the cycle, blood velocity in the at least one compressed vein remains elevated for an extended period of time. (Item 87) 87. The method of claim 86, wherein the increase in blood velocity is at least about 100% compared to the blood velocity in the at least one compressed vein prior to application of force. (Item 88) 87. The method of claim 86, wherein the extended period of time is at least about 15 minutes. (Item 89) Item 87. The method of item 86, wherein the extended period is up to about 1 hour. (Item 90) Item 87. The method of item 86, wherein the appendage is a leg. (Item 91) Item 91. The method of item 90, wherein the at least one vein is a deep vein, a femoral vein, a common femoral vein, a popliteal vein, a posterior tibial vein, an anterior tibial vein, or a peroneal vein. (Item 92) 87. The method of claim 86, wherein the increased blood flow produces a physiological benefit. (Item 93) 87. The method of item 86, wherein the physiological benefit is prevention of deep vein thrombosis. (Item 94) 87. The method of item 86, wherein the physiological benefit is prevention of pulmonary embolism. (Item 95) 87. The method of claim 86, wherein the physiological benefit is increased venous return to the patient's heart. (Item 96) 87. The method of claim 86, wherein the physiological benefit is increased cardiac output. [Brief explanation of the drawings]

[0040] [Figure 1] FIG. 1 is a schematic diagram illustrating an embodiment of a deep vein thrombosis prevention device and system.

[0041] [Figure 2] FIG. 2 is a cross-sectional view of an embodiment of a deep vein thrombosis prevention device.

[0042] [Figure 3A] FIG. 3a is a perspective view of an embodiment of a deep vein thrombosis prevention device showing the applanation device in an undeployed state.

[0043] [Figure 3B] FIG. 3b is a perspective view of an embodiment of a deep vein thrombosis prevention device showing the applanation device in a deployed state.

[0044] [Figure 4A] FIG. 4a is an axial view of the knee area around which the DVT prevention device is positioned, showing the device in a non-deployed state.

[0045] [Figure 4B] FIG. 4b is an axial view of the knee area where the DVT prevention device is positioned around the knee showing the device at the deployment date with the applanation device pressing against the tissue to flatten / compress and close the popliteal vein.

[0046] [Figure 5-1] 5a and 5b are graphs of value versus time, with FIG. 5a showing an embodiment of a pressure cycle and FIG. 5b showing a generalized resulting increase in total femoral venous peak velocity.

[0047] [Figure 5-2] 5c and 5d are pressure versus time graphs depicting different waveforms for the pressure pulses used in the pressure cycle, with FIG. 5c depicting a pressure pulse having a square wave shape, while FIG. 5d depicts a pressure pulse having a sinusoidal wave shape.

[0048] [Figure 6] 6a and 6b are graphs of value versus time, with FIG. 6a showing an embodiment of a pressure cycle and FIG. 6b showing the resulting increase in total femoral venous velocity for the particular individual whose total femoral venous velocity was measured. DETAILED DESCRIPTION OF THE INVENTION

[0049] (Detailed Description of the Invention) Various embodiments of the present invention provide devices, systems, and methods for the prevention of deep vein thrombosis (DVT) in appendages such as the arms and legs. Many embodiments provide devices, systems, and methods for the prevention of deep vein thrombosis (DVT) in the veins of the legs, including, for example, the femoral, popliteal, or tibial veins. Certain embodiments provide a DVT prophylaxis (DVTP) device configured to fit over a patient's knee to prevent DVT in one or more of the distal common femoral, popliteal, posterior tibial, anterior tibial, and peroneal veins. With respect to nomenclature, as used herein, the term "prevent" (and the related terms "prevention" or "preventing") means one or more of the following: reducing the likelihood of occurrence of a medical condition or event (e.g., deep vein thrombosis), reducing the number of occurrences of a medical condition or event, reducing the severity of a medical condition or event, or reducing the duration of a medical condition or event. Such medical conditions or events may include, but are not limited to, vascular thrombosis, venous thrombosis, and deep vein thrombosis, and related conditions or events (e.g., embolism, pulmonary and cerebral embolism, ischemia, and edema). The term "about" means within 10% of a stated value, including those relating to measurements, characteristics, parameters, or properties, and more preferably within 5% of such stated value. Similarly, the term "substantially" means within 10% of a stated property, condition, or state, and more preferably within 5% of such property, condition, or state.

[0050] 1-6, an embodiment of a deep vein thrombosis prevention device 10 can include a cuff 20, an applanation device 30, an expansion device 40, such as an expandable balloon or other expandable member, a pressure source 50, and a controller 60. The applanation device 30 is typically coupled to the inner surface 25 of the cuff. The balloon or other expandable member 40 is positioned between the applanation device 30 and a hinge plate 71 described herein. The pressure source 50 is fluidly coupled to the expandable member 40.

