Deep vein thrombosis (DVT) is a major health problem in the UK. Its incidence is difficult to ascertain as many cases go undetected, but it is probable that about 3 per cent of the population will have a DVT at some stage in their lives'. The most serious immediate risk associated with DVT is pulmonary embolism. Untreated, around 30 per cent of calf DVT and 50 per cent of proximal DVT will produce pulmonary emboli', of which 20-40 per cent will be fatal. Standard anticoagulation reduces the incidence of fatal pulmonary embolism to less than one in 1000.
In the long term it is estimated that over 60 per cent of patients develop symptoms of the post-thrombotic syndrome following an acute DVT, despite anticoagulation. This syndrome, associated with damage to the valves and subsequent venous hypertension, encompasses a range of symptoms and signs, from pain and swelling to skin pigmentation and venous ulceration. Venous ulcers probably develop in about 10 per cent of cases, although values as high as 48 per cent 2years after an iliofemoral DVT have been quoted'. Such ulcers are a source of considerable morbidity in the community, with an estimated incidence of 1 per cent and a cost to the National Health Service of at least f l O O million per annum (f1200 for each unhealed ~l c e r ) ~.
Thrombolysis is an attractive treatment alternative to anticoagulation as it has the potential to lyse thrombus rapidly and may preserve valve function, thereby preventing the post-thrombotic syndrome in the long term. Much of the current thinking on the role of thrombolysis for thromboembolism is based on work carried out with streptokinase in the 1960s and 1970s. Streptokinase was typically given systemically over 3-5 days in roughly double the dose currently recommended. A pooled analysis by Goldhaber et aL5 of six randomized trials of streptokinase versus heparin showed that thrombolysis was achieved 3.7 times more often in the groups treated with streptokinase, but bleeding complications occurred 2.9 times more often than with heparin5. Other reviewers agree that lysis is achieved to a much greater extent with streptokinase but maintain that the incidence of important bleeding complications is similar to that observed with fulldose heparin therapy (about 5 per cent)6. Whether thrombolysis confers any longterm benefit IS more contentious. Kakkar and Lawrence7 failed to demonstrate any significant benefit in 25 patients treated with streptokinase after a follow-up of 2 years. Others, particularly in the USA, have concluded' that 'the weight of evidence indicates that the post-phlebitic syndrome is often avoided by rapid, early and complete vascular reperfusion, especially in symptomatic patients with recently formed thrombi involving the popliteal or iliofemoral veins'. Since these early trials there have been a number of developments in the field of thrombolysis, in particular the advent of new drugs such as urokinase and recombinant tissue-type plasminogen activator (rtPA), lower dosing regimens for systemic infusion and catheter-directed techniques of administration. These have improved success rates and reduced the complications of intra-arterial thrombolysis for acute limb ischaemia. Both rtPA and urokinase have also been used successfully in the treatment of acute DVT. In the largest trial to date with long-term follow-up, lysis was achieved in 45 per cent of patients receiving rtPA compared with 5 per cent of those receiving heparin; the incidence of postthrombotic syndrome was 25 per cent in those with more than SO per cent lysis, compared with 56 per cent in those with less than 50 per cent'.
Perhaps most encouraging of all have been recent reports of catheter-directed techniques rn hich deliver the thrombolytic agent to the site of the thrombus. Semba and Dake' tieated 25 limbs with ileofemoral DVT in 21 patients. Approaching the thrombus usually from the internal jugular vein, they achieved complete lysis in 18 limbs (72 per cent) and partial lysis in a further five (20 per cent), with no major complications. Follow-up was limited, with only 12 patients reviewed at 3 months, but 11 of lhese had maintained patency. Interestingly, the group uncovered