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DISORDERS OF COAGULATION

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Blood leaks or vascular occlusions may compromise blood delivery with potentially fatal consequences. The role of the hemostatic system is to maintain blood fluidity and to stop leaks once the vessel wall is damaged. It is a dynamic system maintained by a balance of factors that promote and factors that inhibit clotting. Disruption of this equilibrium leads to either bleeding or thrombotic complications.

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PATHOPHYSIOLOGY

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The intact vascular endothelium provides a smooth surface that promotes the blood flow and inhibits coagulation. When the endothelial surface is disrupted, blood comes in contact with the subendothelial matrix, which activates the hemostatic system. The first step of the hemostatic process—formation of the platelet plug—consists of adherence of platelets to the margins of the injured vessel, followed by their activation and release of pro-coagulant substances. During this process, von Willebrand factor (vWFct) acts as a bridging protein between platelets and the vascular wall. The next step is the coagulation cascademis, a carefully regulated series of pro-coagulant events initiated by tissue factor released from the subendothelial matrix. Tissue factor along with factor VII activates factor X, which together with factor V forms the prothrombinase complex, which subsequently activates factor II (prothrombin) to generate thrombin. Thrombin is the enzyme that converts fibrinogen to fibrin. Fibrin polymerizes and crosslinks with the help of factor XIII to form a strong mesh that traps red cells, white cells, and more platelets to form the final clot. This pathway, known as the “extrinsic” pathway, feeds an auto-amplification loop to recruit the “intrinsic” coagulation cascade to further clot formation (Figure 92-1). To do so, thrombin activates factors IX and VIII, which in turn activate factor X to increase thrombin production several thousand-fold. The goal of the coagulation cascade is formation of a fibrin-based clot able to achieve hemostasis but to limit coagulation to interfere with normal blood flow. Once enough fibrin is generated, the coagulation cascade is terminated by anticoagulant factors including tissue factor pathway inhibitor (TFPI), activated protein C, and antithrombin. The fibrin clot will persist for a variable amount of time, allowing for the repair of the vascular wall before the clot is broken down by the fibrinolytic system. The main fibrinolytic enzyme is the plasmin, which in turn is kept in check by the inhibitory action of antiplasmin. Thus the coagulation cascade is a finely tuned system consisting of amplification steps limited by important checks to maintain the appropriate balance between clot formation and clot dissolution.

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FIGURE 92-1.

The coagulation cascade, showing the steps of the intrinsic pathway (measured by the PTT) and the extrinsic pathway (measured by the PT).

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CLINICAL PRESENTATION

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The main issues to consider in the clinical presentation of a patient with a suspected bleeding disorder are to determine whether the bleeding episodes are prolonged ...

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