Coagulation factor V and VIII

Protein C functions as an anticoagulant by proteolytically inactivating two protein cofactors of blood coagulation, factors V and VIII.402 It too circulates in a zymogen form and is activated by limited proteolysis. Protein C appears to contain about 16 sites for Ca2+, all of equal affinity, while activated protein C binds about nine Ca2+. Conformational rearrangement during activation results in loss of binding sites. 

I 14 Kane WH, Davie EW. Blood coagulation factors V and VIII structural and functional similarities and their relationship to hemorrhagic and thrombotic disorders. Blood 1988 71 539-555. 

Fig. 7. Schematic representation of the domain organizadon, as well as ligand-, receptor-, and co-receptor-binding preferences of the semaphorins and their neuronal receptors. The individual domains are labeled. PSI, Plexin/Semaphorin//ntegrin domain IPX, /mmunoglobulin-like domain found in Plexins (and Met) and in some Transcription factors CUB, domain homologous to complement-binding factors Clr and Cls FV/VIII, domain homologous to coagulation factor V and VIII (also known as F5/8 type C or discoidin domain) MAM, Meprin/A5/fi domain SP, Sex-Plexin domain. Semaphorins, plexins and scatter-factor receptors (MET) share a common semaphorin domain (black heptagon).

Pereira, L.M.M.B., Langley, P.G., HayRar, K.M., Tredger, J.M., Williams, R. Coagulation factor V and VIII/V ratio as predictors of outcome in paracetamol induced fulminant hepatic failure relation to other prognostic indicators. Gut 1992 33 98-102... 

The cofactor proteins (tissue factor. Factors V and VIII) serve as binding sites for other factors. Tissue factor is not related structurally to the other blood coagulation cofactors and is an integral membrane protein that does not require cleavage for active function. Factors V and VIII serve as procofactors, which, when activated by cleavage, function as binding sites for other factors. 

Lechner D, Eichinger S, Wanivenhaus A, Kyrle PA. Peri-interventional control of haemostasis in a patient with combined coagulation factor V- and factor VIII-deflciency and anaphylaxis to fresh frozen plasma—a rare indication for recombinant factor Vila. Haemophilia 2010 16(4) 704-5. 

A modifier-specifier role for proteins, wherein a new biologic function or enhanced activity is achieved, may well be more common than is presently appreciated. For example, factors V and VIII in the blood coagulation process appear to act in this way (Davie et al., 1979), as do specific protein initiation factors which participate in protein synthesis (Weissbach and Ochoa, 1976). 

Mechanism of action - Argatroban is a synthetic, direct thrombin inhibitor that reversibly binds to the thrombin active site. It inhibits thrombin-catalyzed or induced reactions, including fibrin formation activation of coagulation factors V, VIII, and XIII protein C and platelet aggregation. 

Quick s value A drop in the coagulation factors II, V, Vn, IX and X is a reliable indicator of the still remaining liver function. Factor VIII increases. With massive liver cell destruction, a dangerous decrease in factors V and VII is witnessed within 1 or 2 days (corresponding to the half-life of the factors) together with a reduction in Quick s value and Colombi s index (<60 - 80%). (45, 47, 71) (s. p. 105)... 

Acute renal tubular damage occurs in association with the liver damage, together with muscle necrosis and hyperkalemia. The muscle necrosis, as demonstrated at autopsy in fatal cases (82), can itself exacerbate the severe electrolyte derangement, particularly marked hyperkalemia, that occurs in liver failure. The measurement of serum concentrations of coagulation factors V (below 10%) and VIII (VIII/V ratio over 30) can have predictive value and can thus be helpful in selecting patients who require hver transplantation (SEDA-17, 99). 

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