PLATELET HYPERACTIVATION IN PATIENTS WITH ESSENTIAL THROMBOCYTHEMIA IS NOT ASSOCIATED WITH VASCULAR ENDOTHELIAL-CELL DAMAGE AS JUDGED BY THE LEVEL OF PLASMA THROMBOMODULIN, PROTEIN-S, PAI-1, T-PA AND VWF

The occurrence of thrombotic events remains an important clinical prob lem in Essential Thrombocythemias (ET). Thus, hemostatic, fibrinolytic and vascular status was investigated in 16 patients (5 males and 11 f emales) with ET. Among them five presented thromboses in their past hi story. Platelet hyperactivation, as evidenced by a mean three-fold inc rease in plasma betathromboglobulin (betaTG), was observed in 13 among 16 patients; surprisingly this activation was present even when the p latelet count was normal (in two patients) or subnormal, below 600 x 1 0(9)/l (in 11 patients). The mean value was 104 +/- 57 IU/ml significa ntly different from that of normal controls (35 +/- 16.5 IU/ml) (p < 0 .001). An artefactual in vitro platelet activation was ruled out by th e concomitant measurement of platelet factor 4 (PF4). D-dimers fibrin degradation products (D-Di FDP) were normal in all patients. Vascular endothelial cell function parameters were not markedly modified. The m ean value of plasma thrombomodulin (TM) was found slightly but not sig nificantly increased (60.1 +/- 4.9 ng/ml versus 49.1 +/- 10.0 ng/ml in controls). The values of plasma TM correlated neither with that of th e platelet count nor with that of plasma betaTG or plasma PF4. The mea n values of plasma protein S, von Willebrand factor (vWF), plasminogen activator inhibitor type 1 (PAI-1), tissue plasminogen activator (tPA ) were normal and were not correlated neither with that of plasma TM n or with that of plasma betaTG. In spite of a significant increase in v WF in two patients who presented peripheral thromboses, the markers of vascular endothelial cell function were not significantly different i n patients having presented or not thromboses. Thus, in ET, these data showed the presence of platelet hyperactivation, even in patients in remission; it was not associated with vascular endothelial cell damage which might account for a greater risk of thrombosis.