Warfarin-related Intracerebral Hemorrhage Research Articles

Clinical outcomes after 4F-PCC for warfarin-associated ICH and baseline GCS less than or equal to 8

PurposeThere is limited evidence describing the mortality benefit of utilizing 4-factor prothrombin complex concentrate (4F-PCC) in patients presenting with a warfarin-associated intracerebral hemorrhage (ICH) and a Glasgow Coma Scale (GCS) of ≤8. The aim of this study is to determine the potential mortality benefit of 4F-PCC in this patient population. MethodsThis was a retrospective chart review, performed at a comprehensive stroke center from October 2013 through August 2020. Patients were included if they were ≥ 18 years of age, experienced a spontaneous ICH with baseline GCS ≤ 8, treated with warfarin prior to admission, had a baseline INR ≥ 1.7, and received 4F-PCC for INR normalization due to warfarin-associated ICH. The primary outcome was in-hospital mortality at 30 days. ResultsA total of 252 patients received 4F-PCC in the specified time period. Of those patients, 25 patients met inclusion criteria. Sixteen patients (64%) experienced in-hospital mortality. When compared to a historical estimated 80% mortality rate in the studied patient population, there was no statistically significant difference (p = 0.208) in mortality when 4F-PCC was utilized to reverse INR. ConclusionThe administration of 4F-PCC in patients presenting with warfarin-related ICH and GCS ≤ 8 did not result in statistically significant mortality benefit. Our results are limited by study design and sample size. Thus, larger studies are needed to determine if a benefit exists for 4F-PCC in this patient population. Although the results are not statistically significant, our small study suggests that there may be a clinically significant mortality benefit when 4F-PCC is utilized.

Time in therapeutic range of anticoagulation among patients with atrial fibrillation and cerebral amyloid angiopathy

Atrial fibrillation (AF) and cerebral amyloid angiopathy (CAA) present risks of ischemic stroke and intracerebral hemorrhage (ICH). Vitamin K antagonist use is associated with fluctuations in international normalized ratio (INR), which predispose to a higher bleeding risk. Patients with a diagnosis of AF and ICH while on a vitamin K antagonist were identified using the Rochester Epidemiology Project. Sixty patients were identified (mean age 81.3 years; 24 men). Thirty-three (55%) exhibited characteristics consistent with possible (n = 25) or probable (n = 8) CAA. Mean time in therapeutic range in the 30 days preceding ICH was 55.4%, with no difference between CAA and non-CAA patients. Mean time spent above therapeutic range (INR > 3.0) was 17.7%, with no difference between CAA and non-CAA patients. Following ICH, 21 (35%) died within 30 days, with total mortality at 76.7% after 176.4 person-years of follow-up (mean 2.9 years). Time in therapeutic range in the 30 days prior to ICH had no significant impact on 7-day mortality, nor risk of recurrent ICH or ischemic stroke. Patients with warfarin-related ICH were often outside of the therapeutic range within the month preceding hemorrhage but more frequently were subtherapeutic. Even with careful avoidance of supratherapeutic INR, vitamin K antagonist use in CAA patients is unlikely to have a major effect in preventing ICH and must be used with caution.

Clinical Characteristics and Outcomes Associated With Oral Anticoagulant Use Among Patients Hospitalized With Intracerebral Hemorrhage

