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BLOOD CLOTTING When blood is shed out or collected in a container, it looses its fluidity & becomes a jelly like mass after few minutes. This process is called coagulation or clotting of blood. The clot is a mesh of thin fibrils entangling the blood cells. These fibrils consist of fibrin. The fibrin is formed from fibrinogen.
F A C T O R S I N V O L V E D I N BLOOD CLOTTING Coagulation of blood occurs through a series of reactions due to the activation of a variety of substances. Those substances necessary for clotting are called clotting factors. The clotting factors are :
SEQUENCE OF CLOTTING MECHANISM Normally during circulation, the blood does not clot, because the enzymes involved in clotting are in inactive form. Slight initial activation causes clotting in which each enzyme activates another one in a sequential manner till the conversion of fibrinogen into fibrin. In general, clotting occurs in 3 stages namely:
Formation of prothrombin activator. Conversion of prothrombin into thrombin. Conversion of fibrinogen into fibrin. During the process of blood clotting, the clotting factors, which are in inactive forms, are converted into active forms.
S t a g e 1 : Fo rm a t io n o f prothrombin activator Prothrombin activator is formed in two ways namely: Extrinsic pathway: In this, the formation of prothrombin activator is initiated by the tissue thromboplastin. Intrinsic pathway: In this, the formation of prothrombin activator is initiated by platelets , which are within the blood itself.
E X T R I NS I C P A TH W AY Tissue trauma Tissue thromboplastin (Protein, Glycoprotein, Phospholipid) ↓ Factor X Calcium→ → Activated Factor X ↓ ← Factor V ←Thrombin P r oth r o m b i n A c ti vator
INTRINSIC PATHWAY Blood trauma ↓ Endothelial cells expose collagen fibres Factor XII → Activated Factor XII With Calcium Activates Factor X
Factor X → Activated Factor X C a l c iu m → ↓ ← F a c t o r V ← Th r o m b i n ↓ Prothrombin Activator
S t a g e 2 : C o nve r sio n o f p r o t h r o m b i n in t o thrombin Prothrombin activator converts Prothrombin into Thrombin in the presence of Calcium. Thrombin itself can accelerate this reaction by positive feedback mechanism. That is, the initial Thrombin activates Factor V. This in turn accelerates the formation of both Extrinsic & Intrinsic Prothrombin activator.
S t a g e 3 : C on v e r si o n o f Fibrinogen into Fibrin During this, the soluble Fibrinogen is converted into insoluble Fibrin by Thrombin. Initially, the fibrinogen is converted into activated fibrinogen, which is called fibrin monomer. This polymerizes with other monomer molecules to form Fibrin. The first formed fibrin contains loosely arranged strands. This is modified later into a dense tight aggregate by fibrin stabilizing factor (Factor XII) & this reaction requires the presence of calcium ions.
A N T I C O A G U L A NT S The substances, which prevent or postpone coagulation of blood, are called anticoagulants. Some substances are used to prevent clotting inside the body i.e., in vivo & some substances used to prevent clotting outside the body i.e., in vitro.
The various an t i coagu l a n t s a r e a s follows: Heparin Di cou m o r a l Warfarin EDTA(ethylenediaminetetraacetic acid) Oxalate compounds Citrates(sodium, ammonium or potassium citrate)
Tes t s f o r C lo tt i n g : Bleeding Time - (2-8 Minutes) Clotting Time (5-15 Minutes) by Capillary tube method. Prothrombin Time - (11-13 Seconds)