Clinical experience with thrombolytics in non-coronary disorders is limited to the
plasminogen activators streptokinase,
urokinase and
alteplase; therapeutic trials with
anistreplase (
APSAC) are almost, and with
saruplase completely, limited to acute
myocardial infarction. In terms of
thrombus clearance,
thrombolytic drugs are superior to
heparin in patients with recent
deep vein thrombosis in the pelvis or lower limbs. In aggregate, thrombi younger than 8 days are lysed in approximately 60% of patients treated with
streptokinase,
urokinase or
alteplase. The results of studies assessing the subsequent development of the
postphlebitic syndrome are conflicting, but most suggest that
thrombolytic therapy can reduce symptoms of chronic
venous insufficiency. Currently, the combination of systemic
thrombolytic drugs followed by
heparin is recommended for patients with acute major
pulmonary embolism who are haemodynamically unstable.
Streptokinase,
urokinase and
alteplase have all been shown to accelerate the lysis of pulmonary emboli and to decrease pulmonary vascular obstruction and
pulmonary hypertension. Systemic venous or intrapulmonary infusions of
alteplase offers the same benefit in terms of angiographic and haemodynamic improvement. A short infusion of 100 mg
alteplase over 2 hours seems to be superior to a 24-hour infusion of
urokinase. None of the thrombolytic trials in
pulmonary embolism have been large enough to demonstrate a reduction in mortality. It is now generally accepted that, unless contraindicated,
thrombolytic therapy is the front-line treatment for patients with massive
pulmonary embolism and major haemodynamic disturbance. The local treatment of acute
arterial occlusion in limb arteries results in rapid clearing of the artery in 67% of patients treated with
streptokinase; the corresponding success rates for
urokinase and
alteplase are 81% and 88 to 94%, respectively. The main question appears to be the identification of patients in whom local thrombolysis is the treatment of choice, as opposed to established therapeutic modalities. Thrombolytic treatment following a major
ischaemic stroke is hazardous, although clinical improvement has been noted in a minority of patients with recanalised cerebral arteries. The safety and efficacy of thrombolytic treatment remains unproven for this indication, and its use must be restricted to experimental protocols. Thrombolytic treatment in retinal artery or vein occlusion has, in practice, been abandoned.