title: Platelets acquire a secretion defect after high-dose chemotherapy.
abstract: 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 H2 (PGH2) 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.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: T J
authors.initials: TJ
authors.lastname: Panella
authors.forename: W
authors.initials: W
authors.lastname: Peters
authors.forename: J G
authors.initials: JG
authors.lastname: White
authors.forename: Y A
authors.initials: YA
authors.lastname: Hannun
authors.forename: C S
authors.initials: CS
authors.lastname: Greenberg
mesh_terms: D000255:Adenosine Triphosphate / Q000493:pharmacokinetics; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001791:Blood Platelet Disorders / Q000139:chemically induced; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000188:drug therapy; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006470:Hemorrhage; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009205:Myocarditis / Q000209:etiology; D010974:Platelet Aggregation / Q000187:drug effects*
chemical_list: D000255:Adenosine Triphosphate; D003520:Cyclophosphamide; D002945:Cisplatin; D008558:Melphalan; D002330:Carmustine