Bleeding and coagulation disorders hemostasis

BLEEDING AND COAGULATION

DISORDERSDr. Shamshuddin Patel Sr.

HEMOSTASIS

• Def. : consequence of tightly regulated processes that maintain blood in a fluid, clot-free state in normal vessels while introducing the rapid formation of a localized haemostatic plug at the site of vascular injury.

- from Robbins Basic Pathology 8th edition

• Mechanism vasoconstriction formation of platelet plug coagulation cascade fibrinolysis

WHY BLOOD DOES NOT CLOT NORMALLY IN CIRCULATION?

• ENDOTHELIAL FACTORS:– smoothness of endothelial lining prevents platelet

adhesion

– negatively charged particles present over endothelial lining repel the clotting factors

• VELOCITY OF CIRCULATION, if decreases leads to clotting

• PRESENCE OF NATURAL ANTICOAGULANTS IN BLOOD, Ex: heparin, protein c, thrombomodulin

• SIMULTANEOUS ACTIVATION OF FIBRINOLYTIC SYSTEM ALONG WITH CLOTTING MECHANISM.

Stages

of Hemostasis

5

Vascular Spasm

Vascular spasm results from the:1. Local myogenic contraction of the blood vessels initiated

by direct damage to the vascular wall

2. Release of Local autacoid factors from the traumatized tissues and blood platelets, and

3. Nervous reflexes initiated by pain nerve impulses or other sensory impulses that originate from the traumatized vessel or nearby tissues.

4. Release of a vasoconstrictor substance, Thromboxane A2

by the platelets which for the smaller vessels are responsible for much of the vasoconstriction

Mechanism of the Platelet Plug• When platelets come in contact with a damaged vascular

surface, especially with collagen fibers in the vascular wall, the platelets themselves immediately change their own characteristics drastically

• They begin to swell

• They assume irregular forms with numerous irradiating pseudopods protruding from their surfaces;

• Their contractile proteins contract forcefully and cause the release of granules that contain multiple active factors

• They become sticky so that they adhere to collagen in the tissues and to a protein called von Willebrand factor

Platelet plug formation: platelet adhesion

Mechanism of the Platelet Plug Formation

• They secrete large quantities of ADP and their enzymes form Thromboxane A2

• The ADP and thromboxane in turn act on nearby platelets to activate them as well, and

• The stickiness of these additional platelets causes them to adhere to the original activated platelets

• Thus the damaged vascular wall activates successively increasing numbers of platelets that themselves attract more and more additional platelets, thus forming a platelet plug

Platelet plug formation: platelet release action

Platelet plug formation: platelet aggregation

THE PLATELET ROLE IN

HEMOSTASIS

COAGULATION

• Formation of blood clot

Stages of clotting Phase 1: Extrinsic and intrinsic pathways

produce prothrombinase/prothrombin activator

Phase 2: Prothrombinase converts prothrombin to thrombin

Phase 3: Thrombin converts soluble fibrinogen into insoluble fibrin which is the thread of the clot.

Clotting factors in blood

Intrinsic Pathway1. Blood trauma causes (a) activation of

Factor XII and (b) release of platelet phospholipids (containing platelet factor 3)

2. Activated Factor XII (XIIa)enzymatically activates Factor XI (XIa) which needs kininogen and is accelerated by prekallikrein

3. Factor XIa enzymatically activates Factor IX to IXa

4. Factor IXa+Factor VIIIa+platelet phospholipids and factor 3 activates Factor X to Xa

5. Factor Xa+Factor V+ platelet or tissue phospholipid form the complex called prothrombin activator

6. The prothrombin activator in turn initiates within seconds the cleavage of prothrombin to form thrombin

Extrinsic Pathway

1. Release of tissue factor:Traumatized tissue releases a complex of several factors called tissue factor or tissue thromboplastin

2. Activation of Factor X: Tissue factor further complexes with Factor VII and, in the presence of calcium ions, acts enzymatically on Factor X to form activatedFactor X

• Factor Xa forms prothrombin activator— Factor Xa combines with tissue or plateletphospholipids as well as with Factor V to form the complex called prothrombin activator

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Stage 1 Intrinsic Pathway Extrinsic Pathway

Endothelial damage + Collagen exposureKallikreinHMW Kinogen

XII XIIa

XI XIa

HMW Kinogen

IX IXa

Calcium

X Xa

VIII & Calcium

Platelets

Phospholipid

Tissue trauma + Tissue thromboplastin(Glycoprotein+Phospholipiod)

CalciumV

Prothrombin

Thrombin

Positive feedback

Positive feedbackStage 2

Stage 3

FibrinogenFibrinogen a

Loose strands of Fibrin

Polymerization

XIII & CalciumFibrin tight blood clot

Prothrombin activator

XXa

VII

HOW DOES BLOOD CLOT SUMMARY