Hypercoagulation or a hypercoagulable state results in a tendency to form thrombus. Blood flow problems and changes in blood vessel walls can cause platelets to gather or aggregate and adhere to vessel walls, initiating a pathophysiological clotting process. Clotting system problems are associated with immobility, congestive heart failure, and artificial body surfaces, such as artificial heart valves, oral contraceptives, pregnancy and the post-partum period. Both platelet abnormalities and clotting system abnormalities can lead to thrombus formation. Abnormal platelet function leading to thrombus formation may be due to arteriosclerosis, diabetes mellitus, elevated blood cholesterol and lipids, and smoking.
In most situations in which a patient develops a thrombus, the thrombus is due to overt risk factors, such as illness, surgery, or trauma associated with prolonged bed rest. A significant number of patients, however, have an inherited biochemical deficiency or an acquired disorder that increases the risk of thrombosis.
Inherited hypercoagulable states include deficiencies of protein S, protein C, and antithrombin III. Normal amounts of these substances are needed to stop excessive coagulation. Each of these three disorders is inherited in an autosomal dominant manner. The most common inherited disorder of coagulation inhibitors is protein S deficiency. This inherited trait results in superficial thrombophlebitis, deep vein thrombosis, and pulmonary emboli. Although the age range for the first thrombotic episode ranges from 15 to 68 years, approximately two-thirds of patients with protein S deficiency will have an initial thrombotic event by age 35.
Protein C deficiency occurs in one of 200 to 300 people. Although this condition is associated with deep vein thrombosis and superficial phlebitis, the vast majority of thrombi formed are asymptomatic. Antithrombin III deficiency occurs in one of 2000 to 5000 persons. Almost half of those affected have a thrombus and the majority of these individuals experience their first thrombotic episode before age 35.
Acute thrombosis in patients with inherited hypercoagulation is managed similarly to other causes of thrombosis. The patient is started on intravenous heparin, which is adjusted to maintain the APTT at 1.5 to 2.5 times the control value. Heparin is continued until the prothrombin time is 1.3 to 1.5 times the control value, a process that takes approximately 5 days.
Symptomatic patients with inherited deficiencies of protein S and antithrombin III are at lifelong risk of recurrent thrombosis, which may occur either spontaneously or during events such as pregnancy, childbirth, or surgery. These patients may benefit from long term anticoagulation with coumadin. If a patient elects not to have long term anticoagulation, he or she may have short term prophylaxis with heparin when the risk of thrombosis is increased, such as during severe infections, prolonged bedrest, or during surgery.
An unknown percentage of thromboses are caused by acquired disorders that are not recognized before a thrombotic event occurs. Bone marrow disorders such as polycythemia vera, in which abnormally large numbers of platelets are produced, are commonly associated with thromboembolism. Often, the hematologic disorder is diagnosed before a thrombus occurs. Two acquired disorders associated with thrombosis that are not readily apparent are antiphospholipid antibody syndrome and cancer or Trousseau syndrome. Antiphospholipid antibodies are sometimes associated with infection, autoimmune diseases such as systemic lupus erythematosus, cancer, and medications such as procainamide, chlorpromazine, and quinidine. Studies indicate that high titers of antiphospholipid antibodies are associated with an increased risk of thrombosis, although the reason for the association is not known. It is possible that antiphospholipid antibodies are markers for other antibodies or agents that promote thrombosis.
A relationship between hypercoagulability and cancer was first recognized by Trousseau in the 19th century. It is now well established that occult malignancy as well as overt cancer can be associated with recurrent arterial or venous thrombosis. Tumor cells and their products are known to exert procoagulant effects by activating the coagulation cascade and by inhibiting the fibrinolytic system. Such cells promote thrombosis by interacting with platelets, leukocytes, and endothelial cells. Recent studies have found a significant association between idiopathic venous thrombosis and subsequent development of clinically overt cancers. The relationship was particularly strong in patients with severe venous thrombosis.
Please visit the American Family Physician website for more information about hypercoagulation.
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