Hemostatic Risk Determination via Thrombin Generation Simulation

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Solution Overview

Problem

Current clinical screening techniques fail to accurately identify high-risk individuals for thrombosis, leading to unnecessary cases of thrombosis in untreated patients and bleeding in those receiving anticoagulant treatment due to insufficient specificity in estimating personal thrombosis risk.

Innovation Solution

A computer-implemented method that determines hemostatic risk by comparing the concentration value of tissue factor sufficient to start the clotting process in a subject with reference concentration values, using an in silico simulation of the clotting process to assess the dynamic change in coagulation protein concentrations and determine the risk of thrombosis or bleeding.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If routine screening tools and factor assays are used to identify thrombosis risk, then the screening process is simple and widely available, but high risk individuals are not easily recognized and events are not accurately predicted

Engineering Contradiction:
Improvethrombosis risk identification accuracyVSAvoidscreening methodology complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention transitions from static factor assays to dynamic thrombin generation parameters (lag time, peak thrombin, ETP) that capture the temporal evolution of coagulation. This allows accurate identification of high-risk individuals by measuring how the coagulation system responds over time to tissue factor challenge, rather than just measuring baseline factor levels.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The Thrombin Generation Assay performs a preliminary challenge with tissue factor before measuring thrombin parameters. This preliminary action reveals the functional capacity of the coagulation system to generate thrombin, which is more informative than baseline factor levels for predicting thrombosis risk.

Inventive Principle:
Principle #10Preliminary action

2Reliability

If preventive anticoagulant treatment is administered to at-risk patients, then thrombosis risk is reduced, but bleeding risk (1-3% per year) and issues of cost and inconvenience increase

Engineering Contradiction:
Improvethrombosis prevention effectivenessVSAvoidbleeding risk
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention enables personalized risk assessment by measuring individual thrombin generation parameters, allowing treatment decisions to be tailored to each patient's specific hemostatic profile. High-risk patients (with abnormal TGA parameters) can receive anticoagulation while low-risk patients (with normal TGA parameters) can avoid unnecessary treatment and its associated bleeding risks.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The thrombin generation assay provides feedback on the patient's actual coagulation function, enabling clinicians to adjust anticoagulation therapy based on measured parameters like ETP and peak thrombin, thereby optimizing the balance between thrombosis prevention and bleeding risk.

Inventive Principle:
Principle #23Feedback

3Loss of information

If the Thrombin Generation Assay measures thrombin concentration over time after tissue factor addition, then detailed information on coagulation function is obtained, but the complexity of the measurement process and interpretation increases

Engineering Contradiction:
Improvecoagulation function information completenessVSAvoidmeasurement and interpretation complexity
Core Design Contradiction:
Loss of informationVSDevice complexity

Solution Approach 1:

The complex thrombin generation curve is segmented into distinct phases (lag phase, acceleration phase, peak, decay) with specific parameters extracted from each (lag time, max rate, peak thrombin, ETP). This segmentation transforms the continuous complex signal into discrete, interpretable metrics that retain comprehensive coagulation information while simplifying analysis.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention uses computational modeling and analysis algorithms as intermediaries to process the raw thrombin generation data. These tools automatically extract meaningful parameters from the complex time-concentration curves, reducing the burden of manual interpretation while preserving all relevant coagulation information.

Inventive Principle:
Principle #24Intermediary (Mediator)

Data Source

PatentEP3084429B1Method for determining the hemostatic risk of a subject
Publication Date: 2019.07.10 KONINKLIJKE PHILIPS NV
  • EP3084429B1 patent drawingFigure 1~2
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  • EP3084429B1 patent drawingFigure 4

AI summary

The present invention relates to clinical decision support systems. In detail, the present invention relates to a method for determining the hemostatic risk of a subject, to the use of a biomarker's threshold for determining the hemostatic risk of a subject, to a device for determining the hemostatic risk of a subject, to a computer program comprising a program code for carrying out the method for determining the hemostatic risk of a subject, and to a computer-readable non-transitory storage medium containing instructions for carrying out the method for determining the hemostatic risk of a subject.