Coronary artery thrombosis, treatment

Tissue plasminogen activator has been used successfully to treat acute myocardial infarction, and the benefits of this treatment are well documented.102,116 This drug, however, does not seem to be superior to other thrombolytics when treating coronary artery thrombosis, and streptokinase may be a more cost-effective method of treating myocardial infarction. Alternatively, t-PA may be more effective than other thrombolytics in its ability to initially reopen cerebral vessels this drug is often used preferentially during ischemic stroke.4,44 Hence, the added cost of t-PA may be justified in this situation. 

Mattsson C, Bjorkman JA, Abrahamsson T et al. Local proCPU (TAFI) activation during thrombolytic treatment in a dog model of coronary artery thrombosis can be inhibited with a direct, small molecule thrombin inhibitor (melagatran). Thromb Haemost 2002 87 557-562. 

In contrast to unfractionated heparin, the factor Xa inhibitor tick anticoagulant peptide (TAP) effectively inhibited coronary arterial thrombosis in a canine electrolytic injury model (57). TAP was also effective in inhibition of the procoagulant properties of whole blood clots in vitro however, it was stated that TAP might be not optimal due to its slow binding kinetics (54). Meanwhile, several low molecular weight direct factor Xa inhibitors are in clinical development (Table I), some of them specifically for the treatment and secondary prevention of ACS. DX-9065a, ZK-807834 and otamixaban have been intensively characterized in vitro and in vivo and are in clinical investigations for the treatment of acute arterial thrombosis. 

Urokinase is intended for intravenous use only and indicated for the treatment of pulmonary embolism, coronary artery thrombosis, and intravenous catheter clearance. Typical dosages in peripheral arterial disease consist of an infusion at a rate ranging from 60,000 lU/hr to 240,000 lU/hr infused directly into the thrombus. 

Anistreplase, a thrombolytic enzyme (30 units by direct IV injection over 2 to 5 minutes), is indicated in the treatment of acnte coronary arterial thrombosis (see Figure 94). 

Streptokinase (1,500,000 lU within 60 minutes by fV infusion) is indicated in lysis of coronary artery thrombosis after acute myocardial infarction streptokinase (250,000 lU by IV infusion pump into each occluded limb of the cannula over 25 to 35 minutes) is indicated in arteriovenous cannula occlusion and streptokinase (250,000 lU IV infusion over 30 minutes) is indicated in the treatment of venous thrombosis, pulmonary embolism, and arterial thrombosis and embolism. 

New hybrids of plasminogen activator have been constructed in attempts to increase the specificity toward fibrin polymers and thereby improve the therapeutic value for treatment of coronary artery thrombosis (143, 144). Plasminogen activators are serine proteases that act on plasminogen to release plasmin, also a... 

C. Clinical Use The major application of the thrombolytic agents is in the emergency treatment of coronary artery thrombosis. Under ideal conditions (ie, treatment within 1—4 hours), these agents may cause prompt recanalization of the occluded vessel. Very prompt use (ie, within 3 hours of the first symptoms) of t-PA in patients with ischemic stroke appears to result in a significantly better clinical outcome. Cerebral hemorrhage must be positively ruled out before such use. The thrombolytic agents are also used in cases of multiple pulmonary emboli. 

Thrombosis in stenosed human coronary arteries is one of the most common thrombotic diseases leading to unstable angina, acute myocardial infarction or sudden death. Treatment with angioplasty, thrombolysis, or bypass grafts can expose new thrombogenic surfaces and re-thrombosis may occur. The mechanisms responsible for this process include interactions of platelets with the damaged arterial wall and platelet aggregation. 

These drugs appear to be very useful adjxmcts for the treatment of unstable angina, and in the prevention of thrombosis following percutaneous revascularisation procedures such as angioplasty and coronary artery stenting. Their role in preventing infarction in patients with acutely compromised myocardium is likely to expand rapidly. 

Abciximab is used for prevention of cardiac ischemic events in patients undergoing percutaneous coronary intervention and to prevent myocardial infarction in patients with unstable angina who do not respond to conventional treatment. It has also been used for thrombolysis in patients with peripheral arterial occlusive disease and arterial thrombosis (2). 

The anticlotting drugs are used in the treatment of myocardial infarction and other acute coronary syndromes, atrial fibrillation, ischemic stroke, and deep vein thrombosis (DVT). The anticoagulant and thrombolytic drugs ate effective in treatment of both venous and arterial thrombosis. Antiplatelet dmgs are used primarily for treatment of arterial disease. 

A retrospective study of 616 courses of IVlG in 62 patients (43 male, mean age 58.5 years) with neuropathy found thromboembolic complications in seven patients, five (two myocardial infarction, one acute coronary syndrome, one deep venous thrombosis (DVT) without a pulmonary embolus (PE) and one DVT with PE) of which were deemed early occurring within 14 days of treatment. Daily dose of lVIG>35g was correlated with early thromboembolic complication. Independent risk factors for thromboembolic complications included coronary artery disease and current immobility. Thromboembolic complications were significantly increased in patients with four or more of the risks factors listed in Table 1 [79 ]. 

Indications for treatment with streptokinase include acute occlusion of arteries, deep vein thrombosis, and pulmonary embolism. Streptokinase therapy in coronary thrombosis, which is the usual cause of myocardial infarction (54,71,72), has proved to be valuable. In this frequently fatal condition, the enzyme is adrninistered intravenously at a dose of 1.5 million units over 60 min, or given by intracoronary infusion at a 20,000- to 50,000-unit bolus dose followed by 2000 to 4000 units/min for 60 min therapy must be instituted as soon as practicable after the diagnosis of heart attack is made. For deep vein thrombosis, pulmonary embolism, or arterial occlusion, streptokinase is infused at a loading dose of 250,000 units given over 30 min, followed by a maintenance dose of 100,000 units over a 60-min period. 

There is an association between the rare inborn recessive condition of homocystinemia and arterial and venous thrombosis, and observational data link coronary heart disease, stroke, and venous thromboembolism with increasing plasma homocysteine (Wald et al. 2002, 2004). This led to trials of foUc acid and pyridoxine supplementation to lower homocysteine levels (Hankey 2002 Hankey and Eikelboom 2005). Results from such trials have so far been disappointing the Vitamin Intervention for Stroke Prevention Study (VISP) and the Norwegian Vitamin Trial (NORVIT) (Toole et al. 2004 Bonaa et al. 2006) trials showed no treatment effect on recurrent stroke, coronary events or deaths. Preliminary results from the Study of Vitamins to Prevent Stroke (VITATOPS) trial have shown no evidence of reduced levels of iirflammation, endothelial dysfunction, or the hypercoagulability postulated to be increased by elevated homocysteine levels in patients with previous TIA or stroke treated with foUc acid, vitamin B12 and vitamin Bs... 

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