Porth's Essentials of Pathophysiology, 4e

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Disorders of Hemostasis

C h a p t e r 1 2

thrombosis, repeated fetal loss, and thrombocytopenia. The disorder can manifest either as a primary condition occurring in isolation with signs of hypercoagulability or as a secondary condition most often associated with connective tissue disorders, particularly systemic lupus erythematosus (SLE). Persons with the disorder present with a variety of clinical manifestations, typically those characterized by recurrent venous and arterial thrombi. Cardiac valvu- lar vegetations associated with thrombi adherence and thrombocytopenia due to excessive platelet consump- tion may also occur. Venous thrombosis, especially in the deep leg veins, occurs in up to 50% of persons with the syndrome, half of whom develop pulmonary emboli. Arterial thromboses are less common than venous thromboses and most frequently manifest with features of ischemia and infarction. The cerebral arteries are the most commonly affected. Other sites for arterial thrombosis are the coronary arteries of the heart and the retinal, renal, and peripheral arteries. Women with the disorder commonly have a history of recurrent preg- nancy losses after the 10th week of gestation because of ischemia and thrombosis of the placental vessels. These women also have increased risk of giving birth to a pre- mature infant owing to pregnancy-associated hyperten- sion and uteroplacental insufficiency. In most persons with antiphospholipid syndrome, the thrombotic events occur as a single episode at one anatomic site. In some persons recurrences may occur months or years later and mimic the initial event. Occasionally, someone may present with multiple vascu- lar occlusions involving many organ systems. This rapid- onset condition is termed catastrophic antiphospholipid syndrome and is associated with a high mortality rate. Treatment of the syndrome focuses on removal or reduction in factors that predispose to thrombosis, including tobacco cessation and avoidance of estrogen- containing oral contraceptives by women. The acute thrombotic event is treated with anticoagulants (hepa- rin and warfarin) and immune suppression in refractory cases. Aspirin and anticoagulant drugs may be used to prevent future thrombosis. 13

Bleeding Disorders Bleeding disorders or impairment of blood coagulation can result from defects in any of the factors that contrib- ute to hemostasis. Bleeding can occur as a result of dis- orders associated with platelet count, platelet function, coagulation factors, or blood vessel integrity. Platelet Disorders Bleeding due to platelet disorders reflects a failure of activated platelets to bring about hemostasis through the formation of a platelet plug at the site of injury to the blood vessel wall, an injury that causes physical and biochemical disruption of the endothelium. Thrombocytopenia Thrombocytopenia refers to a decrease in the number of circulating platelets to a level less than 100,000/ μ L. 15,16 The greater the decrease in the platelet count, the greater the risk of bleeding. However, spontaneous bleeding usually does not occur until the platelet count falls below 20,000/ μ L. The anatomic sites of bleeding in persons with thrombocytopenia are the intercellular junctions in the postcapillary venules. 16 Key molecules in the junctions include adhesive proteins and associated intracellular binding components (see Chapter 1). Different vascular beds with varying functions require different types of (primary thrombocytosis) or a reactive process (secondary thrombocytosis).The antiphospholipid syndrome, another cause of venous and arterial clotting, manifests as a primary or a secondary disorder associated with systemic lupus erythematosus. It is associated with antiphospholipid antibodies, which promote thrombosis throughout the body. ■■ Increased platelet function usually results from disorders such as atherosclerosis that damage the vascular endothelium and disturb blood flow, or from conditions such as smoking that increase sensitivity of platelets to factors that promote adhesiveness and aggregation. ■■ Increased activity of the coagulation system results from hereditary (factor V Leiden mutation) or acquired disorders (immobility, hyperviscosity syndromes) causing alterations in the components of the coagulation system (i.e., an increase in procoagulation factors or a decrease in anticoagulation factors). ■■ Thrombocytosis refers to an increase in the platelet count that can occur as an essential

SUMMARY CONCEPTS

■■ Hypercoagulability states increase the risk of clot or thrombus formation in either the arterial or venous circulations. Arterial thrombi are associated with conditions that produce an increase in platelet numbers or turbulence in blood flow with platelet adhesion. Venous thrombi are associated with inherited or acquired conditions that cause a decrease in anticoagulation factors or produce a stasis of blood, thereby causing an increase in procoagulation factors.