Impact of procoagulant concentration on rate, peak and total thrombin generation in a model system.
Using a cell-based model system of coagulation, we performed a systematic examination of the effect of varying individual procoagulant proteins (over the range of 0-200% of pooled plasma levels) on the characteristics of thrombin generation. The results revealed a number of features unique to the different coagulation factors, as well as common features allowing them to be grouped according to the patterns observed. Variation of those factors contributing to formation of the tenase complex, factor (F)VIII, factor (F)IX and factor (F)XI, primarily affected the rate and peak of thrombin production, but had little to no effect on total thrombin production. The effect of decreased FXI was milder than seen with decreased FVIII or FIX, and more variable between platelet donors. In contrast, varying the concentration of factors that contribute to formation of the prothrombinase complex, prothrombin or factor (F)V (with FV-deficient platelets), significantly affected all three measures of thrombin production: rate, peak and total. Additionally, while no thrombin generation was observed with no factor X, only very small amounts (between 1% and < 10% of normal plasma levels) were required to normalize the measured parameters. Finally, our results with this cell-based system highlight differences in thrombin generation on cell surfaces (platelets) compared with phospholipids, and suggest that platelets contribute more than simply a surface for the generation of thrombin.
Duke Scholars
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- Thrombin
- Platelet Activation
- Monocytes
- Models, Biological
- Humans
- Cardiovascular System & Hematology
- Blood Coagulation Factors
- 3202 Clinical sciences
- 3201 Cardiovascular medicine and haematology
- 1103 Clinical Sciences
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Thrombin
- Platelet Activation
- Monocytes
- Models, Biological
- Humans
- Cardiovascular System & Hematology
- Blood Coagulation Factors
- 3202 Clinical sciences
- 3201 Cardiovascular medicine and haematology
- 1103 Clinical Sciences