EXCESSIVE PROLONGATION OF THE BLEEDING-TIME BY ASPIRIN IN ESSENTIAL THROMBOCYTHEMIA IS RELATED TO A DECREASE OF LARGE VON-WILLEBRAND-FACTORMULTIMERS IN PLASMA

Patients with essential thrombocythemia (ET), who frequently have blee ding complications, may manifest an excessive prolongation of the blee ding time (BT) after ingestion of aspirin (ASA). The reason for this e xcessive prolongation of the BT is unknown, but it is attributed to qu alitative platelet defects. Since patients with ET may also have acqui red abnormalities of plasma and platelet von Willebrand factor (vWF), we questioned whether the excessive prolongation of the BT by ASA was related to changes in either plasma or platelet vWF. To that end, we s tudied BT and plasma and platelet vWF in ten ET patients, ten patients with reactive thrombocytosis (RT), and ten normal individuals, both b efore and after administration of 500 mg ASA for 7 days. In a second s tudy, the effect of DDAVP infusion on plasma. vWF in relation to the B T was studied in ten normal individuals and ten ET patients after trea tment with 100 mg ASA for 3 days. In the first study, treatment with A SA resulted in a significant prolongation of the BT in normal subjects , RT patients, and ET patients. However, in five ET patients an excess ive (>2 SD) prolongation of the BT by ASA was observed. Although ASA i nduced no direct changes in either plasma or platelet vWF levels in ei ther normal subjects, RT patients, or ET patients, all five ET patient s who showed an excessive prolongation of the BT by ASA had significan tly decreased levels of large VWF multimers in plasma. In the second s tudy, infusion with DDAVP resulted in a significant increase in plasma large vWF multimers, paralleled by a normalization of (excessively) p rolonged BT. Our data suggest that in ET inhibition of platelet functi on by ASA in the presence of concurrently decreased levels of large vW F multimers in plasma may have provoked the excessive BT prolongation.