APTT Reagent Phospholipid Composition for Lupus Anticoagulant Detection

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Solution Overview

Problem

Current APTT reagents have varying sensitivity to lupus anticoagulant (LA) and heparin, leading to inappropriate coagulation time measurements for normal and abnormal blood samples, which complicates screening tests for intrinsic coagulation factors and heparin therapy monitoring.

Innovation Solution

An APTT reagent with a specific phospholipid composition, including phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylethanolamine (PE), with a PS/PC ratio of 0.16 to 0.25 and PS concentration of 7 to 13 µg/mL, is developed to improve sensitivity to LA while maintaining appropriate sensitivity to heparin.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If APTT reagents with low phospholipid concentration are used to improve sensitivity to LA, then sensitivity to LA is improved, but coagulation time for normal blood samples becomes prolonged

Engineering Contradiction:
Improvesensitivity to LAVSAvoidcoagulation time for normal blood samples
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent applies parameter changes by precisely controlling the phospholipid composition parameters - specifically setting PS concentration at 25 µg/ml or more and establishing a PS/PC ratio between 0.10 and 0.30. This optimized parameter range resolves the contradiction by maintaining sufficient phospholipid concentration to prevent prolonged coagulation times in normal samples while achieving improved sensitivity to LA through the specific PS/PC ratio configuration.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses composite materials by combining three types of phospholipids (PS, PC, and PE) in specific proportions rather than using a single phospholipid type. This composite approach allows the reagent to achieve both high sensitivity to LA and appropriate coagulation times for normal samples, as the different phospholipids work synergistically to balance the competing requirements.

Inventive Principle:
Principle #40Composite materials

2Measurement precision

If APTT reagents with high sensitivity to LA are used, then detection of abnormal samples is improved, but sensitivity to heparin becomes inappropriate

Engineering Contradiction:
Improvesensitivity to LAVSAvoidsensitivity to heparin
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent resolves this contradiction by optimizing the phospholipid composition parameters - specifically setting PS concentration at 25 µg/ml or more and PS/PC ratio between 0.10 and 0.30. This parameter optimization achieves high sensitivity to LA while simultaneously maintaining appropriate sensitivity to heparin, allowing the same reagent to be used for both LA screening and heparin monitoring without compromising either measurement accuracy.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If APTT reagents with varying phospholipid composition are used, then sensitivity to LA varies, but this complicates screening tests for intrinsic coagulation factors

Engineering Contradiction:
Improvesensitivity to LAVSAvoidsuitability for screening tests
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent resolves this issue by establishing specific parameter ranges for phospholipid composition - PS concentration of 25 µg/ml or more and PS/PC ratio of 0.10 to 0.30. Within these optimized parameters, the reagent achieves high sensitivity to LA while maintaining normal coagulation times for normal samples, making it suitable for both LA screening and intrinsic coagulation factor screening without requiring different reagents for different test types.

Inventive Principle:
Principle #35Parameter changes

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 reagent provides improved sensitivity to LA, allowing for accurate detection of abnormal samples while maintaining normal coagulation times for healthy samples and appropriate sensitivity to heparin, enhancing the reliability of coagulation tests.

Implementation Method 1

activators and phospholipids are used for the activation of intrinsic coagulation factors and the promotion of blood coagulation

Methodology Applied
Scientific EffectCoagulation: Coagulation

Implementation Method 2

LA inhibits the phospholipid required for blood coagulation, whereby the APTT becomes prolonged for LA-containing blood samples

Methodology Applied
Scientific EffectInhibition:

Data Source

PatentEP3637107B1Reagent for determination of coagulation time, reagent kit, and method for determination of coagulation time
Publication Date: 2023.12.13 SYSMEX CORP
  • EP3637107B1 patent drawingFigure 1~2
  • EP3637107B1 patent drawingFigure 3~4
  • EP3637107B1 patent drawingFigure 5~6

AI summary

Disclosed is a reagent for determination of activated partial thromboplastin time, comprising: a phosphatidylcholine (PC); a phosphatidylserine (PS); and a phosphatidylethanolamine (PE), wherein a concentration ratio of the PS relative to the PC is not less than 0.16 and not more than 0.25, and a concentration of the PS is not less than 7 µg/mL and not more than 13 µg/mL.