Warfarin-associated intracerebral hemorrhage: Volume, anticoagulation intensity and location
Introduction
Warfarin-associated ICH is a major clinical problem, more common than subarachnoid hemorrhage in the United States [1]. The use of warfarin to prevent atrial fibrillation-related stroke is increasing with aging populations and better recognition [2], [3], [4]. Oral anticoagulant therapy (OAT) not only increases the risk of intracerebral hemorrhage (ICH) [5], but also worsens the severity of ICH in a dose-dependent manner [6]. The underlying mechanism by which warfarin worsens ICH prognosis has not been well established.
Larger baseline hematoma volume and infratentorial location are two major determinants of poor outcome in spontaneous ICH [7], [8]. Given that the risk of ICH increases significantly with increasing international normalized ratio (INR) in patients taking warfarin [9], it is possible that intense anticoagulation may affect the size of ICH. However, previous studies have reported conflicting results on the effect of warfarin on hematoma volume [10], [11], [12], [13]. In addition, the correlation of anticoagulant therapy and hematoma location is controversial [14], [15], [16], [17]. Some studies have suggested a higher proportion of lobar and thalamic location [10], [17], but others reported a higher rate of cerebellar hemorrhage [14], [15], [16]. It follows that the relationship of OAT with hematoma volume and location remains unresolved.
The aim of the present study was to investigate in ICH patients whether higher INR values are associated with larger baseline hematoma volumes, and to determine the relationship between warfarin therapy and hematoma location.
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Study population
The study protocol was approved by the human research ethics committee of the Royal Melbourne Hospital. We identified all subjects aged ≥ 18 years who were hospitalized with ICH between October 1, 2007 and January 31, 2012 at this hospital. All potential cases were extracted from our prospective stroke database. Exclusion criteria were traumatic ICH, hemorrhagic transformation of cerebral infarction, ICH secondary to vascular malformation, aneurysm, vasculitis of the central nervous system, and
Results
There were 553 ICH patients treated at our hospital from October 1, 2007 to January 31, 2012. Of these, 28 were excluded due to secondary ICH, 12 due to primary IVH, 68 due to unavailable baseline CT scans or CT films unfit for computerized image analysis, and 47 due to missing initial INR values, leaving a study population of 404. Baseline characteristics of the study patients are described in Table 1.
The median age of the cohort was 74 years (interquartile range [IQR] 63 to 81), 58.9% of
Discussion
Patients with warfarin-related ICH have worse outcomes, chiefly attributed to larger hematoma volumes. In this study, we have also found a relationship between warfarin-associated ICH and infratentorial location, which may contribute to the worse prognosis in this group.
ICH is the most feared and lethal complication of warfarin therapy. It accounts for approximately 90% of the deaths from warfarin-associated intra- and extracranial hemorrhages and the majority of major functional disability
Conclusions
The results from the present study confirmed that warfarin caused larger volume hemorrhages and in addition, showed a disproportionate number of hemorrhages with infratentorial location. This may be another important determinant of the worse outcome in this population.
Sources of funding
This work was supported by the NHMRC Centre for Research Excellence Grant (1001216).
Conflict of interest statement
None.
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