Evidence
Alert

Thrombolysis may reduce complications of deep vein thrombosis

Blood clots are cleared quickly for people who develop them in the deep leg veins if they receive thrombolysis drugs alongside other treatments directly into their veins. The chance of successful break down of the clot was compared with the chance following standard anti-clotting drugs alone, such as heparin and warfarin.

This Cochrane review found that over twice as many deep clots were completely broken down in the thrombolysis group compared with usual treatments. Thrombolysis also reduced the risk of long-term problems such as pain, swelling and skin damage, known as post-thrombotic syndrome, by a third.

However, bleeding was twice as common in people given thrombolysis (10%) than anticoagulants alone (4%). The specific drug, dose or method of administration used made no difference to the rate of this adverse effect.

This highlights the need for treatment to be targeted at people who are likely to gain most benefit, such as those with clots in the pelvis and thigh which carry higher risk of complications.

Why was this study needed?

Around one person in every 1,000 in the UK develops deep vein thrombosis (DVT) each year. It is usually treated with anticoagulant drugs to stop blood clots forming and reduce risk of the clot travelling to the heart and lungs and causing pulmonary embolism.

Despite anticoagulation, between 20 and 40% of people develop post-thrombotic syndrome, including long term swelling, aching and skin changes, which can have a long-term impact on quality of life.

Thrombolysis is an add on treatment option where drugs are injected into the veins to dissolve the clot. This could reduce risk of permanent damage to the veins and subsequent post-thrombotic syndrome. However, thrombolysis may also increase bleeding risk so isn’t used routinely. There were only 192 instances of thrombolysis recorded in England in 2014-15.

This study is the third update to previous Cochrane reviews, the first published in 2004. The authors were interested in quantifying the relative benefits and harms of thrombolysis treatments. No new trials were found, but additional follow-up results from one of the trials were included in this version.

What did this study do?

This systematic review included 17 randomised controlled trials comparing thrombolysis and anticoagulant drugs with anticoagulant drugs alone in 1,103 adults with confirmed DVT.

Participants were mostly older adults and treated within 21 days of symptom onset. The trials used different doses and types of thrombolytic drugs. Streptokinase and tissue plasminogen activator were most used. These were injected either into the arm veins (systemic), injected locally into the leg, or delivered via catheter. Trials were carried out in the USA, Scandinavia, Germany and the UK.

Fourteen studies were rated as low risk of bias while three were flagged as high risk. Common areas of potential bias related to method of treatment allocation. Overall, the evidence was graded as moderate quality for the main outcomes, which improves the reliability of the review.

What did it find?

  • Thrombolysis increased the chance that the blood clot was completely broken down. In the thrombolysis group 51% had complete clot breakdown at six months to five years after treatment versus 33% of the anticoagulation group (relative risk [RR] 2.44, 95% confidence interval [CI] 1.4 to 4.27; seven trials, 630 participants).
  • Fewer people developed post-thrombotic syndrome when assessed both before and after five years after thrombolysis. For example three trials with 306 people reported post-thrombotic syndrome at between six months and five years follow-up in 45% of the thrombolysis group versus 66% of the anticoagulant group (RR 0.66, 95% CI 0.53 to 0.81). Similar proportions were found in the two trials including that followed people beyond five years.
  • Bleeding complications were more common in people receiving thrombolysis, reported in 10% versus 4% of those receiving anticoagulation (RR 2.23, 95% CI 1.41 to 3.52; 17 trials, 1103 people).
  • Method of drug delivery (systemic injection or catheter) did not influence outcomes.
  • There was insufficient data to give reliable assessment of effects on stroke, death pulmonary embolism or mortality outcomes.

What does current guidance say on this issue?

The NICE guideline on diagnosis and management of venous thromboembolic diseases says that catheter-directed thrombolytic therapy should be considered only in certain circumstances. Patients should have a DVT above calf level, have had symptoms for less than 14 days, have good functional status and a life expectancy of a year or more, and have a low risk of bleeding.

NICE have also published guidance on a type of catheter-directed thrombolysis that uses ultrasound. There isn’t yet enough evidence to recommend routine use of this enhanced procedure.

What are the implications?

Thrombolysis improves the chance of successful clot breakdown and may prevent longer-term complications such as post-thrombotic syndrome. However, patient factors such as duration and location of the clot seem key to a successful balance of risk and benefit.

The strict eligibility criteria of more recent studies improved safety in terms of bleeding. This suggests that thrombolysis should only be considered for patients who meet select criteria. Individuals with clots in the pelvis and thigh, which carry higher risk of complications, may be likely to gain most benefit.

The review is not able to determine which drug, dose or method of delivery is most effective.

 

Citation and Funding

Watson L, Broderick C, Armon MP. Thrombolysis for acute deep vein thrombosis. Cochrane Database Syst Rev. 2016;(11):CD002783.

 

Bibliography

NHS Choices. Complications of deep vein thrombosis. London: Department of Health; 2016.

NHS Digital. Hospital Episode Statistics, Admitted Patient Care – England, 2014-15. London: NHS Digital; 2015.

NICE. Ultrasound-enhanced, catheter-directed thrombolysis for deep vein thrombosis. IPG523. London: National Institute for Health and Care Excellence; 2015.

NICE. Venous thromboembolic diseases: diagnosis, management and thrombophilia. CG144. London: National Institute for Health and Care Excellence; 2015. Updated version NG158; 2020.

Produced by the University of Southampton and Bazian on behalf of NIHR through the NIHR Dissemination Centre

Commentaries

Expert commentary

Post-thrombotic syndrome is a serious long-term complication of deep vein thrombosis (DVT). Patients with this syndrome may present with pain, swelling or even leg ulcers. The standard therapy for DVT is the use of anticoagulants or blood thinners. Up to half of patients develop post-thrombotic syndrome. Compression stockings were claimed to prevent post-thrombotic syndrome but recent studies do not support their use. The use of thrombolysis or clot dissolving drugs provides a further option in selected patients. This approach might reduce this syndrome but at the cost of increased bleeding. The role of thrombolysis in treatment of acute deep vein thrombosis requires clarification.

Roopen Arya, Professor of Thrombosis and Haemostasis, King’s College Hospital