Platelet Dysfunction in Vincristine Treated Patients

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Abstract
Recent revival of interest in the use of vincristine (VCR) for the treatment of idiopathic thrombocytopenic purpura prompted the evaluation of platelet function of patients on VCR. Eighteen patients with acute lymphoblastic leukemia (ALL) in remission, and 9 children with solid tumors were studied on 80 occasions at different time intervals after their last VCR dose. A mildly elevated threshold for epinephrine-induced 2nd phase aggregation and a delay in the onset of collagen-induced aggregation was found in patients with ALL not on VCR. VCR induced unobtainable 2nd phase aggregation to epinephrine in 67%, 38%, 30% and to ADP in 53%, 13%, 33% of the patients 1 wk, 2-3 wk and 4 wk, 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 5 of 12 patients tested. In vitro platelets were a 100-fold less sensitive to VCR than in vivo. Cyclic AMP, cyclic GMP and dimethylsulfoxide did not protect platelets from VCR. The exact mechanism by which VCR abolished 2nd phase aggregation in patients is uncertain. Because of VCR''s narrow therapeutic index between thrombocytopenia and thrombocythemia, the use of VCR should be reserved for life-threatening hematologic disorders when treating non-malignant conditions.