REVIEW

HAEMOSTASIS /BLOOD COAGULATION

Haemostasis defined as arrest or stoppage of bleeding .Coagulation is defined as
the process in which the blood looses its fluidity and become a jelly like mass few
minutes after it is shed out or collected in a container.
Haemostasis
Primary haemostasis
Secondary haemostasia

PRIMARY HAEMOSTASIS
The term used to describe the platelet plug formation at the site of injury.It is an
immediate phenomenon.
It involves three steps:
Platelet adhesion
Platelet granule release
Platelet aggregation
PLATELET ADHESION
Platelets adhere to the collagen in the epithelium. The adhesion is stabilized by
vonWillebrand factor (adhesion glycoprotein).
PLATELET RELEASE
Platelets become activated after adhesion and release.
Three types of granules are released:

 Dense granules
Alpha granules
Lysosomal vesicles
The important products released from these granules are ADP, ATP, calcium,
serotonin, platelet factor 4, factor V, factorVIII, vWF, plasminogen inhibitor
facyor-1, thromboxane A2.
PLATELET AGGREGATION
This is mediated by fibrinogen.

SECONDARY HAEMOSTASIS
This involves the plasma coagulation system resulting in fibrin plug formation and
takes several minutes for completion.
These involve several coagulation factors .They are:

Factor I-Fibrinogen
Factor II-Prothrombin
Factor III-Thromboplastin
Factor IV-Calcium
Factor V-Labile factor
Factor VI-Unknown
Factor VII Stable factor
Factor VIII-Anti hemophilic factor
Factor IX-Christmas factor
Factor X-Stuart prower factor
Factor XI-Plasma thromboplastin
Factor XII-Hegman factor
Factor XIII-Fibrin stabilizing factor

MECHANISM OF CLOTTING

Most of the clotting factors are protein in the form of enzymes (inactive pro
enzymes).These proenzymes must be activated into active enzyme to enforce clot
formation.
Enzyme cascade theory explains how various reactions involved in the conversion
of proenzyme to active enzyme .Cascade refers to a process that occurs through a
series of steps, each step initiating the next ,until the final active enzyme thrombin
is formed.
STAGES OF CLOTTING
Formation of prothrombin activator
Conversion of prothrombin into thrombin
Conversion of fibrinogen into fibrin
FORMATION OF PROTHROMBIN ACTIVATOR
The prothrombin activator is formed either within the blood itself or outside the
blood.
A. Extrinsic pathway: The formation is initiated by the tissue thromboplastin (III)
which is formed from injured tissue.
B.Intrinsic pathway: Formation is initiated by platelets, which are within the blood
itself.
CONVERSION OF PROTHROMBIN INTO THROMBIN
The prothrombin activator formed either in extrinsic or /and intrinsic pathway
converts the prothrombin to thrombin.Once the thrombin is formed, it definitely
leads to clot formation. The calcium act as co-factor for prothrombin activator.

Thus formed thrombin initiate the formation of more thrombin molecules.Initially

formed thrombin activates factor V.This in turn accelerate the formation of both
extrinsic and intrinsic prothrombin activator, which converts the prothrombin into
thrombin (positive feedback).
FORMATION OF FIBRIN FROM FIBRINOGEN
The thrombin formed by prothrombin activator converts the fibrinogen into fibrin.
The fibrin stabilizing factor (XIII) in the presence of calcium modifies the loose
strands of fibrin into dense tight fibrin threads.

PATHWAY

INVESTIGATIONS OF HAEMOSTATIC FUNCTION

The primary functions of haemostatic mechanism are:
To promote local haemostasis at the site of injured blood vessels.
To ensure that the circulating blood remains in fluid state while in the
vascular bed that is to prevent the occurrence of generalized thrombosis.
Formation of haemostatic plug is a complex mechanism with the involvement of
maintenance of delicate balance among atleast 5 components.

Blood vessel wall

Platelets
Plasma coagulation factor
Inhibitors and
Fibrinolytic system

Anything that interferes with any of these components results in defective

haemostasis with abnormal bleeding.
The following schemes are used for the diagnosis in any case suspected to have
abnormal haemostatic function.
INVESTIGATION OF DISORDERED VASCULAR HAEMOSTASIS
:Disorders may be due to increased vascular permeability, reduced capillary
strength and failure to contract after injury.
The tests are:
A. Bleeding time (BT): Bleeding time is the time interval from oozing of
blood after a cut or injury till arrest of bleeding. There are two methods
available to determine the BT.

1. Ivys method
2. Dukes method
INVESTIGATION OF PLATELET AND PLATELET FUNCTION:
Disorders may due to abnormality in platelet number, morphology, or function.
Tests are: i) peripheral blood platelet count
ii) Skin bleeding time
iii) Peripheral blood smears examination to see the morphologic abnormalities of
platelet
INVESTIGATION OF BLOOD COAGULATION
i)
Whole blood coagulation time Lee white method : Clotting time (CT) :
CT is the time interval from oozing of blood after a cut or injury till the
formation of a clot .done by two method
A) Capillary tube method
B) Lee white method
ii) Activated partial thromboplastin time (APTT): In presence of calcium ions,
cephaloplastin activates coagulation factors of the intrinsic system in plasma
leading to clot formation. Clotting time is proportional to the concentration of
factor VIII, IX, XI, XII as well as common pathway factor II and V and X.
iii) Prothrombin time (PT): Tissue thromboplastin in the presence of calcium
activates the extrinsic pathway of human blood coagulation mechanism.
When liquiplastin reagent is added to normal anticoagulated blood. The clotting
mechanism is initiated, forming a solid gel clot within a specified period of time.

The time required for the clot formation could be prolonged if there is a deficiency
of factor /factor activity in the extrinsic pathway of the coagulation pathway.
iv) Measurement of fibrinogen
Thrombin time (TT): Time taken for the blood to clot after adding thrombin to it. It
is done to investigate the fibrinogen abnormality

BLEEDING DISORDERS
The bodys haemostatic system requires careful regulation in order to work
properly. If the does not clot sufficiently, it may be due to any of the bleeding
disorders.
The bleeding disorders are:
1. VASCULAR BLEEDING DISORDERS: Also called non- thrombocytopenic
purpura confined to skin and mucous membrane. May be inherited or acquired
2. PLATELET DISORDERS: Bleeding disorders produced by disorders of platelet
by one of the following three mechanisms:
A. Due to reduction in platelet number (Thrombocytopenia)
B.Due to rise in platelet count
C.Due to defect in platelet function
3. COAGULATION DISORDERS: Deficiency of any of the coagulation factor
which may be inherited or acquired leads to coagulation disorders.
ACQUIRED DISORDERS: Usually characterized by deficiency of multiple
coagulation factors.The most common disorders are: vitamin K deficiency,
fibrinolytic defect and DIC.

HEREDITARY DISORDERS: This may be due to quantitative or qualitative

defect in single coagulation factor. Most common disorders are:
A. Classic haemophilia or Haemophilia A: Due to the inherited deficiency of
factor VIII.
B. Haemophilia B or Christmas disease: Due to the deficiency of factor IX.
C. Von Willebrand disease: Due to the deficiency of von Willebrand factor
4. DUE TO FIBRINOLYTIC DEFECT: Excessive fibrinolysis may sometimes
cause bleeding.
5. DISSEMINATED INTRAVASCULAR COAGULATION (DIC): Also called
Defibrination syndrome, is a complex thrombo haemorrhagic disorder occurring
as a secondary complication in some systemic disease.