The effect of hospitalization on oral anticoagulation control: a population-based study

BACKGROUND: For patients taking oral anticoagulants (OAC), the proportion of time spent in the therapeutic range is strongly associated with bleeding and thromboembolic risk. Previous studies examining OAC control may not generalize because the patient population was select or INR capture was incomplete. OBJECTIVES: Measure OAC control for an entire population of elderly people and determine patient factors associated with OAC control. PATIENTS: People in Eastern Ontario without valve replacement aged 65 years or greater who were treated with warfarin between 1 September 1999 and 1 September 2000. DESIGN: Retrospective cohort study using population-based administrative databases. OAC control was measured as the proportion of days in therapeutic range (PDTR), defined as the number days with the INR between 2 and 3 divided by total number of days observation. Linear interpolation was used to determine INR levels between measures. Negative binomial regression was used to identify patient factors independently associated with PDTR. We also determined which factors were associated with proportion of days with a critically low (<1.5) or critically high (>/=5) INR. RESULTS: 7179 people were followed for a total of 3238 years. 15% of people were hospitalized during the study. Overall, PDTR was 59.2% (95% CI 59.1%-59.2%). Independent of all other significant factors, hospitalization was associated with a 15% decrease in the PDTR 15% (rate ratio 0.85, 95% CI 0.83-0.87). Hospitalization was also independently associated with greater proportion of time with a critically low INR (rate ratio 1.68, 95% CI 1.51-1.88) and a critically high INR (1.70, 95% CI 1.38-2.08). CONCLUSIONS: Elderly people in eastern Ontario taking warfarin were therapeutic 59.2% of the time. Independent of other patient factors, patients who are hospitalized have the greatest risk of poor anticoagulation control. Control for anticoagulated patients who get hospitalized should be reviewed to determine if and how it could be improved.     

Obesity increases risk of anticoagulation reversal failure with prothrombin complex concentrate in those with intracranial hemorrhage

Background: Not all patients with warfarin-related acute intracranial hemorrhage (ICH) achieve full reversal of international normalized ratio (INR) after the first dose of weight-based prothrombin complex concentrate (PCC). We sought to identify factors associated with anticoagulation reversal failure after the first dose of PCC. Methods: Consecutive patients who were hospitalized with warfarin-related acute ICH at a tertiary center between 1 January 2010 and 31 December 2012 were studied. Anticoagulation reversal failure was defined as INR ≥ 1.5 after the first dose of PCC. Logistic regression was performed to determine the predictors of anticoagulation reversal failure. Results: Fifty-one patients with acute ICH received PCC for warfarin reversal using a weight-based protocol. Overall, 23 (45%) patients did not achieve full reversal of INR after the first dose. Those with anticoagulation reversal failure were obese (body mass index > 30 kg/m²) (41% vs. 14%, p = 0.03), had a higher initial INR (3.0 ± 1.4 vs. 2.0 ± 0.7, p = 0.001), and had a higher prevalence of initial INR >2.0 (22% vs. 67%, p = 0.001), compared with those who were successfully reversed. Multivariable logistic regression identified obesity (odds ratio 7.88, 95% CI 1.12 to 55.68) and initial INR >2.0 (odds ratio 12.49, 95% CI 2.27 to 68.87) as independent predictors of anticoagulation reversal failure. Conclusions: Obesity and elevated initial INR are independently associated with anticoagulation reversal failure using the weight-based PCC protocol in patients with warfarin-related acute ICH. Further studies are needed to determine more effective dosing protocols and individualized strategies for anticoagulation reversal after acute ICH, especially among obese patients.     

