Blood Pressure and Anticoagulation Reversal Management during Off-Hours in Oral Anticoagulation-Associated Intracerebral Hemorrhage

2020 ◽  
Vol 49 (2) ◽  
pp. 177-184
Author(s):  
Anne Mrochen ◽  
Maximilian I. Sprügel ◽  
Stefan T. Gerner ◽  
Jochen A. Sembill ◽  
Stefan Lang ◽  
...  

Background: Prevention of hematoma enlargement in oral anticoagulation-associated intracerebral hemorrhage (OAC-ICH) focuses on blood pressure (BP) reduction and OAC reversal. We investigated whether treatment efficiency and clinical outcomes differ between OAC-ICH patients admitted outside versus during regular working hours. Methods: Based on pooled data of multicenter cohort studies, we grouped OAC-ICH patients (vitamin K antagonist [VKA], non-vitamin K oral anticoagulant [NOAC]) according to on- vs. off-hour admission. Primary outcome was the functional outcome using the modified Rankin scale (mRS) dichotomized into favorable (mRS 0–3) and unfavorable (mRS 4–6) and mortality at 3 months. Secondary outcome measures included the occurrence of hematoma enlargement, the proportions of patients with systolic BP <140 mm Hg and with anticoagulation treatment achieving international normalized ratio (INR) levels <1.3 at 4 h. Propensity score matching (PSM) was performed to account for imbalances in baseline characteristics. Results: The study population consisted of 76/126 NOAC-ICH patients and 1,005/1,470 VKA patients presenting during off-hours. Functional outcome and mortality rates were not significantly different among PSM patients with VKA-ICH and NOAC-ICH during on- vs. off-hours (mRS 4–6 VKA-ICH: on-hour: 239/357 [66.9%] vs. 253/363 [69.7%] off-hour; p = 0.43; NOAC-ICH: on-hour 26/42 [61.9%] vs. off-hour: 37/57 [64.9%]; p = 0.76; mRS 6 VKA-ICH: on-hour: 127/357 [35.6%] vs. off-hour: 148/363 [40.8%]; p = 0.15; ­NOAC-ICH: on-hour 17/42 [40.5%] vs. off-hour: 16/57 [28.1%]; p = 0.20). There were no differences detectable regarding the secondary outcome measures (i.e., hematoma enlargement, the proportion of patients who achieved systolic BP levels <140 mm Hg at 4 h as well as anticoagulation treatment achieving INR levels <1.3 at 4 h) in OAC patients. Conclusion: Our study implies that BP reduction and anticoagulation reversal management are well established and associated with similar rates of hematoma enlargement and clinical outcomes in on- vs. off-hour admitted OAC-ICH patients.

2019 ◽  
pp. 174749301989566 ◽  
Author(s):  
Maximilian I Sprügel ◽  
Joji B Kuramatsu ◽  
Stefan T Gerner ◽  
Jochen A Sembill ◽  
Dominik Madžar ◽  
...  

Aims This study determined the influence of age on bleeding characteristics and clinical outcomes in primary spontaneous (non-OAC), vitamin K antagonist-related (VKA-) and non-vitamin K antagonist oral anticoagulant-related (NOAC-) ICH. Methods Pooled individual patient data of multicenter cohort studies were analyzed by logistic regression modelling and propensity-score-matching (PSM) to explore the influence of advanced age on clinical outcomes among non-OAC-, VKA-, and NOAC-ICH. Primary outcome measure was functional outcome at three months assessed by the modified Rankin Scale, dichotomized into favorable (mRS = 0–3) and unfavorable (mRS = 4–6) functional outcome. Secondary outcome measures included mortality, hematoma characteristics, and frequency of invasive interventions. Results In VKA-ICH 33.5% (670/2001), in NOAC-ICH 44.2% (69/156) and in non-OAC-ICH 25.2% (254/1009) of the patients were ≥80 years. After adjustment for treatment interventions and relevant parameters, elderly ICH patients comprised worse functional outcome at three months (adjusted odds ratio (aOR) in VKA-ICH: 1.49 (1.21–1.84); p < 0.001; NOAC-ICH: 2.01 (0.95–4.26); p = 0.069; non-OAC-ICH: 3.54 (2.50–5.03); p < 0.001). Anticoagulation was significantly associated with worse functional outcome below the age of 70 years, (aOR: 2.38 (1.78–3.16); p < 0.001), but not in patients of ≥70 years (aOR: 1.21 (0.89–1.65); p = 0.217). The differences in initial ICH volume and extent of ICH enlargement between OAC-ICH and non-OAC-ICH gradually decreased with increasing patient age. Conclusions As compared to elderly ICH-patients, in patients <70 years OAC-ICH showed worse clinical outcomes compared to non-OAC-ICH because of larger baseline ICH-volumes and extent of hematoma enlargement. Treatment strategies aiming at neutralizing altered coagulation should be aware of these findings.


