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

Abstract

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.

Bleeding risk in warfarinized patients with a therapeutic international normalized ratio: the effect of low factor IX levels

“…Thus, our results strongly suggest that the appropriate target INR level might not be the same for all patients. Those with FIX levels that are significantly lower than the mean of the population might need more careful follow‐up or they might be better managed by selecting a target INR that is based on their level of thrombin generation . We envision that this could be accomplished by running a thrombin generation assay on any patient who suffers an adverse event, either bleeding or thrombosis, while on therapy.…”

SYT‐SSX breakpoint peptide vaccines in patients with synovial sarcoma: A study from the Japanese Musculoskeletal Oncology Group

“…Intracranial hemorrhage is a known complication of anticoagulant therapy, with an estimated annual incidence in the US of nearly 3000 . In addition, approximately half the cases of anticoagulant‐associated intracranial hemorrhage occurred within or below the INR therapeutic range (2.0–3.0) . It is therefore more likely that the intracranial hemorrhage in Patient 16 was associated with anticoagulants rather than the peptide vaccine or IFN.…”

Genetic Risk Factors for Major Bleeding in Patients Treated With Warfarin in a Community Setting

“…We also conducted post hoc validation and exploratory analyses to assess the associations between clinical and demographic covariates and major bleeding; genetic variant associations stratified by warfarin treatment duration; and self‐reported leafy green vegetable intake level and variability associations stratified by genetic status 31 , 32 , 42 , 43 , 44 , 45 . We report all post hoc analyses as univariate associations and intend them for validation and exploratory purposes only.…”