Although the use of factor Xa (FXa) inhibitors has increased substantially over the past decade, there are limited data on characteristics and outcomes of FXa inhibitor-associated intracerebral hemorrhage (ICH). To investigate the association between prior oral anticoagulant use (FXa inhibitors, warfarin, or none) and in-hospital outcomes among patients with nontraumatic ICH. This is a cohort study of 219 701 patients with nontraumatic ICH admitted to 1870 hospitals in the Get With The Guidelines-Stroke registry between October 2013 and May 2018. Data analysis was performed in December 2019. Anticoagulation therapy before ICH. The primary outcome was in-hospital mortality. Secondary outcomes were a composite measure of in-hospital mortality or discharge to hospice, discharge home, independent ambulation, and modified Rankin Scale (mRS) score at discharge. Of 219 701 patients (mean [SD] age, 68.2 [15.3] years; 104 940 women [47.8%]), 9202 (4.2%) were taking FXa inhibitors, 21 430 (9.8%) were taking warfarin, and 189 069 (86.0%) were not taking any oral anticoagulant before ICH. Patients taking FXa inhibitors or warfarin were older and had higher prevalence of cardiovascular risk factors. Compared with those not taking an oral anticoagulant (42 660 of 189 069 patients [22.6%]), the in-hospital mortality risk was higher for both FXa inhibitors (2487 of 9202 patients [27.0%]; adjusted odds ratio [aOR], 1.27; 95% CI, 1.20-1.34; P < .001) and warfarin (7032 of 21 430 patients [32.8%]; aOR, 1.67; 95% CI, 1.60-1.74; P < .001). Both FXa inhibitors (3478 of 9202 patients [37.8%]; aOR, 1.19; 95% CI, 1.13-1.26; P < .001) and warfarin (9151 of 21 430 patients [42.7%]; aOR, 1.50; 95% CI, 1.44-1.56; P < .001) were associated with higher odds of death or discharge to hospice compared with not taking oral anticoagulation (58 022 of 189 069 patients [30.7%]). Although the rates of discharge home, independent ambulation, mRS scores of 0 or 1, and mRS scores of 0 to 2 were numerically lower among patients taking FXa inhibitors, these differences were not significant compared with patients not taking oral anticoagulants. In contrast, patients taking FXa inhibitors were less likely to die (aOR, 0.76; 95% CI, 0.72-0.81; P < .001) or to experience death or discharge to hospice (aOR, 0.79; 95% CI, 0.75-0.84; P < .001), more likely to be discharged home (aOR, 1.18; 95% CI, 1.10-1.26; P < .001), and had better mRS scores at discharge (eg, mRS scores of 0-1: aOR, 1.24; 95% CI, 1.09-1.40; P < .001) than those treated with warfarin. Concomitant warfarin and antiplatelet therapy (either single or dual) was associated with worse outcomes compared with taking warfarin alone (eg, in-hospital mortality for dual-antiplatelet agents: aOR, 2.07; 95% CI, 1.72-2.50; P < .001). However, such incremental risk was not significant in patients taking FXa inhibitors. In this cohort study, FXa inhibitor-associated ICH was associated with higher risk of mortality or death or discharge to hospice than not taking an oral anticoagulant, but patients taking FXa inhibitors had better outcomes than those with warfarin-related ICH.

Abstract WP418: Characteristic of Intracerebral Hemorrhage Related to Direct Oral Anticoagulant versus Warfarin: Results From the PASTA Registry

Background and Purpose: The characteristics of direct oral anticoagulant (DOAC)-related intracerebral hemorrhage (ICH) have not been fully clarified. We planned to recruit patients prospectively and to investigate the characteristics and outcomes in patients with ICH receiving direct oral anticoagulant (DOAC) and warfarin treatment. Methods: The prospective analysis of stroke patients taking anticoagulants (PASTA) registry study is an observational, multicenter, prospective registry of stroke patients receiving OAC. Patient enrollment started in April 2016 at 25 tertiary centers across Japan. We compared imaging, clinical characteristics, and discharge modified Rankin Scale (mRS) between DOAC- and warfarin-related ICH patients with atrial fibrillation (AF). Results: A total of 154 patients (51 women; median age 77 [quartiles 69-87] years) were analyzed. Of these, 111 patients (72%) received prior DOAC treatment and the remaining 43 (28%) received prior warfarin treatment (Fig. A, B and C). There were no relevant differences in clinical and hematoma characteristics between DOAC- and warfarin-related ICH regarding baseline hematoma volume (median [quartiles]: DOAC, 11 [5-23] mL vs. warfarin, 12 [5-30] mL; P =0.95), rate of hematoma expansion (DOAC, 12/111 [11%] vs. warfarin, 4/43 [9%]; P =0.80), rate of subcortical hemorrhage (DOAC, 15/111 [11%] vs. warfarin, 10/43 [9%]; P =0.80) and the proportion of patients with unfavorable outcome (mRS, 4-6: DOAC 76/108 [70%] vs. warfarin 23/38 [61%]; P =0.26). Cerebral microbleeds (CMBs) were detected more frequently in DOAC group than in warfarin (47/76 [62%] vs. 11/32 [34%]; P &lt;0.01). Subgroup analyses showed that type of DOAC agent did not result in relevant differences in imaging characteristics or outcome (Fig. D and E). Conclusions: Our results showed that there were no significant differences in hematoma characteristics and functional outcome among AF patients with DOAC- or warfarin-related ICH.