INR comparison between the CoaguChek S and a standard laboratory method among patients with self-management of oral anticoagulation

INTRODUCTION: Portable coagulation monitors have been developed to measure International Normalised Ratio (INR) in orally anticoagulated patients using capillary whole blood from a finger stick. Because of unsatisfactory precision of some of the monitors in comparison with laboratory methods new devices are being developed. In the present study we compared INR determination with the CoaguChek S device with a standard laboratory method among patients with self-management of oral anticoagulation (OAC). METHODS: Two hundred and forty-two patients performing self-management of OAC were enrolled into this study. Parallel INR measurements were performed within one hour. Capillary INR measurements (INRcap) were done by the patients with the CoaguChek S and venous INR (INRven) by qualified medical staff using a standard laboratory method. RESULTS: We found a correlation coefficient (r(S)) of 0.85 (95% CI: 0.81-0.88) among the 242 patients between INRven and INRcap. In 84.4% of the INR parallel measurements the difference between the two values was below 0.5 INR units. In only 2 of 242 cases the difference was >1 INR unit (1.1 and 1.3). The slope of the Passing Bablok regression line was 0.91 (95% CI: 0.83-1.0) and the y-intercept 0.06 (95% CI: -0.20-0.25). Agreement between both methods was 90.5% (95% CI: 86.8-94.2) and standard-agreement even 97.1% (95% CI: 95-99.2). CONCLUSIONS: INR measurement with CoaguChek S device by trained patients revealed reliable results in comparison to the values obtained with a standard laboratory method.     

Evaluation of the yield of 24-h close observation in patients with mild traumatic brain injury on anticoagulation therapy: a retrospective multicenter study and meta-analysis

Background/aims

Patients with mild traumatic brain injury (mTBI) on anticoagulants have an increased risk of intracranial hemorrhage (ICH). However, consensus is lacking on whether to admit them after normal initial cranial CT. We evaluated the yield of 24-h neurological observation.

Methods

Retrospective multicenter study including adult patients admitted over a 5-year period with mTBI on anticoagulation [therapeutic dose heparin, direct oral anticoagulant, or vitamin K antagonist (VKA) with international normalized ratio (INR) ≥ 1.7] and reportedly normal cranial CT obtained within 24 h after trauma. Primary endpoint was symptomatic ICH within 24 h of injury. Literature on delayed ICH in patients with mTBI and anticoagulation use was reviewed.

Results

Of 17.643 mTBI patients, 905 met the inclusion criteria (median age 82 years). 97% used VKA (median INR 2.9). None developed delayed ICH within 24 h. Nine patients deteriorated neurologically due to ICH, four within 24 h (0.4%, 95% CI 0.1–1.2) and five on day 2, 18, 22, 36 and 52, respectively. In six patients, including all four that developed symptoms within 24 h, ICH was found upon reevaluation of initial imaging. The meta-analysis comprised of 9 studies with data from 2885 patients. The estimated pooled proportion of symptomatic delayed ICH or delayed diagnosis of ICH within 24 h was 0.2% (95% CI 0.0–0.5).

Conclusions

Delayed (diagnosis of) ICH within 24 h is very rare in mTBI patients on anticoagulants after reportedly normal initial CT. Routine hospitalization of these patients seems unwarranted when the initial cranial CT is scrupulously evaluated.

     

Ischemia-modified albumin in acute stroke

BACKGROUND: Ischemia-modified albumin (IMA)is a new biological marker of ischemia. Previous studies have found increased serum IMA levels after myocardial ischemia, but no study has investigated the possibility that stroke modifies IMA blood levels. MATERIALS AND METHODS: We studied 118 consecutive patients presenting within 3 h of the onset of an acute neurological deficit [84 brain infarctions (BI), 18 brain hemorrhages (ICH) and 16 transient ischemic attacks lasting less than 1 h or epileptic seizures]. Serum samples were obtained for all patients at initial presentation and repeated only in patients with stroke at 6, 12 and 24 h. IMA was measured by the albumin-cobalt-binding test (Ischemia Technologies, Denver, Colo., USA). RESULTS: The initial median IMA (bootstrap 95% confidence interval, CI) was 83 U/ml (79-86) and 86 U/ml (75-90) in patients with BI and ICH, respectively (p = 0.76), and was 73 U/ml (58-79) in others (p = 0.003 compared with BI, and p = 0.017 with ICH). Baseline IMA levels correlated with the National Institutes of Health Stroke Scale [Spearman correlation coefficient: 0.34 (p = 0.002) in BI, 0.61 (p = 0.008) in ICH]. During the first 24 h, IMA levels increased in BI patients (median, 9.1%; bootstrap 95% CI, 5.2-11.5), whereas no change was observed in ICH patients (median, 1.2%; bootstrap 95% CI, -7.8 to 6.8). CONCLUSIONS: IMA blood levels may be a biomarker for early identification of acute stroke. Further studies are required to investigate the role of IMA in the early detection of acute stroke.     

