Pleiotropic effects of intravascular haemolysis on vascular homeostasis

• Published in: British journal of haematology Vol. 148; no. 5; pp. 690 - 701
• Main Authors: Kato, Gregory J., Taylor, James G.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2010; Blackwell
• Subjects: Anemia, Sickle Cell - complications; Anemias. Hemoglobinopathies; Biological and medical sciences; Diabetes Mellitus - physiopathology; Diseases of red blood cells; haemolysis; Hematologic and hematopoietic diseases; Hematologic Diseases - complications; Hematologic Diseases - physiopathology; Hemolysis - physiology; Humans; Inflammation - complications; Medical sciences; Nitric Oxide; sickle cell disease; thalassaemia; Thalassemia - complications; Vascular Diseases - etiology; Vascular Diseases - physiopathology; vasculopathy; Hemolysis; Hemoglobinopathy; Sickle cell anemia; thalassaemia; Hematology; Homeostasis; Cardiovascular disease; Thalassemia; Hemopathy; Genetic disease; sickle cell disease; Vascular disease; Hemolytic anemia; haemolysis; Nitric oxide; Blood vessel; Circulatory system; vasculopathy
• ISSN: 0007-1048; 1365-2141; 1365-2141
• DOI: 10.1111/j.1365-2141.2009.08004.x

Summary The breakdown of senescent or defective red blood cells releases red cell contents, especially haemoglobin, which scavenges nitric oxide (NO) and decomposes to haem and free iron. These are potent oxidants, all of which have promoted the evolution of inducible and vasculoprotective compensatory pathways to rapidly clear and detoxify haemoglobin, haem and iron. Chronic haemolytic red cell disorders as diverse as sickle cell disease, thalassaemia, unstable haemoglobinopathy, cytoskeletal defects and enzymopathies have been linked to a clinical constellation of pulmonary hypertension, priapism, leg ulceration and possibly cerebrovascular disease and thrombosis. Besides free haemoglobin, haemolysis has been associated with extracellular arginase that limits substrate availability to NO synthase, endogenous inhibitors of NO synthase activity, and inappropriate activation of haemostatic pathways. This article reviews the haemolytic disorders that have been reported to manifest vascular complications, and explores the speculative possibility that haemolysis mediates some of the vascular complications of inflammation and diabetes.