Altered von Willebrand factor molecule in children with thrombosis following asparaginase-prednisone-vincristine therapy for leukemia.
Eleven consecutive leukemia patients with thrombosis induced by asparaginase-prednisone-vincristine therapy were studied to gain insight into the pathogenesis of this complication. Measurement of anti-thrombin III, plasminogen, factor V, and fibrin degradation products as well as platelet aggregation sensitivity to adenosine diphosphate disclosed no consistent abnormalities that would explain pathologic thrombus formation. A decrease in platelet counts observed in nine of 11 patients, prompted us to investigate the possible involvement of factor VIII in this disorder. Levels of factor VIII procoagulant activity, von Willebrand factor (vWF) and ristocetin cofactor were similar to findings for an identically treated comparison group who remained free of thrombotic complications. However, qualitative examination of vWF by crossed immunoelectrophoresis (CIE) revealed a distinct right shift of the immunoprecipitin lines in each of three thrombotic patients tested, whereas a normal profile was found in three similarly treated patients without the complication. This altered pattern had reverted to normal when CIE was repeated 2 to 7 months later. We postulate that the abnormal vWF is related to the development of thrombosis.
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects; D001779:Blood Coagulation Factors / Q000032:analysis*; D001780:Blood Coagulation Tests; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007945:Leukemia, Lymphoid / Q000097:blood / Q000188:drug therapy*; D008297:Male; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced* / Q000628:therapy; D013997:Time Factors; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects; D014841:von Willebrand Factor / Q000032:analysis*
D001779:Blood Coagulation Factors; D014841:von Willebrand Factor; D014750:Vincristine; D001215:Asparaginase; D011241:Prednisone