Computed tomographic angiography for patients with acute spontaneous intracerebral hemorrhage

With the advanced technology of multi-slice CT scans, we explored the effectiveness of CT angiography (CTA) in place of digital subtraction angiography (DSA) in patients with acute spontaneous intracerebral hemorrhage (ICH). We performed a computerized PubMed search of the literature from inception to 27 July 2011 to find reports of similar comparative studies and performed a meta-analysis of diagnostic accuracy. The pooled sensitivity was 97.0% (95% confidence interval [CI]: 93.2-99.1%), specificity was 98.9% (95% CI: 97.0-99.7%), accuracy was 98.2% (95% CI: 96.6-99.2%), positive predictive value was 97.8% (95% CI: 94.2-99.5%) and negative predictive value was 98.5% (95% CI: 96.6-99.5%). The false negative rate was 1% (95% CI: 0.4-2.6%). We concluded that CTA with venography could replace DSA as the initial vascular investigation in patients presenting with spontaneous ICH during the acute phase. Future studies should focus on whether refinement of the techniques could preclude the false negative results.     

Modified ASPECTS for DWI including deep white matter lesions predicts subsequent intracranial hemorrhage

We hypothesized that extensive early ischemic changes increase subsequent intracranial hemorrhage (ICH) in patients within 3?h of onset regardless of intravenous tPA (IV-tPA). We have established a modified scoring method, ASPECTS+W, including deep white matter lesions on DWI (DWI-W) in addition to the original ASPECTS regions. We aimed to elucidate whether CT-ASPECTS, DWI-ASPECTS, and ASPECTS+W could be useful tools in helping to predict subsequent ICH in acute ischemic stroke. One-hundred sixty-four consecutive patients with anterior circulation ischemic stroke were enrolled. All patients underwent both MRI and CT within 3?h of onset. ASPECTS+W was defined as an 11-point method combining the ten ASPECTS regions and DWI-W. The relationships of CT-ASPECTS, DWI-ASPECTS, and ASPECTS+W with ICH within the initial 36?h were assessed. Thirty-six patients (22%) were treated with IV-tPA. Follow-up CT was obtained in 159 patients, and 19 (12%) developed ICH. Patients with ICH had higher baseline NIHSS scores (median, 25 vs. 13, p?=?0.010), a higher rate of IV-tPA (42 vs. 20%, p?=?0.041), lower CT-ASPECTS (median, 7 vs. 10, p?=?0.008), lower DWI-ASPECTS (6 vs. 9, p?=?0.001), lower ASPECTS+W (6 vs. 9, p?=?0.001), and higher DWI-W lesions (74 vs. 47%, p?=?0.048) than those without ICH. ICA or M1 proximal occlusion was more frequently seen in patients with ICH (68 vs. 32%, p?=?0.004) than in those without ICH. On multivariate regression analysis, lower ASPECTS+W (OR 0.75, 95% CI 0.58-0.96, p?=?0.027) and administration of IV-tPA (OR 9.13, 95% CI 2.15-46.21, p?=?0.004) independently predicted ICH development. In conclusion, ASPECTS+W is a useful tool for predicting ICH development independent of IV-tPA.     

