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Vitamin K. Dr.S.Chakravarty MD. Vitamin K:. K1 – phylloquinone – plant source K2 – menaquinone – bacterial source K3 – Menadione – synthetic form. Sources of VIT K:. Spinach , brocolli , lettuce Soya bean oil and canola oil. Bacterial source from gut. Functions of vitamin K.
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Vitamin K Dr.S.Chakravarty MD
Vitamin K: K1 – phylloquinone – plant source K2 – menaquinone – bacterial source K3 – Menadione – synthetic form
Sources of VIT K: Spinach , brocolli, lettuce Soya bean oil and canola oil. Bacterial source from gut.
Functions of vitamin K Helps in extrinsic pathway of blood coagulation – gamma carboxylation of factor (II, VII, IX and X) – calcium binding. Helps in synthesis of bone calcium binding proteins like osteocalcin and matrix Gla protein (MGP) – bone formation Gamma carboxylation of protein C, protein S and Protein Z which are normal anticoagulants.
Coagulation cascade: Factor III
Anti-coagulants in blood; Heparin Protein C – half life 8 hrs Protein S - Protein Z 3-5 days 4-6 hrs 1 day 2 days
Mechanism of vitamin K All the processess involve gamma carboxylation of glutamic acid residues of the protein. Post translational modification of protein Does not require a carboxylase, bicarbonate and ATP.
Vitamin K carboxylation cycle (-) (-) Warfarin First step
Hemorrhagic disease of the newborn Vitamin K deficiency bleeding : (VKDB) Reasons for hemorrhage in the newborn: Low placental transfer of phylloquinone Low clotting factor levels Sterile gut Low VIT K content in breast milk. Leads to intracranial, umbilicus, mucous membranes, gastrointestinal tract, circumcision and venipunctures bleeding. Treatment : 1mg menadioneIM.
Anticoagulation: Vitamin K dependent clotting factors can be inhibited by Warfarin and dicumarol. Warfarin inhibits vitamin K epoxide and quinonereductase inhibiting regeneration of hydroquinone form of vitamin K which is required for gamma carboxylation of clotting factors of extrinsic pathway. Warfarin therapy is monitored by prothrombin time.
Warfarin: No effect on already carboxylated clotting factors 2-3 days for anticoagulation to take place – New proteins protein C and Protein S inhibit Va and VIIIa Heparin should also be given – due to initial procoagulanteffect of warfarin due to inhibition of protein C and S – skin necrosis by warfarin.
Warfarinindued skin necrosis: Causes: Initial pro-coagulant effect of warfarin (why?) Protein C deficiency Obese patients Occurs on breasts, thighs, buttocks- excess fatty tissue. Occurs between 3-9 days of warfarin treatment. Treatment : vitamin K and Heparin:
Fetal warfarin syndrome: Poor carboxylation of bone forming proteins like osteocalcin, MGP and protein S Results from oral anticoagulation of pregnant women in first trimester. Features:chondrodysplasiapunctata hypoplasia of nasal bridge punctate calcification of growth plate.
Prothrombin time: Time taken for the anticoagulated blood to clot. Anticoagulant used is sodium citrate 3.8% Ratio of anticoagulant to blood is 1:9 Reagent for clotting is (tissue thromboplastin +calcium+ phospholipids). PT normal = 13-17 secs INR = (PT of patient /PT of mean population)ISI INR –international normalized ratio (N= 0.8-1.2) ISI – international sensitivity index.
Vitamin K in ruling out the type of jaundice: Hepatic or obstructive jaundice? Inject vitamin K to the jaundiced person who has prolonged prothrombin time. Prothrombin time becomes normal in ……………….? Why prothrombin time elevated in Hepatocellular jaundice?...................................... Obstructive jaundice?..........................................
Vitamin K def in adults: Malabsorption syndromes – poor absorption Liver cirrhosis – obstructive jaundice Prolonged antibiotic therapy Phenytoin – Inhibits absorption of vitamin K.