Cerebral Microbleeds as Biomarker for Hemorrhage Risk in Anticoagulated AFib

MRI hypertensive microbleeds
MRI hypertensive microbleeds
Investigators assessed the presence of cerebral microbleeds as a biomarker for identifying patients at increased risk for intracranial hemorrhage as a result of anticoagulation for atrial fibrillation.

The presence of cerebral microbleeds may predict the risk of symptomatic intracranial hemorrhage in patients with atrial fibrillation who have received anticoagulation therapy following an ischemic stroke or transient ischemic attack (TIA). Additionally, a combined prediction model consisting of the HAS-BLED [hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drug/alcohol use] clinical bleeding risk score, presence of cerebral microbleeds, anticoagulant type, and diabetes status can also predict symptomatic intracranial hemorrhage risk in these patients.  These results were reported in an observational study published in Lancet Neurology,

Researchers enrolled hospitalized adult patients with atrial fibrillation who had received a vitamin K antagonist or direct oral anticoagulant following an ischemic stroke or TIA (N=1490). Patients were followed for ≤24 months, with follow-up data obtained via general practitioner and patient postal questionnaires, hospital visits, telephone interviews, and National Health Service digital data on hospital admissions or mortality.

The primary outcome was identified as the occurrence of a symptomatic intracranial hemorrhage prior to the final 24-month follow-up. The investigators compared patients with cerebral microbleeds (n=311) vs those without (n=1179) in terms of the rates of intracranial hemorrhage.

The majority of study participants took a vitamin K antagonist vs a direct oral anticoagulant (62% vs 37%, respectively). Among the enrolled patients who had follow-up data available (n=1447), the rates of symptomatic intracranial hemorrhage were 9.8 per 1000 patient-years (95% CI, 4.0-20.3) vs 2.6 per 1000 patient-years (95% CI, 1.1-5.4) in patients with vs without cerebral microbleeds, respectively (adjusted hazard ratio 3.67; 95% CI, 1.27-10.60).

Prediction models that incorporated the HAS-BLED clinical bleeding risk score and the presence of cerebral microbleeds (C-index 0.66; 95% CI, 0.53-0.80) as well as models using cerebral microbleeds, diabetes status, the type of anticoagulant used, and the HAS-BLED score (C-index 0.74; 95% CI, 0.60-0.88) provided significantly greater prediction value for the primary outcome than use of the HAS-BLED score alone (C-index 0.66; 95% CI, 0.53-0.80) (difference in C-index 0.25; 95% CI, 0.07-0.43, P =.0065 and 0.33; 95% CI, 0.14-0.51, P =.00059, respectively).

Related Articles

The findings from the study may hold limited generalizability across centers that primarily use direct oral anticoagulants, considering most of the study participants were administered vitamin K antagonists.

Overall, the researchers believe their findings may ultimately improve “the predictive ability of clinical risk scores for intracranial haemorrhage — a potentially deadly complication of oral anticoagulation — which could help clinicians and patients to make better informed anticoagulation decisions.”


Wilson D, Ambler G, Shakeshaft C, et al; on behalf of the CROMIS-2 collaborators. Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2): a multicentre observational cohort study. Lancet Neurol. 2018;17(6):539-547.