Hypercoagulable state

This category includes patients with rare causes of strokes such as nonatherosclero-tic vasculopathies, cerebral venous thrombosis, hypercoagulable states, or hematologic disorders. Two such disorders are discussed below. 

The risk of venous thromboembolism (VTE) is related to several easily identifiable factors including age, prior history of VTE, major surgery (particularly orthopedic procedures of the lower extremities), trauma, malignancy, pregnancy, estrogen use, and hypercoagulable states. These risks are additive. 

Tests for hypercoagulable states, such as protein C deficiency and antiphospholipid antibody, should be done only when the cause of stroke cannot be determined based on the presence of well-known risk factors for stroke. 

Hypercoagulable state A disorder or state of excessive or frequent thrombus formation also known as thrombophilia. 

Laboratory tests for hypercoagulable states should be done only when the cause of the stroke cannot be determined based on the presence of well-known risk factors. Protein C, protein S, and antithrombin III are best measured in steady state rather than in the acute stage. Antiphospholipid antibodies are of higher yield but should be reserved for patients aged less than 50 years and those who have had multiple venous or arterial thrombotic events or livedo reticularis. 

Hypercoagulable states include malignancy activated protein C resistance deficiency of protein C, protein S, or antithrombin factor VIII or XI excess antiphospholipid antibodies and other situations. Estrogens and selective estrogen receptor modulators have been linked to venous thrombosis, perhaps due in part to increased serum clotting factor concentrations. Although a thrombus can form in any part of the venous circulation, the majority of thrombi begin in the lower extremities. Once formed, a venous... 

Assessment of the patient s status should focus on the search for risk factors (e.g., increased age, major surgery, previous VTE, trauma, malignancy, hypercoagulable states, and drug therapy). Signs and symptoms of DVT are nonspecific, and objective tests are required to confirm or exclude the diagnosis. 

Major surgery, age >40 years, and prior history of VTE Major surgery, age >40 years, and malignancy Major surgery, age >40 years, and hypercoagulable state Spinal cord injury or stroke with limb paralysis... 

Estrogens have a dose-related effect in the development of venous thromboembolism (VTE) and pulmonary embolism. This is especially true in women with underlying hypercoagulable states or who have acquired conditions (e.g., obesity, pregnancy, immobility, trauma, surgery, and certain malignancies.)... 

Hypercoagulable states, in turn, have been traditionally associated with venous thrombosis. Consequently, attention has been paid to alterations of the hemostatic balance. Although this is a systemic variable, focality is favored due to the contribution of decreased blood flow, as confirmed by the preferential development of venous thrombi at the level of valves, an area of stasis where low-velocity flow is moderately turbulent. 

There is discussion on the adequacy of tests to identify the hypercoagulable states underlying susceptibility to VTED. The complexity of factors and interactions involved in the hemostatic equilibrium has favored the use of functional tests. Among the several options available the measurement of fragments 1 + 2 (F1 + 2), the amino terminus fragment split during the activation of prothrombin has been widely considered the test of choice. The sparse information available for SERMs, however, is unclear. Raloxifene did not modify... 

Venous thrombi (red thrombi) are formed mainly from fibrin in simations where vascular stasis exists or in hypercoagulability states. Here the symptoms consist of deep vein thrombosis with the risks of pulmonary embolism and the mainstay of therapy is anti-coagulation with heparin and oral anticoagulants. 

Heparin-induced thrombocytopenia (HIT) is a systemic hypercoagulable state that occurs in 1-4% of individuals treated with UFH for a minimum of 7 days. Surgical patients are at greatest risk. The reported incidence of HIT is lower in pediatric populations outside the critical care setting and is relatively rare in pregnant women. The risk of HIT may be higher in individuals treated with UFH of bovine origin compared with porcine heparin and is lower in those treated exclusively with LMWH. 

