Increased risk of ischaemic stroke while initiating warfarin in patients with atrial fi brillation
A recent article revealed an increased risk of ischaemic stroke while initiating warfarin.1 We recently saw two such patients in their late seventies who suffered ischaemic strokes 4 and 5 days after initiation of warfarin. Their international normalised ratios (INRs) at the time of the stroke were 1.7 and 1.5 respectively, CT scans of the head were normal, neither received thrombolysis and there was no evidence of thrombus on their transthoracic echocardiograms.
During initiation of warfarin, there is a transient hypercoagulable state which could potentially increase the risk of ischaemic events. Until recently the risk was thought to be just theoretical. However a recent case control study showed an increased risk of stroke in the first 30 days of warfarin use (relative risk 1.71, 95% confidence interval 1.39–2.12) with the highest risk in the first seven days.1 Also an increased risk of ischaemic stroke was seen in the two novel anticoagulant trials when patients were switched back to warfarin at the end of the study.2,3
The hypercoagulable state is due to earlier depletion of vitamin-K-dependent anticoagulant factors (proteins C and S) due to their shorter half-lives compared with the vitamin-K-dependant clotting factors II, VII, IX and X. The half-life of inactivated protein C is 6.5 hours compared with 60–72 hours of factor II.4,5 It is well known that individuals with protein C deficiency may suffer widespread thrombosis indicating that protein C is an important anticoagulant and regulator of the natural coagulation pathway.
Bridging therapy with heparin has always been part of clinical practice while initiating warfarin in venous and pulmonary thromboembolism. However there is no evidence for such practice in atrial fibrillation. It is debatable to suggest a change in practice based on few cases and retrospective study. However one should consider bridging therapy with heparin in high-risk patients, or the use of novel anticoagulants.
- © 2015 Royal College of Physicians
References
- 1 .↵
- Azoulay L
- 2 .↵
- 3 .↵
- Granger CB
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- 5 .↵
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