Prothrombin activator

Activated factor X, along with Ca++ ion, factor V, and PF3 (collectively referred to as the prothrombin activator), catalyzes the conversion of prothrombin into thrombin. Thrombin then catalyzes the conversion of fibrinogen into fibrin, an insoluble, thread-like polymer. The fibrin threads form a meshwork that traps blood cells, platelets, and plasma to form the blood clot. The clotting cascade may be elicited by means of two mechanisms (see Figure 16.1) ... 

Hepatotoxicity manifested by alterations in liver function, including hyperbilirubinemia, and decreased prothrombin activity, is associated with exposure in both animals and humans. ... 

Warfarin acts as a vitamin K antagonist and suppresses the hepatic formation of prothrombin and of factors VII, IX, and X, causing a markedly reduced prothrombin activity of the blood.Warfarin also causes dilatation and engorgement of blood vessels and an increase in capillary fragility. The two effects can combine to produce hematomas, severe blood... 

Converting to oral anticoagulant therapy Perform baseline coagulation tests to determine prothrombin activity when heparin activity is too low to affect PT or INR. When the results of the initial prothrombin determinations are known, initiate the oral anticoagulant in the usual amount. Thereafter, perform coagulation tests and prothrombin activity at appropriate intervals. When the prothrombin activity reaches the desired therapeutic range, discontinue heparin and continue oral anticoagulants. 

Conversion from heparin therapy Because the anticoagulant effect of warfarin is delayed, heparin is preferred initially for rapid anticoagulation. Conversion to warfarin therapy may begin concomitantly with heparin therapy or may be delayed 3 to 6 days. To ensure continuous anticoagulation, it is advisable to continue full dose heparin therapy and that warfarin therapy be overlapped with heparin for 4 to 5 days, until warfarin therapy has produced the desired therapeutic response as determined by PT/INR. When warfarin has produced the desired PT/INR or prothrombin activity, heparin may be discontinued. 

Bleeding during anticoagulant therapy does not always correlate with prothrombin activity. Bleeding that occurs when the PT or INR is within the therapeutic range warrants investigation because it may unmask a previously unsuspected lesion (eg, tumor, ulcer). 

Treatment with warfarin should be initiated with standard doses of 5-10 mg rather than the large loading doses formerly used. The initial adjustment of the prothrombin time takes about 1 week, which usually results in a maintenance dose of 5-7 mg/d. The prothrombin time (PT) should be increased to a level representing a reduction of prothrombin activity to 25%... 

Vitamins Ki and K2 require bile salts for absorption from the intestinal tract. Vitamin Kl is available clinically in oral and parenteral forms. Onset of effect is delayed for 6 hours but the effect is complete by 24 hours when treating depression of prothrombin activity by excess warfarin or vitamin deficiency. Intravenous administration of vitamin Ki should be slow, because rapid infusion can produce dyspnea, chest and back pain, and even death. Vitamin repletion is best achieved with intravenous or oral administration, because its bioavailability after subcutaneous administration is erratic. Vitamin Ki is... 

Tricyclic antidepressants can interfere with the metabolism of oral anticoagulants, increase their serum concentrations, and prolong their half-lives by as much as 300% (SEDA-21,10) (161). Prothrombin activity should be carefully monitored in patients taking oral anticoagulants. 

The cascade is not a simple linear one. The concerted action of activated Factors Vlll and fX is required in the intrinsic pathway for the activation of Factor X. The rate of prothrombin activation by activated Factor X alone is inadequate to meet physiological needs an additional protein, proaccelerin or Factory, is also required. In addition to prothrombin. Factors VII, IX, and X contain y-carboxyglutamate and hence are vitamin K-dependent, as are three... 

IRacy PB, Mann KG. Amodel for assembly of coagulation factor complexes on cell surfaces Prothrombin activation on piatdets. In Btodiemistry of Plaldets. Eds DR Phillips and MA Shuman, Academic (Orlando), pp 296,1986. 

Rosing,)., Zwaal, R, F., and Tans, G. (1936). Formation of meiz.othrombin as intermediates in factor Xa-cata yzed prothrombin activation.). Beal. Chem. 261, 4224r-4228. 

Tijburg, R, Heerde, W Leenhouts, IL, ilessing, M., Bounia, B., and de Gioot, P. (1991). Formation of meizothrombin as intermediate in factor Xa-catalyzed prothrombin activation on endothelial cells. /. Riol. Chan. 266, 4017-4022. 

In contrast to heparin, coumarins are secreted into the breast milk, but it has long been known that prothrombin activity in the plasma of neonates whose mothers take coumarins is not significantly reduced (88-90) and that warfarin does not have anticoagulant effects in breast-fed infants when given to nursing mothers (89,91). These conclusions are subject to the reservation that in some of the studies the dose of anticoagulant was low (89). Acenocoumarol-treated breastfeeding mothers can as a rule safely breastfeed their infants (92,93) nevertheless, it is prudent to check the infant s prothrombin time in such cases. 

Viperidae endopeptidase, factor X activator, fibrinogenase, kininogenase, metalloproteinase, prothrombin activator, serine protease, thrombin-like enzyme... 

D Angelo A, Della Valle P, Crippa L, et al. Relationship between international normalized ratio values, vitamin K-dependent clotting factor levels and in vivo prothrombin activation during the early and steady phases of oral anticoagulant treatment. Haematologica 2002 87(10) 1074 SO... 

The first and most completely characterized of the activation complexes of the procoagulant subsystem is that of prothrombin activation. Because of this, the prothrombin activation complex will be described in greater detail than the other, similar activation complexes (Figure 36-9) The general principles described below apply to all of the complexes. 

Tl. Tocantins, L. M., and O Neill, J. F., Increased plasma prothrombin activity after epinephrine injections relation to hyperglycemia. Proc. Soc. ExpU. Biol. Med. 47, 477-479 (1941). 

B4. Bauer, K. A., Teitel, J. M., and Rosenberg, R D., Assays for the quantitation < antitfarombin 111 thrombin-antithrombin complex and prothrombin activation fragments. In Disorders of Thrombin Formation (R W. Colman, ed.), pp. 142-155. Churchill-Ljvingstone, Edinburgh and London, 1983. 

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