PROTHROMBIN MADRID - NEW FAMILIAL ABNORMALITY OF PROTHROMBIN

An abnormal prothrombin has been detected in a 13 yr-old girl, with history of excessive bleeding. Prothrombin time and activated partial thromboplastin time were markedly prolonged. Prothrombin activity was very low when measured by biological assay using either physiological activators (3% by one stage assay and 20 US u/ml by two stage assay) or Taipan snake venom (3 %) ; in contrast the level was found to be normal both by immunoassay and by assaying with the venom of either Echis carinatus or Dispholidus typus. In keeping with current nomen-clature practices, the condition has been designated prothrombin Madrid. The family history revealed consanguinity between the propositus' mother and father. A 50 % reduced prothrombin level was found in both parents' plasma when using physiological activators. The pattern of inheritance appears to be autosomal recessive, the propositus being homozygote and her parents heterozygotes. Immunologic properties of prothrombin Madrid seem identical with those of the normal zymogen. The electrophoretic properties and the calcium binding of the abnormal molecule do not differ significantly from normal, as assessed by crossed immunoelectrophoresis. Prothrombin Madrid has been isolated by chromatography onto DEAE Sephadex and dextran sulphate agarose. The abnormal molecule was found to bind DEAE Sephadex more tightly than normal. Purified prothrombin Madrid activation by physiological activators was found to be much slower than normal. The use of SDS gel electrophoresis and alkaline disc gel electrophoresis did not allow detection of a significant difference between prothrombin Madrid and normal prothrombin. © 1979.