Characteristics of Acute Spontaneous Intracerebral Hemorrhage in Patients Receiving Oral Anticoagulants

ObjectiveWe investigated the precise clinical and radiologic characteristics of intracerebral hemorrhage associated with direct oral anticoagulant use. MethodsPatients with acute spontaneous intracerebral hemorrhage admitted to our department from September 2014 to November 2017 were retrospectively analyzed. Clinical and neuroradiological characteristics of patients with direct oral anticoagulant-related intracerebral hemorrhage, and effects of prior treatment on the severity at admission and on outcome at discharge were assessed. ResultsOf the 301 enrolled patients (103 women; median age 68 years), 261 received no oral anticoagulants (86.8%), 20 received warfarin (6.6%), and 20 received direct oral anticoagulants (DOACs) (6.6%). Median initial National Institutes of Health Stroke Scale scores differed significantly among the groups (P = .0283). Systolic blood pressure (P = .0031) and estimated glomerular filtration rate (P = .0019) were significantly lower in the oral anticoagulant-related intracerebral hemorrhage group than in other groups. Total small vessel disease scores were significantly higher in the oral anticoagulant-related intracerebral hemorrhage group than in the warfarin group (P = .0413). Multivariate analysis revealed that prior oral anticoagulant treatment (odds ratio: 0.21, 95% confidence interval: 0.05-0.96, P = .0445) was independently negatively associated with moderate-to-severe neurological severity (stroke scale score ≥10) after adjusting for intracerebral hemorrhage location and various risk factors. There were significant differences in hematoma volume in the basal ganglia (P = .0366). ConclusionsDOAC-related intracerebral hemorrhage may occur particularly in patients with a high risk of bleeding; however, they had a milder initial neurological severity than those with warfarin-related intracerebral hemorrhage, possibly due to relatively smaller hematoma volume, especially in the basal ganglia.

Perihematomal Edema Expansion Rates and Patient Outcomes in Deep and Lobar Intracerebral Hemorrhage.

Perihematomal edema (PHE) expansion rate may predict functional outcome following spontaneous intracerebral hemorrhage (ICH). We hypothesized that the effect of PHE expansion rate on outcome is greater for deep versus lobar ICH. Subjects (n=115) were retrospectively identified from a prospective ICH cohort enrolled from 2000 to 2013. Inclusion criteria were age≥18years, spontaneous supratentorial ICH, and known onset time. Exclusion criteria were primary intraventricular hemorrhage (IVH), trauma, subsequent surgery, or warfarin-related ICH. ICH and PHE volumes were measured from CT scans and used to calculate expansion rates. Logistic regression assessed the association between PHE expansion rates and 90-day mortality or poor functional outcome (modified Rankin Scale>2). Odds ratios are per 0.04mL/h. PHE expansion rate from baseline to 24h (PHE24) was associated with mortality for deep (p=0.03, OR 1.13[1.02-1.26]) and lobar ICH (p=0.02, OR 1.03[1.00-1.06]) in unadjusted regression and in models adjusted for age (deep p=0.02, OR 1.15[1.02-1.28]; lobar p=0.03, OR 1.03[1.00-1.06]), Glasgow Coma Scale (deep p=0.03, OR 1.13[1.01-1.27]; lobar p=0.02, OR 1.03[1.01-1.06]), or time to baseline CT (deep p=0.046, OR 1.12[1.00-1.25]; lobar p=0.047, OR 1.03[1.00-1.06]). PHE expansion rate from baseline to 72h (PHE72) was associated with mRS>2 for deep ICH in models that were unadjusted (p=0.02, OR 4.04[1.25-13.04]) or adjusted for ICH volume (p=0.02, OR 4.3[1.25-14.98]), age (p=0.03, OR 5.4[1.21-24.11]), GCS (p=0.02, OR 4.19[1.2-14.55]), or time to first CT (p=0.03, OR 4.02[1.19-13.56]). PHE72 was associated with poor functional outcomes after deep ICH, whereas PHE24 was associated with mortality for deep and lobar ICH.

Blood pressure burden and outcome in warfarin-related intracerebral hemorrhage.

