Fibrinogen Determination With Factor XIII for Single-Run Range
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Solution Overview
Problem
Existing methods for determining fibrinogen concentration, such as the Clauss method, have a limited measuring range, requiring multiple measurements at different dilutions due to rapid coagulation in samples with slightly elevated fibrinogen levels and insufficient clot formation in samples with low fibrinogen content.
Innovation Solution
The addition of Factor XIII to the reaction mixture extends the measuring range by stabilizing clots, allowing for a single measurement to determine fibrinogen concentrations across a broader range, including low levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If the Clauss method is used with high thrombin concentration to determine fibrinogen, then the measuring range is limited and multiple measurements are required, but the method provides sufficient clot formation for detection
Solution Approach 1:
The patent changes the thrombin concentration parameter to a low level (opposite of the high concentration used in Clauss method), which fundamentally alters the reaction kinetics. This parameter change enables a single measurement to cover a broad fibrinogen concentration range by creating a reaction profile with a clearly detectable lag phase even at low thrombin levels, eliminating the need for multiple measurements at different dilutions
Solution Approach 2:
The patent uses a low thrombin concentration that is intentionally suboptimal for rapid clot formation. This partial action (using less thrombin than the Clauss method) creates a slower reaction that extends the measurable time window, allowing detection of fibrin formation across a broader concentration range in a single measurement
2Productivity
If the Clauss method is used with high thrombin concentration, then rapid coagulation occurs in samples with slightly elevated fibrinogen levels, but this limits the measuring range
Solution Approach 1:
The patent creates a dynamic measurement system where the lag phase duration varies with fibrinogen concentration. By using low thrombin concentration, the system adapts to different fibrinogen levels by adjusting the observable lag phase length, enabling the same reaction conditions to measure across a broad concentration range from low to elevated levels
Solution Approach 2:
The patent measures the lag phase (time before fibrin formation begins) as the primary parameter. This preliminary time measurement before actual clot formation provides information about fibrinogen concentration without being constrained by the speed of subsequent clot development, allowing accurate measurement even when final clot formation would be too rapid to distinguish between different concentrations
3Adaptability or versatility
If diluted plasma samples are used in the Clauss method to achieve low fibrinogen concentration, then the measuring range is extended, but this limits the measuring range in the lower fibrinogen concentration range
Solution Approach 1:
Instead of diluting the sample to extend the measuring range (conventional approach), the patent inverts the approach by using undiluted or concentrated samples with low thrombin concentration. This inversion allows the reaction kinetics to naturally accommodate a broad concentration range without sample preparation dilution, maintaining measurement precision across all concentration levels
Solution Approach 2:
The patent creates a universal measurement system using low thrombin concentration that can handle both low and high fibrinogen concentrations in the same reaction conditions. This multi-functional approach eliminates the need for different measurement protocols (undiluted vs. diluted) that are required in the Clauss method, allowing a single procedure to accurately measure across the entire clinically relevant range
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 enables reliable determination of fibrinogen concentration in samples with low fibrinogen levels without the need for multiple measurements, reducing time and cost by clearly differentiating between low and higher concentrations.
Implementation Method 1
The coagulation protease thrombin (factor IIa) cleaves fibrinogen, thereby activating fibrin formation, i.e., clot formation
Implementation Method 2
Factor XIII is known as the enzyme that plays a key role in clot formation by cross-linking fibrin strands. This cross-linking stabilizes the clot
Implementation Method 3
Due to fibrin formation, the reaction mixture becomes increasingly cloudy, allowing fibrin formation to be measured quantitatively using an absorption measurement
Data Source
Figure 1A~1B
Figure 2A~2B
AI summary
The present invention lies in the field of blood coagulation diagnostics and relates to an improved method for the quantitative determination of fibrinogen in a sample. The method comprises the addition of factor XIII to the reaction mixture.