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Thromb Haemost 2001; 86(02): 660-667
DOI: 10.1055/s-0037-1616110
Scientific and Standardization Committee Communications
Schattauer GmbH

Platelets and Phospholipids in Tissue Factor-initiated Thrombin Generation

Saulius Butenas
1   University of Vermont, Departments of Biochemistry and Medicine, Burlington, Vermont, USA
,
Richard F Branda
1   University of Vermont, Departments of Biochemistry and Medicine, Burlington, Vermont, USA
,
Cornelis van ’t Veer
1   University of Vermont, Departments of Biochemistry and Medicine, Burlington, Vermont, USA
,
Kevin M Cawthern
1   University of Vermont, Departments of Biochemistry and Medicine, Burlington, Vermont, USA
,
Kenneth G Mann
1   University of Vermont, Departments of Biochemistry and Medicine, Burlington, Vermont, USA
› Author AffiliationsThis study was supported by Program Project Grant HL 46703 from the National Institutes of Health (KGM) and by a TALENT stipend of the Netherlands Organization of Scientific Research (CvV).
Further Information

Publication History

Received 28 December 2000

Accepted after revision 16 March 2001

Publication Date:
12 December 2017 (online)

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Summary

The influence of platelets on tissue factor (TF)-initiated thrombin generation in a reconstituted model of blood coagulation and in whole blood was evaluated. No thrombin generation was observed over 15 min in the reconstituted model when either TF or platelets and phospholipids were omitted. At 25 pM TF, the rates of thrombin generation were platelet and PCPS concentration-dependent and achieved maximum (1.0 nM/s) in the physiological range of platelet concentration. Similar rates were achieved in the absence of platelets when 1-2 μM phospholipid was used. However, the maximum rates of thrombin generation (5.2-6.0 nM/s) and the shortest initiation phase (1 min) were attained between 25 and 100 μM phospholipid. In the reconstituted model, an increase in platelet concentration from 0.125 × 108/ml to 0.5 × 108/ml decreased the duration of the initiation phase (in the absence of phospholipids) from 4.3 min to 2 min. Further increases in platelet concentration did not affect this phase. Sequential whole blood studies were conducted in blood of a chemotherapy patient who developed reduced platelet counts. The TF (12.5 pM) initiated clotting of patient’s blood was accelerated from ~10 min to 5 min when the platelet concentration increased from 0.05 × 108/ml to 0.11 × 108/ml. Clotting times were essentially unchanged for platelet concentrations exceeding 0.5 × 108/ml (range 0.5-3.1 × 108/ml). Similarly, clotting of whole blood obtained from healthy volunteers was not affected by the platelet count, which varied from 1.5 × 108/ml to 3.1 × 108/ml (4.0 ± 0.5 min). The data obtained in both models are consistent with in vivo observations that clinical bleeding is most likely to occur at platelet counts <0.1 × 108/ml.

Portions of this work were presented at the 40th Annual Meeting of the American Society of Hematology, December 4-8, 1998, Miami Beach, Florida (abstracts #140 and #738).

Keywords

Platelets - phospholipids - thrombocytopenia - tissue factor - factor V
 

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