Background and purpose Blood pressure reduction is a promising intervention for acute intracerebral hemorrhage, but clinical trials of this treatment often exclude those with anticoagulant-associated intracerebral hemorrhage, leaving it unclear whether this population might benefit. We examined whether persistently elevated blood pressure values (blood pressure burden) over the first 24 h are associated with hematoma expansion and mortality in anticoagulant-associated intracerebral hemorrhage. Methods We retrospectively identified consecutive patients with primary anticoagulant-associated intracerebral hemorrhage (warfarin anticoagulation) who presented within 6 h after symptom onset and a matched set of non-anticoagulant-associated intracerebral hemorrhage patients. Associations between 24 h blood pressure burden, hematoma expansion, and mortality were evaluated using univariable and multivariable logistic regression. Results Sixty-nine anticoagulant-associated intracerebral hemorrhage and 69 matched non-anticoagulant-associated intracerebral hemorrhage patients were included. Hematoma expansion occurred in 25 anticoagulant-associated intracerebral hemorrhage patients (36%) and 15 control patients (22 %; p = 0.091). Twenty-four-hour blood pressure burden was in fact lower in anticoagulant-associated intracerebral hemorrhage than in non-anticoagulant-associated intracerebral hemorrhage patients (p = 0.033). No association was found in anticoagulant-associated intracerebral hemorrhage and non-anticoagulant-associated intracerebral hemorrhage between BP burden, hematoma expansion, and 30-day mortality. Conclusion We found no evidence that higher 24 h blood pressure burden is associated with hematoma expansion or mortality in anticoagulant-associated intracerebral hemorrhage.

Abstract WMP88: Perihematomal Edema Expansion Rate Predicts Functional Outcome in Deep Intracerebral Hemorrhage

Introduction: Perihematomal edema (PHE) expansion rate may be an independent predictor of poor functional outcome following spontaneous intracerebral hemorrhage (ICH). We examined whether this association varies by ICH location. Hypothesis: The effect size of PHE expansion rate on mortality and poor functional outcome will be greater for deep ICH compared to lobar ICH. Methods: Subjects (n=139) were retrospectively identified from a prospective ICH cohort enrolled from 2000-2013. Inclusion criteria: ≥18 years of age, spontaneous supratentorial ICH, and known time of onset. Exclusion criteria: infratentorial or primary intraventricular hemorrhage, subsequent surgery, trauma, or warfarin-related ICH. ICH, PHE, and intraventricular hemorrhage (IVH) volumes were measured from CT scans. PHE expansion rates were calculated from serial PHE volume measurements. Logistic regression assessed the association between PHE expansion rate and mortality or poor functional outcome (modified Rankin Scale &gt;2) at 90 days. Odds ratios are per 0.04 mL/h. Results: PHE expansion rate from baseline to 24 hours (PHE24) predicts mortality for deep (p=0.03, OR 1.13[1.02-1.26]) and lobar ICH (p=0.02, OR 1.03[1.00-1.06]) in unadjusted regression, and in models adjusted for age (Deep: p=0.02; Lobar: p=0.03), blood pressure (Deep: p=0.02; Lobar: p=0.04), IVH volume (Deep: p=0.02; Lobar: p=0.05), Glasgow Coma Scale (Deep: p=0.03; Lobar: p=0.02), or time to baseline CT (Deep: p=0.05; Lobar: p=0.05). PHE24 also predicts mortality for lobar ICH adjusting for ICH volume (p=0.05, OR 1.03[1-1.06]). A significant interaction exists between ICH location and PHE expansion rate from baseline to 72 hours (PHE72) in models predicting mRS&gt;2 (p=0.04). PHE72 predicts mRS&gt;2 for deep but not lobar ICH (p-values not shown) in models that are unadjusted (p=0.02, OR 4.04[1.25-13.04]) or adjusted for ICH volume (p=0.02, OR 4.3[1.25-14.98]), age (p=0.03, OR 5.4[1.21-24.11]), blood pressure (p=0.05, OR 3.28[1.02-10.57]), IVH volume (p=0.02, OR 4.59[1.28-16.41]), GCS (p=0.02, OR 4.19[1.2-14.55]), or time to first CT (p=0.03, OR 4.02[1.19-13.56]). Conclusion: PHE72 predicts poor functional outcomes exclusively after deep ICH, whereas PHE24 predicts mortality for deep and lobar ICH.

