Combination chemotherapy for breast carcinoma using a combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) causes a platelet aggregation defect.

Various coagulation parameters including platelet aggregation were evaluated during the course of treatment in 25 patients with breast carcinoma receiving a combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). No significant changes were found in whole blood clotting time (WBCT), prothrombin time (PT), kaolin cephalin clotting time (KCCT), platelet count (PC) and prothrombin consumption index (PCI). The CMF combination induced a significant reduction in platelet factor-3 (PF3) availability and reduction in platelet aggregation to ADP and adrenaline. These defects occurred without development of thrombocytopenia. The changes occurred on the 8th day of chemotherapy and a progressive suppression in platelet aggregation was noted during subsequent follow-up. This acquired abnormality in platelet aggregation and PF3 availability may be responsible for various hemorrhagic manifestations such as mucositis, epistaxis and hemorrhagic cystitis following CMF therapy. Further, these changes precede the onset of life-threatening complication of thrombocytopenia. The study of platelet aggregation should be considered besides platelet counting in patients on CMF combination to assess bleeding diathesis.