title: Excessive prolongation of the bleeding time by aspirin in essential thrombocythemia is related to a decrease of large von Willebrand factor multimers in plasma.
abstract: Patients with essential thrombocythemia (ET), who frequently have bleeding complications, may manifest an excessive prolongation of the bleeding time (BT) after ingestion of aspirin (ASA). The reason for this excessive prolongation of the BT is unknown, but it is attributed to qualitative platelet defects. Since patients with ET may also have acquired 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 studied BT and plasma and platelet vWF in ten ET patients, ten patients with reactive thrombocytosis (RT), and ten normal individuals, both before and after administration of 500 mg ASA for 7 days. In a second study, the effect of DDAVP infusion on plasma vWF in relation to the BT was studied in ten normal individuals and ten ET patients after treatment with 100 mg ASA for 3 days. In the first study, treatment with ASA resulted in a significant prolongation of the BT in normal subjects, RT patients, and ET patients. However, in five ET patients an excessive (> 2 SD) prolongation of the BT by ASA was observed. Although ASA induced no direct changes in either plasma or platelet vWF levels in either normal subjects, RT patients, or ET patients, all five ET patients who showed an excessive prolongation of the BT by ASA had significantly decreased levels of large vWF multimers in plasma. In the second study, infusion with DDAVP resulted in a significant increase in plasma large vWF multimers, paralleled by a normalization of (excessively) prolonged BT. Our data suggest that in ET inhibition of platelet function by ASA in the presence of concurrently decreased levels of large vWF multimers in plasma may have provoked the excessive BT prolongation.
authors.affiliation: Department of Hematology, University Hospital Dijkzigt, Rotterdam, The Netherlands.
authors.forename: P J
authors.initials: PJ
authors.lastname: van Genderen
authors.forename: H H
authors.initials: HH
authors.lastname: van Vliet
authors.forename: F J
authors.initials: FJ
authors.lastname: Prins
authors.forename: D
authors.initials: D
authors.lastname: van de Moesdijk
authors.forename: R
authors.initials: R
authors.lastname: van Strik
authors.forename: F J
authors.initials: FJ
authors.lastname: Zijlstra
authors.forename: U
authors.initials: U
authors.lastname: Budde
authors.forename: J J
authors.initials: JJ
authors.lastname: Michiels
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use*; D001760:Bleeding Time; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D013922:Thrombocytosis / Q000097:blood / Q000188:drug therapy*; D014841:von Willebrand Factor / Q000032:analysis*
chemical_list: D010975:Platelet Aggregation Inhibitors; D014841:von Willebrand Factor; D001241:Aspirin