Time-to-INR reversal, Predictors of Hematoma Expansion and In-hospital Mortality in Warfarin-related Intracerebral Hemorrhage. (P3.092)

Time-to-INR reversal, Predictors of Hematoma Expansion and In-hospital Mortality in Warfarin-related Intracerebral Hemorrhage. (P3.092)

APOE ε variants increase risk of warfarin-related intracerebral hemorrhage.

We aimed to assess the effect of APOE ε variants on warfarin-related intracerebral hemorrhage (wICH), evaluated their predictive power, and tested for interaction with warfarin in causing wICH. This was a prospective, 2-stage (discovery and replication), case-control study. wICH was classified as lobar or nonlobar based on the location of the hematoma. Controls were sampled from ambulatory clinics (discovery) and random digit dialing (replication). APOE ε variants were directly genotyped. A case-control design and logistic regression analysis were utilized to test for association between APOE ε and wICH. A case-only design and logistic regression analysis were utilized to test for interaction between APOE ε and warfarin. Receiver operating characteristic curves were implemented to evaluate predictive power. The discovery stage included 319 wICHs (44% lobar) and 355 controls. APOE ε2 was associated with lobar (odds ratio [OR] 2.46; p < 0.001) and nonlobar wICH (OR 1.67; p = 0.04), whereas ε4 was associated with lobar (OR 2.09; p < 0.001) but not nonlobar wICH (p = 0.35). The replication stage (63 wICHs and 1,030 controls) confirmed the association with ε2 (p = 0.03) and ε4 (p = 0.003) for lobar but not for nonlobar wICH (p > 0.20). Genotyping information on APOE ε variants significantly improved case/control discrimination of lobar wICH (C statistic 0.80). No statistical interaction between warfarin and APOE was found (p > 0.20). APOE ε variants constitute strong risk factors for lobar wICH. APOE exerts its effect independently of warfarin, although power limitations render this absence of interaction preliminary. Evaluation of the predictive ability of APOE in cohort studies is warranted.

Abstract W MP90: APOE Variants are Associated With Increased Risk of Warfarin-Related Intracerebral Hemorrhage

Background: Epsilon (e) variants in the Apolipoprotein E (APOE) gene are well-established risk factors for spontaneous intracerebral hemorrhage (s-ICH). We tested the hypothesis that APOE-e variants are also associated with warfarin-related ICH (w-ICH) and examined interactions between APOE and warfarin. Methods: Prospective multicenter 2-stage (discovery and replication) study. ICH was classified as lobar and non-lobar based on admission head CT. In the discovery stage, w-ICH cases were matched with warfarin-exposed controls (w-controls). In replication, w-ICH cases were matched with non-warfarin controls (nw-controls). APOE was directly genotyped. Association testing was performed using multivariable logistic regression. Gene-environment interaction between APOE and warfarin was formally tested using a case only approach (combining s-ICH and w-ICH cases). Results: The discovery stage included 316 w-ICHs (43% lobar and 57% non-lobar) and 355 w-controls. Results are presented in the Table: APOE-e2 was associated with lobar and non-lobar w-ICH, and APOE-e4 was associated with lobar but not with non-lobar w-ICH. In case-only analysis, 885 s-ICHs were combined with w-ICHs (total n=1201) and no evidence of interaction between APOE and warfarin was found (all p&gt;0.20). The replication included 63 w-ICHs (44% lobar and 56% non-lobar) and 990 nw-controls. The distribution of APOE variants was similar in w-controls (discovery) and nw-controls (replication) for both e2 (p=0.81) and e4 (p=0.88). In replication, APOE-e2 and e4 were associated with lobar but not with non-lobar w-ICH. Conclusions: APOE-e variants constitute strong risk factors for lobar w-ICH. An effect may also exist between APOE-e2 and non-lobar hemorrhages, but given the lack of replication larger sample sizes are required to properly assess this association. APOE exerts its effect independently of warfarin, although power limitations render this absence of interaction preliminary.