[0051] 4a and 4b are axial views illustrating the use of device 10 to compress the popliteal vein (PV) or other deep vein (DV). The figures show the cuff wrapped around the knee area (KA) with the balloon in an inflated / undeployed state (FIG. 4a) and a deployed state (FIG. 4b). When the balloon or other expandable member 40 is expanded, it applies a force to the applanation device 30, which is transferred by the tissue-contacting surface 35 of the applanation device as a force / pressure to the surface of the leg (in this case, the posterior portion of the knee (PP)), causing the deep vein (DV), such as the popliteal vein (PV), to be flattened or otherwise compressed to minimize blood flow through the deep vein (DV). When the expandable balloon 40 is deflated, the pressure applied to the leg from the applanation device is discontinued, and the vein expands with the resumption of blood flow.

[0052] Cuff 20 is desirably sufficiently elastic to be placed over and positioned over a desired area of a user's leg L, such as the knee area KA. As such, it may comprise various elastomers known in the polymer arts, such as silicone, polyurethane, etc. In additional or alternative embodiments, cuff 20 may be configured to be wrapped over and around leg L (or other appendage, such as an arm) and then held in place by fastening means 28. In various embodiments, fastening means 28 may correspond to one or more of VELCRO®, clamps, clips, bands, straps, or other fastening devices known in the art.

[0053] The applanation device 30 is configured to apply a force to the outer surface of the leg, such as that behind the knee (e.g., to flatten or otherwise compress selected deep veins DV and intermittently substantially stop or reduce blood flow through the leg). Accordingly, as used herein, the term "applanation device" refers to a device or structure for applying a force to an external tissue surface of the body to flatten or otherwise compress veins beneath the tissue surface, typically deep veins. An embodiment of the applanation device 30 has a tissue-contacting surface 35 having a curved or other shape 39 configured to apply sufficient force (per unit area) to the surface of the leg to compress deep veins in the leg, such as the popliteal vein. Typically, the shape 39 will be semicircular or other convex. The force may be in the range of approximately 0.5 to 10 pounds, and in specific embodiments, 1, 2, 3, 5, 6, 7, 8, and 9 pounds. Therefore, the applanation device 30 will desirably be fabricated from a material having sufficient rigidity to apply such a force. Suitable materials include various thermosetting polymers known in the art, as well as rigid metals. Typically, the tissue-contacting surface 35 of the applanation device will have a semicircular shape to concentrate force on the center of the leg or other area containing the selected deep vein. In the case of a popliteal vein (PV), the applanation device diameter 38 is configured to concentrate force between the medial gastrocnemius muscle and tendon and the lateral gastrocnemius muscle and tendon, where the PV is located. Thus, in such embodiments, the diameter 38 of the tissue-contacting surface 35 may also correspond approximately to the distance between the lateral gastrocnemius muscle, tendon / ligament, and the medial gastrocnemius muscle, tendon / ligament, on either side of the popliteal vein, or a divisor thereof, such as one-half, one-third, or one-quarter of that distance. In various embodiments, the applanation device 30 can be custom-fitted to an individual patient (e.g., based on these or other measurements, depending on the area to be treated) and / or custom-fabricated using 3D printing methods. Furthermore, the applanation device 30 is desirably positioned on the cuff so that it is centered over the selected deep vein to be compressed. In the case of the popliteal vein, it corresponds approximately to the center behind the knee.

[0054] The applanation device 30 will typically include a base portion 36 having a rectangular or square shape and a curved tissue-contacting portion 35 attached to or integral with the base portion. As explained above, the tissue-contacting portion 35 of the applanation device 30 will typically have a semicircular or other convex shape, with the convex portion contacting the tissue. In many embodiments, the base portion 36 of the applanation device is attached to a hinge 70 that includes a hinge plate 71 (also known as the base portion 71) that is attached either directly or indirectly to the cuff 20. As shown in Figures 3A and 3B, the hinge 70 also includes a hinge element 77 on one side of the plate 71 that engages a corresponding hinge element 37 on the applanation device 30, allowing the applanation device to pivot up into the tissue when the balloon or other expandable member 40 is inflated. The base portion 71 of the hinge 70 may have a recessed portion 75 in its central area having a contour approximating that of at least a portion of the balloon so as to hold the balloon 40 in place when the balloon is inflated. Additionally, as described below with respect to the support structure, the hinge plate desirably has sufficient rigidity so that it does not significantly deform upon inflation of the balloon and mechanically acts, in a manner similar to the support structure, to prevent expansion of the cuff 20 and direct the balloon inflation force to the applanation device 30 and, in turn, to the underlying tissue compressed by the applanation device.

[0055] According to one or more embodiments, as shown in Figures 3a and 3b, DVT device 10 may also include a support structure 80 attached to cuff 20 and positioned between the cuff and hinge plate 71. Support structure 80 is mechanically constructed, for example, in terms of its shape and rigidity, so that the force generated by balloon or other expansion device 40 is directed inward onto applanation apparatus 30 rather than being dissipated by causing expansion of cuff 20. Desirably, support structure 80 is made of a sufficiently rigid material, such as a thermosetting plastic or metal, that does not deform when the balloon is inflated.

