Rizwan Kalani, MD

Akoudad S, Darweesh SKL, Leening MJG, Koudstaal PJ, Hofman A, van der Lugt A, et al. Use of Coumarin Anticoagulants and Cerebral Microbleeds in the General Population. Stroke. 2014

The worst complication of anticoagulation use is intracerebral macro-hemorrhage. In this study, Akoudad et al evaluated the effect of coumarins on microbleeds (MB) from a large, prospective, population-based cohort study (Rotterdam Study).

Evaluating data on 4945 subjects with a baseline brain MRI (with T2*-GRE sequences) and 3069 with follow-up MRI’s, the prevalence and incidence of MB was compared between those on coumarin vs those who were never exposed to it. After adjusting for age, sex, and vascular risk factors, the association between coumarin use and MB’s was evaluated. The authors also looked at the relationship between maximum INR as well as its variability with MB presence.

8.6% of participants (427/4945) had used coumarin anticoagulants (at some time) prior to the first MRI and 19.4% (957) had ≧1 MB present. 5.9% (181/3069) of those with follow-up MRI’s had used them at some point prior to the second scan. The cumulative incidence was 6.9% over an average follow-up period of approximately 4 years. Anticoagulated subjects had a higher prevalence of deep or infratentorial MB (with or without lobar MB) compared to those who had never been exposed (OR 1.70, 95% CI 1.24-2.34). A trend toward increased risk of developing new MB was found in those using coumarin vs those who never had, but this was not statistically significant (OR 1.44, 95% CI 0.89-2.32). Results were similar even after excluding those who used other antithrombotics and those with infarcts on MRI. Deep/Infratentorial MB were more frequent in those with higher maximal INR compared to never-users. Amongst those using coumarin, higher INR variability was associated with deep/infratentorial MB.

This study is unique as it comes from a large cohort study involving a population from the suburbs of Rotterdam, making it more generalizable. Notable limitations from this observational study include – 1) some MB could have been present prior to anticoagulant use and; 2) participants more likely to be on coumarin were the same as those with increased risk of MB (i.e. those with vascular risk factors). Furthermore, as noted by the authors, results may not apply for novel oral anticoagulants (NOACs).

Future studies will have to evaluate the safety of anticoagulation over time in distinct cohorts that are separated by age, blood pressure control, APOe genotype, and suspected MB pathology (hypertensive, amyloid angiopathy). The effect of NOACs on MB will also need to be investigated.

Nevertheless, this study reaffirms the fact that we should be vigilant about blood pressure control and INR monitoring in patients on coumarin anticoagulants.