Prediction of the probability of hemorrhagic transformation to clarify the possible timing of initiation of anticoagulant therapy in patients with ischemic stroke and atrial fibrillation

Background. Anticoagulant therapy (AT) is the main method of primary and secondary prevention of ischemic stroke (IS) in patients with atrial fibrillation (AF). However, its too early initiation after IS is associated with a high risk of hemorrhagic transformation (HT), and too late initiation - with recurrent IS and systemic embolism. In this regard, the issue of the timing of the initiation of AT in patients with IS and AF is actively discussed by leading world experts, since evidence-based facts are still missing. Objective. Prediction of hemorrhagic transformation (HT) using the Hemorrhagic Transformation Index (HTI) score to refine possible timing for anticoagulation in patients with atrial fibrillation (AF) and acute ischemic stroke (AIS) in the middle cerebral artery (MCA) territory. Methods. Clinical, laboratory, and brain imaging data were analyzed in 304 consecutive patients with any AF. The patients were randomized into derivation (DC) and validation (VC) cohorts. To make the HTI more convenient for a refinement of anticoagulation timing, its initial scores were grouped into fewer categories. As a result, 4 models were created which were tested in the DC by comparing against each other and the current standard, the Diener's rule, using binary logistic regression (BLR) and receiver operating characteristic (ROC) analysis. After choosing the final model, the same set of tests was done in the VC. Possible timing for anticoagulation was matched between the Diener's rule and the final model using predicted HT probabilities. As an illustration of the results, a clinical case was described. Results. The most optimal predictive ability was determined in the HTI model with the score arrangement as follows: 0-1, 2-3, 4-5, 6-8. The results of BLR and ROC-analysis were equal in the DC and VC; thus, the HTI reliability was validated. Moreover, the HTI score could distinguish a group of patients who were at very high risk of HT. The low-risk patients (HT probability of <50%; the HTI score of 0-1 or 2-3) could be advised to start anticoagulation from the day 3 to 6 after the AIS onset, and the high-risk group (HTprobability of 50-80%; the HTI score of 4-5) - in 12 days. Conclusions. The Diener's rule and the HTI score are compatible tools for HT prediction in MCA AIS patients within 2 weeks after the index stroke onset. Further researches are needed in patients who are at very high risk of HT (HT probability of >80%, the HTI score of 6-8) to refine their timing for anticoagulation.

ischemic stroke, atrial fibrillation, anticoagulant, hemorrhagic transformation