Factor H, membrane cofactor protein, and factor I mutations in patients with hemolysis, elevated liver enzymes, and low platelet count syndrome

• Published in: Blood Vol. 112; no. 12; pp. 4542 - 4545
• Main Authors: Fakhouri, Fadi, Jablonski, Mathieu, Lepercq, Jacques, Blouin, Jacques, Benachi, Alexandra, Hourmant, Maryvonne, Pirson, Yves, Dürrbach, Antoine, Grünfeld, Jean-Pierre, Knebelmann, Bertrand, Frémeaux-Bacchi, Véronique
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.12.2008; Americain Society of Hematology
• Subjects: Adult; Biological and medical sciences; Complement Factor H - genetics; Complement System Proteins - genetics; DNA Mutational Analysis; Female; Fibrinogen - genetics; Genetic Predisposition to Disease; Gestational Age; HELLP Syndrome - genetics; Hematologic and hematopoietic diseases; Humans; Medical sciences; Membrane Cofactor Protein - genetics; Mutation, Missense; Other diseases. Hematologic involvement in other diseases; Pregnancy; Risk Factors; Young Adult; Kidney disease; Human; Immunopathology; Factor H; Urinary system disease; Serine endopeptidases; Enzyme; Alternative pathway complement; HELLP syndrome; Hemopathy; Immune deficiency; Complement Factor I; Peptidases; Acute renal insufficiency; Gene; Complement deficiency; Membrane cofactor protein; Genetics; Hydrolases; Complication; Mutation
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2008-03-144691

The HELLP syndrome, defined by the existence of hemolysis, elevated liver enzymes, and low platelet count, is a serious complication of pregnancy-related hypertensive disorders and shares several clinical and biologic features with thrombotic microangiopathy (TMA). Several recent studies have clearly shown that an abnormal control of the complement alternative pathway is a major risk for the occurrence of a peculiar type of TMA involving mainly the kidney. The aim of this study was to screen for complement abnormalities in 11 patients with HELLP syndrome and renal involvement. We identified 4 patients with a mutation in one of the genes coding for proteins involved in the regulation of the alternative pathway of complement. Our results suggest that an abnormal control of the complement alternative pathway is a risk factor for the occurrence of HELLP syndrome.