Blood coagulation

Coagulation of blood is a sequential process by which multiple

coagulation factors of blood interact resulting in formation of an
insoluble clot. The system works by two modes. Extrinsic system is
activated in response to tissue damage and is a rapid acting system while
intrinsic system is slow and works in response to vascular damage.
Anticoagulants
Anticoagulants prevent the process of clotting but do not break a clot
that is already formed. A clot that adheres to vessel wall is called
thrombus where as intravascular clot that floats in the blood are termed
as embolus.
Anticoagulants include
1. Parenteral anticoagulant: Heparin
2. Oral anticoagulant: Warfarin
Indication for anticoagulants
Usually heparin is used to initiate the treatment for short prevention and
oral anticoagulants for maintenance.
Indication for anticoagulants
1. To prevent formation of thrombus in high risk situations like:

a. Atrial fibrillation

b. Prosthetic heart valves

c. Fractures

2. Myocardial infarction

3. Prophylaxis prior to some surgeries.

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 4. To prevent extension of established thrombus.

5. To prevent pulmonary embolism.

6. Evolving stroke

7. Deep vein thrombosis.

8. Rheumatic heart disease

Heparin
Heparin is present in mast cells. Richest source of heparin in body are
lungs, liver and intestinal mucosa. It is commercially produced from ox
lung and pig intestinal mucosa.
Mechanism of action
Heparin enhances the activity of antithrombin, a protein that inactivates
two major clotting factors: thrombin and factor Xa. In absence of
thrombin and factor Xa production of fibrin is reduced and hence
clotting is suppressed.
Adverse Effects: Haemorrhage, Heparin induced thrombocytopenia,
Hypersensitivity reaction, Local irritation, Hematomas, Osteoporosis on
long term use.
Overdose: Treated with protamine sulphate.
Safe in pregnancy (only heparin)
Contraindication: Thrombocytopenia, Bleeding, Severe hypertension,
during and immediately after surgery of eye, brain and spinal cord,
Lumbar puncture and regional anesthesia.
Monitoring

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By Activated partial thromboplastin time (aPTT) Normal is 40 sec. At
therapeutic level it is 60-80 sec.
Warfarin
Warfarin suppresses by acting as an antagonist of vitamin K. Four
clotting factors (VII, IX, X and prothrombin) require vitamin K for their
synthesis. By antagonizing vitamin K, warfarin blocks the biosynthesis
of Vitamin K dependent factors.
Adverse Effects: Bleeding, Nausea, Pyrexia and Diarrhoea

Contraindication: same as heparin with additional in pregnancy and

lactation.
Overdose: Treated with Vit K
Drug interaction
Drug that increase effect of warfarin: Aspirin, Sulphonamides, Broad
spectrum antibiotics, Phenytoin
Drug that decrease effect of warfarin: Vit K, Oral contraceptives,
Barbiturates
Monitoring: Prothrombin time
Summary of contrasts between heparin and warfarin
Heparin Warfarin
Meachanism of action Promote action of Inhibit the synthesis of
antithrombin vitamin dependent
clotting factors
Route IV or SC Oral
Onset Rapid (mins) Slow(hrs)
Duration Brief (hrs) Prolong (days)

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Monitoring aPTT Prothrombin time
Antidote Protamine sulphate Vitamin K
Fibrinolytics (thrombolytics)
These drugs are used to lyse thrombi/clot
They are curative rather than prophylactic
It includes streptokinase, urokinase and alteplase.
These drugs bind to plasminogen to form an active complex. The drug
plasminogen complex then catalyzes the conversion of other
plasminogen molecules into plasmin an enzyme that digests the fibrin
meshwork of clots.
Indications
Myocardial Infarction, Deep vein thrombosis, Pulmonary embolism,
Peripherial arterial occlusion.
Adverse effects: Bleeding, Hypersensitivity reaction, Hypotension and
fever.
Coagulants
These are the drugs which promote coagulation and are indicated in
hemorrhagic states. Fresh whole blood or plasma provide all the factors
needed for coagulation and are the best therapy for deficiency of any
clotting factors also they act immediately.
Vitmin K
Vitamin K acts as a cofactor at a late stage in the synthesis of
coagulation proteins-prothrombin factors VII, IX and X. It increases the
binding to Calcium which help in coagulation.
Uses

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For prophylaxis and treatment of bleeding due to deficiency of clotting
factors as in obstructive jaundice, liver disease, prolonged antimicrobial
therapy.