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.