Thromboembolism

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. 

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. 

Vascular injury may result from major orthopedic surgery (e.g., knee and hip replacement), trauma (especially fractures of the pelvis, hip, or leg), or indwelling venous catheters. 

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 

FIGURE 14-1. Coagulation cascade. (AT, antithrombin HCII, heparin cofactor II TFPI, tissue factor pathway inhibitor.) 

The goal in the treatment of deep venous thrombosis and pulmonary embolism is the prevention of recurrent, fatal embolism. 

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Thromb o cy top athy Thrombocytopenia Thromboembolism Thrombolytic agents... 

Congenital deficiency of Factor XII is inherited as an autosomal recessive trait. Deficiency of this factor is rarely associated with any coagulopathy. It has been observed that people deficient in this factor may have an increased frequency of thromboembolic compHcations. 

Infusion devices have been used for diabetes, cancer chemotherapy, pain control (patient-controUed analgesia, ie, PGA), infection, Alzheimer s disease, Parkinson s, nausea, thalassemia, thromboembolism, and to treat severe spasms resulting from spiaal cord iajury (140—143). 

The most common arrhythmia in humans is atrial fibrillation. Because of the lack of rhythmic atrial activation, irregular ventricular rhythms and thromboembolism result. There are two possible therapeutic goals ... 

Fondaparinux, the factor Xa-binding pentasaccharide (Arixtra, MW 1,728 Da), is prepared synthetically, unlike UFH, LMWH and danaparoid, which are obtained from animal sources. Despite only inactivating free factor Xa, clinical trials indicate that fondaparinux is an effective antithrombotic agent, both for venous thromboembolism prophylaxis and treatment, as well as for acute coronary syndrome and ST elevation myocardial infarction [4]. 

The daily dose of sulfinpyrazone is 200-400 mg. The side effects of sulfinpyrazone are comparable with those of probenecid. A potential therapeutic advantage of sulfinpyrazone in patients with coronary heart disease and thromboembolic diseases is its inhibitory effect on platelet aggregation. 

GPIIb/IIIa Integrin Receptor Antagonists In the Rapid Diagnosis of Thromboembolic Events... 

The role of the platelet integrin GPIIb/IIIa receptor and its potential utility as a radio-diagnostic agent in the rapid detection of thromboembolic events has been demonstrated [6]. This approach may be useful for the noninvasive diagnosis of various thromboembolic disorders. 

Due to the pivotal role of platelets in thrombus formation, especially in the arterial system, inhibition of platelet function has become a central pharmacological approach. Antiplatelet drugs are given in order to prevent and treat thromboembolic diseases such as coronary heart disease, peripheral and cerebrovascular disease. They have also revolutionized the procedures of invasive coronary interventions as they reduce the risk of restenosis and thrombosis. 

Celecoxib, which has a low selectivity for COX-2 compared to COX-1, is still available, although its more selective successor, valdecoxib has been withdrawn. Etoricoxib, the successor to rofecoxib, is marketed in Europe but not in the USA. In a large multinational clinical trial, etoricoxib caused no more thromboembolic events than diclofenac, but after 18 months the incidence of gastrointestinal ulcers and bleeding was the same for both drugs [4]. 

COX-2 synthesises PGI2 (prostacyclin) and the high incidence of myocardial infarctions with selective COX-2 inhibitors has been attributed to inhibition of COX-2 in vascular tissues. Prostacyclin, made by blood vessel walls, inhibits aggregation of platelets and maintains a balance with thromboxane. Thromboxane, which is released by platelets, promotes clotting. Prostacyclin is synthesised mostly by COX-1, but in humans selective COX-2 inhibition reduces its biosynthesis in vivo. This reduced synthesis may lead to an overactive thromboxane system and increased risk of thromboembolism. 

Bosentan (Tracleer ) Actelion, Switzerland ETA/ETB receptor Grade III and IV PAH and chronic thromboembolic pulmonary hypertension (European approval in 2002 as orphan medicine) Program for CHF was terminated in phase III... 

