These recommendations of the Joint Thrombolysis Committee were accepted and ratified by the main JRCALC Committee at its meeting on 3 July 2003.
- Heparin is required as adjunctive therapy with current thrombolytic agents, except for streptokinase. Previously it was believed that it was important in achieving good fibrin binding for the agent to act effectively but this belief seems now to have been discounted. The principal reason is to prevent re-thrombosis, particularly as all thrombolytics are – paradoxically – potent activators of platelets.
- Only unfractionated heparin has a licence for this indication at present, but in the future one or more of the low molecular weight (LMW) heparins will be approved – and will be easier to use.
- Ambulance paramedics are not permitted to use heparin under the POMs legislation apart from the low dose needed to keep open venous lines but they may legally, of course, use heparin or even a low molecular weight derivative under a PGD.
- JRCALC and the Joint Thrombolytic Committee (representing JRCALC, ASA, British Cardiac Society, and the Department of Health) do have some concerns about the use of a drug ‘off label’ on a PGD, especially when inevitably some patients will develop cerebral haemorrhage as a result of the treatment. There would be medico-legal implications even if the use were appropriate from a medical viewpoint – but there remain some unresolved dose issues with the LMW fractions especially for older patients.
- For these reasons, JRCALC considers that the use of heparin can be deferred until hospital admission if treatment can be given within 30 minutes of an IV dose of tenecteplase or within 20 minutes of the first dose of reteplase. The half life of these agents should ensure that re-thrombosis is not a serious concern over this period
- But if the journey times are of such a duration that longer delays are possible, heparin should be used within the dose range recommended in the SPCs. For tenecteplase, this depends on body weight, ‘not exceeding’ 4000 units or 5000 units depending on weight being above or below 67Kg – to be followed by an infusion. JRCALC believes that over-dosage of heparin in the pre-hospital environment (or any perception of it) must be avoided – given that heparin is an important cause of cerebral haemorrhage after thrombolysis. As a compromise solution, JRCALC recommends that the pre-hospital dose should be restricted to 4000 units (still compatible with the words ‘not exceeding’ in the SPC even for heavier patients). Those services using reteplase may wish to use 5000 units since no dose variation for body weight is recommended.
- In preliminary discussions, the MRHA have not expressed any concern with these compromise suggestions, although formal approval for the use of the bolus agents under the POMs legislation is still awaited.