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Method for Determining Condition of Disseminated Intravascular Coagulation

a technology of disseminated intravascular coagulation and condition determination, which is applied in the direction of instruments, biochemical equipment and processes, material analysis, etc., can solve the problems of affecting the survival rate of patients, so as to reduce the mortality rate, improve the survival rate, and improve the effect of accuracy diagnosis

Inactive Publication Date: 2009-01-01
MITSUBISHI CHEM MEDIENCE +1
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  • Summary
  • Abstract
  • Description
  • Claims
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AI Technical Summary

Benefits of technology

The present invention relates to a method for diagnosing disseminated intravascular coagulation (DIC) using a combination of fibrin formation and platelet consumption. DIC is a severe disease that can lead to organ failure and bleeding if not treated early. The current diagnostic criteria are not suitable for an early diagnosis, and there are many cases where the disease is at an advanced stage when it is too late for effective treatment. The invention provides a method for early diagnosis and treatment of DIC using a combination of fibrin formation and platelet consumption. This method can also be used to diagnose other conditions such as microangiopathic hemolytic anemia (MAHA) and sepsis.

Problems solved by technology

The microthrombi damage the microcirculation and cause organ dysfunction or a bleeding tendency.
(1) The microthrombus formation causes a microcirculatory failure, and a variety of organs fall into dysfunction due to ischemia.
(2) The microthrombus formation promotes a consumption coagulopathy, that is, an increase in tissue factor production on the surface of endothelial cells leads to activation of an extrinsic coagulation pathway. Further, coagulation factors and platelets are consumed, and a bleeding tendency occurs.
(3) Hyperfibrinolysis, that is, the fibrinolytic system activated due to the activation of coagulation, generates plasmin, which degrades fibrin. When the α-plasmin inhibitor (α2PI), which inhibits plasmin, is consumed and decreased to less than 60% of the normal level, fibrin is degraded by the plasmin and a bleeding tendency occurs.
The diagnostic criteria are suitable for a definitive diagnosis of DIC, but are not suitable for an early diagnosis of DIC.
Where a clinical treatment of DIC is carried out in accordance with the diagnosis criteria, there are many cases in which DIC is at such an advanced stage that it is too late.
Further, there are not a few cases, in the clinical field, where it is difficult to carry out a differentiation as to whether or not a decreased platelet count is caused by DIC.
These conditions or diseases are sometimes accompanied by elevated FDPs and / or elevated D-dimer as well as decreased platelets, and it becomes more difficult to carry out a differentiation of DIC.
Erythrocytes which forcibly have passed through these narrowed portions are mechanically broken, and hemolysis occurs.
Therefore, the administration of FFP alone is insufficient to treat acquired and idiopathic TTP, and a plasma exchange (PE) is the first option.
The mortality rate before the introduction of the PE or the FFP transfusion therapy was more than 80%, and the prognosis was very poor.
However, many refractory cases and recurrent cases are known, and there remain problems to be solved.
Further, advanced TTP is refractory and has a poor prognosis, and thus, an early diagnosis and an early treatment are necessary.

Method used

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  • Method for Determining Condition of Disseminated Intravascular Coagulation
  • Method for Determining Condition of Disseminated Intravascular Coagulation
  • Method for Determining Condition of Disseminated Intravascular Coagulation

Examples

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example 1

Measurements of Coagulation and Fibrinolysis Marker Levels in Patients with DIC and Patients with TTP

[0049]Samples of 3.8% citrated plasma were collected from patients with DIC (n=23) and patients with TTP (n=2). Marker levels except for a platelet count were measured with LPIA-NV7 (Mitsubishi Kagaku Iatron) using commercially available kits (LPIA series; Mitsubishi Kagaku Iatron). Samples of 3.2% citrated plasma were collected, and a platelet count was measured with KX-21 (Sysmex).

[0050]The results of the measurements are shown in Table 1. In Table 1, PAI-1 means a plasminogen activator inhibitor-1, D-D means D-dimer, Fbg means fibrinogen, FDP-P means plasma FDPs, PLT means platelets, and TAT means a thrombin / antithrombin III complex. The patients diagnosed with DIC included patients with a remarkably decreased platelet count, but these patients could not be distinguished from patients with TTP, based on only conventional coagulation and fibrinolysis marker levels.

TABLE 1PICPAI-1D-...

example 2

Analysis of Amount of ADAMTAS13 Antigen, Enzyme Activity of ADAMTS13, and Amount of vWF Antigen in Patients with DIC and Patients with TTP

[0051]Samples of 3.8% citrated plasma were collected from healthy persons (n=12), patients suffering from DIC (n=23) and patients suffering from TTP (n=2). In this regard, the DIC patients were diagnosed with DIC in accordance with the diagnostic criteria for DIC as described above, and the TTP patients were diagnosed with TTP in accordance with clinical findings. The amount (Aag) of an ADAMTS13 antigen was determined using a commercially available kit (ADAMTS-13 ELISA kit; Mitsubishi Kagaku Iatron). The enzyme activity (Aact) of ADAMTS13 was determined by an SDS-agarose gel electrophoresis [Furlan M. et al., Blood, (U.S.A.), 1997, vol. 89, p. 3097-3103]. The amount (Vag) of a vWF antigen was determined using a commercially available kit (STA LIAtest: Roche Diagnostics).

[0052]The results of the measurements are shown in Table 2. In Table 2, Aag an...

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Abstract

A method for determining a condition of disseminated intravascular coagulation (DIC), by analyzing the amount and / or enzyme activity of a von Willebrand factor (vWF)-cleaving protease (ADAMTS13) (preferably also the amount of vWF) in a patient suffering from DIC, and a kit for determining a condition of DIC, comprising an antibody or a fragment thereof which specifically binds to ADAMTS13, are disclosed. According to the present invention, a differential diagnosis of patients with thrombotic thrombocytopenic purpura (TTP) can be carried out from among patients with DIC, which could not be distinguished on the basis of only clinical findings or known markers.

Description

TECHNICAL FIELD[0001]The present invention relates to a method for determining a condition of disseminated intravascular coagulation (hereinafter referred to as DIC).BACKGROUND ART[0002]In DIC, microthrombi are formed in microvasculature, in the presence of a severe underlying disease. The microthrombi damage the microcirculation and cause organ dysfunction or a bleeding tendency. The following three failures or reactions are observed in DIC:(1) The microthrombus formation causes a microcirculatory failure, and a variety of organs fall into dysfunction due to ischemia.(2) The microthrombus formation promotes a consumption coagulopathy, that is, an increase in tissue factor production on the surface of endothelial cells leads to activation of an extrinsic coagulation pathway. Further, coagulation factors and platelets are consumed, and a bleeding tendency occurs.(3) Hyperfibrinolysis, that is, the fibrinolytic system activated due to the activation of coagulation, generates plasmin, ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): G01N33/53C12Q1/56
CPCC12Q1/37G01N33/573G01N33/6893Y10T436/106664G01N2333/96486G01N2800/32G01N2333/755
Inventor ONO, TOMOKOWATANABE, SHINICHIROFURUSAKI, FUMIOIGAMI, KO
Owner MITSUBISHI CHEM MEDIENCE
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