Peripheral Monocyte Count Is Associated with Case Fatality after Intracerebral Hemorrhage

Introduction: Preclinical models suggest an inflammatory response mediated by monocytes may contribute to secondary injury after intracerebral hemorrhage (ICH). We recently found an association of absolute monocyte count (AMC) with 30-day case fatality following ICH. We sought to validate this finding in an independent cohort of ICH patients. Hypothesis: AMC is independently associated with 30-day case-fatality following ICH. Methods: The Ethnic/Racial Variations of ICH (ERICH) study is a prospective, multi-center, case-control study of ICH among Caucasian, Black, and Hispanic patients. In 241 adult patients with nontraumatic ICH within 24 hours of symptom onset, demographic information, Glasgow Coma Scale (GCS), ICH volume, 30-day case-fatality, total white blood cell (WBC) count, absolute neutrophil count (ANC), AMC, and hemoglobin concentration were determined. Participating centers were requested to obtain WBC differentials on the 30 most recently enrolled cases. After receiving data on 411 subjects, we excluded 170 subjects whose initial WBC was >24 hours from onset and in those where monocytes and neutrophils were not available, resulting in 241 cases for the analysis. Linear regression was used to evaluate factors associated with ICH volume (log transformed), and logistic regression for factors associated with 30-day case-fatality. Results: Mean age was 62.8 years (SD ± 14 years), 61.8% were men and 33.6% were Black. Median ICH volume was 9.7ml (IQR 4.3-26.7). After adjusting for patient age and initial hemoglobin, higher ANC (p= 0.001) and total WBC count (p=0.0005) were associated with larger ICH volume, whereas AMC was not (p=0.14). After adjusting for age, GCS, and ICH volume, baseline AMC was independently associated with higher 30-day case-fatality (OR 5.24, 95% CI 1.62-16.89, p=0.0056) whereas ANC (OR 0.85, CI 0.15-4.68, p=0.85) and WBC count (OR 0.58, CI 0.04-7.67, p=0.68) were not. Conclusions: In this independent cohort an association between higher admission monocytes and case fatality was corroborated independent of known clinical variables. This suggests a specific role of monocytes in secondary injury following ICH. Inflammatory and neuronal apoptotic pathways mediated by monocytes may be a target for neuroprotection in ICH.

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Monocyte Count and 30-Day Case Fatality in Intracerebral Hemorrhage

Stroke ◽

10.1161/strokeaha.115.009880 ◽

2015 ◽

Vol 46 (8) ◽

pp. 2302-2304 ◽

Cited By ~ 27

Author(s):

Kyle B. Walsh ◽

Padmini Sekar ◽

Carl D. Langefeld ◽

Charles J. Moomaw ◽

Mitchell S.V. Elkind ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Case Fatality ◽

Monocyte Count ◽

Day Case

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Faculty Opinions recommendation of An Intracerebral Hemorrhage Care Bundle Is Associated with Lower Case Fatality.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.736177681.793564819 ◽

2019 ◽

Author(s):

Stephan Mayer

Keyword(s):

Intracerebral Hemorrhage ◽

Case Fatality ◽

Care Bundle ◽

Lower Case

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Abstract TP188: Location of Intracerebral Hemorrhage in a Tri-ethnic Cohort: The ERICH Study

Stroke ◽

10.1161/str.44.suppl_1.atp188 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Lee Birnbaum ◽

Anne Leonard ◽

Julio Andino ◽

Charles J Moomaw ◽

Carl Langfeld ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Univariate Analysis ◽

Case Fatality ◽

Final Model ◽

Location Data ◽

History Of ◽

Race Ethnicity ◽

Pairwise Testing ◽

Racial Ethnic ◽

Control Study

Background: The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) is an ongoing case-control study of spontaneous ICH among non-hispanic whites, non-hispanic blacks, and Hispanics. Prior studies have identified hypertension as a greater risk for non-lobar (NL) ICH as compared with lobar (L) ICH. Given the greater reported prevalence of hypertension among black and Hispanic populations, we hypothesized that the location of ICH may differ by race/ethnicity. Methods: At the time of this analysis, we had ICH location data, lobar vs. non-lobar, on 648 subjects. We performed univariate analysis on known and potential predictors of ICH location: age, sex, race/ethnicity, hypertension, diabetes, BMI, creatinine, cholesterol, aspirin use, smoking, alcohol use, caffeine use, and INR. INR was dichotomized at >1.1. After forcing in age, sex, race, history of diabetes, aspirin use and INR, we added significant and near-significant (p<0.2) variables in a stepwise fashion to complete our final logistic regression model. Our outcome measure was lobar ICH. Conditional pairwise testing was performed for race/ethnicity. Results: Of the 648 subjects (mean age 61.12 ± 14.51 years; 39.8% female; 35.0% Hispanic, 26.5% white, 38.4% black), 181 (27.9%) presented with lobar ICH. Hypertension was present in 525 subjects (75.1% L, 83.3% NL; p=.018), diabetes in 152 (26.0% L, 22.5% NL; p=.348), high cholesterol in 244 (45.9% L, 34.5% NL; p=.008), aspirin use in 200 (37.0% L, 28.5% NL; p=.035), and INR >1.1 (24.1% L, 21.8% NL; p=.535) In our final model, race/ethnicity (p<.024) was associated with location of ICH. Furthermore, white race/ethnicity was associated with L ICH, compared with black (b=.57, p=.016) or Hispanic (b=.56, p=.018). Hypertension (b=-0.63, p=.009) was associated with NL ICH, and smoking (b=0.51, p=.007) was associated with L ICH. Discussion: Our results suggest that there are significant racial/ethnic differences in the distribution of lobar and non-lobar ICH. The conditional pairwise testing for race/ethnicity showed a significantly higher rate of lobar ICH in whites, compared with blacks or Hispanics. These findings are intriguing given the differences in case-fatality rates and age at ICH onset.