Intracranial Hemorrhages Related with Warfarin Use and Comparison of Warfarin and Acetylsalicylic Acid

Acetylsalicylic acid (ASA) and warfarin are used to prevent ischemic cerebrovascular events. They have serious complications including intracranial hemorrhages (ICHs). Warfarin-related intracerebral hemorrhage (ich) incidence is .2%-5% in population that accounts for 10%-12% of all ichs. In this article, we investigated the profile of ASA and warfarin-related spontaneous ICHs in comparison with ICHs without any drug use (WADU) with their clinical, radiological, and biochemical properties. In all, 486 patients aged 18-101 years with spontaneous ICHs were included. Patients constituted 4 separate groups: users of warfarin, ASA, ASA + warfarin, and WADU. Clinical, neurological, etiological, and radiological data of these patients were compared. There were 32 patients in warfarin, 58 patients in ASA, and 7 in warfarin + ASA group. Most of the patients were in no drug group (389 patients). The most frequent type of hemorrhage was supratentorial intraparenchymal hemorrhage. The most common accompanying disease was hypertension. The number of female patients was statistically significant in the warfarin group. Glasgow Coma Scale (GCS), accompanying diseases, opening of the hematoma to the ventricle, localization of the hemorrhage, age of the patient, and activated partial thromboplastin time level are all related to the outcome of patients. Warfarin users had worst mortality rate. Use of warfarin, low GCS score, opening to ventricle, older age, accompanying diabetes, and/or hypertension were worse prognostic factors. It is possible that patients with these unfavorable prognostic factors cannot survive.

Nationwide survey of neuro-specialists' opinions on anticoagulant therapy after intracerebral hemorrhage in patients with atrial fibrillation

Purpose A nationwide survey was conducted regarding anticoagulant therapy in patients with acute intracerebral hemorrhage (ICH) on warfarin with nonvalvular atrial fibrillation (NVAF). Methods A questionnaire on standard therapeutic strategy for warfarin-related ICH in patients with NVAF was mailed to 416 institutes. Results A total of 329 physicians (79%) responded with a completed questionnaire. On admission, all respondents stopped warfarin medication and 94% normalized the international normalized ratio (INR) mainly by Vitamin K (63%), followed by fresh frozen plasma (20%), and prothrombin complex concentrate (10%). Afterwards, 91% of the respondents restarted anticoagulation and 3% used antiplatelet for prevention of thromboembolism, but the remaining 6% disagreed with restarting antithrombotic therapy. As contraindications for resuming anticoagulation, recurrent ICH (59%) and poor functional condition (59%) were often chosen. Of those who restarted anticoagulation, the timing was within 4 days in 7%, 5 to 7 days in 21%, 8 to 14 days in 25%, 15 to 28 days in 28% and 29 days or later in 18%. The major key finding on follow-up CT to restart anticoagulation was the absorption tendency of hematomas (47%). When restarting anticoagulation, 76% of the respondents used warfarin alone and 20% used either unfractionated heparin plus warfarin or heparin alone. Conclusion A large majority of respondents responsible for ICH management stopped oral warfarin medication and normalized INR on admission, and restarted anticoagulation after acute ICH in patients with NVAF. However, the strategies to normalize INR and to restart anticoagulant therapy varied greatly and depended on each individual physician's decision.

Medical management of acute intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is the most serious but least treatable form of stroke, with prognosis critically dependent on both the size and degree of hematoma expansion. Treatments that target hematoma expansion offer potential to improve outcomes. This review analyzes the recent literature pertaining to the medical management of ICH. Modern imaging studies have confirmed the dynamic nature of ICH. At least one-third of patients experience significant continued bleeding and hematoma expansion in the first few hours after onset, more so in warfarin-related ICH. Despite a strong biological rationale for benefit, a large clinical trial of recombinant activated factor VII failed to show any treatment effects on substantive outcomes despite clear attenuation of hematoma growth. The impact of recombinant activated factor VII is therefore severely restricted because of uncertain efficacy, definite hazard, and high cost. Accumulating evidence indicates beneficial effects from the early normalization of international normalized ratio levels and replacement of coagulation factors in warfarin-related ICH. Although high blood pressure (BP) is common and associated with poor outcomes in ICH, there is insufficient evidence to recommend a specific early BP management strategy, although recent randomized evidence indicates that such treatment is well tolerated and readily incorporated into routine clinical practice. Definitive evidence to support a low-cost, widely applicable treatment is urgently required for a condition in which therapy is primarily supportive. In patients with acute ICH, rapid intensive BP-lowering treatment may provide protection against hematoma growth without concerns about safety and tolerability. How well such treatment can translate into overall benefits to patients is yet to be determined. At present, recombinant activated factor VII cannot be recommended for routine use, although BP lowering should generally follow conservative guidelines.

