defibrotide and Pulmonary-Veno-Occlusive-Disease

Endothelial cells are unique multifunctional cells with basal and inducible metabolic and synthetic functions. Various stimuli can induce physiological or pathological changes in endothelial cell biology. Hematopoietic stem cell transplantation (HSCT) requires high-dose irradiation and/or chemotherapy and is associated with increased risk of bacterial infections and immune reactions. These factors can affect endothelial cells. This review provides an overview of the effects of HSCT on endothelial cells, based on findings observed in cultured cells as well as in patients. We first describe to what extent irradiation and chemotherapy constitute direct and indirect triggers for endothelial cell activation and injury. Then, we highlight the role of the endothelium in several complications of HSCT, including capillary leak syndrome, engraftment syndrome, transplant-associated microangiopathy, graft-versus-host disease, and diffuse alveolar hemorrhages. We also analyze in detail available data on sinusoidal obstruction syndrome, previously known as veno-occlusive disease of the liver, where liver sinusoidal endothelial cells are first injured and eventually lead to sinusoid occlusion and liver cell damage. Finally, we open the question of the possible contribution of endothelial damage to cardiovascular events occurring long after HSCT.

Topics: Angiogenic Proteins; Animals; Anticoagulants; Bone Marrow Transplantation; Capillary Leak Syndrome; Cardiovascular Diseases; Cell Adhesion Molecules; Cell-Derived Microparticles; Endothelium, Vascular; Fever; Graft vs Host Disease; Hematologic Diseases; Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease; Humans; Immunosuppressive Agents; Inflammation; Nitric Oxide; Polydeoxyribonucleotides; Pulmonary Veno-Occlusive Disease; Radiation Injuries; Syndrome; Thrombotic Microangiopathies; Transplantation Conditioning

Veno-occlusive disease is among the most serious complications following hematopoietic stem cell transplantation. While hepatic veno-occlusive disease occurs more commonly, the pulmonary variant remains quite rare and often goes unrecognized antemortem. Endothelial damage may represent the pathophysiologic foundation of these clinical syndromes. Recent advances in the treatment of hepatic veno-occlusive disease may have application to its pulmonary counterpart.

Topics: Endothelium; Fibrinolytic Agents; Hematopoietic Stem Cell Transplantation; Humans; Polydeoxyribonucleotides; Pulmonary Veno-Occlusive Disease

Pulmonary venoocclusive disease (PVOD) is a rare form of pulmonary vascular disease with pulmonary hypertension characterized by preferential involvement of the pulmonary venous system. Hepatic venoocclusive disease (HVOD), also known as sinusoidal obstruction syndrome, is a condition that occurs in 13% to 15% of patients after hematopoietic stem cell transplantation (HSCT). Although hepatic and pulmonary venoocclusive diseases may share some pathologic features as well as some etiologies such as HSCT, these two disorders have never been described together in a single adult patient. We report the case of a patient who received HSCT and developed HVOD and PVOD within 9 months. Despite their differences, PVOD and HVOD share common risk factors and associated conditions, suggesting that in the context of HSCT, the two diseases share common pathophysiological mechanisms. Optimal treatment for HSCT-related PVOD remains to be determined.

Topics: Ascites; Cardiac Catheterization; Endothelin Receptor Antagonists; Female; Fibrinolytic Agents; Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease; Humans; Hyperbilirubinemia; Leukemia, Myeloid, Acute; Middle Aged; Phenylpropionates; Polydeoxyribonucleotides; Pulmonary Arterial Hypertension; Pulmonary Veno-Occlusive Disease; Pyridazines; Transplantation, Homologous; Treatment Outcome; Ultrasonography

Topics: Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease; Humans; Male; Mastocytosis, Systemic; Middle Aged; Platelet Aggregation Inhibitors; Polydeoxyribonucleotides; Pulmonary Veno-Occlusive Disease; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome; Vascular Diseases

The present study reports a case of biopsy-proven pulmonary veno-occlusive disease as a cause of severe pulmonary hypertension in a patient suffering from a chronic myeloproliferative disorder. The pulmonary disease evolved favourably under treatment with defibrotide, a pro-fibrinolytic medication used in hepatic veno-occlusive disease.

Topics: Aged; Female; Fibrinolytic Agents; Humans; Myeloproliferative Disorders; Polydeoxyribonucleotides; Pulmonary Veno-Occlusive Disease