Frågedatum: 2005-08-31
RELIS database 2005; id.nr. 22000, DRUGLINE
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How soon can warfarin be started after thrombolytic treatment of embolic stroke with alteplase (Act



Fråga: How soon can warfarin be started after thrombolytic treatment of embolic stroke with alteplase (Actilyse)?

Sammanfattning: Alteplase has a short pharmacokinetic half-life and also a relatively short duration of effect. It has a different mechanism of action than warfarin, which also has a slow onset of effect. Therefore it should be possible to start warfarin when it is reasonably certain that no hemorrhagic complication of thrombolysis has occured.

Svar: Alteplase is recombinant human tissue plasminogen activator (rtPA). It has a half-life of 3-11 minutes in alpha-phase. The concentration is less than 10% of Cmax after after 20 minutes. The terminal half-life is 30-40 minutes. Its mechanism of action is to cleave plasminogen to plasmin, which degrades fibrin. By binding to fibrin, which also binds plasminogen, the affinity between rtPA and plasminogen can be enhanced. Twenty-four hours after alteplase plasminogen, plasmin, fibrin and fibrinogen have returned to 80% of normal (1,2).

Warfarin acts as a vitamin-K antagonist and primarily inhibits the formation of coagulation factor II, VII, IX and X. The half-lives of these factors are 4-50 hours (shortest for factor VII and longest for factor II). Thus anticoagulative effect is reached after 3-5 days of therapy (1,3).

There are no controlled studies on the interaction between thrombolytics and anticoagulants. In patients on warfarin, there is an increased risk of bleeding complications after thrombolysis for myocardial infarction (3). However, there are case-reports of intraarterial thrombolysis after cerebral infarction in patients on warfarin with an INR of 1,7-2,0 (4).

Most studies where thrombolysis has been followed by oral anticoagulants seem to have started the anticoagulant within 0-48 hours after thrombolysis (5,6,7,8). Most of these studies are after myocardial infarction (6,7,8), but one is after deep venous thrombosis (5). We have not found any study where thrombolysis has been followed by oral anticoagulants in cerebrovascular disease.

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