Coagulation proteins hepatic synthesis

Pharmacology Vitamin K promotes the hepatic synthesis of active prothrombin (factor II), proconvertin (factor VII), plasma thromboplastin component (factor IX), and Stuart factor (factor X). The mechanism by which vitamin K promotes formation of these clotting factors involves the hepatic post-translational carboxylation of specific glutamate residues to gamma-carboxylglutamate residues in proteins involved in coagulation, thus leading to their activation. 

Hemorrhagic disease of the newborn can develop readily because of (1) poor placental transfer of vitamin K, (2) hepatic immaturity leading to inadequate synthesis of coagulation proteins, and (3) the low vitamin K content of early breast milk. Prothrombin levels during this period are only about 25% of the adult levels. Severe diarrhea and antibiotics used to suppress diarrhea readily exacerbate the situation, so prothrombin levels can drop below 5% of the adult level and bleeding can occur. This condition is routinely prevented by the prophylactic administration of 0.5 to 1.0 mg of phylloquinone intramuscularly, or 2.0 mg given orally immediately after birth. 

Answer C. Warfarin inhibits the hepatic synthesis of factors II (prothrombin), VII, IX, and X. Its onset of anticoagulation activity is slow, and its impact on individual coagulation factors depends on their half-lives. Factor VII and protein C have much shorter half-lives than prothrombin, and so the extrinsic pathway and protein C system are the first to be affected by warfarin. The intrinsic pathway continues to function for 2 to 3 days, causing a state of hypercoagulability with possible vascular thrombosis. 

Coagulation factors are proteins with varying but usually short half-lives, (s. tab. 5.12) Their determination allows the assessment of hepatic function. However, the respective half-life has to be considered. Disorders of coagulation factors are therefore important functional parameters in hepatic diseases - both in severe acute and in chronic cases. In liver diseases, there may be a lack of coagulation factors, which is predominantly and primarily caused by a disorder of the hepatocyte synthesis capacity. This lack can also be due to other causes (1.) accelerated catabolism, (2.) altered biosynthesis of inhibitors, (3.) production of abnormal factors, and (4.) increased demand due to intravasal coagulation. 

Effects on hepatic protein synthesis are caused by many hepatotoxins, but the changes may take some time to become apparent given the half-lives of the involved proteins. Reductions of plasma albumin and acid glycoprotein may affect the binding and exposures to xenobiotics and plasma bilirubin. Other effects on proteins may also be due to reduced food intake due to toxicity. The production of many plasma proteins, including those involved in complement and coagulation cascades, can be affected by reductions of hepatic protein synthesis. 

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). 

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