Determinants of intracranial hemorrhage incidence in patients on oral anticoagulation followed at the Lahey clinic.

Oral anticoagulation with warfarin is widely used to treat venous and arterial thromboembolic disease (Ansell et al. Chest 133(6 suppl):160S-198S, 2008). Its administration is associated with a risk of intracranial hemorrhage (ICH), a devastating complication which usually results in death or severe disability (Fang et al. Am J Med,120(8):700-705, 2007; Rosand et al. Arch Intern Med, 164(8):880-884, 2004). The international normalized ratio (INR) is one of the factors which can help determine the risk of ICH in a given individual (Singer et al. Circ Cardiovasc Qual Outcomes, 2(4):297-304, 2009). Using the DoseResponse(®) patient database at our institution, we carried a retrospective nested matched case-control study to identify patient characteristics associated with the occurrence of ICH. The database was queried for the years 2004-2009. Each case was matched by month to four control patients having a routine INR determination for the monitoring of chronic anticoagulation. The following characteristics were captured: bleeding type, INR, age, sex, blood pressure, hemoglobin, creatinine, presence or history of pertinent comorbid conditions, intake of antiplatelet agents (aspirin or thienopyridine) and indication for anticoagulation. The relationship between those risk factors and the odds ratio of ICH was determined with conditional logistic regression. Fifty cases of ICH were retrieved. When correcting for pertinent variables, the odds ratio of ICH increased significantly for higher INR values, with a quadratic relationship noted in the model. Increasing mean blood pressure seemed to be associated with a higher risk of ICH, also in an exponential manner. Rising hemoglobin values on the other hand seemed to have a protective effect against such events. About 50% of cases of ICH occurred in or below the therapeutic INR range. The intake of antiplatelet agent was found to be associated with ICH in univariate analysis only. The INR is an important predictor for the incidence of ICH, but in this study an elevated measurement was found in only half of cases. Mean blood pressure appears to be another important determinant of the risk of ICH in the anticoagulated patient population.