Progression of warfarin-associated intracerebral hemorrhage after INR normalization with FFP

To identify hematoma progression in patients with warfarin-associated intracerebral hemorrhage (ICH) despite international normalized ratio (INR) normalization with fresh-frozen plasma (FFP), we reviewed 45 patients with warfarin-associated ICH given FFP. The median time for door to INR normalization was 30 hours (14 to 49.5), with 4 patients' hematomas enlarging after INR normalization. FFP is associated with substantial time delay to actual administration and pulmonary edema and may not prevent progression of ICH despite INR normalization.     

Both antiplatelet and anticoagulant therapy may favorably affect outcome in patients with advanced heart failure. A retrospective analysis of the PRIME-II trial

INTRODUCTION: Current guidelines of chronic heart failure (CHF) do not recommend the use of oral anticoagulants (OAC) or antiplatelet therapy (APT). We performed a post-hoc analysis to evaluate the effect of the use of anti-thrombotic therapy with APT and OAC. PATIENTS AND METHODS: We examined 427 patients with advanced CHF, and assessed the effects of the use of APT or OAC at baseline on mortality. We employed a Cox-proportional hazard model to value the effects of APT or OAC use. RESULTS: After a mean follow-up of 3.4 years (range 2.0-5.4), 214 patients died (51%). Forty-one (41) percent (95%CI: 29-53%) of the patients on APT died, and 52% (47-57%) of the patients not on APT (P=0.07). Forty-eight (48) percent (42-54%) of the patients on OAC died, and 55% (46-63%) of the patients not on OAC (P=0.20). This effect of OAC was seen both in patients in sinus rhythm and in atrial fibrillation. After adjusting for important prognostic variables, such as age, LVEF, renal function, and NYHA class, both the use of APT (hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.40-0.97; P=0.04) and the use of OAC (HR 0.60, 95%-CI 0.43-0.83; P<0.01) were related to an improved prognosis. CONCLUSION: This post-hoc analysis suggests that in CHF patients the use of APT or OAC is associated with a higher survival.     

Effect of warfarin on intracranial hemorrhage incidence and fatal outcomes

Introduction

Avoiding intracranial hemorrhage (ICH) during warfarin therapy is critical but little is known about factors that affect warfarin-related ICH outcomes. We aimed to define the impact of warfarin on ICH incidence rates and to identify baseline clinical characteristics of patients who experienced ICH and factors associated with fatal ICH.

Materials and Methods

The primary outcome of this retrospective cohort study was the incident ICH rate per 10,000 person-years for patients receiving and not receiving warfarin therapy. Cox proportional hazards modeling was used to adjust for potential confounding factors in assessment of the association of warfarin with fatal ICH.

Results

A total of 1348 patients with incident ICH, 259 (19%) who were receiving warfarin therapy, were included. The incident ICH rates were 74/10,000 (warfarin) and 5/10,000 (non-warfarin) person-years (p < 0.001). Warfarin patients were older and carried a higher burden of chronic disease. The unadjusted hazard ratio (HR) for fatal ICH was 1.64 (95% confidence interval [CI] 1.31-2.05) for warfarin patients compared to non-warfarin patients. However, the HR was no longer significant after adjustment for confounding variables (1.10; 95% CI 0.84-1.42). An INR greater than 3.5 at presentation doubled the adjusted risk for fatal ICH with warfarin therapy. Subarachnoid and subdural ICHs were less likely to be fatal than other ICH types, and each year increase in age was associated with 4% increased risk of fatal ICH.

Conclusions

Although warfarin use increases the rate of incident ICH, other factors impact the risk of fatal ICH, even among anticoagulated patients.     

