Coagulation factors vitamin K-dependent

Warfarin exerts its anticoagulant effect by inhibiting the production of the vitamin K-dependent coagulation factors... 

The levels of vitamin K-dependent coagulation factors are physiologically low in neonates. Absence of vitamin K impairs y-carboxylation, and the inactive precursors of factors II, VII, IX, and X accumulate in the plasma, unable to bind calcium and cell membranes. Consequently, the precursor levels may decline further, impairing coagulation and potentially leading to VKDB. 

The most commonly used oral anticoagulant drug in the U.S. is warfarin. It acts by altering vitamin K so that it is unavailable to participate in synthesis of vitamin K-dependent coagulation factors in the liver (coagulation factors II, VII, IX, and X). Because of the presence of preformed clotting factors in the blood, the full antithrombotic effect of warfarin therapy may require 36 to 72 h. 

Hepatic injury Serious liver injury (eg, cirrhosis) may enhance the anticoagulant effect of lepirudin caused by coagulation defects secondary to reduced generation of vitamin K-dependent coagulation factors. 

Inhibits the synthesis of vitamin K-dependent coagulation factors, leading to sequential depression of Factors VII, IX, X, and II... 

In some patients with combined deficiency of vitamin K-dependent coagulation factors, the deficiency can be partially corrected by high doses of vitamin K, suggesting that the defect is in the affinity of the carboxylase for its coenzyme (Mutucumarana et al., 2000). 

A marked reduction in vitamin K-dependent coagulation factors, which was prevented by vitamin K administration, has been described in patients with acute myeloid leukemia who were given GM-CSF (SEDA-19, 342). 

Hepatic injury can also alter the synthesis of the blood coagulation cascade and prolong prothrombin and activated partial thromboplastin times. These effects on vitamin K dependent coagulation factors II (prothrombin), VII, IX, and X and protein C, protein S, and protein Z tend to affect the prothombin time (PT) more frequently than the activated partial thromboplastin time (APTT) however in some cases of hepatotoxicity, the APTT changes may be more marked than those for PT (Pritchard et al. 1987). 

I. Mechanism of toxicity. All these compounds inhibit hepatic synthesis of the vitamin K-dependent coagulation factors II, VII, IX, and X. Only the synthesis of new factors is affected, and the anticoagulant effect is delayed until currently circulating factors have been degraded. Peak effects are usually not obsen/ed for 2-3 days because of the long halt-lives of factors IX and X (24-60 hours). 

No changes in the anticoagulant activity (thromboplastin time or partial thromboplastin time) of warfarin was observed in rats orally coadministered single doses of 500 mg/kg of Pelargonium sidoides and 0.05 mg/kg of warfarin or in rats orally administered 500 mg/kg daily for 2 weeks prior to administration of a single dose of warfarin. The authors noted that coumarin-type anticoagulants inhibit the synthesis of vitamin K-dependent coagulation factors via identical mechanisms in rats and humans, and have a similar pattern of metabolism in both species (Koch and Biber 2007). 

A simplified diagram of the cascade of mammalian blood coagulation is given in Fig. 5. A complex of coagulation initiator factor Vila, tissue factor, phospholipids, and calcium ions, activates factor IX. Then, factor X and prothrombin are sequentially activated to factor Xa and alpha-thrombin, respectively. These coagulation factors such as factor VII, factor IX, factor X, and prothrombin are vitamin K-dependent coagulation factors, and contain gamma-... 

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