Liver Disease and Vitamin K Deficiency PDF

liver disease and Vitamin K deficiency Presented by Dr. Sahar Gamal Elbager Assistant Professor of Haematology UMST  liver disease liver disease contribute to multiple haemostatic abnormalities: 1. Biliary obstructi...

liver disease and Vitamin K deficiency Presented by Dr. Sahar Gamal Elbager Assistant Professor of Haematology UMST  liver disease liver disease contribute to multiple haemostatic abnormalities: 1. Biliary obstruction results in impaired absorption of vitamin K and therefore decreased synthesis of factors II, VII, IX and X by liver parenchymal cells. 2. With severe hepatocellular disease, in addition to a deficiency of these factors, there are often reduced levels of factor V and fibrinogen and increased amounts of plasminogen activator. 5/26/2022 2  liver disease 3. Functional abnormality of fibrinogen (dysfi brinogenaemia) is found in many patients. 4. Decreased thrombopoietin production from the liver contributes to thrombocytopenia. 5. Hypersplenism associated with portal hypertension frequently results in thrombocytopenia. 5/26/2022 3  liver disease 6. Disseminated intravascular coagulation (DIC; see below) may be related to release of thromboplastins from damaged liver cells and reduced concentrations of antithrombin, protein C and α2 - antiplasmin. In addition, there is impaired removal of activated clotting factors and increased fi brinolytic activity. 7. The net haemostatic inbalance in liver disease may be prothrombotic rather than haemorrhagic. 5/26/2022 4  Vitamin K Fat - soluble vitamin K is obtained from green vegetables and bacterial synthesis in the gut. Deficiency may present in the newborn due to liver immaturity, lack of gut bacterial synthesis of the vitamin and low quantities in breast milk may (haemorrhagic disease of the newborn). Deficiency of vitamin K children or dults is caused by an inadequate diet, malabsorption or inhibition of vitamin K by drugs such as warfarin which act as vitamin K antagonists. 5/26/2022 5  Vitamin K Warfarin is associated with a decrease in the functional activity of factors II, VII, IX and X and proteins C and S, but immunological methods show normal levels of these factors. The non - functional proteins are called PIVKA (proteins formed in vitamin K absence). Conversion of PIVKA factors to their biologically active forms is a post - translational event involving carboxylation of glutamic acid residues in the N - terminal region where these factors show strong sequence homology. 5/26/2022 6  Vitamin K Gamma - carboxylated glutamic acid binds calcium ions, inducing a reversible shape change in the N - termini of vitamin K dependent proteins. This exposes hydrophobic residues which bind to phospholipid. In the process of carboxylation, vitamin K is converted to vitamin K epoxide which is cycled back to the reduced form by a reductase (VKORC - 1). Warfarin interferes with the action of vitamin K epoxide reductase leading to a functional vitamin K deficiency. 5/26/2022 7  Vitamin K deficiency in children or a dults Vitamin K deficiency in children or a dults resulting from obstructive jaundice, pancreatic or small bowel disease occasionally causes a bleeding diathesis in children or adults. Diagnosis 1. Both PT and APTT are prolonged. 2. There are low plasma levels of factors II, VII, IX and X. 5/26/2022 8  Vitamin K deficiency in children or a dults Treatment 1. Prophylaxis: vitamin K 5 mg/day orally. 2. Active bleeding or prior to liver biopsy: vitamin K 10 mg slowly intravenously. Some correction of PT is usual within 6 hours. The dose should be repeated on the next 2 days after which optimal correction is usual. 3. Rapid correction may be achieved by infusion of prothrombin complex concentrate. 5/26/2022 9  Thank you 5/26/2022 10