Effect of anticoagulant and antiplatelet therapy in patients with spontaneous intra-cerebral hemorrhage: Does medication use predict worse outcome?

Abstract 

Objectives

To assess the impact of anticoagulants and antiplatelet agents on the severity and outcome of spontaneous non-traumatic intra-cerebral hemorrhage (ICH). To evaluate associations between reversal of anticoagulation and mortality/morbidity in these patients.

Methods

Data was collected on a consecutive cohort of adults presenting with ICH to an academic Emergency Department over a 3-year period starting January 2006.

Results

The final cohort of 245 patients consisted of 125 females (51.1%). The median age of the cohort was 73 years [inter-quartile (IQR) range of 59–82 years]. Antiplatelet (AP) use was seen in 32.6%, 18.4% were using anticoagulant (AC) and 8.9% patients were on both drugs (AC+AP).

Patients on AC had significantly higher INR (median 2.3) and aPTT (median 31s) when compared to patients not on AP/AC (median INR 1.0, median aPTT 24s; p<0.001). Similarly patients on AC+AP also had higher INR (median 1.9) and aPTT (median 30s) when compared to those not on AC/AP (p<0.001).

Hemorrhage volumes were significantly higher for patients on AC alone (median 64.7cm³) when compared to those not on either AC/AP (median 27.2cm³; p=0.05). The same was not found for patients using AP (median volume 20.5cm³; p=0.813), or both AC+AP (median volume 27.7cm³; p=0.619). Patients on AC were 1.43 times higher at risk to have intra-ventricular extension of hemorrhage (IVE) as compared to patients not on AC/AP (95% CI 1.04–1.98; p=0.035).

There was no relationship between the use of AC/AP/AC+AP and functional outcome of patients. Patients on AC were 1.74 times more likely to die within 7 days (95% CI 1.0–3.03; p=0.05). No relationship was found between use of AP or AC+AP use and mortality.

Of the 82 patients with INR>1.0, 52 patients were given reversal (minimum INR 1.4, median 2.3). Therapy was heterogeneous, with fresh frozen plasma (FFP) being the most commonly used agent (86.5% patients, median dose 4U). Vitamin K, activated factor VIIa and platelets were the other agents used. Post reversal, INR normalized within 24h (median 1.2, IQR 1.1–1.3). There was no association between reversal and volume of hemorrhage, IVE, early mortality (death<7 days) or functional outcome.

Conclusions

Anticoagulated patients were at 1.7 times higher risk of early mortality after ICH. Reversal of INR to normal did not influence mortality or functional outcome.

Keywords: Cerebral hemorrhage, Platelet aggregation inhibitors, Anticoagulants