Morbidity and mortality in HIT are related to thrombotic events. Venous thrombosis occurs most commonly, but occlusion of peripheral or central arteries is not infrequent. If an indwelling catheter is present, the risk of thrombosis is increased in that extremity. Skin necrosis has been described, particularly in individuals treated with warfarin in the absence of a direct thrombin inhibitor, presumably due to acute depletion of the vitamin -dependent anticoagulant protein C occurring in the presence of high levels of procoagulant proteins and an active hypercoagulable state. 

A review identified 54 other reports of thromboembolic disease associated with ovulation induction 60% were in upper limb veins and two-thirds of the patients had OHSS (77). The mechanism for the increased risk of thrombosis in these patients has not been determined, but hemoconcentration or a hypercoagulable state associated with high estrogen concentrations could be responsible. 

Carr, M.E., 2001, Diabetes mellitus a hypercoagulable state. J Diabetes Complications 15, 44-54. 

The hypercoagulable state of nephrotic subjects is further worsened with immobilization, hemoconcentration in patients with decreased intravascular volume (usually due to diuretic therapy), and corticosteroid therapy. Prophylactic anticoagulant therapy should be administered to high-risk patients, for example, patients with membranous nephropathy with nephrotic proteinuria and serum albumin level below 20 g/L. 

The pathogenesis of the hypercoagulable state in nephrotic syndrome is complex because plasma levels of both fibrinolytic and regulatory proteins may be altered. Routine coagulation tests (Quick test and activated partial thromboplastin... 

The thrombotic disorders include atherothrombosis, endothelial dysfunction, hypercoagulable states, and the thrombophilias. Atherothrombosis or atherosclerosis is a systemic disease of the vessel wall occuring in the aorta, carotid, coronary, and peripheral arteries. The associated inflammatory response is mediated by macrophages and T-lymphocytes with continued smooth muscle cell proliferation, The levels of endothelin-l (ET-I), an extremely potent... 

The hypercoagulable states can be inherited or acquired. One inherited hypercoagulable state is antithrombin (AT) deficiency. AT deficiency is an autosomal dominant condition. The type I antithrombin deficiency is characterized by reduced synthesis of normal protease inhibitor molecules. The antigenic and functional activities of antithrombin are reduced due to small deletions or insertions or single base substitutions. Type II antithrombin deficiency is due to defects within the protease inhibitor. While the immunologic activity levels are normal, the plasma levels of antithrombin are reduced. About 42% of afflicted individuals develop clinical manifestations spontaneously. Manifestations related to pregnancy, parturition, oral contraceptives, or trauma occur in 58% of AT deficient individuals (190). 

The inherited (primary) hypercoagulable states include activated protein C resistance due to the factor V Leiden mutation, prothrombin gene mutation, antithrombin deficiency, protein C or protein S deficiency, and dysfibrino-genemia. The most important cause of activated Protein C resistance is the defect in factor V involving the mutation of Arg506 to Gln506 (191). 

Bauer KA. Inherited and acquired hypercoagulable states. In LoscalzoJ, Schafer Al, eds. Thrombosis and Hemorrhage, 2nd ed. Baltimore, MD Williams Wilkins, 1998. 

I 99 Fareed D, Bick R, Bacher P et al, Blood levels of nitric oxide, C-reactive protein and TNF-a are upregulated in patients with malignancy-associated hypercoagulable state pathophysiologic implications. Pathophysiol Haemost Thromb 2003 33(suppl I ) 69—76. 

Rosenberg RD, Aird WC. Vascular bed specific hemostasis and hypercoagulable states. N Engl J Med 1999 340 1555-1564. 

Advances in Neurology 92 197-202 Mas JL, Arquizan C, Lamy C et al. (2001). Patent Foramen Ovale and Atrial Septal Aneurysm Study Group. Recurrent cerebrovascular events associated with patent foramen ovale atrial septal aneurysm or both. New England Journal of Medicine 345 1740-1746 Masuda J, Yutani C, Wald R et al. (1992). Histopathological analysis of the mechanisms of intracranial haemorrhage complicating infective endocarditis. Stroke 23 843-850 Matijevic N, Wu K (2006). Hypercoagulable states and strokes. Current Atherosclerosis Reports 8 324-329... 

---