Association of soluble fms‐like tyrosine kinase‐1 with pulmonary hypertension and haemolysis in sickle cell disease

• Published in: British journal of haematology Vol. 152; no. 4; pp. 485 - 491
• Main Authors: Ataga, Kenneth I., Brittain, Julia E., Jones, Susan K., May, Ryan, Delaney, John, Strayhorn, Dell, Desai, Payal, Redding‐Lallinger, Rupa, Key, Nigel S., Orringer, Eugene P.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2011; Blackwell
• Subjects: Adult; Anemia, Sickle Cell - blood; Anemia, Sickle Cell - complications; Anemia, Sickle Cell - physiopathology; Anemias. Hemoglobinopathies; Biological and medical sciences; Case-Control Studies; Diseases of red blood cells; endothelial activation; Endothelium, Vascular - physiopathology; Female; Follow-Up Studies; haemolysis; Hematologic and hematopoietic diseases; Hemoglobins - metabolism; Hemolysis - physiology; Humans; Hypertension, Pulmonary - blood; Hypertension, Pulmonary - etiology; Hypertension, Pulmonary - physiopathology; Male; Medical sciences; Middle Aged; Pneumology; pulmonary hypertension; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Sickle cell disease; soluble fms‐like tyrosine kinase‐1 (sFLT‐1); Vascular Endothelial Growth Factor Receptor-1 - blood; Vascular Endothelial Growth Factor Receptor-1 - physiology; Hemolysis; Hemoglobinopathy; Endothelial cell; Sickle cell anemia; Hematology; Enzyme; Respiratory disease; Transferases; Cardiovascular disease; Hemopathy; Soluble form; Pulmonary hypertension; soluble fms-like tyrosine kinase-1 (sFLT-1); Genetic disease; endothelial activation; Hemolytic anemia; haemolysis; Sickle cell disease; Protein-tyrosine kinase
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2010.08410.x

Summary The pathophysiology of pulmonary hypertension (PHT) in sickle cell disease (SCD) is probably multifactorial. Soluble fms‐like tyrosine kinase‐1 (sFLT‐1) is a member of the vascular endothelial growth factor receptor (VEGFR) family. By adhering to and inhibiting VEGF and placenta growth factor, it induces endothelial dysfunction. We sought to evaluate the association of sFLT‐1 with clinical complications of SCD. We confirmed that sFLT‐1 was significantly elevated in SCD patients compared to healthy, race‐matched control subjects. The level of sFLT‐1 was significantly higher in patients with PHT, but no association was observed between sFLT‐1 and the frequency of acute pain episodes or history of acute chest syndrome. sFLT‐1 was correlated with various measures of haemolysis, erythropoietin and soluble vascular cell adhesion molecule‐1. By inducing endothelial dysfunction, sFLT‐1 may contribute to the pathogenesis of SCD‐associated PHT, although this effect does not appear to be independent of haemolysis.