Vitamin KDr.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
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.
Coagulation cascade:
Factor III
Anti-coagulants in blood;
HeparinProtein C – half life 8 hrsProtein S - Protein Z
4-6 hrs
1 day
2 days
3-5 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.
Warfarin
(-)
(-)First step
Vitamin K carboxylation cycle
Hemorrhagic disease of the newborn
Vitamin K deficiency bleeding : (VKDB)• Reasons for hemorrhage in the newborn:1. Low placental transfer of phylloquinone2. Low clotting factor levels3. Sterile gut4. Low VIT K content in breast milk.
• Leads to intracranial, umbilicus, mucous membranes, gastrointestinal tract, circumcision and venipunctures bleeding.
• Treatment : 1mg menadione IM.
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.
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.
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:
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.
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 1. Hepatocellular jaundice?......................................2. Obstructive jaundice?..........................................
Vitamin K def in adults:
• Malabsorption syndromes – poor absorption
• Liver cirrhosis – obstructive jaundice
• Prolonged antibiotic therapy
• Phenytoin – Inhibits absorption of vitamin K.