A bleeding disorder due to deficiency of alpha 2-antiplasmin.
A deficiency of alpha 2-antiplasmin has been identified in a female patient with severe and frequent bleeding episodes. Routine coagulation and platelet assays of the patient's plasma were within normal limits. However, abnormally rapid whole blood or dilute plasma clot lysis times and an abnormal FXIII test in which clots were lysed in the presence of urea or saline suggested an abnormal fibrinolytic system. Analysis of alpha 2-antiplasmin levels by radioimmunoassay revealed less than 1.0 microgram/ml alpha 2-antiplasmin. Functional assays indicated an alpha 2-antiplasmin level less than or equal to 10% of normal. Addition of purified alpha 2-antiplasmin to the patient's plasma restored its ability to inhibit plasmin in in vitro assays, and mixtures of patient plasma with normal plasma did not interfere with the antiplasmin activity of the normal plasma. Whereas normal platelets contain 68 ng alpha 2-antiplasmin/10(9) platelets, platelets from the patient contained 30% of the normal level of antigen. Analysis of alpha 2-antiplasmin functional and antigenic levels in the plasma of both parents and four siblings of the propositus provided evidence consistent with an autosomal mechanism of inheritance of alpha 2-antiplasmin deficiency. One sibling appeared to be homozygous and three siblings and the parents were heterozygous for the deficiency. Two heterozygotes had positive bleeding histories. The association of a bleeding disorder with a deficiency of alpha 2-antiplasmin emphasizes that lack of regulation of the fibrinolytic system can result in a hemostatic dysfunction.
D000293:Adolescent; D000328:Adult; D001777:Blood Coagulation; D002648:Child; D002675:Child, Preschool; D005260:Female; D005342:Fibrinolysis; D006474:Hemorrhagic Disorders / Q000097:blood / Q000209:etiology* / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D010974:Platelet Aggregation; D000979:alpha-2-Antiplasmin / Q000032:analysis / Q000172:deficiency*
D000979:alpha-2-Antiplasmin