Porth's Essentials of Pathophysiology, 4e

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Disorders of Hemostasis

C h a p t e r 1 2

Intrinsic pathway

Blood Coagulation. Blood coag- ulation is a complex process involv- ing the sequential activation of various factors in the blood. There are two coagulation pathways: (1) the intrinsic pathway which begins in the circulation and is initiated by activation of circulating fac- tor XII, and (2) the extrinsic path- way which is activated by a cellular lipoprotein called tissue factor that becomes exposed when tissues are injured. Both pathways lead to the activation of factor X, conversion of prothrombin (II) to thrombin (IIa), and conversion of fibrinogen (I) to the insoluble fibrin (Ia) threads that hold the clot together. 3 Clot Retraction. Within a few minutes after a clot is formed, the actin and myosin in the platelets that are trapped in the clot begin to contract in a manner similar to that in muscles. As a result, the fibrin strands of the clot are pulled toward the platelets, thereby squeez- ing serum (plasma without fibrino- gen) from the clot and causing it to shrink. 4 Clot Dissolution or Lysis. Clot dissolution begins shortly after a clot is formed. It begins with acti- vation of plasminogen, an inactive precursor of the proteolytic enzyme, plasmin. When a clot is formed, large amounts of plasminogen are trapped in the clot. The slow release from injured tissues and vascular endothelium of a very powerful acti- vator called tissue plasminogen acti- vator (t-PA) converts plasminogen to plasmin, which digests the fibrin strands, causing the clot to dissolve. 5

Prothrombin

Xa

Factor X

Extrinsic pathway

Thrombin

Fibrin

Fibrinogen

Collagen

Thrombin

Protein C

Plasminogen activators

Plasmin

Plasminogen

Collagen