Prothrombin Clamart: prothrombin variant with defective Arg 320-IIe cleavage by factor Xa.
An abnormal prothrombin has been detected in a 23 yr-old healthy female and her mother. Both patients appeared to be heterozygous for the abnormality, plasma prothrombin being 50% of normal using the usual one stage assay, but normal when measured either by using Echis carinatus venom or by immunoassay. No abnormality in the immunoelectrophoretic pattern was observed. Prothrombin isolation on DEAE Sephadex failed to separate the abnormal population (prothrombin Clamart) from the normal one. The rates of prothrombin activation by factor Xa, in the presence or absence of phospholipids and/or factor Va, were determined by measuring the production of both clotting and amidolytic activities. The thrombin generation rate from prothrombin isolated from the propositus plasma was 50% slower than normal whatever the method of measurement and the composition of the activation mixture. Analysis of the final activation products by SDS polyacrylamide gel electrophoresis revealed that equal amounts of prethrombin 2 and thrombin had been formed. Prethrombin 2 Clamart was shown to be resistant to proteolysis upon further incubation with factor Xa, whereas it was readily converted to thrombin by Echis carinatus venom. Prothrombin Clamart appears to be characterized by an impairment of Arg 320-IIe cleavage by factor Xa.
D000328:Adult; D001120:Arginine / Q000378:metabolism; D001778:Blood Coagulation Disorders / Q000235:genetics; D005170:Factor X / Q000502:physiology*; D015951:Factor Xa; D005260:Female; D014644:Genetic Variation; D006579:Heterozygote; D006801:Humans; D007123:Immunoelectrophoresis, Two-Dimensional; D011516:Prothrombin / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D011517:Prothrombin Time; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000032:analysis / Q000378:metabolism
C050800:prothrombin Clamart; D011516:Prothrombin; D005170:Factor X; D001120:Arginine; D013917:Thrombin; D015951:Factor Xa