[0056] In certain embodiments, the support structure 80 may comprise a flat surface or may comprise two portions: a recessed portion and a larger flat portion surrounding the recessed flat portion (which, although not shown, may generally correspond to the base 71 (e.g., hinge plate) and contoured portion 75 of the hinge 70). Like the hinge plate, the recessed portion may have a contour corresponding to at least a portion of that of an inflated balloon to partially retain the balloon when inflated. The larger flat portion serves to distribute the force from the balloon expansion over a larger area of the cuff, reducing the pressure on the cuff and therefore the amount of cuff expansion resulting from balloon inflation. This, in turn, reduces the dissipation of force from the balloon expansion by causing the cuff to expand or the VELCRO® constriction portion on the cuff to release. This, in turn, causes a greater amount of balloon expansion force to be transmitted to the applanation device 40 and to the tissue surface, causing compression / flattening of the selected deep vein directly below the applanation device, such as the popliteal vein. Such embodiments are particularly useful for elastic cuff embodiments or those using VELCRO® fastening portions that can become unfastened due to the force from the balloon expanding the cuff. Additionally, desirably having a larger surface area than the overlying hinge plates, the support structure flat portions provide additional mechanical resistance to forces from balloon expansion that tend to cause cuff expansion, while also distributing those forces over a larger area of the cuff, thus reducing the amount and likelihood of cuff expansion.

[0057] The dilation device 40 will typically correspond to various expandable balloons or other expandable members known in the medical device art, including balloon catheter art. For ease of discussion, the dilation device 40 will be referred to herein as either the expandable member 40 or the balloon. According to various embodiments, the expandable balloon 40 can be fabricated from one of various expandable balloon materials known in the medical art, including, for example, silicone, polyurethane, and copolymers thereof. In preferred embodiments, the expandable balloon or other expandable member is fabricated from a relatively inflexible material, such as PET, polyethylene (e.g., HDPE), irradiated polyethylene (e.g., via electron beam technology), and other polymers and copolymers thereof, so that the balloon retains a fixed expanded shape and is capable of applying a force to an applanation device rather than continuing to expand outward beyond its expanded shape. In alternative or additional embodiments, the dilation device may comprise an electromechanically-based dilation device, including, for example, a piezoelectric-based device, a solenoid, an electric motor, or the like. For embodiments using electromechanically based devices, a pressure source is not required and can simply be a power source such as a portable battery known in the art, for example, an alkaline or lithium ion battery.

[0058] The pressure source 50 will typically correspond to a pump 51, such as a pneumatic pump, which may be fluidly connected to the balloon 40 using pneumatic hoses or tubing or connectors 55. The pump is selected and configured to generate sufficient pressure for the expandable member to apply sufficient compressive force from the applanation device to the target tissue surface to flatten / compress the selected deep vein beneath the tissue surface as described herein. The generated pressure may be in the range of approximately 0.5 to 20 atmospheres, and in specific embodiments, 2, 5, 7, 10, and 15 atmospheres. Higher ranges are also contemplated. In various embodiments, the pressure source may correspond to a pneumatic or mechanical pump. In alternative or additional embodiments, the pressure source 50 may correspond to a compressed gas source, including a compressed gas or an inert gas. In various embodiments, the pump 51 (or other pressure source 50) and / or tubing or other connections 55 to the balloon 40 may be acoustically insulated or otherwise acoustically damped using acoustic insulators 52 so that inflation of the balloon 40 or other expandable member 40 is relatively quiet and / or imperceptible to the user. One configuration of such acoustic insulator 52 positioned around pump 51 is shown in FIG. 1 . In various embodiments, acoustic insulator 52 can correspond to open-cell foam rubber, polymer fibers, and polymer sealants (e.g., silicone). Acoustic attenuation can also be achieved through the use of acoustic insulators (e.g., foam) within cuff 20 that cover all or a portion of pump 51 and tubing 55. Other means of acoustic attenuation of pump 51 and / or tubing 55 can include noise-canceling generators known in the art that can be controlled by controller 60. In various embodiments, device 10 can be configured so that the volume of inflation of expandable member 40 by pump 51 or other pressure source 50 is less than about 40 decibels, more preferably less than about 30 decibels, even more preferably less than about 20 decibels, and even more preferably less than about 10 decibels.

[0059] According to one or more embodiments, the pressure source 50 may be directly connected to the balloon 40 or other expandable member 40. The direct connection in this case may include optional connector tubing 55. In additional or alternative embodiments, the balloon or other expandable member 40 may be indirectly connected to the pressure source using a valve 56 fluidly coupled to at least one of the pressure source 50 or the expandable member 40. The valve 56 is configured and positioned to control the pressure released from the pressure source 50 to the balloon or other expandable member 40. Typically, the valve 56 will be positioned between the pressure source 50 and the expandable member 40, but may be positioned elsewhere relative to these elements as well. In other embodiments, the valve 56 may be integral to one or both of the pressure source or the balloon.

[0060] In various embodiments, valve 56 may correspond to one or more control valves known in the art, including, for example, various electronically controlled valves 57, including solenoid valves. For the latter embodiments, valve 56 may be operably coupled to controller 60 such that the controller can send and receive signals to open the valve according to a particular timeline and / or based on pressure measurements. In the latter embodiments, device 10 may also include a pressure sensor 58 fluidly coupled to one or more of pressure source 50 and / or expandable member 40, and operably coupled to controller 60 to send a signal corresponding to the measured pressure to the controller. Pressure sensor 58 may correspond to various electronic and / or solid-state pressure sensors known in the art.

