Reversal of antiplatelet therapy in traumatic intracranial hemorrhage: Does timing matter?

Highlights

• Platelet transfusion timing does not worsen TICH in patients on preinjury APT.

• SDH may worsen TICH in patients on preinjury APT.

• Lower admission GCS may worsen TICH in patients on preinjury APT.

Abstract

Reversal of antiplatelet therapy with platelet transfusion in traumatic intracranial hemorrhage remains controversial. Several studies have examined this topic but few have investigated whether the timing of transfusion affects outcomes. Patients admitted to a level 1 trauma center from 1/1/14 to 3/31/16 with traumatic intracranial hemorrhage taking pre-injury antiplatelet therapy were retrospectively analyzed. Patients on concurrent pre-injury anticoagulant therapy were excluded. Per institutional guideline, patients on pre-injury clopidogrel received 2 doses of platelets while patients on pre-injury aspirin received 1 dose of platelets. Patients with worsening hemorrhage defined by an increase in the Rotterdam score on follow up CT were compared to those without worsening. Mortality, need for neurosurgical intervention, and timing of platelet transfusion were analyzed. A total of 243 patients were included with 23 (9.5%) having worsening hemorrhage. Patients with worsening hematoma had higher injury severity score, head abbreviated injury scale, incidence of subdural hematoma, mortality, and lower Glasgow coma scale. There was no significant difference in the number of minutes to platelet transfusion between groups. After logistic regression analysis the presence of subdural hematoma and lower admission Glasgow coma scale were predictors of worsening hematoma, while there remained no significant difference in minutes to platelet transfusion. The timing of platelet transfusion did not have any impact on rates of worsening hematoma for patients with traumatic intracranial hemorrhage on pre-injury antiplatelet therapy. Potential risk factors for worsening hematoma in this group are the presence of subdural hematoma and lower admission Glasgow coma scale.

Introduction

Antiplatelet therapy (APT) for the management of cardiovascular disease, peripheral vascular disease and stroke is increasingly prevalent in an ever aging U.S. population [1], [2]. Aspirin works by irreversibly acetylating platelet cyclooxygenase thereby inhibiting the formation of prostaglandin and subsequent platelet aggregation, while clopidogrel blocks the ADP P2Y12 receptor, thereby inhibiting aggregation through a different pathway [3]. The routine use of APT has shown a reduction in non-fatal myocardial infarction (–32%), non-fatal stroke (−25%) and cardiovascular death (−17%) [4]. While use of APT has shown benefit in cardiovascular disease, it is also known to increase the risk of bleeding complications [5].

Previous investigations have demonstrated that the use of antiplatelet agents is associated with higher mortality in patients with traumatic intracranial hemorrhage [6], [7], [8], [9], [10], [11]. For this reason, many trauma centers around the country have instituted standardized platelet transfusion protocols for patients on pre injury APT that sustain traumatic intracranial hemorrhage (TICH) [12].

Hemorrhage expansion has been shown to be associated with increased mortality [13], [14], [15], [16], [17], [18]. It remains unclear which factors most contribute to the risk of hemorrhage expansion in patients on APT. Previous investigations have been unable to demonstrate a benefit to platelet transfusion in this patient population [2], [19], [20], [21], [22], [23]. These investigations, however, have all suffered from suboptimal methodologies and none have examined the effect of the timing of transfusion on patient outcomes. As a significant proportion of TICH expansion occurs within the first few hours after injury [13], [14], [15], [18], it stands to reason that the effect of platelet transfusion may be time sensitive with earlier transfusion being of greater benefit. Hence, the purpose of this study was to determine whether the timing of platelet transfusion affects the rate of worsening TICH. Secondary outcomes of interest were in hospital mortality and the need for neurosurgical intervention. In addition, we sought to better define what clinical and radiologic characteristics are risk factors for worsening TICH in patients on pre injury APT.