Patients receiving high-dose chemotherapy (HDC) and autologous bone marrow transplantation (ABMT) may experience life-threatening hemorrhagic myocarditis. The authors investigated whether HDC was associated with an acquired platelet defect. Platelet aggregation and release were evaluated after HDC in ten patients with either metastatic breast carcinoma or melanoma. Platelets underwent shape change and a primary wave of aggregation. High-dose chemotherapy was associated with the inhibition of secondary aggregation of platelets induced by adenosine diphosphate (ADP), arachidonic acid, prostaglandin H, (PGH,) analog (U44619), and collagen. Although electron microscopic study of the platelets revealed normal morphologic features with an adequate number of dense bodies and alpha-granules, release of adenosine triphosphate (ATP) from dense granules was less than 20% of normal. The acquired platelet defect occurred before development of thrombocytopenia. Aggregation of platelets from normal volunteers was not inhibited by either the addition of the chemotherapeutic agents, chemotherapy metabolites, or the patients' sera. In conclusion, HDC induces an acquired abnormality in platelet secretion and aggregation which may contribute to the development of hemorrhagic complications after ABMT. Cancer 65:1711-1716,1990.
EMORRHAGIC MYOCARDITIS is a life-threatening H complication of high-dose chemotherapy (HDC) and autologous bone marrow transplantation (ABMT). The clinical expression of the myocardial toxicity ranges from isolated tachycardia to severe cardiac failure and death.' Although a direct toxic effect of high-dose cyclophosphamide chemotherapy on endothelial cells has been postulated to play a role in the pathogenesis of this disorder,',2 the effect of HDC on platelet function has not been reported.
From the Departments of *Medicine. Β§Pathology. IICoagulation, and 7Hospital Laboratories, and the ?Bone Marrow Transplant Program,