2. INTRODUCTION
• Haemostasis – The process of arrest of
blood loss & blood coagulation.
• Involves complex interactions between
injured vessel wall, platelets & coagulation
factors.
• A cascading series of proteolytic reactions
is responsible for blood coagulation.
3. CLOTTING FACTORS
• These are proteins present in the plasma in the
inactive 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 bleeding
disorders.
4. FACTORS NAME
FACTOR - I FIBRINOGEN
FACTOR - II PROTHROMBIN
FACTOR - III THROMBOPLASTIN
FACTOR - IV CALCIUM
FACTOR - V LABILE FACTORS
FACTOR - VI DOES NOT EXIST
FACTOR - VII STABLE FACTOR
FACTOR - VIII ANTIHEMOPHILIC FACTOR - A
FACTOR - IX ANTIHEMOPHILIC FACTOR - B
FACTOR - X STUART PROWER FACTOR
FACTOR - XI ANTIHEMOPHILIC FACTOR -
C
FACTOR - XII HAGEMAN FACTOR
FACTOR - XIII FIBRIN STABILISING FACTOR
6. COAGULANTS
• These are substances which promote
coagulation.
• They are indicated in hemorrhagic states.
• Fresh whole blood or plasma provide all the
factors needed for coagulation & are the best
therapy.
• Also, they act immediately.
7. OTHER DRUGS
1. VITAMIN K
• K1(From plants)
– Phytonadione (Phylloquinone)
• K3(Synthetic)
i. Fat soluble
– Menadione
– Acetomenaphthone
ii. Water soluble
– Menadione sodium bisulfate
– Menadione sodium diphosphate
9. VITAMIN K
• A fat soluble vitamin required for synthesis of
clotting factors.
• Dam(1929) found that bleeding disorder in
chicken (due to prothrombin deficiency) could be
corrected by a fat soluble fraction of hog liver.
• This factor was called Koagulations Vitamin.
• Soon, its structure was worked out.
10. Contd:
• A similar vitamin was isolated from alfalfa grass in
1939, & 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.
11. CHEMISTRY & SOURCE
• Has a basic Naphthoquinone structure, with or
without a side chain at position 3.
• Dietary sources – Green leafy
vegetables like cabbage, spinach;
& liver, cheese, etc.
• RDA – Uncertain, because of production of vit. K2 by
colonic bacteria.
– Total daily requirement of 50-100µg/day is
estimated.
12. ACTION
• Vitamin K acts as a cofactor for synthesis of
clotting 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 γ
position of the glutamate residues of these
proteins.
– This potentiate them to bind Ca & to get bound
to phospholipid surfaces.
14. UTILIZATION
• Absorption
– Fat soluble forms via lymph & require bile salts
for absorption.
– Water soluble forms absorbed directly into portal
blood.
– Vit.K1 is absorbed actively, while K2 & K3 are
absorbed by simple diffusion.
• Storage
– only temporarily concentrated in liver.
– No significant stores in body.
15. • Excretion
– Metabolized in liver by side chain cleavage
& glucuronide conjugation.
– Metabolites are excreted in bile & urine
16. DEFICIENCY
• Occurs due to liver disease, obstructive
jaundice, malabsorption, long term
antimicrobial therapy which alters intestinal
flora.
• Deficient diet is rarely responsible.
• Most important manifestation is bleeding
tendency due to low levels of clotting factors
in blood.
• Hematuria occurs first usually.
• Other sites of bleeding include g.i.t., nose, &
under the skin – ecchymoses.
17. USES
a) Dietary deficiency of Vit. K
i. Rare in adults
ii. Corrected by 5-10mg/day orally/parenterally.
b) Prolonged antimicrobial therapy
i. 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.
18. e) Newborns
i. All newborns have low levels of clotting
factors.
ii. Vit. K 1mg i.m recommended routinely.
iii. Menadione should not be used for this.
f) Overdose of oral anticoagulants
i. Most Imp. Indication of vit.K.
ii. Phytonadione is the drug of choice.
iii. Higher doses produce unresponsiveness to
oral anticoagulants for several days.
19. TOXICITY
• Rapid i.v infusion of emulsified Vit. K produce
flushing, breathlessness, chest constriction, fall in
B.P., probably due to emulsion form.
• Death is very rare.
• Menadione causes hemolysis in a dose dependent
manner – Patients with G-6-PD deficiency &
neonates are more susceptible.
• Menadione cause Kernicterus in newborns.
Note: Due to poor efficacy & higher toxicity, there is
little justification to use Menadione.
20. OTHER COAGULANTS
•Fibrinogen:
– Employed in Hemophilia, antihemophilic
globulin(AHG) deficiency & acute afibrinogenemic
states.
– 0.5 mg i.v is infused.
• Antihemophilic Factor:
– Concentrated human AHG preparation.
– Indicated in Hemophilia & AHG deficiency
– Highly effective, short acting.
21. •Desmopressin:
– Releases factor VIII & von Willebrand’s factor
from vascular endothelium.
– Checks bleeding in hemophilia & von
Willebrand’s disease.
• Adrenochrome monosemicarbazone:
– Reduce capillary fragility, control oozing from
raw surfaces & prevent microvessel bleeding.
– Efficacy is uncertain.
– Dose: 1-5 mg oral, i.m.
22. • Rutin:
– A plant glycoside claimed to reduce capillary
bleeding.
– Used along with Vit. C, which is believed to
facilitate its action.
– Dose: 60 mg b.d/t.d.s orally.
– Efficacy is uncertain.
• Ethamsylate:
– Reduces capillary bleeding when platelets are
adequate.
– Used in prevention & treatment of capillary
bleeding in menorrhagia, epistaxis, malena, etc.
– Dose: 250-500 mg t.d.s orally
23. LOCAL HAEMOSTATICS(STYPTICS)
• Substances used to control bleeding from a local &
approachable site.
• Particularly effective on oozing surfaces, e.g. tooth
socket, abrasions, etc.
• Substances include:
– Fibrin – From human plasma, dried as sheets.
– Gelatin foam
– Oxidized cellulose – As strips.
– Thrombin – From bovine plasma, as dry
powder or fresh solution.
– Vasoconstrictors like 0.1% adrenaline – Soaked in
sterile cotton gauze.
– Astringents like tannic acid or metallic salts.
24. 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.)
