Platelet dysfunction in vincristine treated patients.
Recent revival of interest in the use of vincristine (VCR) for the treatment of idiopathic thrombocytopenic purpura prompted us to evaluate the platelet function of our patients on VCR. Eighteen patients with acute lymphoblastic leukaemia (ALL) in remission, and nine children with solid tumours were studied on 80 occasions at different time intervals after their last VCR dose. A mildly elevated threshold for epinephrine-induced second phase aggregation and a delay in the onset of collagen-induced aggregation was found in patients with ALL not on VCR. Vincristine induced unobtainable second phase aggregation to epinephrine in 67%, 38%, 30% and to ADP in 53%, 13%, 33% of the patients 1 week, 2-3 weeks and 4 weeks respectively after administration. The thrombocytopathy was relative, not absolute, since collagen induced aggregation at all times. Platelet counts, uptake and release of serotonin, bleeding times, clot retractions and release of platelet factor 3 were normal. Platelet adhesion was abnormal in five of 12 patients tested. In vitro platelets are a hundred-fold less sensitive to VCR than in vivo. Cyclic adenosine monophosphate, cyclic guanosine monophosphate and dimethylsulfoxide do not protect platelets from VCR. The exact mechanism by which VCR abolishes second phase aggregation in patients is uncertain. Because of VCR's narrow therapeutic index between thrombocytopenia and thrombocythaemia, the use of VCR should be reserved for life-threatening haematologic disorders when treating non-malignant conditions.
D000244:Adenosine Diphosphate / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects*; D002648:Child; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004837:Epinephrine / Q000378:metabolism; D006801:Humans; D007945:Leukemia, Lymphoid / Q000188:drug therapy; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D014750:Vincristine / Q000009:adverse effects*
D012701:Serotonin; D014750:Vincristine; D000244:Adenosine Diphosphate; D000242:Cyclic AMP; D006152:Cyclic GMP; D004837:Epinephrine; D004121:Dimethyl Sulfoxide