Abnormalities on ECG and telemetry predict stroke outcome at 3 months

BACKGROUND: ECG is a useful tool in monitoring vital functions in patients with acute stroke; however, fairly little evidence is available concerning the prevalence and the prognostic impact of ECG findings in patients with acute cerebral infarction and acute intracerebral haemorrhage (ICH). METHODS: This analysis was based on data from 692 patients with acute cerebral infarction, 155 patients with intracerebral haemorrhage (ICH), and 223 patients with transient ischaemic attack (TIA), who were admitted to hospital within 6 h of symptom onset. A 12 lead ECG was obtained on admission, and the patient was on telemetry for the first 12-24 h of hospitalisation. RESULTS: ECG abnormalities were observed in 60% of patients with cerebral infarction, 50% of patients with ICH, and 44% of patients with TIA. In multivariate analyses 3-month mortality in patients with ischaemic stroke was predicted by atrial fibrillation OR 2.0 (95% CI 1.3-3.1), atrio-ventricular block OR 1.9 (95% CI 1.2-3.9), ST-elevation OR (2.8, 95% CI 1.3-6.3), ST-depression OR 2.5 (95% CI 1.5-4.3), and inverted T-waves OR 2.7 (95% CI 1.6-4.6). This was independent of stroke severity, pre-stroke disability and age. In patients with ICH, sinus tachycardia OR 4.8 (95% CI 1.7-14.0), ST-depression OR 5.2 (95% CI 1.1-24.9), and inverted T-wave 5.2 (95% CI 1.2-22.5) predicted poor outcome. None of the changes reached significance in patients with TIA. In patients with severe cerebral infarction or ICH, heart rate did not decrease within the first 12 h after admission, which was the case in patients with mild to moderate stroke. Rapid heart rate predicted 3-month mortality in multivariate testing OR 1.7 (95% CI 1.02-2.7). CONCLUSIONS: ECG abnormalities are frequent in acute stroke and may predict 3-month mortality.     

Coagulopathy Disproportionately Predisposes to Lobar Intracerebral Hemorrhage

Background

Anticoagulation increases the risk of intracerebral hemorrhage (ICH), yet whether different underlying disease processes are equally affected is unknown. We tested the hypothesis that coagulopathy, measured by admission international normalized ratio (INR), disproportionately increases the risk for lobar hemorrhages.

Methods

Patients with primary ICH were enrolled into a registry between December 2006 and February 2012 with prospective data acquisition and systematic follow up. Logistic regression was used to test whether lobar versus deep ICH location was independently associated with INR, and then whether INR had an influence on mortality. Spearman’s correlation coefficient was used to test for an association between INR and hematoma volume separately in the lobar and deep ICH groups.

Results

221 patients were studied. Patients with lobar ICH were older (71 vs. 62 years old, p < 0.001) and more likely to have prior ICH (10 vs. 0 %, p < 0.001). INR >1.4 was observed on admission more frequently in lobar versus deep ICH (19 vs. 8 %, p = 0.02). Lobar ICH location was independently associated with INR >1.4 (OR: 2.51, 95 % CI: 1.03–6.14, p = 0.043). ICH volume correlated with INR in lobar ICH (p = 0.009), but not deep ICH (p = 0.8). Death at 1 month was independently associated with INR >1.4 (OR: 7.6, 95 % CI: 2.4–24.1, p = 0.001) after correction for the ICH Score.

Conclusions

Abnormal coagulation occurs disproportionally in lobar versus deep ICH, and is associated with larger ICH volumes and higher mortality. These findings suggest a unique risk interaction between coagulopathy and underlying brain pathology due to cerebral amyloid angiopathy.     

Prothrombin complex concentrate for vitamin K antagonist reversal in traumatic intracranial hemorrhage

ObjectiveAdministration of prothrombin complex concentrate (PCC) is recommended for vitamin K antagonist (VKA) reversal in patients with severe bleeding complications. However, there are only limited data available on its use for VKA reversal in patients with traumatic intracranial hemorrhage (ICH).MethodsData from all anticoagulated patients referred to our hospital for treatment of traumatic ICH and who received PCC for anticoagulation reversal were retrospectively analysed with specific focus on bleeding and thromboembolic complications during the further in-hospital course.ResultsA total of 142 patients were included in the present study. The median age was 78 years (Interquartile range [IQR]: 72–84) and the median Glasgow Coma Scale (GCS) score on admission was 12 (IQR: 7–14). Median International Normalized Ratio (INR) on admission was 2.5 [IQR: 2.0–3.3] and decreased to 1.2 [IQR: 1.1–1.3] following administration of a median dose of 2000 I.U. PCC [IQR: 1500–2625]. The in-hospital mortality rate was 13% and the median GCS of survivors at discharge was 14 [IQR: 12–15]. Thromboembolic events after PCC administration occurred in 4 patients (2.8%). The overall one-year mortality rate in this patient cohort was 49%.ConclusionsPCC administration rapidly normalises INR and facilitates urgent neurosurgical procedures in anticoagulated patients with traumatic ICH.     