Cerebral microbleeds are a risk factor for warfarin-related intracerebral hemorrhage

Cerebral microbleeds are known to be indicative of bleeding-prone microangiopathy and may predict incident intracerebral hemorrhage (ICH). In this study, we investigated whether microbleeds are associated with the incidence of warfarin-related ICH. Twenty-four patients with ICH while on outpatient treatment with warfarin were selected from a consecutive cohort. Control, warfarin-using subjects with no history of ICH were randomly selected during the same time period (n = 48). We compared demographic factors, vascular risk factors, laboratory findings, and radiologic findings including microbleeds between the groups. There were more cases of patients with microbleeds in the ICH than control group (79.2% vs 22.9%: p < 0.001), and the number of microbleeds was much higher for the ICH group (9.0 +/- 26.8 vs 0.5 +/- 1.03: p < 0.001). Moreover, the number of microbleeds was significantly correlated with the presence of warfarin-related ICH (r = 0.299; p < 0.001). Conditional logistic regression analysis showed that increased prothrombin time and the presence of microbleeds were independently related to the incidence of warfarin-related ICH (microbleeds: adjusted OR, 83.12). This study suggests that underlying microbleeds are independently associated with an incidence of warfarin-related intracerebral hemorrhage. Future research should focus on elucidating the risks and benefits of warfarin medication in patients with microbleeds.

Patient-Specific Decision-Making for Warfarin Therapy in Nonvalvular Atrial Fibrillation

Background and Purpose— Intracerebral hemorrhage (ICH) accounts for a majority of long-term morbidity and mortality associated with bleeding while on warfarin. Both ICH and warfarin-related ICH appear to have a genetic component. Furthermore, advanced neuroimaging using MRI can now identify individuals at increased risk of ICH. We explore whether screening strategies that include genetic profiling and neuroimaging might improve the safety of chronic anticoagulation for atrial fibrillation by identifying individuals from whom warfarin should be withheld. Methods— We used a Markov state transition decision model. Effectiveness was measured in quality-adjusted life-years. Data sources included the English language literature using MEDLINE searches and bibliographies from selected articles along with empirical data from our institutions. The base case was a 69-year-old man with newly diagnosed nonvalvular atrial fibrillation. Results— For patients at average risk for thromboembolic events and known to possess a hypothetical genetic profile increasing risk for warfarin ICH, anticoagulation remains the preferred strategy until the relative hazard of ICH exceeds 23.8. Genetic profiling would be favored for patients at low risk of thromboembolism (1.5% per year) if the hypothetical gene variant(s) conferred a relative risk of ICH &gt;4.1. Screening strategies in which patients underwent genotyping and MRI before anticoagulation did not improve aggregate patient outcomes unless the predictive power of MRI exceeded current best guess estimates and patients were at low to moderate risk of thromboembolism. Conclusion— Currently identified genetic markers of bleeding risk do not confer a risk of ICH sufficiently high to warrant routine genetic testing for patients at average risk of thromboembolism. Even if patients undergo screening with MRI as well as genotyping, currently available data on the role of MRI on risk of ICH and warfarin ICH do not support use of these tests for withholding anticoagulation in patients with atrial fibrillation.

Restarting Anticoagulation Therapy After Warfarin-Associated Intracerebral Hemorrhage

Reinitiating warfarin sodium therapy in a patient with a recent warfarin-related intracerebral hemorrhage (WAICH) is a difficult clinical decision. Therefore, it is important to assess the outcome of resumption or discontinuation of warfarin therapy after WAICH. To compare patients who survived an episode of WAICH and restarted warfarin therapy with a group of WAICH patients who did not resume warfarin therapy. Design, Setting, and Patients We conducted a follow-up study from November 1, 2001, through December 31, 2005, in a cohort from a single center. Long-term outcome was assessed at last clinical follow-up or via questionnaire. Recurrent WAICH and thromboembolic events. Fifty-two patients were discharged from the hospital after a diagnosis of WAICH. Four patients were lost to follow-up. Mean follow-up among all patients was 43 (range, 1-108) months. Of the 23 patients who restarted warfarin therapy, 1 had a recurrent nontraumatic WAICH, 2 had traumatic intracerebral hemorrhages, and 2 had major extracranial hemorrhages. Of the 25 patients who did not restart warfarin therapy, 3 had a thromboembolic stroke, 1 had a pulmonary embolus, and 1 had a distal arterial embolus. Restarting warfarin therapy in patients with a recent WAICH is associated with a low risk of recurrence, but patients are subjected to known, substantial risks of warfarin use. Withholding warfarin therapy is associated with a risk of thromboembolization.

