COAGULATION
PATHWAYS
ADNAN ALI
EMT (KMU)
Intrinsic system
• The initial reaction in this system is conversion of inactive factor XII to XIIa
• This activation is catalysed by high-molecular weight kininogen (HMW
kininogen) and kallikrein
• Can be brought about in vitro by exposing the blood to electro-negatively
charged wettable surfaces such as glass & collagen fibers
• Activation in vivo occurs when blood is exposed to collagen fibers
underlying the endothelium in the vessels
Cont..
Contact factors do not have an in vivo procoagulant function. But responds to the
negatively charged surfaces: non siliconized glass
In vivo activated by
Valve prostheses
Artificial implants in surgery
Exposure to foreign substances: sub endothelial collagen
Cont..
Active factor XII then activates factor XI
Active factor XI activates factor IX
Activated factor IX forms a complex with factor VIII leading
to activation of factor X; factor VIII itself needs activation by
thrombin inorder to participate in the activation of factor X
Phospholipids (PF-3) from aggregated PLTs & Ca++ are
necessary for full activation of factor X
Cont..
Although intrinsic pathway is more complex & slower, it accounts for the majority of the
coagulation activity in vivo
Factor XII, Prekallikrein, HMW kininogen are referred to as the contact proteins, because
their activation occurs on contact with an abnormal surface or (glass)
Cont..
THROMBIN
1) cleaves Fibrinopeptides A and B from Fibrinogen
2)Amplifies coagulation mechanism- activates co factors V
and VIII and F XI
3)activates
F XIII
Because of Multiple autocatalytic functions THROMBIN is
considered the most important protease of the coagulation pathway
Extrinsic system
Coagulation is triggered by the exposure of tissue thromboplastin to
plasma protein ( F-V II)
-Tissue thromboplastin is not circulating in the blood but released when cells
are damaged e.g. intravascular hemolysis, spontaneous abortion, traumatic
head injury
Concentrated sources of tissue thromboplastin (factor III) are:
-RBC membranes,Platelets,Brain tissue,Placenta,Lung tissue
Cont..
•The extrinsic system activates factor X rapidly since there are fewer reaction steps
involved. Tissue factor forms a complex with factor VIIa and activates factor X to X
??/Tissue thromboplastin VIIaFactor VII
DIAGRA
M
Cont..
•Interdependence between the extrinsic and intrinsic pathways has been
demonstrated; the tissue factor- Factor VIIa complex can activate factor IX,
providing a mechanism for bypassing the initial steps of the intrinsic pathway
•Role of contact factors is questionable, because patients lacking the contact factors
(factor XII, PK, HMWK) do not have bleeding problems whereas patients who have
deficiencies of factors VIII, IX, or X bleed.