Purpose: Intracerebral hemorrhage (ICH) accounts for a majority of long-term morbidity and mortality associated with bleeding on warfarin. Both ICH and warfarin-related ICH appear to have a strong genetic component. Furthermore, advanced neuroimaging using MRI can now identify individuals at increased risk of ICH. We explore whether screening strategies that include genetic profiling and neuroimaging might improve the safety of chronic anticoagulation for atrial fibrillation.

Methods: We used a Markov state transition decision model. Effectiveness was measured in quality-adjusted life years (QALYs). Data sources included the English language literature using MEDLINE searches and bibliographies from selected articles, along with empirical data from our institution. The base case focused on a 69 year-old man with newly diagnosed non-valvular atrial fibrillation.

Results: For patients at average risk for thromboembolic events and known to possess a hypothetical warfarin-ICH genetic profile, anticoagulation would remain the preferred strategy until the relative hazard of ICH exceeded 23.8. For patients at low risk of thromboembolism (1.5% per year) or at higher risk of ICH (0.11% per year, as in older patients) genetic profiling would be favored if the relative hazard of ICH in patients with a positive genetic profile were greater than 4.1 and 6.6, respectively. Screening strategies involving both genetic profiling and MRI (treat with aspirin or withhold anticoagulant therapy if both are positive) were almost as effective as anticoagulation without screening. Furthermore, using more optimistic estimates for the predictive power of MRI gradient-echo (e.g., relative hazard of 12.8), screening for both genetic and neuroimaging risk markers is preferred for patients at low to moderate risk of thromboembolism (1% to 6.1% per year).

Conclusion: Current genetic markers of increased bleeding risk such as Apo Є2 and Є4 do not predict a significantly enough increased risk of ICH to warrant routine genetic testing for patients at average risk of thromboembolism. The addition of MRI to screening makes this a more compelling option, but the gain is still small given technology available today. However, given the explosion in our understanding of the relationship between common genetic variation and complex diseases such as ICH, as well as the likelihood of advances in sophisticated neuroimaging it is likely that complex screening strategies that combine genetic profiling and neuroimaging will warrant further consideration in the future.