Potential triggering factors of intracerebral hemorrhage

The distributions of intracerebral hemorrhage (ICH) according to place of onset, degree of physical activity at onset and potential triggering factors were analyzed in 848 patients with ICH. Patients were grouped according to the presumed cause of ICH: hypertensive ICH, secondary ICH and ICH of undetermined origin. The influence of demographic and temporal factors on the relative frequency of events was also assessed. In 30% of the cases, ICH occurred during inactivity or sedentary activity, in 50% during light exertion and in 20% during moderate/vigorous exertion. During inactivity or sedentary activity, hypertensive ICH was significantly less frequent than secondary ICH (OR 0.32; 95% CI 0.21-0.47) and undetermined ICH (OR 0.36; 95% CI 0.23-0.55), whereas during moderate or vigorous exertion hypertensive ICH was more frequent than secondary (OR 1.88; 95% CI 1.16-3.05) and undetermined ICH (OR 2.29; 95% CI 1.31-4.00) Potential triggering factors were observed in 27% of patients and were significantly more frequent in patients with hypertensive ICH than in patients with secondary ICH (OR 2.90; 95% CI 1.85-4.54) or undetermined ICH (OR 2.44; 95% CI 1.54-3.87). Our findings suggest that many potential external triggers that act mainly by raising blood pressure may interact, and their concurrence may favor cerebral hemorrhage, particularly in hypertensive patients. In many cases, these circumstances of increased risk may be mitigated by preventive measures.     

Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial

BACKGROUND: There is much uncertainty about the effects of early lowering of elevated blood pressure (BP) after acute intracerebral haemorrhage (ICH). Our aim was to assess the safety and efficiency of this treatment, as a run-in phase to a larger trial. METHODS: Patients who had acute spontaneous ICH diagnosed by CT within 6 h of onset, elevated systolic BP (150-220 mm Hg), and no definite indication or contraindication to treatment were randomly assigned to early intensive lowering of BP (target systolic BP 140 mm Hg; n=203) or standard guideline-based management of BP (target systolic BP 180 mm Hg; n=201). The primary efficacy endpoint was proportional change in haematoma volume at 24 h; secondary efficacy outcomes included other measurements of haematoma volume. Safety and clinical outcomes were assessed for up to 90 days. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00226096. FINDINGS: Baseline characteristics of patients were similar between groups, but mean haematoma volumes were smaller in the guideline group (12.7 mL, SD 11.6) than in the intensive group (14.2 mL, SD 14.5). From randomisation to 1 h, mean systolic BP was 153 mm Hg in the intensive group and 167 mm Hg in the guideline group (difference 13.3 mm Hg, 95% CI 8.9-17.6 mm Hg; p<0.0001); from 1 h to 24 h, BP was 146 mm Hg in the intensive group and 157 mm Hg in the guideline group (10.8 mm Hg, 95% CI 7.7-13.9 mm Hg; p<0.0001). Mean proportional haematoma growth was 36.3% in the guideline group and 13.7% in the intensive group (difference 22.6%, 95% CI 0.6-44.5%; p=0.04) at 24 h. After adjustment for initial haematoma volume and time from onset to CT, median haematoma growth differed between the groups with p=0.06; the absolute difference in volume between groups was 1.7 mL (95% CI -0.5 to 3.9, p=0.13). Relative risk of haematoma growth >or=33% or >or=12.5 mL was 36% lower (95% CI 0-59%, p=0.05) in the intensive group than in the guideline group. The absolute risk reduction was 8% (95% CI -1.0 to 17%, p=0.05). Intensive BP-lowering treatment did not alter the risks of adverse events or secondary clinical outcomes at 90 days. INTERPRETATION: Early intensive BP-lowering treatment is clinically feasible, well tolerated, and seems to reduce haematoma growth in ICH. A large randomised trial is needed to define the effects on clinical outcomes across a broad range of patients with ICH. FUNDING: National Health and Medical Research Council of Australia.     

