INTRODUCTION• Haemostasis – The process of arrest ofblood loss & blood coagulation.• Involves complex interactions betweeninjured vessel wall, platelets & coagulationfactors.• A cascading series of proteolytic reactionsis responsible for blood coagulation.
CLOTTING FACTORS• These are proteins present in the plasma in theinactive form.• On partial proteolysis, they become active &activate the next factor.• There are 13 clotting factors present in plasma &tissues.• Deficiency of any of the factors leads to bleedingdisorders.
FACTORS NAMEFACTOR - I FIBRINOGENFACTOR - II PROTHROMBINFACTOR - III THROMBOPLASTINFACTOR - IV CALCIUMFACTOR - V LABILE FACTORSFACTOR - VI DOES NOT EXISTFACTOR - VII STABLE FACTORFACTOR - VIII ANTIHEMOPHILIC FACTOR - AFACTOR - IX ANTIHEMOPHILIC FACTOR - BFACTOR - X STUART PROWER FACTORFACTOR - XI ANTIHEMOPHILIC FACTOR -CFACTOR - XII HAGEMAN FACTORFACTOR - XIII FIBRIN STABILISING FACTOR
COAGULANTS• These are substances which promotecoagulation.• They are indicated in hemorrhagic states.• Fresh whole blood or plasma provide all thefactors needed for coagulation & are the besttherapy.• Also, they act immediately.
VITAMIN K• A fat soluble vitamin required for synthesis ofclotting factors.• Dam(1929) found that bleeding disorder inchicken (due to prothrombin deficiency) could becorrected by a fat soluble fraction of hog liver.• This factor was called Koagulations Vitamin.• Soon, its structure was worked out.
Contd:• A similar vitamin was isolated from alfalfa grass in1939, & labelled vit. K1.• Another one was isolated from Sardine (sea fish)meal, & labelled vit. K2.• Synthetic compounds have also been produced &are labelled vit K3.
CHEMISTRY & SOURCE• Has a basic Naphthoquinone structure, with orwithout a side chain at position 3.• Dietary sources – Green leafyvegetables like cabbage, spinach;& liver, cheese, etc.• RDA – Uncertain, because of production of vit. K2 bycolonic bacteria.– Total daily requirement of 50-100µg/day isestimated.
ACTION• Vitamin K acts as a cofactor for synthesis ofclotting factors, mainly factors II, VII, IX & X.• The process involved is known as Vitamin K cycle.• Gamma Carboxylation– Carboxyl group of Vitamin K is attached to the γposition of the glutamate residues of theseproteins.– This potentiate them to bind Ca & to get boundto phospholipid surfaces.
UTILIZATION• Absorption– Fat soluble forms via lymph & require bile saltsfor absorption.– Water soluble forms absorbed directly into portalblood.– Vit.K1 is absorbed actively, while K2 & K3 areabsorbed by simple diffusion.• Storage– only temporarily concentrated in liver.– No significant stores in body.
• Excretion– Metabolized in liver by side chain cleavage& glucuronide conjugation.– Metabolites are excreted in bile & urine
DEFICIENCY• Occurs due to liver disease, obstructivejaundice, malabsorption, long termantimicrobial therapy which alters intestinalflora.• Deficient diet is rarely responsible.• Most important manifestation is bleedingtendency due to low levels of clotting factorsin blood.• Hematuria occurs first usually.• Other sites of bleeding include g.i.t., nose, &under the skin – ecchymoses.
USESa) Dietary deficiency of Vit. Ki. Rare in adultsii. Corrected by 5-10mg/day orally/parenterally.b) Prolonged antimicrobial therapyi. Rx same as above.c) Obstructive jaundice or malabsorption syndromes.i. 10 mg i.m/day or orally with bile salts.d) Liver disease(cirrhosis, viral hepatitis)i. Responds poorly due to hepatocellular damage.
e) Newbornsi. All newborns have low levels of clottingfactors.ii. Vit. K 1mg i.m recommended routinely.iii. Menadione should not be used for this.f) Overdose of oral anticoagulantsi. Most Imp. Indication of vit.K.ii. Phytonadione is the drug of choice.iii. Higher doses produce unresponsiveness tooral anticoagulants for several days.
TOXICITY• Rapid i.v infusion of emulsified Vit. K produceflushing, breathlessness, chest constriction, fall inB.P., probably due to emulsion form.• Death is very rare.• Menadione causes hemolysis in a dose dependentmanner – Patients with G-6-PD deficiency &neonates are more susceptible.• Menadione cause Kernicterus in newborns.Note: Due to poor efficacy & higher toxicity, there islittle justification to use Menadione.
OTHER COAGULANTS•Fibrinogen:– Employed in Hemophilia, antihemophilicglobulin(AHG) deficiency & acute afibrinogenemicstates.– 0.5 mg i.v is infused.• Antihemophilic Factor:– Concentrated human AHG preparation.– Indicated in Hemophilia & AHG deficiency– Highly effective, short acting.
•Desmopressin:– Releases factor VIII & von Willebrand’s factorfrom vascular endothelium.– Checks bleeding in hemophilia & vonWillebrand’s disease.• Adrenochrome monosemicarbazone:– Reduce capillary fragility, control oozing fromraw surfaces & prevent microvessel bleeding.– Efficacy is uncertain.– Dose: 1-5 mg oral, i.m.
• Rutin:– A plant glycoside claimed to reduce capillarybleeding.– Used along with Vit. C, which is believed tofacilitate its action.– Dose: 60 mg b.d/t.d.s orally.– Efficacy is uncertain.• Ethamsylate:– Reduces capillary bleeding when platelets areadequate.– Used in prevention & treatment of capillarybleeding in menorrhagia, epistaxis, malena, etc.– Dose: 250-500 mg t.d.s orally
LOCAL HAEMOSTATICS(STYPTICS)• Substances used to control bleeding from a local &approachable site.• Particularly effective on oozing surfaces, e.g. toothsocket, abrasions, etc.• Substances include:– Fibrin – From human plasma, dried as sheets.– Gelatin foam– Oxidized cellulose – As strips.– Thrombin – From bovine plasma, as drypowder or fresh solution.– Vasoconstrictors like 0.1% adrenaline – Soaked insterile cotton gauze.– Astringents like tannic acid or metallic salts.
SCLEROSING AGENTS• These are irritants, cause inflammation, coagulation &ultimately fibrosis.• Injected into hemorrhoids & varicose vein mass.• Used only for local injection.• The substances include:– Phenol(5%) in almond oil or peanut oil.– Ethanolamine oleate– Sod. tetradecyl sulfate– Polidocanol(3% inj.)