Predictors of Outcome in Warfarin-Related Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) associated with warfarin sodium therapy is becoming more common as the use of this medication increases in the aging population. To delineate factors associated with early mortality, determine variables responsible for poor functional outcome, and evaluate possible reasons for expansion of hemorrhage and associated parenchymal edema. Retrospective study of clinical and radiologic information for 88 patients with warfarin-associated ICH. A single hospital. Patients Eighty-eight consecutive patients with warfarin-associated ICH. Patients were included if the international normalized ratio (INR) at presentation with ICH was 1.5 or greater. Computed tomographic scans were reviewed for volumetric analysis of hematoma and perihematomal edema volume. Outcome variables included 7-day mortality, hematoma enlargement, and functional outcome based on the modified Rankin Scale score. Seven-day mortality (39.8%) was associated with a lower Glasgow Coma Scale sum score and larger ICH volume at presentation. Univariate analysis revealed that a lower Glasgow Coma Score sum score, larger initial ICH volume, higher initial and 48-hour maximum glucose concentrations, and higher percentage of ICH expansion were significantly associated with poor functional outcome at hospital discharge. At multivariate analysis, only Glasgow Coma Score and ICH volume remained significantly associated with functional outcome measured at hospital discharge and at the last follow-up visit. Conversely, INR at presentation, time to INR correction, initial blood pressure, and enlargement of edema were not associated with functional outcome either at hospital discharge or at the last follow-up. Neither serum glucose concentration at admission nor highest level during the first 48 hours had any correlation with ICH or parenchymal edema enlargement. In addition, neither initial INR nor time to INR correction correlated with expansion of ICH or parenchymal edema. Lower level of consciousness at presentation and larger initial ICH volume predict poor prognosis in patients with warfarin-associated ICH. In our study population, INR at presentation was not associated with functional outcome.

Management of intracerebral hemorrhage

Following quickly behind improvements in acute ischemic stroke care have been important advances in the understanding and management of intracerebral hemorrhage (ICH). Among these are accurate diagnosis of cerebral amyloid angiopathy (CAA) during life, recognition of the association between CAA and warfarin-related ICH, use of newer hemostatic treatments, and the combination of minimally invasive surgery with hematoma thrombolysis. Currently recommended management includes prompt evaluation of the patient at a facility with stroke and neurosurgical expertise, consideration of early surgery for patients with clinical deterioration or cerebellar hemorrhages larger than 3 cm, and early treatment of coagulopathies and other neurologic and medical complications. Over the past 2 years, two major randomized studies in ICH (comparing early surgery with best medical management and testing the utility of hemostatic treatment within 4 hours using recombinant factor VIIa) have yielded neutral results. This review focuses on comprehensive management of ICH in light of recent evidence.

Warfarin-Related Intracerebral Hemorrhage: How to Proceed

Warfarin-related intracerebral hemorrhage (WICH) is a devastating stroke subtype and represents a medical and neurosurgical emergency with a 1-month mortality of approximately 50%. Warfarin is commonly prescribed to prevent ischemic stroke in patients with atrial fibrillation and to prevent pulmonary embolism (PE) in patients with deep vein thrombosis (DVT). Owing to the aging population and the increased incidence of atrial fibrillation with age and subsequent warfarin use, the incidence of WICH is expected to rise in the future. When WICH occurs, immediate discontinuation of warfarin and simultaneous rapid warfarin-reversal remain the first-line interventions, sometimes with neurosurgical intervention. The optimal agent for the most rapid warfarin anticoagulation reversal remains to be defined owing to the lack of prospective randomized trials. We review current literature about WICH pathogenesis, risk factors, acute management strategies and prospects for future research for this devastating neurologic emergency.