Predisposing factors for enlargement of intracerebral hemorrhage in patients treated with warfarin

To elucidate predisposing factors for enlargement of intracerebral hematoma (ICH) during warfarin therapy, we reviewed 47 patients on warfarin who developed acute ICH and determined relationships among ICH enlargement, INR reversal and clinical data. Among 36 patients treated to counteract the effects of warfarin within 24 h of onset, ICH increased in 10 patients (enlarged group), but remained unchanged in the remaining 26 (unchanged group), while ICH remained unchanged in another 11 patients in whom the effect of warfarin was reversed after 24 h. The international normalized ratio (INR) was counteracted immediately in 11 patients treated with prothrombin complex concentrate (PCC) but gradually in the other 36 treated by reducing the dose of warfarin, or by administering vitamin K or fresh frozen plasma. Multivariate analysis with a logistic regression model showed an INR value <2.0 at admission or for 24 h after immediate INR correction with PCC prevented ICH enlargement (OR 0.069, 95%CI 0.006-0.789, p = 0.031). An INR value of >2.0 within 24 h of ICH seems an important predisposing factor for ICH enlargement.     

Serum D-dimer as a predictor of mortality in patients with acute spontaneous intracerebral hemorrhage

It has been found that the hemostatic system is activated following a brain injury. To explore the role of D-dimer in spontaneous intracerebral hemorrhage (ICH), this prospective study aimed to evaluate the association between serum D-dimer concentration, clinical outcome and radiographic findings of ICH patients in the emergency department (ED). Patients with acute (<24 hours) spontaneous ICH were enrolled in this study. The D-dimer concentration was related to: baseline ICH volume (r=0.198, p=0.01); Glasgow Coma Scale (GCS) score 3-8 (p=0.01); GCS score 13-15 (p=0.002); midline shift >15 mm (p=0.016); and to subarachnoid extension of the blood (p<0.0001). Diabetes mellitus (odds ratio [OR]: 2.93; 95% confidence interval [CI]: 1.1-7.76, p=0.031), ICH volume (OR: 1.16; 95% CI: 1.07-1.27, p<0.0001) and D-dimer concentration (OR: 2.72; 95% CI: 1.08-6.9, p=0.002) were associated with 30-day mortality. This study shows that in patients with spontaneous ICH, a higher initial D-dimer concentration is associated with higher 30-day mortality.     

Association of pretreatment ASPECTS scores with tPA-induced arterial recanalization in acute middle cerebral artery occlusion.

