1. Vitamin K Dr.S.Chakravarty MD

2. Vitamin K: K1 – phylloquinone – plant source K2 – menaquinone – bacterial source K3 – Menadione – synthetic form

3. Sources of VIT K: Spinach, brocolli, lettuce Soya bean oil and canola oil. Bacterial source from gut.

4. Functions of vitamin K 1.Helps in extrinsic pathway of blood coagulation – gamma carboxylation of factor (II, VII, IX and X) – calcium binding. 2.Helps in synthesis of bone calcium binding proteins like osteocalcin and matrix Gla protein (MGP) – bone formation 3.Gamma carboxylation of protein C, protein S and Protein Z which are normal anticoagulants.

5. Coagulation cascade: Factor III

6. Anti-coagulants in blood; Heparin Protein C – half life 8 hrs Protein S - Protein Z 4-6 hrs 1 day 2 days 3-5 days

7. 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.

8. Warfarin (-) First step Vitamin K carboxylation cycle

9. Hemorrhagic disease of the newborn Vitamin K deficiency bleeding : (VKDB) Reasons for hemorrhage in the newborn: 1.Low placental transfer of phylloquinone 2.Low clotting factor levels 3.Sterile gut 4.Low VIT K content in breast milk. Leads to intracranial, umbilicus, mucous membranes, gastrointestinal tract, circumcision and venipunctures bleeding. Treatment : 1mg menadione IM.

10. Anticoagulation: Vitamin K dependent clotting factors can be inhibited by Warfarin and dicumarol. Warfarin inhibits vitamin K epoxide and quinone reductase  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.

11. 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 procoagulant effect of warfarin due to inhibition of protein C and S – skin necrosis by warfarin.

12. Warfarin indued 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:

13. 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:chondrodysplasia punctata hypoplasia of nasal bridge punctate calcification of growth plate.

14. 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 ISI INR = (PT of patient /PT of mean population) ISI INR – INR –international normalized ratio (N= 0.8-1.2) ISI – international sensitivity index.

15. 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 1.Hepatocellular jaundice?...................................... 2.Obstructive jaundice?..........................................

16. Vitamin K def in adults: Malabsorption syndromes – poor absorption Liver cirrhosis – obstructive jaundice Prolonged antibiotic therapy Phenytoin – Inhibits absorption of vitamin K.