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Abstract TP326: Lymphopenia, Infectious Complications and Outcome in Spontaneous Intracerebral Hemorrhage

Stroke ◽

10.1161/str.48.suppl_1.tp326 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Andrea Morotti ◽

Sandro Marini ◽

Michael J Jessel ◽

Kristin Schwab ◽

Alison M Ayres ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Lymphocyte Count ◽

Cox Regression ◽

Case Fatality ◽

Retrospective Chart Review ◽

Infectious Complications ◽

Multiple Infections ◽

Spontaneous Intracerebral Hemorrhage ◽

Poor Outcome ◽

Increased Risk

Background and Purpose: lymphopenia is increasingly recognized as a consequence of acute illness and may predispose to infections. We investigated whether admission lymphopenia (AL) is associated with increased risk of infectious complications and poor outcome in patients with spontaneous intracerebral hemorrhage (ICH). Methods: we analyzed a prospectively collected cohort of ICH patients ascertained between 1994 and 2015. Subjects were included if they had a lymphocyte count obtained within 24 h from onset and AL was defined as lymphocyte count<1000/uL. Infectious complications were assessed through retrospective chart review and the association between AL, infectious complications and mortality was investigated with a multivariable Cox regression and logistic regression respectively. Results: 2014 patients met the inclusion criteria (median age 75, males 54.0%) of whom 548 (27.2%) had AL and 605 (30.0%) experienced an infectious complication. Overall case fatality at 90 days was 36.9%. Patients with AL were more severely affected, as highlighted by larger hematoma volume, higher frequency of intraventricular hemorrhage and lower Glasgow Coma Scale score (all p<0.001). AL was independently associated with increased risk of pneumonia (Hazard Ratio [HR] 1.65, 95% confidence interval [CI] 1.32-2.05, p<0.001) and multiple infections (HR 1.75, 95% CI 1.22-2.51, p=0.002). The association with urinary tract infection, sepsis or other infections was not significant. AL was also an independent predictor of 90-day mortality (odds ratio 1.55, 95% CI 1.18-2.04, p=0.002) after adjusting for confounders. Conclusions: AL is common in ICH and associated with increased risk of infectious complications and poor outcome. Further studies will be needed to determine whether prophylactic antibiotics in ICH patients with AL can improve outcome.

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Abstract W MP110: INR reversal of Oral Anticoagulant-Associated Intracerebral Hemorrhage

Stroke ◽

10.1161/str.46.suppl_1.wmp110 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Fernando Testai ◽

Faisal Mukarram ◽

Andrew Culpepper ◽

Maureen Hillmann ◽

Padmini Sekar ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Oral Anticoagulants ◽

Case Fatality ◽

Fresh Frozen Plasma ◽

Factor Vii ◽

Hematoma Expansion ◽

Racial Variations ◽

Fresh Frozen ◽

Time And Being ◽

Admission Variables

Background: The use of oral anticoagulants (OAC) is associated with poor outcome in intracerebral hemorrhage (ICH). In this study we investigated the effect of delayed INR reversal and the factors influencing it in patients with OAC-associated ICH (OAC-ICH). Methods: Data were obtained from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study which is a prospective, multi-ethnic multicenter study of ICH. Exclusion criteria included missing initial hematoma volume, INR or ED arrival time and being on heparin. Baseline characteristics, INR at baseline and 12h, hematoma location and volume, treatment received, hematoma expansion at 24h, and mortality at 3 months were recorded. INR reversal was defined as INR<1.4 at 12h post admission. Variables associated with INR reversal and case fatality at 3 months in non-OAC users and OAC users with and without INR <1.4 were compared. Results: A total of 1,746 of 2,276 subjects were included in the analysis. A higher proportion of OAC users (n=185) were white and had hypertension, diabetes, hypercholesterolemia, and lobar ICH than non-users (P<0.05). Baseline INRs for the OAC group were 3.1 (28.7%). Subjects on OAC received fresh frozen plasma (FFP, 44%) monotherapy, either recombinant factor VII or prothrombin complex (FVII/PCC, 7%), or a combination of FFP/FVII/PCC (11%). Increasing age (OR=0.96, 95% CI 0.94-0.98), elevated baseline INR (OR=0.34, 95% CI 0.26-0.43), and use of FFP only (OR=0.07, 95% CI 0.04-0.13) was associated with lack of INR reversal at 12h. Median INR at 12h (IQR) were 1.4 (1.3-1.6), 1.1 (0.9-1.1), and 1.0 (1.0-1.3) for the FFP, PCC/FVII, and FFP/FVII/PCC groups, respectively (p1.4 did not influence the rate of hematoma expansion at 24h. Case fatality at 3 months was 22% for non-OAC-ICH, 34% for OAC-ICH with INR<1.4, and 44% for OAC-ICH with INR>1.4 (p=.0005). Conclusion: In the ERICH study, patients treated with FFP monotherapy were less likely to have a normalized INR at 12h and this was associated with increased case fatality at 3 months. The use of FVII/PCC may shorten time to INR correction and improve outcome in OAC-ICH.

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