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Summary
Activated factor IX concentrates contain significant levels of factor IXa, a key factor in thrombogenicity. Assays reveal factor IXa concentration correlates with clotting time, suggesting its role in concentrate-related thrombosis.
Area of Science:
- Biochemistry
- Hematology
- Clinical Chemistry
Background:
- Human factor IX concentrates are used therapeutically.
- The activation state of these concentrates can influence their clinical safety and efficacy.
- Specific assays are needed to accurately quantify activated clotting factors.
Purpose of the Study:
- To precisely quantify activated factors (IXa, Xa, thrombin) in human factor IX concentrates.
- To determine the primary activated factor responsible for the thrombogenicity of these concentrates.
Main Methods:
- Development and application of specific assays for factors IXa, Xa, and thrombin.
- Measurement of initial reaction rates for factor X activation and chromogenic substrate hydrolysis.
- Correlation analysis between activated factor levels and nonactivated partial thromboplastin time (aPTT).
Main Results:
- Activated factor IX concentrates contained 1.0-2.3 microgram/ml of factor IXa, while unactivated concentrates had <0.2 microgram/ml.
- Small amounts of factor Xa (4-34 ng/ml) and thrombin (12-76 ng/ml) were found in both activated and unactivated concentrates.
- Factor IXa concentration significantly correlated with the nonactivated partial thromboplastin time (aPTT).
Conclusions:
- The degree of activation in factor IX concentrates is primarily related to factor IXa concentration.
- Factor IXa may be responsible for the thrombogenicity observed in some clinical settings.
- Antithrombin III complex formation with activated factors is suggested by antigen-activity discrepancies.