[0061] The controller 60 is configured to control the inflation of the expandable balloon or other expandable member by controlling one or more of the pressure source and / or control valve embodiments described herein. According to various embodiments, the controller is configured to control the inflation of the expandable member 40 to generate a selected pressure cycle and / or compression regimen described herein. In many embodiments, this can be accomplished through the use of a module 61 (typically a software module) containing a set of algorithmic electronic instructions for performing these tasks. The module 61 may also include a pump driver module 64 and a valve driver module 65 to control the generation of pressure and the subsequent inflation of the balloon 40. The controller 60 will typically correspond to a microprocessor, which may be off-the-shelf or incorporated into an ASIC. In other cases, the controller may correspond to a hardware device that may correspond to various analog devices, including various state devices. Combinations of microprocessor- and analog device-based controllers are also contemplated. In certain embodiments, the controller 60 may correspond to a first controller 63 and a second controller 64 for performing different functions. For example, controller 63 may handle communications between device 10 and external device 110 via transmitter 95, while second controller 64 performs various measurement and control functions related to controlling inflation and pressure cycling 200 of balloon 40 as well as power management functions (e.g., battery monitoring). In certain embodiments, controller 63 may correspond to a Lillypad microcontroller board, while second controller 64 may correspond to an electronics board 64 that includes one or more circuits or devices related to control and measurement functions including, for example, controlling valve 56, measuring inflation pressure via sensor 58, and monitoring and controlling charging of battery 90 via battery monitoring and charging circuitry 91. Board 64 may also include or be operably coupled to a user-accessible on-off switch or button 66.

[0062] In many embodiments, DVT prevention device 10 will also include an internal power source 90 for powering controller 60, pressure source 50, or one or more of the other electronic devices or components included within DVT prevention device 10. Suitable power sources 90 include supercapacitors and various electrochemical storage batteries, such as alkaline, lithium, or lithium-ion batteries, although other battery chemistries are also contemplated. For battery-powered embodiments, device 10 may include a battery monitoring circuit 91. The use of rechargeable batteries is also contemplated. In such embodiments, device 10 may include a battery monitoring circuit and may also include a battery charging circuit. In these and related embodiments, the device may be configured to be plugged into an external power source to power the device and recharge the battery. In various embodiments, the external power source may include a wall outlet or a USB source. In these embodiments, device 10 may include a USB charging port or charging port 93. During use, embodiments employing an external power source allow for the conservation of battery power and the provision of a means for recharging batteries and replacing them. For embodiments using battery power, the use of circuitry and / or algorithms to detect the state of battery charge and alert the user is also contemplated.

[0063] In many embodiments, the DVT prevention device 10 will also include a transmitter 95 for wireless communication with external devices, networks, or the cloud. Typically, the transmitter will comprise a small RF transmitter 95 and will be operably coupled to at least the controller. The RF or other transmitter 96 is further configured to transmit and receive signals from external devices, such as a mobile phone, tablet device, or other similar device, allowing the DVT device, including the controller, to communicate wirelessly with these external devices. The RF transmitter 95 may be connected to or integral with the controller. Typically, the transmitter and / or controller will be configured to communicate via the BLUETOOTH® protocol, although other wireless protocols known in the art are also contemplated. For BLUETOOTH® embodiments, the responder 95 may comprise a BLUETOOTH® responder 96 known in the art. In use, such wireless communication capabilities enable a user or physician to do one or more of the following: 1) custom program the DVT device (e.g., specific pressure cycles) for an individual user, 2) receive data regarding device performance (e.g., number of pressure cycles implemented, pressure generated, compression hold time, battery life data), 3) share data with others (e.g., physicians) via the cloud or other network, and 4) reprogram the device as needed depending on the date or changes in patient or mobility status. For example, in the latter case, the device could be specifically programmed with a unique compression regimen for an extended airline trip in which the user will be seated for an extended period of time (e.g., 3-14 hours).

[0064] In alternative or additional embodiments, the DVT prevention device 10 may also include one or more of push buttons 66, a display 67, and an audio alarm 68, one or more of which may be coupled to the controller 60, and in certain embodiments, to the controller 64. The push buttons 66 may be configured to allow a user to do one or more of the following: 1) turn the device on and off, 2) select or adjust a compression regimen and / or pressure cycle, and 3) select or adjust a pressure level. The display 67 may display various information, including the pressure level being used, information about the pressure cycle (e.g., a graph of pressure versus time, the particular cycle / pressure regimen selected and / or implemented, and the time remaining in the cycle), and information about the battery life. In various embodiments, the display 67 may be a touch screen, allowing a user to input information and / or otherwise interact with the device and perform various functions, such as those described with respect to the push buttons. The audio alarm 68 may be configured to alert the user to various events and / or information, including, for example, the start or end of a pressure cycle, interruption of a pressure cycle, and alarms about battery charge / life. Still other information and events are also considered for alerting via alarm 68. In various embodiments, the controller can also be configured to send information about the alarm event to an external device and / or via the cloud, which creates an audio alarm on the external device and / or creates an audio alarm via the cloud to a monitoring physician.

