Pathogenesis Of Thrombosis

Hemostatic changes that are important in the pathogen-esis of thrombosis are vascular injury due to the toxic effect of chemotherapy; platelet abnormalities (more important in arterial thrombosis); coagulation abnormalities, fibrinolytic defects, and deficiencies of the antithrombotic factors.

Vascular Injury

Vascular injuries play an important role in arterial thrombosis. Vascular injury initiates platelet adhesion to exposed subendothelium. The adherent platelets release the contents of alpha and dense granules such as ADP, calcium, and serotonin, causing platelet aggregation and platelet plug formation. In addition, blood coagulation is initiated by tissue factor released from the damaged endothelial cells. The fibrin clot formed would then stabilize the platelet plug. The vascular endothelial injury may occur by endothelial cell injury, atherosclerosis, hyperhomocysteinemia, or other disorders that may interfere with arterial blood flow. In cancer patients, vascular endothelial cell injury may occur as a result of the toxic effect of chemotherapeutic drugs.

Platelet Abnormalities

Platelets are the main components of arterial thrombosis. As platelets interact with the injured vessels, platelet adhesion and aggregation occur. In normal hemostasis, excess platelet activation is prevented by antiplatelet activities of endothelial cells such as generation of prostacyclin. In the disease state, excess platelet activation can reflect thromboembolic disease or exacerbation of thrombotic episodes.1


Figure 19.1 Risk factors for thrombosis.

Coagulation Abnormalities

Risk factors associated with hypercoagulability can be divided into environmental, acquired, or inherited factors1,2 (Fig. 19.1) .

Environmental factors are linked to transient conditions that may result from surgery, immobilization, and pregnancy or therapeutic complications associated with oral contraceptives, hormone replacement therapy, chemotherapy, and heparin treatment.

Acquired risk factors are associated with conditions that hinder normal hemostasis such as cancer, nephrotic syndrome, vasculitis, antiphospholipid antibodies, myeloproliferative disease, hyperviscosity syndrome, and others1 (Table 19.1). Inherited risk factors are associated with genetic mutations that result in deficiency of naturally occurring inhibitors such as protein C, protein S, or antithrombin (AT); accumulation of procoagulant factor as in prothrombin G20210A1,3; or clotting factor resistance to anticoagulant activities of physiological inhibitors as in activated protein C resistance (APCR) (Table 19.2). These conditions disturb the

Table 19.1

Conditions Associated

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