Bone Marrow Transplantation Related Thrombotic and Hemorrhagic Complications: An Updated Review

Introduction

Hemostatic challenges occur throughout the period of bone marrow transplantation (BMT). Endothelial cell injury is a dominant contributing factor to the hemostatic impairments via chemotherapy 1, growth factors 1, intravenous catheters, and graft versus host reaction 2. Thrombocytopenia is also a major contributor to the bleeding manifestations. A number of changes in procoagulant, anticoagulant and, to a lesser extent, fibrinolytic factors have been described. These include reduction in levels of factor VII, factor X, protein C, antithrombin III, and plasminogen 3–7. Conversely, levels of fibrinogen, von Willebrand factor (VWF), plasminogen activator inhibitor (PAI-1), and tissue plasminogen activator (t-PA) are increased 3–5, 8, 9. Collectively, major changes in the coagulation system predispose BMT patients to hemostatic complications. In a retrospective analysis of 364 allogeneic and 83 autologous transplants, 83% presented with at least one hemostatic complication from the start of conditioning therapy and 4–10 years follow-up 10. Most bleeding episodes occurred within the first 4 weeks after transplantation and were relatively mild. However, 27% of the patients hemorrhaged severely, doubling the overall mortality of the BMT recipients. Bleeding was strongly associated with prolonged thrombocytopenia and graft versus host disease (GVHD) 10. Thromboembolic events, hepatic veno-occlusive disease (VOD), and thrombotic microangiopathy (TMA) occurred most frequently in allogeneic transplant recipients, for whom the incidence was 15%, 4.7%, and 14.6%, respectively, leading to an increased overall mortality 10.

Abstract

Thrombotic and hemorrhagic complications are common in bone marrow transplantation (BMT) recipients. Endothelial cell injuries due to chemotherapy, growth factors, intravenous catheter, graft versus host disease, as well as profound thrombocytopenia are major components involved in the hemostatic complications. Common thrombotic manifestations include veno-occlusive disease (VOD) and thrombotic microangiopathy (TMA). Diffuse alveolar hemorrhage and hemorrhagic cystitis are severe bleeding manifestations in BMT recipients with high morbidity and mortality rate and no effective treatment. More intensive conditioning regimens and mismatched donors increase the risk of hemostatic complications. Management of thrombotic and bleeding complications is discussed including current data on the role of recombinant factor VIIa for severe hemorrhage and defibrotide for VOD.

Keywords

bone marrow transplantation, diffuse alveolar hemorrhage, hemorrhagic cystitis, veno-occlusive disease, thrombotic microangiopathy