BACKGROUND AND PURPOSE: The Alberta Stroke Program Early CT-Score (ASPECTS) assesses early ischemic changes within the middle cerebral artery (MCA) and predicts poor outcome and increased risk for thrombolysis-related symptomatic ICH. We evaluated the potential relationship between pretreatment ASPECTS and tPA-induced recanalization in patients with MCA occlusions. SUBJECTS & METHODS: Consecutive patients with acute ischemic stroke due to MCA occlusion were treated with standard IV-tPA and assessed with transcranial Doppler (TCD) for arterial recanalization. Early recanalization was determined with previously validated Thrombolysis in Brain Ischemia (TIBI) flow-grading system at 120 minutes after tPA-bolus. All pretreatment CT-scans were prospectively scored by trained investigators blinded to TCD findings. Functional outcome at 3 months was evaluated using the modified Rankin Scale (mRS). RESULTS: IV-tPA was administered in 192 patients (mean age 68 +/- 14 years, median NIHSS-score 17). Patients with complete recanalization (n= 51) had higher median pretreatment ASPECTS (10, interquartile range 2) than patients with incomplete or absent recanalization (n= 141; median ASPECTS 9, interquartile range 3, P= .034 Mann-Whitney U-test). An ASPECTS < or =6 was documented in 4% and 17% of patients with present and absent recanalization, respectively (P= .019). Pretreatment ASPECTS was associated with complete recanalization (OR per 1-point increase: 1.54; 95% CI 1.06-2.22, P= .023) after adjustment for baseline characteristics, risk factors, NIHSS-score, pretreatment TIBI grades and site of arterial occlusion on baseline TCD. Complete recanalization (OR: 33.97, 95% CI 5.95-185.99, P < .001) and higher ASPECTS (OR per 1-point increase: 1.91; 95% CI 1.17-3.14, P= .010) were independent predictors of good functional outcome (mRS 0-2). CONCLUSIONS: Higher pretreatment ASPECT-scores are associated with a greater chance of complete recanalization and favorable long-term outcome in tPA-treated patients with acute MCA occlusion.     

Computed tomography findings for intracerebral hemorrhage have little incremental impact on post-stroke mortality prediction model performance

Background: Stroke outcome studies often combine cases of intracerebral hemorrhage (ICH) and ischemic stroke (IS). These studies of mixed stroke typically ignore computed tomography (CT) findings for ICH cases, though the impact of omitting these traditional predictors of ICH mortality is unknown. We investigated the incremental impact of ICH CT findings on mortality prediction model performance. Methods: Cases of ICH and IS (2000-2003) were identified from the Brain Attack Surveillance in Corpus Christi (BASIC) project. Base models predicting 30-day mortality included demographics, stroke type, and clinical findings (National Institutes of Health Stroke Scale (NIHSS) +/- Glasgow Coma Scale (GCS)). The impact of adding CT data (volume, intraventricular hemorrhage, infratentorial location) was assessed with the area under the curve (AUC), unweighted sum of squared residuals (?), and integrated discrimination improvement (IDI). The model assessment was performed first for the mixed case of IS and ICH, and then repeated for ICH cases alone to determine whether any lack of improvement in model performance with CT data for mixed stroke type was due to IS cases naturally forming a larger proportion of the total sample than ICH. Results: A total of 1,256 cases were included (86% IS, 14% ICH). Thirty-day mortality was 16% overall (11% for IS; 43% for ICH). When both clinical scales (NIHSS and GCS) were included, none of the model performance measures showed improvement with the addition of CT findings whether considering IS and ICH together (ΔAUC: 0.002, 95% CI -0.01, 0.02; Δ?: -3.0, 95% CI -9.1, 2.6; IDI: 0.017, 95% CI -0.004, 0.05) or considering ICH cases alone (ΔAUC: 0.02, 95% CI -0.02, 0.08; Δ?: -2.0, 95% CI -9.7, 3.4; IDI 0.065, 95% CI -0.03, 0.21). If NIHSS was the only clinical scale included, there was still no improvement in AUC or ? when CT findings were added for the sample with IS/ICH combined (ΔAUC: 0.005, 95% CI -0.01, 0.02; Δ?: -5.0, 95% CI -11.6, 1.0) or for ICH cases alone (ΔAUC: 0.05, 95% CI -0.002, 0.11; Δ?: -4.2, 95% CI -11.5, 2.3). However, IDI was improved when NIHSS was the only clinical scale for IS/ICH combined (IDI: 0.029, 95% CI 0.002, 0.065) and ICH alone (IDI: 0.12, 95% CI 0.005, 0.26). Conclusions: Excluding ICH CT findings had only minimal impact on mortality prediction model performance whether examining ICH and IS together or ICH alone. These findings have important implications for the design of clinical studies involving ICH patients.