Acquired storage-pool disorders occurring late after allogeneic bone marrow transplantation: partial activation of platelets in asymptomatic patients

Abstract

Bone marrow transplantation (BMT) may be complicated by coagulation abnormalities. The present study evaluated whether platelets might be activated in patients who had undergone BMT without significant coagulopathy. The patients selected had received allogeneic BMTs a median of 39 months before the study (range, 11-124 months) and had not received cyclosporine, FK506 (tacrolimus), or other medication affecting cyclo-oxygenase for at least 3 months prior to the collection of blood samples. Furthermore, patients had platelet counts greater than 100 x 10(9) cells/L and normal serum creatinine levels. Twenty-five healthy volunteers acted as controls. Platelet aggregation studies and a mepacrine assay of platelets showed abnormal aggregation and decreased staining in some patients. The platelet storage-pool adenosine 5'-triphosphate (ATP) level in 15 patients after BMT was 0.45+/-0.24 micromol per 10(11) platelets, whereas the level in 18 controls was 1.03+/-0.36 micromol per 10(11) platelets (P = .00078). The total ATP levels of platelets in patients and controls were 4.33+/-1.14 and 5.63+/-1.51 micromol per 10(11) platelets, respectively (P = .016). With the exception of 1 patient, plasma levels of thrombomodulin and von Willebrand factor were all within the normal range. The average plasma level of 11-dehydrothromboxane B2 was significantly increased in 15 patients after BMT compared with controls, 20.6+/-8.2 and 10.3+/-1.2 pg/mL, respectively (P = .0004). These findings suggest a long-term process of platelet activation in patients after BMT and, following the cessation of cyclosporine, development of acquired storage-pool disorder of platelets.