Biology of Disease

The Extrinsic Pathway

The extrinsic pathway is so called because it requires the nonplasma protein,

thromboplastin to initiate the cascade (Figure 13.11). Thromboplastin is an

integral membrane protein found in many tissues but especially the walls of

blood vessels, brain, lung and placenta. The initial reaction is the conversion

of Factor VII (proconvertin) to Factor VIIa in a reaction that requires Ca2+

and phospholipids released from the injured tissue or from the surface of

aggregated platelets. Damaged tissues also release thromboplastin which,

in combination with Factor VIIa and Factor IXa from the intrinsic pathway,

directly activates Factor X to Xa. The final result of this part of the pathway is

the production of Factor Xa. Thus the final product of the extrinsic pathway,

like the intrinsic, is the production of Factor Xa. Despite this, deficiencies in

either pathway result in prolonged bleeding times.

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Intrinsic pathway

XII

XI

XIIa

XIa

IX IXa

X

Extrinsic pathway

VII

Xa X

VIIa

VIIIa

Prothrombin Thrombin

Fibrinogen Fibrin-aggregate

Damaged tissue

surface

Kininogen

Kallikrein

Trauma

Final

common

pathway

Tissue

factor

II IIa

I Ia

XIIIa

Cross-linked

Fibrin clot

Figure 13.11 A simplified form of the blood

clotting cascade consisting of the intrinsic,

extrinsic and final common pathways. See text for

details.

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