Thromboembolic events (myocardial infarction and stroke, see below)... 

Cardiovascular system—hypertension, edema, congestive heart failure, and thromboembolism ... 

Thromboembolism or fat embolism, thrombophlebitis, necrotizing angiitis, syncopal episodes, cardiac arrhythmias, aggravation of hypertension... 

Miscellaneous—edema changes in libido breast pain, enlargement, and tenderness reduced carbohydrate tolerance venous thromboembolism ... 

Warning associated with the administration of estrogen include an increased risk of endometrial cancer, gallbladder disease, hypertension, hepatic adenoma (a benign tumor of the liver), cardiovascular disease, increased risk of thromboembolic disease and hypercalcemia in those with breast cancer and bone metastases. 

ASSESSMENT OF THE HOSPITALIZED PATIENT The hospitalized patient receiving a female hormone requires careful monitoring. The nurse takes the vital signs daily or more often, depending on the patient s physical condition and the reason for drug use. The nurse observes the patient for adverse drug reactions, especially those related to the liver (the development of jaundice) or the cardiovascular system (thromboembolism). The nurse weighs the patient weekly or as ordered by the primary health care provider. The nurse... 

Ineffective Tissue Perfusion related to adverse reactions (thromboembolic elfeds)... 

MANAGING THROMOOEMOOLIC EFFECTS. The nurse monitors the patient for signs of thromboembolic effects, such as pain, swelling, tenderness in die extremities, headache, chest pain, and blurred vision. These adverse effects are reported to die primary health care provider. Patients with previous venous insufficiency, who are on bed rest for other medical reasons, or who smoke are at increased risk for tiiromboembolic effects. The nurse encourages the patient to elevate the lower extremities when sitting, if possible, and to exercise the lower extremities by walking. 

There is an increased risk of post-operative thromboembolic complications in women taking oral contraceptives Ifposs-bte, use of the drug is discontinued at least 4 weeks before a surgical procedure associated with thromboembolism or during prolonged immobilization. 

Headache, dizziness, intolerance to contact lens, edema, thromboembolism, hypertension, nausea, weight changes, testicular atrophy, acne, breast tenderness, gynecomastia... 

Heparin and warfarin are widely used in the treatment of thrombotic and thromboembolic conditions, such as deep vein thrombosis and pulmonary embolus. Heparin is administered first, because of its prompt onset of action, whereas warfarin takes several days to reach full effect. Their effects are closely monitored by use of appropriate tests of coagulation (see below) because of the risk of producing hemorrhage. 

Papadopoulos SM, Chandler WF, Salamat MS, Topol EJ, Sackellares JC. Recombinant human tissue-type plasminogen activator therapy in acute thromboembolic stroke. J Neurosurg. 1987 67 394-398. 

Middle Cerebral Artery Occlusion and the PROACT Trial The safety and efficacy of lAT in the anterior circulation have been evaluated in two randomized, multicenter, placebo-controlled trials. In the Prolyse in Acute Cerebral Thromboembolism (PROACT) 1 and 11 trials, patients with proximal MCA (Ml or M2 segment) occlusions within 6 hours of symptom onset were treated with recombinant prourokinase (r-pro-UK) or placebo. ... 

Barnwell SL, Clark WM, Nguyen TT, O Neill OR, Wynn ML, Coull BM. Safety and efficacy of delayed intraarterial urokinase therapy with mechanical clot disruption for thromboembolic stroke. Am J Neuroradiol 1994 15 1817-1822. 

Furlan A, Higashida R, Wechsler L, Gent M, Rowley H, Kase C, Pessin M, Ahuja A, Callahan F, Clark WM, Silver F, Rivera F. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. JAMA 1999 282 2003-2011. 

Zeumer H, Hacke W, Ringelstein EB. Local intraarterial thrombolysis in vertebrobasilar thromboembolic disease. Am J Neuroradiol 1983 4 401 04. 

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