Persistent Prothrombinase Complex for Stable Thrombin Serum
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Solution Overview
Problem
Current methods for preparing thrombin serum for medical applications are impractical due to instability, contamination risks, and lengthy preparation times, which hinder rapid and safe hemostasis during surgeries.
Innovation Solution
A two-stage method and apparatus for preparing thrombin serum from a patient's blood fluid, involving activation of a procoagulant agent with calcium ions to form a persistent prothrombinase enzyme complex, allowing rapid conversion of prothrombin to thrombin without the need for cytotoxic stabilizers like ethanol, enabling on-demand production and extended stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional methods are used to prepare thrombin serum, then thrombin can be obtained, but the preparation time is lengthy and stability is poor
Solution Approach 1:
The procoagulant agent is pre-activated with calcium ions to form a persistent prothrombinase enzyme complex before actual thrombin production is needed. This preliminary activation allows rapid thrombin generation when blood fluid is added, eliminating lengthy preparation times while ensuring stability through the persistent nature of the pre-formed enzyme complex
Solution Approach 2:
A persistent procoagulant agent serves as an intermediary between calcium ions and prothrombin. This activated procoagulant agent remains stable for extended periods and can be stored ready-to-use, mediating the rapid conversion of prothrombin to thrombin without requiring complex stabilizers or lengthy preparation procedures
2Reliability
If ethanol is used to stabilize thrombin, then stability is improved, but cytotoxicity and biocompatibility issues arise
Solution Approach 1:
The harmful ethanol stabilizer is completely removed from the system. Instead of using ethanol to stabilize thrombin, the invention extracts this toxic component and replaces it with a biocompatible persistent procoagulant agent that provides stability through its persistent enzyme complex formation, eliminating cytotoxicity while maintaining thrombin stability
Solution Approach 2:
The stabilization mechanism changes from chemical (ethanol) to enzymatic (persistent prothrombinase complex). By changing the stabilization parameter from a cytotoxic chemical agent to a biocompatible enzyme complex, the system achieves both stability and biocompatibility without the harmful effects of ethanol
3Quantity of substance
If pooled human or animal blood is used as the source, then thrombin can be obtained, but contamination risks and immunogenicity increase
Solution Approach 1:
The patient's own blood fluid serves as the source for thrombin production through the persistent procoagulant agent system. This self-service approach eliminates the need for pooled human or animal blood products, thereby eliminating contamination risks and immunogenicity while still achieving the required thrombin concentration for effective hemostasis
Solution Approach 2:
The persistent procoagulant agent acts as an intermediary that enables thrombin generation from a single patient's blood fluid. This intermediary system allows adequate thrombin concentration to be achieved from individual donor blood without requiring pooling, thereby eliminating the harmful effects associated with pooled blood products
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The method provides a rapid, safe, and biocompatible thrombin serum with prolonged stability, suitable for prolonged surgical procedures without the risks associated with ethanol or animal-derived products, ensuring effective hemostasis and wound healing.
Implementation Method 1
Binding to these negatively charged surfaces induces a conformational change in Factor XII (FXII) that allows it to proteolytically activate prekallikrein (PK). PK proteolytically activates FXII, producing a positive feedback loop that amplifies the system and leads to activation of FXI and cleavage of high-molecular-weight kininogen (HK) by kallikrein.
Implementation Method 2
The prothrombinase enzyme complex catalyzes the conversion of prothrombin (Factor II), an inactive zymogen, to thrombin (Factor IIa), an active serine protease.
Implementation Method 3
The addition of calcium salt to citrate anti-coagulated blood fluids to enable the coagulation cascade to proceed is often specifically referred to as recalcification. The prothrombinase enzyme complex assembles on negatively charged phospholipid membranes in the presence of calcium ions.
Implementation Method 4
Thrombin is an enzyme that hydrolyses fibrinogen into fibrin units that polymerize into a fine mesh, which, in turn, causes plasma to form a gel or clot.
Data Source
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AI summary
A method for preparing thrombin serum, the method comprising obtaining blood fluid sample, contacting a first aliquot of the blood fluid with a procoagulant agent to form prothrombinase enzyme complex bound to the surface of the procoagulant agent so as to obtain an activated procoagulant agent that may be stored. The activated procoagulant agent may then be contacted with a second aliquot of the blood fluid containing prothrombin so as to obtain thrombin serum, which may be extracted and contacted with fibrinogen to obtain fibrin.