[0065] Various embodiments of the present invention also provide a system 100 for preventing deep vein thrombosis (DVT) that includes an embodiment of the DVT prevention device 10 described herein and an external device 150, such as a mobile phone, tablet device, or the like, configured to communicate with the DVT prevention device as shown in FIG. 1. In many embodiments, the external device 100 and the DVT device 10 are configured to communicate with each other using the BLUETOOTH® communication protocol; in such embodiments, each device would include a BLUETOOTH® transponder, as known in the art. Typically, the device 150 has a display 160 and may also have one or more buttons or switches or other user-activated actuators 155.

[0066] External device 150 will typically include a software module (not shown) for displaying and / or wirelessly adjusting one or more parameters of the balloon inflation process, including, for example, the set balloon inflation pressure, the actual balloon inflation pressure, the balloon inflation time, the interval between inflations, and the time remaining in the current balloon inflation or inflation cycle described herein, as well as related parameters and metrics. This can be accomplished using buttons or switches 155 (e.g., accessible through display 160), which may be real or virtual. Display 160 of external device 150 may also be configured to allow a user to select, view, or wirelessly change one or more of the above or other parameters used by the DVT device. Thus, in use, the software module on external device 150 functions as a chimeric application, allowing the patient or physician to wirelessly view and control various parameters and metrics of the DVT device.

[0067] Various methods of using embodiments of the deep venous prevention device 10 to prevent deep vein thrombosis and related embolic events, such as pulmonary embolic events (PEE), will now be described. In one embodiment, the method includes placing an embodiment of the DVT prevention device 10 described herein around a patient's limb, such as the leg, at risk of developing a DVT due to poor circulation. In a specific embodiment, the device is placed around the patient's knee to compress one or more of the popliteal, femoral, or tibial veins. The device may be placed over or wrapped around the knee. A balloon or other expansion device is then expanded according to a pressure cycle or compression regimen.

[0068] One embodiment of such a pressure cycle or compression regimen 200, depicted in Figure 5A, includes periods 210 of intermittent balloon inflation and application of compression force to tissues down the leg (herein, force application periods 220), followed by periods 220 of balloon inflation and application of applied compression force (herein, compression hold periods 220), followed by relaxation periods 230 corresponding to balloon deflation and little or no compression force as shown in Figures 5A and 6A. The intermittent inflation compression application periods 210 may, in some embodiments, correspond to a series of compression pulses 215 (corresponding to balloon inflation) with intervals of relaxation 217 (corresponding to balloon deflation) between them, as shown in Figures 5A, 5C, 5D, and 6A. In the embodiment of pressure cycle 200 depicted in Figures 5A and 6A, the successive pressure pulses 215 are numbered 1, 2, 3, 4, 5, and the compression hold periods 220 are indicated by a horizontal line extending from point A to point B. The corresponding increase in venous blood velocity (e.g., that of the common femoral vein) after each pressure pulse 215 is indicated by points 1, 2, 3, 4, and 5 in Figures 5B and 6B. The corresponding increase from the compression hold period 230 is indicated in Figures 5B and 6B by the increasing rate going from point A to B. The end of the compression hold period 230 is indicated by point C in Figures 5A and 5B. The baseline venous blood velocity is indicated by point VB in Figures 5A and 5B. The increase in venous velocity baseline after completion of the pressure cycle 200 is also indicated by point C in Figure 5A.

[0069] In various embodiments, the compression pulses 215 (also described herein as pressure pulses or force pulses) may be in the form of a square wave, as shown in FIG. 5C , or a sinusoidal wave, as shown in FIG. 5D , although other shapes, such as sawtooth, are also contemplated. In additional or alternative embodiments, the pulse amplitude of the pulses 215 can be continuously increased (or decreased) in a selected manner (e.g., linear, geometric, first order, second order, etc.) to optimize the resulting increase in blood velocity in the selected compressed vein. One or more of the timing, sequence, number, morphology (i.e., waveform), or other characteristics of the compression pulses 215 may be controlled by the controller 60, for example, through the use of the pump drive module 64 and / or the valve drive module 65 or other modules 61.

[0070] Furthermore, in additional or alternative embodiments, the compression pulses 215 may be synchronized or counter-synchronized to the user's heartbeat. Such embodiments may be implemented through pulse detection means operably coupled to the controller 60. Exemplary pulse detection means may include, but are not limited to, pulse oximetry devices, acoustic sensing devices, and EKG sensing devices known in the art.

[0071] A cycle 200, including a compression pulse 215, a compression hold period 220, and a relaxation period 230, can be repeated multiple times (e.g., 2, 3, 4, 5, etc.) over a selected period of time. As shown in FIGS. 5b and 6b, femoral blood velocity not only increases immediately above baseline with the first compression pulse 215 and steadily increases with each subsequent compression pulse 215 (e.g., pulse numbers 1, 2, 3, 4, 5, etc.), but also reaches a new baseline velocity at point C' after the hold period 220 continues to increase. In FIG. 6b, which depicts venous blood velocity for an actual patient, the increase in blood velocity above baseline VB after the first pulse 215 is dramatic—an almost three-fold increase—and then each subsequent compression pulse results in a six-fold increase at the beginning of the hold period 230 (indicated by point A) and an eight-fold increase at the end of the hold period (indicated by point B).

