Blood Composition, Disorders and Coagulation and its Role in Hemostatsis.

1. BLOOD COAGULATION, ITS
MECHANISM DISORDERS AND
ITS ROLE IN HUMAN LIFE
Presenter: Muhammad Asad Ishaq
262/FBAS/BSBT/F12

2. • Blood
The fluid that circulates in the blood vessels of the body.
• Homeostasis:
Constant conditions within organisms in interaction
with external environment.
Coagulation is a process for homeostasis of the body

3. This over all process consists of 4 parts.
I.
Vascular constriction
II.
Platelet activation by thrombin
III. The clot formed
IV. Fibrinolysis by Plasmin

4. Coagulation:
The process of forming clots/semisolid
lumps in a Liquid.
Mechanism
Two pathways lead to the formation of a fibrin clot: the intrinsic
and extrinsic pathway. Although they are initiated by distinct
mechanisms.
The end product is common and Both pathways are complex and
involve numerous different proteins termed clotting factors.

5. Extrinsic Pathway:
Fibrin clot formation in response to tissue injury is the most
clinically relevant event of homeostasis under normal
physiological conditions. This process is the result of the
activation of the extrinsic pathway.
Intrinsic Pathway:
The formation of a red thrombus or a clot in response to an
abnormal vessel wall in the absence of tissue injury is the
result of the intrinsic pathway.

6. Factors Pathway
Activities
XII
Intrinsic
Binds to exposed collagen at site of vessel wall injury.
XI
Intrinsic
Activated by factor XIIa
IX
Intrinsic
Activated by factor XIa in presence of Ca2+
X
Both
Activated on surface of activated platelets by tenase complex
and by factor VIIa in presence of tissue factor and Ca2+.
VII
Extrinsic
Activated by thrombin in presence of Ca2+.
VIII
Intrinsic
Activated by thrombin; factor VIIIa is a cofactor in the activation
of factor X by factor IXa.
V
Both
Activated by thrombin; factor Va is a cofactor in the activation
of prothrombin by factor Xa

8. Activation of Prothrombin to Thrombin
The common point in both pathways is the activation of
factor X to factor Xa. Factor Xa activates prothrombin
(factor II) to thrombin (factor IIa). Thrombin, in turn,
converts fibrinogen to fibrin. The activation of thrombin
occurs on the surface of activated platelets and
requires formation of a prothrombinase complex. This
complex is composed of the platelet phospholipids,
phosphatidylinositol and phosphatidylserine, Ca2+,
factors Va and Xa, and prothrombin. Factor V is a
cofactor in the formation of the prothrombinase
complex, similar to the role of factor VIII in tenase
complex formation. Like factor VIII activation, factor V is
activated to factor Va by means of minute amounts
and is inactivated by increased levels of thrombin.
Factor Va binds to specific receptors on the surfaces of
activated platelets and forms a complex with
prothrombin and factor Xa.

9. Disorders
Defects in the process of homeostasis, leading to bleeding
disorders, have been identified at the level of the proteins of the
clotting cascades, platelet activation and function, contact
activation and antithrombin function.
Hemophilia
Disorders of Fibrinogen and Factor XIII
vonWillebrand Disease (Deficiency of vWF results in
defective platelet adhesion and causes a secondary deficiency
in factor VIII, results are similar to Hemophilia)
Antithrombin Deficiency (Antithrombin functions to inhibit several
activated coagulation factors including thrombin, factor IXa and factor
Xa, by forming a stable complex with the various factors.)