Venous Thromboembolism

Sunday, February 9th 2014. | Other
Venous thromboembolism (VTE) results from clot formation in the venous circulation and is manifested as deep vein thrombosis (DVT) and pulmonary embolism (PE). A DVT is a thrombus composed of cellular material (red and white blood cells, platelets) bound together with fibrin strands. A PE is a thrombus that arises from the systemic circulation and lodges in the pulmonary artery or one of its branches, causing complete or partial obstruction of pulmonary blood flow.
Pathophysiology of Venous thromboembolism :
  1. The coagulation cascade is a stepwise series of enzymatic reactions that results in the formation of a fibrin mesh. It can be triggered through either the intrinsic or extrinsic pathways. The intrinsic pathway is activated when negatively charged surfaces in contact with the blood activate factor XII, and activated platelets convert factor XI. The extrinsic pathway is activated when damaged vascular tissue releases tissue thromboplastin. Vascular injury also exposes the subendothelium, causing adherence, activation, and aggregation of platelets. The intrinsic and extrinsic pathways meet at a common point with the activation of factor X. With its partner, factor Va, factor Xa converts prothrombin (II) to thrombin (IIa), which then cleaves fibrinogen-forming fibrin monomers. Factor XIII covalently bonds fibrin strands together. The fibrinolytic protein plasmin ultimately degrades the fibrin mesh into soluble end products known as fibrin split products.
  2. Three primary components venous stasis, vascular injury, and hypercoagulability (Virchow’s triad)—play a role in the development of a pathogenic thrombus.
  3. Venous stasis is slowed blood flow in the deep veins of the legs resulting from damage to venous valves, vessel obstruction, prolonged periods of immobility, or increased blood viscosity. Conditions associated with venous stasis include major medical illness (e.g., heart failure, myocardial infarction), major surgery, paralysis (e.g., stroke, spinal cord injury), polycythemia vera, obesity, or varicose veins.
Diagnosis of Venous thromboembolism :
  • 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.
  • Radiographic contrast studies are the most accurate and reliable method for diagnosis of VTE. Contrast venography allows visualization of the entire venous system in the lower extremity and abdomen. Pulmonary angiography allows visualization of the pulmonary arteries. The diagnosis of VTE can be made if there is a persistent intraluminal filling defect on multiple x-ray films.
  • Because contrast studies are expensive, invasive, and technically difficult to perform and evaluate, noninvasive tests (e.g., ultrasonography and the ventilation-perfusion [V/Q] scan) are used frequently for the initial evaluation of patients with suspected VTE.
  • Clinical assessment improves the diagnostic accuracy of objective noninvasive tests. Major features suggestive for DVT include: (1) active cancer; (2) prolonged immobility or paralysis; (3) recent surgery or major medical illness; and (4) clinical features of DVT.
  • If the results of the clinical assessment and ultrasonogram are discordant, veno- graphy or angiography should be performed to make the definitive diagnosis
Treatment of Venous thromboembolism :
  • Unfractionated heparin (UFH) is a heterogeneous mixture of sulfated glycosaminoglycans of variable lengths and pharmacologic properties. The molecular weight of these molecules ranges from 5000 to 30,000 daltons (mean 15,000 daltons).
  • The anticoagulant effect of UFH is mediated through a specific pentasaccharide sequence on the heparin molecule that binds to antithrombin, provoking a conformational change. The UFH-antithrombin complex is 100 to 1000 times more potent as an anticoagulant than antithrombin alone. Antithrombin inhibits the activity of factors IXa, Xa, XIIa, and thrombin (IIa). It also inhibits thrombin-induced activation of factors V and VIII.
  • Contraindications to heparin therapy include hypersensitivity to the drug, active bleeding, hemophilia, severe liver disease with elevated prothrombin time (PT), severe thrombocytopenia, malignant hypertension, and inability to meticulously supervise and monitor treatment.
  • UFH must be given parenterally, preferably by the intravenous (IV) or subcutaneous (SC) route. Intramuscular administration is discouraged because absorption is erratic and it may cause large hematomas.
  • IV administration is needed when rapid anticoagulation is required. Continuous IV infusion is preferable because intermittent boluses produce high peaks in anticoagulation activity and have been associated with a greater risk of major bleeding.
  • Doses should be based on actual body weight; adjusted body weight may be used for obese patients (greater than 130% of ideal body weight). A loading dose of 80 to 100 units/kg (maximum 10,000 units) is followed by a continuous IV infusion at an initial rate of 17 to 20 units/kg/h (maximum 2300 units/h).
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