title: Severe hemolysis and red cell fragmentation caused by the combination of a spectrin mutation with a thrombotic microangiopathy.
abstract: Two patients are described who presented with severe hemolysis and erythrocyte fragmentation. One patient had renal allograft rejection and disseminated intravascular coagulation, and the other had thrombotic thrombocytopenia purpura. The severity of hemolysis and the red cell abnormalities were considerably more profound than usually seen in patients with thrombotic microangiopathies. After evaluation of blood smears prepared before the onset of the disease and biochemical characterization of proteins of the red blood cell skeleton, a mutation of the skeletal protein spectrin, designated Sp alpha l/65, was identified. In the heterozygous form, this mutation manifests as mild, often asymptomatic, hereditary elliptocytosis. We conclude that in these two patients with thrombotic microangiopathy, the intrinsic red cell membrane instability resulting from the underlying skeletal defect aggravated the mechanical red cell fragmentation, producing morphological features similar to the severe hemolytic form of hereditary elliptocytosis or hereditary pyropoikilocytosis.
authors.affiliation: Department of Biomedical Research, St. Elizabeth's Hospital of Boston, MA 02135.
authors.forename: P
authors.initials: P
authors.lastname: Jarolim
authors.forename: J
authors.initials: J
authors.lastname: Palek
authors.forename: T L
authors.initials: TL
authors.lastname: Coetzer
authors.forename: J
authors.initials: J
authors.lastname: Lawler
authors.forename: E
authors.initials: E
authors.lastname: Velez-Garcia
authors.forename: J
authors.initials: J
authors.lastname: Fradera
authors.forename: A
authors.initials: A
authors.lastname: Charles
authors.forename: H S
authors.initials: HS
authors.lastname: Jacob
authors.forename: J L
authors.initials: JL
authors.lastname: Moake
mesh_terms: D000293:Adolescent; D000328:Adult; D004912:Erythrocytes / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006084:Graft Rejection; D006461:Hemolysis; D006801:Humans; D016030:Kidney Transplantation; D009154:Mutation; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood; D013049:Spectrin / Q000097:blood / Q000235:genetics*; D013329:Structure-Activity Relationship; D013927:Thrombosis / Q000097:blood*; D014652:Vascular Diseases / Q000097:blood*
chemical_list: D013049:Spectrin