[0072] As shown in the Examples section, use of such a pressure cycle 200 on test subjects resulted in an average increase in peak blood velocity in the common femoral vein of approximately 388 to 506%, depending on whether the test subjects were seated with their knees bent or recumbent with their knees straight. The largest increase was obtained after the pressure hold period 220. After completion of the cycle, baseline peak velocity remained elevated for periods of 5 to 60 minutes, and two specific individual baseline levels remained elevated for 15 and 60 minutes, respectively, thus demonstrating the long-term effectiveness of cycle 200 in maintaining elevated levels of venous circulation in the tissue region of the leg or other limb compressed by the applanation device. Such long-term increases in venous blood velocity not only prevent DVT in the affected veins, but also prevent pulmonary embolism or related thrombotic events caused by DVT. In some embodiments, cycle 200 may include only a series of compression force pulses 215 with intervals of relaxation 217 between them. As shown in the Examples section, such cycling resulted in increases in peak venous velocity ranging from 281 to 483%.

[0073] A discussion of values for the cycle parameters discussed above (e.g., pulse duration, etc.) will now be presented. In various embodiments, the number of compression pulses 215 can be in the range of approximately 2 to 20, and in specific embodiments, 4, 5, 10, 12, 15, and 20. In the embodiment described in the Examples, five pressure pulses were used, resulting in an increase in peak venous velocity in the range of 281 to 483%. An increased number of pulses can be used to obtain higher subsequent blood velocities. Furthermore, the pressure pulses 215 can have a selected duration 216, for example, in the range of approximately 1 to 20 seconds, and in specific embodiments, 5, 10, and 15 seconds. Longer durations are also contemplated. The interval of relaxation 217 between pulses can be in the range of approximately 1 to 20 seconds, and in specific embodiments, 5, 10, and 15 seconds. Longer durations are also contemplated. The compression hold period 220 ranges from approximately 30 seconds to 5 minutes, and in specific embodiments, can be 1, 2, 3, and 4 minutes, with longer periods also being contemplated. As discussed herein, one or more of the above parameters can be adjusted for an individual patient depending on their age, weight, previous history of deep vein thrombosis, anticoagulation treatment (e.g., type and amount of a given drug dosage, such as ZARELTO or WARFARIN), and one or more of various hemodynamic parameters (e.g., mean blood velocity, peak venous blood velocity, blood pressure, and pulse for the selected vein). In specific embodiments, one or more of the above parameters can be obtained using ultrasound imaging and Doppler blood velocimetry approaches described in the Examples section and / or known in the art. In this manner, the patient can obtain an optimized or otherwise improved response in device use to increase venous blood velocity and flow within the treated area, which in turn reduces the risk of DVT. Additionally, these parameters may be adjusted by a user or physician in response to changes in one or more of the patient's physical condition, activity level, or medications (e.g., anticoagulants or blood pressure medications) using the external device embodiments described herein.In related embodiments, they may be adjusted based on the duration the patient is expected to be in a sedentary position with limited mobility (e.g., an airplane flight or ride) to prevent the development of DVT during that period.

[0074] In other aspects of the invention, embodiments of the DVT prevention device can be used to increase venous blood velocity and flow to produce one or more physiological benefits. Such benefits (in addition to DVT and associated PE prevention) may include, for example, increased venous return, increased cardiac output, or reduced lactate and / or CO2 levels (in the leg, arm, or other limb or tissue site compressed by an embodiment of the device 10). In certain embodiments, the device 10 and pressure regimen 200 can be adapted to increase venous blood velocity and flow to increase venous return in patients suffering from venous insufficiency. In other embodiments, the device 10 and pressure regimen 200 can be adapted to increase venous blood velocity and flow to increase cardiac output in patients suffering from one or more forms of heart failure, particularly left ventricular failure. Because under the Frank-Starling mechanism (known to those skilled in the art of circulatory physiology), an increase in venous return results in an equal or nearly equal increase in cardiac output (due, inter alia, to an increase in ventricular filling volume), embodiments of device 10 and pressure regimens can be used to generate increases in cardiac output that correspond to the increases in venous blood flow generated by device 10 and a particular pressure cycle 200. In certain embodiments, cardiac output monitoring methods and instrumentation known in the art can be used to develop correlations between increased venous blood velocity and increases in cardiac output. These correlations can then be used to adjust the increases in venous blood velocity generated by a pressure cycle to result in a desired amount of increase in cardiac output.

[0075] In certain embodiments, patients requiring increased cardiac output (e.g., patients suffering from left ventricular heart failure) may use device 10 to undergo multiple pressure cycles over the course of a day to maintain their cardiac output at a desired level (e.g., 5 liters / minute). The patient may do so by wearing device 10 continuously to receive the desired number of pressure cycles, or may wear the device at set intervals (e.g., once every hour, every two hours, etc.). The patient may wear device 10 multiple times, for example, once on each leg, to produce an enhanced increase in venous return and a resulting increase in cardiac output. This approach may also allow a reduced number of pressure cycles to be implemented over the course of the day.

