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
