title: Platelets treated with ticlopidine are less reactive to unusually large von Willebrand factor multimers than are those treated with aspirin under high shear stress.
abstract: Much attention has recently been focused on the interaction between unusually large von Willebrand factor multimers (UL-VWFM) and platelets under high shear stress in pathological thrombus formation. The antiplatelet drugs acetylsalicylic acid (aspirin) and a thienopyridine derivative (ticlopidine) are commonly used to treat cerebral ischemia but exert different effects on high-shear-stress-induced platelet aggregation (H-SIPA) in the plasma. To examine the effects of these drugs in the absence of plasma factors, we studied H-SIPA using washed platelets (WPs) and purified UL-VWFM. WPs were prepared from the blood of 9 aspirin-treated and 11 ticlopidine-treated patients with cerebral ischemia, and H-SIPA in the presence of UL-VWFM was measured using a cone plate aggregometer. Plasma levels of VWF antigen with its multimer analysis, ristocetin cofactor and VWF-cleaving protease (ADAMTS13) activity were also measured. Forty-six healthy volunteers from 2 age groups, 20-40 years (n=20) and 41-60 years old (n=26), were also tested as controls. H-SIPA was significantly inhibited for ticlopidine-treated platelets, but it was observed to a lesser extent for aspirin-treated platelets. For both groups, no difference in the plasma levels of VWF antigen, ristocetin cofactor and ADAMTS13 activity was noted. All patients possessed UL-VWFM, and it was detected in healthy volunteers with increasing frequency with increasing age. Under plasma-free conditions, platelets from aspirin-treated patients exhibit marginal but significant inhibition of H-SIPA. Furthermore, the presence of UL-VWFM in the plasma of patients and normal volunteers is directly related to their age rather than being a consequence of underlying disease.
authors.affiliation: Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: S
authors.initials: S
authors.lastname: Kawaguchi
authors.forename: H
authors.initials: H
authors.lastname: Ishizashi
authors.forename: H
authors.initials: H
authors.lastname: Yagi
authors.forename: J
authors.initials: J
authors.lastname: Iida
authors.forename: T
authors.initials: T
authors.lastname: Sakaki
authors.forename: Y
authors.initials: Y
authors.lastname: Fujimura
mesh_terms: D051722:ADAM Proteins / Q000097:blood; D000071120:ADAMTS13 Protein; D000328:Adult; D000367:Age Factors; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage*; D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D046912:Multiprotein Complexes / Q000032:analysis*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D013314:Stress, Mechanical; D013988:Ticlopidine / Q000008:administration & dosage*; D014841:von Willebrand Factor / Q000032:analysis*
chemical_list: D046912:Multiprotein Complexes; D010975:Platelet Aggregation Inhibitors; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human; D013988:Ticlopidine; D001241:Aspirin