[0076] Embodiments of device 10 and regimen 200 can also be configured to produce one or more of the physiological benefits described above to provide improved athletic performance, for example, by increasing cardiac output and / or reducing lactic acid buildup and / or CO2 levels in exercising muscles. Improved athletic performance may include improved performance in running, swimming, weightlifting, or other aerobic or anaerobic exercise. In certain embodiments, pressure regimen 200 can be adapted to produce increased venous velocity and blood flow rates tailored for improved performance in selected exercises or activities, such as running or cycling. Maximal oxygen uptake and various blood gas measurements (e.g., P CO2, P O2, PSpecific metrics of athletic performance, such as H, HCO, etc., can be used to adjust or fine-tune pressure cycles 200 to optimize or otherwise increase user performance in a given exercise (e.g., running, cycling, swimming, weightlifting, etc.) and for a given intensity level and duration of exercise (sprints versus longer distances). The optimized pressure cycles 200 for a given exercise and exercise duration can then be stored in memory on controller 60 (e.g., in the form of module 61) or in a memory resource coupled to the controller. In one or more methods for using device 10 to enhance performance in a given exercise, a user may wear one or more devices 10 (e.g., on a leg or arm), select a particular pressure cycle 200, and undergo one or more pressure cycles 10 for a selected period of time before a given exercise (e.g., running). In some embodiments, a user may wear device 10 and undergo one or more pressure cycles 200 while the user is exercising to maintain enhanced venous blood flow while the user is exercising. A user may keep the device 10 on for a selected period of time after exercise is completed, or wear it thereafter, to maintain increased venous blood flow after exercise. In use, such embodiments serve to reduce the levels of metabolites in tissues after exercise that cause muscle soreness and fatigue. This, in turn, shortens muscle recovery time from exercise, particularly intense anaerobic exercise such as sprinting or weightlifting, or prolonged aerobic exercise such as long-distance running, cycling, or swimming.

[0077] (Example)

[0078] Various embodiments of the present invention will now be further illustrated with reference to the following examples, however, it should be understood that these examples are presented for illustrative purposes and that the invention is not limited by these specific examples or the details therein.

[0079] Experimental Design: To demonstrate that embodiments of the DVT device improve the efficiency of peripheral and central venous return and are comparable to previously approved devices, a brief study was conducted to evaluate the amount of increase in peripheral and central venous velocity using embodiments of the DVT prophylaxis device. Five healthy adult volunteers with no history of DVT or pulmonary embolism were selected for the study.

[0080] Study Protocol: The study protocol was as follows. First, the superficial, deep, and common femoral veins were imaged with the volunteer in the sitting and semi-recumbent positions. In the semi-recumbent position, the subject's knees were straight, their legs were extended, and their torso was upright. In the sitting position, the subject's knees were flexed. Baseline peak total femoral venous blood velocity was measured. Second, the popliteal vein was imaged and demonstrated to be compressible with the ultrasound probe, demonstrating the absence of any DVT in the popliteal vein at the time of the experiment. Third, the device was placed on the volunteer, and occlusion of the popliteal vein by the device was demonstrated under live ultrasound imaging. Fourth, the ultrasound probe was placed over the common femoral vein, and peak total femoral venous blood velocity was measured during the device cycle. The device was then allowed to cycle through five compression pulse periods, followed by a period of holding compression force, as described above. Fifth, the device was turned off and after 5 minutes, peak total femoral venous blood velocity was measured using Doppler ultrasound.

[0081] (result)

[0082] The results of the study are shown in Tables 1 and 2, with subjects in a semi-recumbent position with their knees straight (Table 1) or in a seated position with their knees bent (Table 2). The results for both positions were dramatic and unexpected. For the semi-recumbent position with straight knees, the device demonstrated an average increase of approximately 388% in peak total femoral venous blood velocity (PCVV) after device pulsing and an average increase of approximately 484% in peak total femoral venous blood velocity after the backpressure development phase of the cycle. For the seated position with bent knees, the device demonstrated an average increase of approximately 387% in peak total femoral venous blood velocity (PCFVV) after device pulsing and an average increase of approximately 506% in peak total femoral venous blood velocity after the backpressure development phase of the cycle. Furthermore, after completion of the cycle, baseline PCFVV remained elevated for extended periods, e.g., 15–60 min, demonstrating the long-term effectiveness of the device and procedure in maintaining elevated velocities in the common femoral vein. [Table 1] [Table 2]

