Thrombin Generation Kit for Immunoglobulin Thrombogenicity
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Solution Overview
Problem
The use of intravenous immunoglobulins (IvIGs) can lead to serious side effects such as thromboembolic events due to the presence of coagulation factors like Factor VII, Factor IX, Factor XI, Factor XII, and Factor X, necessitating a reliable method to determine their activated forms in human immunoglobulin products.
Innovation Solution
A kit comprising platelet-poor human blood plasma, phospholipids, CaCl2, and optionally human tissue factor is used to assess the thrombogenic power of human immunoglobulins, employing a thrombin generation test to measure the presence of activated coagulation factors, with a plasma deficient in Factor XI providing a specific reaction medium for accurate determination.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If intravenous immunoglobulins are administered to treat immunodeficiency or auto-immune diseases, then therapeutic effect is achieved, but thromboembolic events occur as serious side effects
Solution Approach 1:
The invention performs preliminary detection of activated coagulation factors in the immunoglobulin product before administration to patients. By using the thrombin generation test with fluorometric measurement, the method identifies the presence of activated factors VII, IX, XI, XII, or X in advance, allowing the product to be screened for thrombogenic risk before clinical use, thus preventing thromboembolic events.
2Measurement precision
If conventional coagulation tests are used to detect coagulation factors, then general coagulation status is assessed, but specific activated factors in immunoglobulin products cannot be reliably determined
Solution Approach 1:
The invention replaces conventional mechanical or visual coagulation testing methods with a fluorometric measurement system. By using a fluorogenic substrate that emits fluorescence upon cleavage by thrombin, the method enables precise quantitative detection of thrombin generation, which directly reflects the presence and activity of activated coagulation factors in the immunoglobulin sample.
Solution Approach 2:
The invention introduces a fluorogenic substrate as an intermediary to detect thrombin activity. The substrate contains a fluorophore that is non-fluorescent in its intact form but becomes highly fluorescent when cleaved by thrombin. This intermediary allows indirect but highly sensitive detection of activated coagulation factors through their enzymatic activity on the substrate.
3Reliability
If activated coagulation factors are present in immunoglobulin products, then thrombogenic power increases, but reliable determination methods are lacking
Solution Approach 1:
The invention creates a universal testing system that can detect multiple activated coagulation factors (VII, IX, XI, XII, and X) using a single thrombin generation assay platform. The method employs a standardized reaction mixture containing phospholipids, calcium ions, and fluorogenic substrate, which works for all these factors through their common downstream effect of generating thrombin, eliminating the need for separate tests for each factor.
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
This method allows for the sensitive and reliable determination of the thrombogenic power of human immunoglobulins, enabling the identification of activated coagulation factors and reducing the risk of thromboembolic events by providing a biologically acceptable product.
Implementation Method 1
Thrombinography consists of using a thrombin calibrator and a specific fluorescent substrate in platelet-poor plasma or in platelet-rich plasma, in order to establish a thrombinogram
Implementation Method 2
A thrombus results from blood coagulation, due to platelet aggregation and the activation of the coagulation system, this being a chain reaction which involves the platelets and the coagulation factors
Data Source
AI summary
A kit for the determination of the thrombogenic power of human immunoglobulins contained in a biologically acceptable product. Also a process making it possible to determine the thrombogenic power linked to the presence of activated Factor XI and/or activated Factor IX and/or activated Factor XII, and/or activated Factor VII and/or activated Factor X in a sample capable of being administered to humans.