Antiplatelet therapy and the outcome of subjects with intracranial injury: the Italian SIMEU study

Abstract

IntroductionPre-injury antithrombotic therapy might influence the outcome of subjects with head injuries and positive computed tomography (CT) scans. We aimed to determine the potential risk of pre-injury antiplatelet drug use on short- and long-term outcome of head injured subjects admitted to emergency departments (EDs) in Italy for extended observation.MethodsA total of 1,558 adult subjects with mild, moderate and severe head injury admitted to Italian EDs were studied. In multivariable logistic regression analyses, the short-term outcome was assessed by an evaluation of head CT scan at 6 to 24 hours after trauma and the long-term outcome by the Glasgow outcome scale (GOS) at six months.ResultsHead CT scan comparisons showed that 201 subjects (12.9%) worsened. The risk of worsening was increased two fold by the use of antiplatelet drugs (106, 19.7% treated versus 95, 9.3% untreated; relative risk (RR) 2.09, 95% CI 1.63 to 2.71). The risk was particularly high in subjects on clopidogrel (RR 5.76, 95% CI 3.88 to 8.54), independent of the association with aspirin. By logistic regression, 5 of 14 items were independently associated with worsening (Glasgow coma scale (GCS), Marshall category, antiplatelet therapy, intraventricular hemorrhage, number of lesions). After six months, only 4 of 14 items were predictors of unfavorable outcome (GOS 1 to 3) (GCS score, Marshall category, age in decades, intracerebral hemorrhage/contusion). The risk increased by 50% in the group treated with antiplatelet therapy (RR 1.58, 95% CI 1.28 to 1.95; P < 0.001).ConclusionsAntithrombotic therapy (in particular clopidogrel) is a risk factor for both short-term and long-term unfavorable outcome in subjects with head injury, increasing the risk of progression and death, permanent vegetative state and severe disability.

High prevalence of pharmacologically induced platelet dysfunction in the acute setting of brain injury

“…The use of antithrombotic agents leading to subsequent impairment of the hemostatic system in patients suffering from TBI, pICH and pSAH is known to be one of the most relevant risk factors for early neurological deterioration, hematoma growth, need for neurosurgical intervention, unfavorable neurological outcome and increased mortality [11,12,15,17,19,25]. Although in univariable analysis a pathological Multiplate result was associated with unfavorable outcome, this association did not persist when multivariable analysis was performed.…”

“…In addition, over the last decades TBI has increasingly been recognized not only as the leading cause of mortality among patients under 45 years of age, but also as a growing disease in the aging population of industrialized countries, underscoring the immense socioeconomic impact of acute brain injury. While of course antiplatelet medication significantly reduces ischemic cardiovascular and cerebrovascular events [21], an impaired platelet function in the case of intracranial trauma and/or acute bleeding has been shown to significantly increase the risk for hematoma progression with subsequent neurological deterioration and increased mortality rates [11,17,19,26]. Thus, it has been suggested that clinicians should always consider and be aware of this increased risk profile when treating respective patients [4].…”

“…While of course antiplatelet medication significantly reduces Vincent Prinz and Tobias Finger contributed equally to this work. ischemic cardiovascular as well as cerebrovascular events [21], compromised platelet function in the case of intracranial trauma and bleeding has been demonstrated to significantly increase the risk for hematoma progression with subsequent neurological deterioration and increased mortality rates [11,26]. Moreover, if emergency neurosurgical procedures have to be performed, these patients are further exposed to an additional risk due to impaired platelet function.…”

“…In patients suffering from TBI or ICH, the use of antithrombotic agents as well as subsequent impairment of the hemostatic system is known to be one of the most relevant risk factors for early neurological deterioration, unfavorable neurological outcome and increased mortality [11,12,15,25]. However, in particular patients suffering from acute brain injury are often found with a reduced level of consciousness.…”

Point of care coagulation testing in neurosurgery

“…Antiplatelet medication was identified as the most important risk factor for re-bleeding after neurosurgical procedures [49] and it is associated with an increased risk of morbidity and mortality after TBI and spontaneous intracranial haemorrhage [50,51]. The degree of platelet inhibition through intake of antiplatelet medication varies considerably among individuals and depends on several factors such as genetic profile and patient compliance.…”