[0083] The foregoing description of various embodiments of the invention has been presented for purposes of illustration and description. It is not intended to limit the invention to the precise form disclosed. Many modifications, variations, and refinements will be apparent to those skilled in the art. For example, various embodiments of DVT prevention devices can be adapted for appendages other than legs, including arms. They can also be sized and otherwise adapted for various pediatric uses. Furthermore, they can be adapted to allow a user to sit, lie, or stand. Still further, they can be adapted to allow a user to ambulate. This includes engaging in various ambulatory activities, including walking, running, or cycling, and similar activities. This includes various exercises on devices that simulate one or more of these activities, such as various elliptical exercise machines. In these and related embodiments, the cuff can be configured with increased flexibility to allow a user to easily bend and flex their knee. Additionally, embodiments of the DVT prevention device can be used and / or adapted to increase venous blood flow to produce one or more other physiological benefits (in addition to DVT or PE prevention), including, for example, increased venous return, increased cardiac output, reduced lactate accumulation and / or CO2 levels in the leg, arm, or other limb or tissue site so compressed by embodiments of the DVT prevention device 10. One or more of these benefits can be selected to improve user performance in exercise or activities such as walking, running, swimming, or cycling.

[0084] Elements, features, or acts from one embodiment can be readily combined with or substituted for one or more elements, features, or acts from other embodiments to form numerous additional embodiments within the scope of the present invention. Furthermore, elements shown or described as being combined with other elements can exist as stand-alone elements in various embodiments. Furthermore, embodiments of the present invention specifically contemplate the exclusion of an element, act, or feature when that element, act, or feature is affirmatively recited. Accordingly, the scope of the present invention is not limited to the details of the described embodiments, but instead is limited only by the appended claims.

Claims

1. A method of operation of a deep vein thrombosis prevention system, the system including a wearable device, the wearable device including a cuff, an applanation device, an expandable member, a pressure source fluidly coupled to the expandable member, and a controller operably coupled to the pressure source, the cuff configured to be positioned over a user's knee, the applanation device located on the cuff and positioned over a posterior aspect of the knee when the cuff is placed over the knee, the applanation device having a tissue contacting surface, the tissue contacting surface having a shape configured to apply pressure to the posterior aspect of the knee to compress deep veins in the user's leg, the expandable member coupled to the applanation device for applying a force to the applanation device when expanded, the device configured to function when the user is engaged in ambulatory activity, the method comprising: the controller using the pressure source to expand the expandable member, the expandable member being cyclically expanded in cycles comprising: i) a pulse period comprising a series of pulses with intervals of relaxation between pulses; ii) a hold period of constant expansion; and iii) a relaxation period of little or no expansion. A method comprising:

2. The method described in claim 1, wherein the cycle is controlled by the controller operably coupled to the pressure source.

3. The method of claim 2, wherein the controller is configured to adjust one or more cycle parameters based on feedback from a pressure sensor fluidly coupled to at least one of the expandable member or the pressure source.

4. A method described in any one of claims 1 to 3, wherein one or more cycle parameters are adjusted based on user attributes including at least one of the user's knee size, the user's hemodynamic parameters or the user's physical condition.

5. A method according to any one of claims 1 to 4, wherein the wearable device is configured to be activated while the user is walking, running, or engaged in other ambulatory activity.

6. A method according to any one of claims 1 to 5, wherein the deep vein is a popliteal vein, and the wearable device is configured to be placed over the user's knee such that the applanation device is configured to compress the popliteal vein when the device is activated.

7. A method as described in any one of claims 1 to 6, wherein the applanation device has a diameter that is custom-fitted to the user's leg so as to be configured to compress the user's popliteal vein.

8. A method described in any one of claims 1 to 7, wherein the applanation device has a diameter corresponding to approximately 1 to 3 times the distance between the user's medial gastrocnemius tendon and lateral gastrocnemius tendon behind the user's knee or the diameter of the user's popliteal vein.

9. A method described in any one of claims 1 to 8, wherein the pulse duration is in the range of approximately 1 to 20 seconds.

10. A method described in any one of claims 1 to 9, wherein the relaxation interval is within the range of approximately 1 to 20 seconds.

11. A method described in any one of claims 1 to 10, wherein the holding period is within the range of approximately 1 to 5 minutes.

12. A method according to any one of claims 1 to 11, wherein the series of pulses comprises five pulses.

13. The method of claim 1, further comprising repeating the cycle.

14. A method according to any one of claims 1 to 13, wherein the system includes an external device configured to communicate with the wearable device, and the method further includes sending or receiving signals between the wearable device and the external device.

15. The method of claim 14, further comprising programming or reprogramming the cycle using the external device.

16. The method described in claim 14 or 15, wherein the external device is a mobile phone.

17. A method described in any one of claims 14 to 16, wherein the signal is transmitted via the cloud.

18. A method according to any one of claims 1 to 17, wherein the wearable device includes a support structure coupled to the cuff and positioned between the cuff and the expandable member, the support structure configured to direct forces generated by expansion of the expandable member inwardly onto the applanation device, and the generated forces are not dissipated by expansion of the cuff.

19. A method according to any one of claims 1 to 18, wherein a base portion of the applanation device is attached to a hinge plate which is attached either directly or indirectly to the cuff so as to allow the applanation device to pivot into tissue when the expandable member is inflated, and the hinge plate has a recessed portion having a contour approximating at least a portion of the contour of the expandable member so as to hold the expandable member in a fixed position when the expandable member is inflated.

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