Patients who present with central nervous system (CNS) hemorrhage while on anticoagulation (AC) for thromboembolic (TE) risk factors are a challenge to manage.

We sought to inform decisions surrounding the timing and intensity of AC resumption by performing a systematic review.

Three reviewers screened publications from Medline and EMBASE and extracted data. Hemorrhagic and TE adverse events that occurred subsequent to the index hemorrhage were recorded, as was their timing relative to presentation and covariates that might influence their occurrence.

Data were extracted from 63 publications detailing 492 patients; 7.7% of patients experienced hemorrhagic complications and 6.1% experienced TE complications. Hemorrhagic complications were more common within 72 h of presentation while TE complications were more common thereafter. Patients restarted on AC after 72 h were significantly more likely to have a TE complication (P = 0.006) and those restarted before 72 h were more likely to hemorrhage (P = 0.0727). Factors associated with re-hemorrhage included younger age, traumatic cause, subdural hematomas and failure to reverse AC. TE complications were more common in younger patients and those with spinal hemorrhage, multiple hemorrhages, and non-traumatic causes of the index hemorrhage. Re-initiation of AC at a lower intensity also significantly increased the risk of TE complications.

Our results suggest that it may be prudent to re-initiate AC earlier than previously thought, with the timing and intensity modified based on predictors of TE and hemorrhagic complications. These findings must be explored in a prospective study because of limitations inherent to the analyzed studies.