Warfarin-associated Intracerebral Hemorrhage is Increasing in Prevalence in the United States
Warfarin-associated intracerebral hemorrhage (WAICH) is expected to increase in prevalence as the population ages. We sought to evaluate national trends, characteristics, and in-hospital outcomes among intracerebral hemorrhage (ICH) patients taking warfarin at baseline.
We reviewed the Nationwide Inpatient Sample to identify all admissions with primary diagnosis of ICH by International Classification of Diseases, Ninth Revision code (431) from 2005 to 2008. We identified premorbid warfarin use by the V code (V58.93) and calculated the proportion of WAICH among all ICH patients in each year. We employed univariate statistics and generalized estimating equation regression models to assess whether warfarin use independently increased the risk of in-hospital mortality after adjusting for relevant covariates. P value less than .05 was considered significant.
There were 52,993 patients (mean age 68.8 years; 49.7% male) coded for ICH between 2005 and 2008. The proportion with WAICH increased each year (2005, 5.8%; 2006, 6.5%; 2007, 6.9%; 2008, 7.3%; P < .001). While in-hospital mortality declined each year for non-WAICH (29.0%-25.4%, P < .001), it remained unchanged for WAICH (42.1%-40.0%, P = .346). In multivariable analysis, warfarin use (adjusted odds ratio 1.35; 95% confidence interval 1.24-1.47) remained an independent predictor of in-hospital mortality.
WAICH is increasing in prevalence in the United States and is associated with a 35% higher mortality than non-WAICH. While mortality has declined over time for non-WAICH, mortality after WAICH is unchanged. Specific strategies to decrease the mortality of WAICH such as rapid reversal of anticoagulation are warranted.
Available from: Bernard Vigué
- "The rate of severe bleeding complications is above 3.8% per person-year and the associated mortality rate ranges between 10 to 60%, especially in case of intracranial hemorrhage (ICH), in the first week following the onset of the hemorrhage [1-4]. In case of severe hemorrhage, the two main predictors of poor prognosis are over anticoagulation, that is, an international normalized ratio (INR) above the therapeutic range, and late VKA reversal (over eight hours after presentation) [5,6]. "
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ABSTRACT: In vitamin K antagonist (VKA)-treated patients with severe hemorrhage, guidelines recommend prompt VKA reversal with prothrombin complex concentrate (PCC) and vitamin K. The aim of this observational cohort study was to evaluate the impact of guideline concordant administration of PCC and vitamin K on 7-day mortality.
Data from consecutive patients treated with PCC were prospectively collected in 44 emergency departments. Type of hemorrhage, coagulation parameters, type of treatment and 7-day mortality were recorded. Guideline-concordant administration of PCC and vitamin K (GC-PCC-K) were defined by at least 20 IU/kg factor IX equivalent PCC and at least 5 mg of vitamin K performed within a predefined time frame of 8 hours after admission. Multivariate analysis was used to assess the effect of appropriate reversal on 7-day mortality in all patients and in those with intracranial hemorrhage (ICH).
Data from 822 VKA-treated patients with severe hemorrhage were collected over 14 months. Bleeding was gastrointestinal (32%), intracranial (32%), muscular (13%), and "other" (23%). In the whole cohort, 7-day mortality was 13% and 33% in patients with ICH. GC-PCC-K was performed in 38% of all patients and 44% of ICH patients. Multivariate analysis showed a two-fold decrease in 7-day mortality in patients with GC-PCC-K (odds ratio (OR) = 2.15 (1.20 to 3.88); P = 0.011); this mortality reduction was also observed when only ICH was considered (OR = 3.23 (1.53 to 6.79); P = 0.002).
Guideline-concordant VKA reversal with PCC and vitamin K within 8 hours after admission was associated with a significant decrease in 7-day mortality.
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The aim of the study was to analyse non-warfarin-associated bleeding adverse drug events reported to the Norwegian spontaneous reporting system, with characterisation of the bleeding locations, outcome and drug interactions. In addition, concordance in assessments between reporters and evaluators, trend shifts in reporting, and detection of potentially new adverse drug interaction signals were studied.
Data on bleeding events reported between 1 January 2003 and 31 December 2005 were retrieved from the Norwegian spontaneous reporting system database.
Of 327 case reports of non-warfarin-associated bleeding events, 270 reports (82.6 %) were characterised as serious and 69 (21.1 %) had a fatal outcome. One hundred and eighty-seven bleeds (57.5 %) were gastrointestinal, 57 (17.4 %) were cerebral, and 81 (24.8 %) were from other bleeding sites. The bleeding sites differed with respect to the patient's age, drug use, diagnoses and outcomes. Of drugs associated with bleeding, nonsteroidal anti-inflammatory drugs (NSAIDs)/COX-2 inhibitors (145 reports) and acetylsalicylic acid (128 reports) were most frequently used. Only fibrinolytics were associated with increased mortality. There was a 67.4 % correlation between reporters and evaluators in assessment of drugs associated with bleeding (P < 0.001), with considerable variation in concordance between drug groups.
Non-warfarin-associated bleeding events are associated with substantial mortality. Old age, cerebral bleeds, number of drugs used, and use of fibrinolytics are all independently associated with increased mortality. The recognition of the bleeding risk of commonly used drugs such as acetylsalicylic acid and heparins may be insufficient among prescribers.
Available from: Giancarlo Castaman
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ABSTRACT: Bleeding symptoms are frequently reported even in otherwise healthy subjects, and differentiating a normal subject from a patient with a mild bleeding disorder (MBD) can be extremely challenging. The concept of bleeding rate, that is, the number of bleeding episodes occurring within a definite time, could be used as the unifying framework reconciling the bleeding risk observed in congenital and acquired coagulopathies into a single picture. For instance, primary prevention trials have shown that the incidence of non-major bleeding symptoms in normal subjects is around five per 100 person-years, and this figure is in accordance with the number of hemorrhagic symptoms reported by normal controls in observational studies on hemorrhagic disorders. The incidence of non-major bleeding in patients with MBDs (e.g. in patients with type 1 VWD carrying the C1130F mutation) is also strikingly similar with that of patients taking antiplatelet drugs, and the incidence in moderately severe bleeding disorders (e.g. type 2 VWD) parallels that of patients taking vitamin K antagonists. The severity of a bleeding disorder may therefore be explained by a bleeding rate model, which also explains several common clinical observations. Appreciation of the bleeding rate of congenital and acquired conditions and of its environmental/genetic modifiers into a single framework will possibly allow the development of better prediction tools in the coming years and represents a major scientific effort to be pursued.
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