Hematological disorders and pulmonary hypertension

Abstract

Pulmonary hypertension (PH), a serious disorder with a high morbidity and mortality rate, is known to occur in a number of unrelated systemic diseases. Several hematological disorders such as sickle cell disease, thalassemia and myeloproliferative diseases develop PH which worsens the prognosis. Associated oxidant injury and vascular inflammation cause endothelial damage and dysfunction. Pulmonary vascular endothelial damage/dysfunction is an early event in PH resulting in the loss of vascular reactivity, activation of proliferative and antiapoptotic pathways leading to vascular remodeling, elevated pulmonary artery pressure, right ventricular hypertrophy and premature death. Hemolysis observed in hematological disorders leads to free hemoglobin which rapidly scavenges nitric oxide (NO), limiting its bioavailability, and leading to endothelial dysfunction. In addition, hemolysis releases arginase into the circulation which converts L-arginine to ornithine, thus bypassing NO production. Furthermore, treatments for hematological disorders such as immunosuppressive therapy, splenectomy, bone marrow transplantation, and radiation have been shown to contribute to the development of PH. Recent studies have shown deregulated iron homeostasis in patients with cardiopulmonary diseases including pulmonary arterial hypertension (PAH). Several studies have reported low iron levels in patients with idiopathic PAH, and iron deficiency is an important risk factor. This article reviews PH associated with hematological disorders and its mechanism; and iron homeostasis and its relevance to PH.

Keywords: Anemia, Hemolysis, Iron homeostasis, Myelofibrosis, Pulmonary hypertension

Core tip: Oxidant injury, inflammation, impaired nitric oxide bioavailability and coagulopathy that occur in hematological diseases lead to endothelial dysfunction and thrombo-embolism with subsequent development of pulmonary hypertension (PH). In addition, treatment used for these disorders such as immunosuppressive drugs, splenectomy, bone marrow transplantation and radiation therapy are also known to cause endothelial damage and thrombo-embolism leading to PH. Furthermore, there is a causal relationship between vascular and hematopoietic systems. Patients with chronic myeloproliferative diseases are at a risk of developing PH; and the occurrence of myelofibrosis contributing to impaired hematopoiesis is not uncommon in PH.