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.

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

“…A subclinical or overt alteration in hemostasis manifesting as clinical thrombosis has been recognized (Gagliano et al, 1976;Goodnough et al, 1984;Canobbio et al, 1986). Non-thrombocytopenic bleeding episodes have been reported and attributed to a hypocoagulable state induced by cytotoxic chemotherapy and leading to clinical hemorrhage (Kumar et at., 1984;Panella et al, 1990;Mahraj et al, 1993).…”

Evaluation of mean platelet volume as a predictive marker for cancer-associated venous thromboembolism during chemotherapy

“…12 Since then, many studies have attempted to define the adverse circumstances leading to platelet modifications, both in terms of platelet count and size and platelet function, ultimately supporting the idea of an acquired platelet defect following administration of various anti-neoplastic drugs, [13][14][15][16] including platinum analogs. 16 Several mechanisms have been suggested to explain this hypothesis, including interference with protein kinase C signaling 12 or disturbance of the circumferential microtubule ring 15 which is responsible for platelet contraction, and centralization of the secretory granules and consequent degranulation.…”

Acute Systolic Dysfunction within Two Weeks of High‐Dose Chemotherapy Conditioning before Autologous Bone Marrow Transplant: A Case Report

“…Diagnostic procedures could not be performed because consistently low platelets precluded invasive endomyocardial biopsy 5 . Regarding the low platelet count, basic science data does suggest that HDC may induce an acquired abnormality in platelet secretion and aggregation, which can contribute to the development of hemorrhagic myocarditis after ABMT 6 …”

“…5 Regarding the low platelet count, basic science data does suggest that HDC may induce an acquired abnormality in platelet secretion and aggregation, which can contribute to the development of hemorrhagic myocarditis after ABMT. 6 One recent experimental study demonstrated a decrease in the activities of TCA cycle enzymes such as succinate dehydrogenase, malate dehydrogenase, and isocitrate dehydrogenase in CY-treated rats with a simultaneous decrease in the activities of mitochondrial complexes of electron transport chain in the myocardium. Electron microscopic observations were also in agreement with the above changes.…”