IRB 00006477.

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A dysprothrombin designated prothrombin Segoviawas isolatedfrom the plasmaof an individual withnormal prothrombin antigen andprothrombin activity lesserthan25°Aof the control prothrombin activity.Activationby prothrombinase complex showed a lower amidolytic thanclottingactivity, whichsuggests a lessergeneration of activeintermediates thannormalprothrombin. Whenprothrombin Segoviawas activated by protbrombinase complexm the absenceof iktor Va, no tbrombinformationwas found by fictional activities. SDS-PAGEanalysis of themolecules derived by activation withprotbrombrnase comple> Taipansnakevenom andEchis carinafusvenom showedan accumulation of molecules not cleavedatbondArg320-lle321. Ihis wasmoreevident withEchiscarinutus veno~whichonlyactson thisbond.Ourdatasuggestthatthealteration of prothrombin Segoviaimpairs thescission of bondArg320-Ile321. Q1997ElsevierScience.QdDysprothrombinemias represent oneof themostuncommoncoagulation defects; so fir, 21variantsj all of them charactetid by a decreasem the fictional level of prothrombincomparedto the immunologically detectable prothrombin (l), have beenreported (2-7).The conversionof humanprothrombin to thrombrn requirestwo cleavages(8): one at bond A (Arg271-Thr272), thatsplitsprothrombin rntofragment1+2 (F1+2) andprethrombin 2 (P2), and another atbondB (Arg320-lle321), whichexposesthe activesite(9) andyieldsthe disulfide-linked two-chain (A andB chains) enzyme thrombin. Thesecleavages canbe producedm theoppositeorder, yieldingfirst the disulfiddinkedtwo-chainactiveintermediate meizothrombin (MT), and thq tbrombin. Thereare alsotwo morepeptidebondssusceptible to autocatalysis; bond C (Arg155-Ser156), and bondD, (Arg286-Thr287). Cleavage of bondC fromprothrombin producesprethrombin