Uses Ofthrombolytic Drugs

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Coronary artery thrombolysis

Timing of administration. The earlier thrombolysis is given the better the outcome. Treatment commencing within the first 3 h of onset is a realistic aim but thrombolysis up to 12 h is still worthwhile. Benefit is most striking in patients with anterior myocardial infarction treated within 4 h of onset.

Anistreplase can be given i.v. over 4-5 min (and so more easily out of hospital); its effect persists for 6-9 h. Other agents are normally infused i.v. over 1-3 h with most of the dose being given early in that period. Retelpase is given as a double bolus 30 min apart.

Reduction in mortality (see also Myocardial infarction, p. 485). There is now compelling evidence that streptokinase, anistreplase, alteplase and retelpase reduce mortality with an acceptable frequency of adverse effects.14 Comparisons between these drugs show no apparent survival advantage of one over the others in respect of survival.15,16 Both streptokinase and t-PA decrease mortality by about 25% when used alone but by 40-50% when either agent is used with aspirin17 which reduces the incidence of re-infarction. Those under 75 years appeared to gain most from thrombus dispersal but 'physiological' age is more important than chronological age.

Stroke may complicate myocardial infarction and is considered usually to be embolic, for its incidence correlates with the extent of myocardial infarction. Evidence18 indicates that the combination of thrombolysis plus aspirin lowers the overall risk of stroke, possibly by limiting the size of the infarct, or by reducing thromboembolic episodes, or by both.

Thrombolysis may also be valuable in persistent unstable angina and especially where arteriography demonstrates substantial thrombus in coronary arteries.

Adverse effects. Bleeding is the most important complication and usually occurs at a vascular lesion, e.g. the site of injection, for fibrinolytic therapy does not distinguish between an undesired thrombus and a useful haemostatic plug. If the contraindications are followed, the incidence of bleeding severe enough to require transfusion is < 1%. Nausea and vomiting may occur.

Midtiple microemboli from disintegration of preexisting thrombus anywhere in the vascular system may endanger life; these commonly originate in an enlarged left atrium, or a ventricular or aortic aneurysm.

Cardiac arrhythmias result from reperfusion of ischaemic tissue. These vary in type and are often transient, a factor which may influence the decision whether or not to treat.

Allergy. Streptokinase and anistreplase are antigenic and anaphylactic reactions with rash, urticaria and hypotension may occur for most people have circulating antibodies to streptococci. Antibodies persist after exposure to these drugs and their reuse should be avoided between 5 days and 12 months as the recommended dose may not overcome immune resistance to plasminogen activation.

Contraindications to thrombolytic drug use (see Myocardial infarction, p. 485).

Noncoronary thrombolysis

Pulmonary embolism. Thrombolysis is superior to heparin at relieving obstructed veins demonstrated radiologically. While a reduction in mortality is thus implied, the numbers of cases reported in clinical trials of thrombolytics have been insufficient to

14 Carins J A et al 1992 Chest 102 (Suppl): 482S-507S.

15 The International Study Group 1990 Lancet 336: 71-75.

16ISIS-3 Collaborative Group 1992 Lancet 339: 753-770.

17 Carins J A et al 1998 Chest 114:634S-657S

18ISIS-2 Collaborative Group 1988 Lancet 2: 349-360.

provide conclusive statistical proof. There is, nevertheless, a strong impression that thrombolysis is beneficial where pulmonary embolism is accompanied by signs of haemodynamic decompensation (raised jugular venous pressure, pulse rate >100 beats /min, systolic pressure <100 mmHg, arterial oxygen desaturation). Alteplase 100 mg may be infused over 2 h, followed by an i.v. infusion of heparin.

Deep vein thrombosis. Thrombolysis may be justified where the affected vessels are proximal and the risk of pulmonary embolism is high. Complete lysis may be achieved in 50% of cases treated within 7 days of onset.

Arterial occlusion Systemic or local thrombolysis may be considered for arterial occlusions distal to the popliteal artery (thrombectomy being the usual therapeutic approach for occlusion of < 24 h duration proximal to this site). Intravenous streptokinase will lyse 80% of occlusions if infusion begins within 12 h, and 60% if it is delayed for up to 3 days.

Ischaemic stroke. There is little evidence of benefit and most trials have shown increased short-term mortality in patients treated with thrombolysis.

Thrombolysis may also be considered for ocular thrombosis (urokinase) and for thrombosed arteriovenous shunts (streptokinase).

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