Stroke ◽  
2021 ◽  
Vol 52 (2) ◽  
pp. 611-619
Author(s):  
Anne Mrochen ◽  
Maximilian I. Sprügel ◽  
Stefan T. Gerner ◽  
Jochen A. Sembill ◽  
Stefan Lang ◽  
...  

Background and Purpose: The impact of platelets on hematoma enlargement (HE) of intracerebral hemorrhage (ICH) is not yet sufficiently elucidated. Especially the role of reduced platelet counts on HE and clinical outcomes is still poorly understood. This study investigated the influence of thrombocytopenia on HE, functional outcome, and mortality in patients with ICH with or without prior antiplatelet therapy (APT). Methods: Individual participant data of multicenter cohort studies (multicenter RETRACE program [German-Wide Multicenter Analysis of Oral Anticoagulation-Associated Intracerebral Hemorrhage] and single-center UKER-ICH registry [Universitätsklinikum Erlangen Cohort of Patients With Spontaneous ICH]) were grouped into APT and non-APT ICH patients according to the platelet count, that is, with or without thrombocytopenia (cells <150×10 9 /L). Of all patients, 51.5% (1124 of 2183) were on vitamin K antagonist. Imbalances in baseline characteristics including proportions of vitamin K antagonist patients were addressed using propensity score matching. Outcome analyses included HE (>33%), as well as mortality and functional outcome, after 3 months using the modified Rankin Scale, dichotomized into favorable (modified Rankin Scale score, 0–3) and unfavorable (modified Rankin Scale score, 4–6). Results: Of overall 2252 ICH patients, 11.4% (52 of 458) under APT and 14.0% (242 of 1725) without APT presented with thrombocytopenia on admission. The proportion of patients with HE was not significantly different between patients with or without thrombocytopenia among APT and non-APT ICH patients after propensity score matching (HE: APT patients: 9 of 40 [22.5%] thrombocytopenia versus 27 of 115 [23.5%] nonthrombocytopenia, P =0.89; non-APT patients: 54 of 174 [31.0%] thrombocytopenia versus 106 of 356 [29.8%] nonthrombocytopenia, P =0.77). In both (APT and non-APT) propensity score matching cohorts, there were no significant differences regarding functional outcome. Mortality after 3 months did not differ among non-APT patients, whereas the mortality rate was significantly higher for APT patients with thrombocytopenia versus APT patients with normal platelet count (APT: 29 of 46 [63.0%] thrombocytopenia versus 58 of 140 [41.4%] nonthrombocytopenia, P =0.01; non-APT: 95 of 227 [41.9%] thrombocytopenia versus 178 of 455 [39.1%] nonthrombocytopenia, P =0.49). Conclusions: Our study implies that thrombocytopenia does not affect rates of HE and functional outcome among ICH patients, neither in patients with nor without APT. In light of increased mortality, the significance of platelet transfusions for ICH patients with thrombocytopenia and previous APT should be explored in future studies.


2017 ◽  
Vol 01 (04) ◽  
pp. E275-E286 ◽  
Author(s):  
Joji Kuramatsu ◽  
Stefan Gerner ◽  
Hagen Huttner ◽  
Stefan Schwab

AbstractThe incidence of anticoagulation-associated intracerebral hemorrhage (OAC-ICH) is increasing along with demographic changes and patients requiring oral anticoagulation for atrial fibrillation. OAC-ICH is one of the most detrimental sub-types of hemorrhagic stroke, characterized by larger hemorrhage volumes, more frequent intraventricular hemorrhage, increased and prolonged hematoma enlargement. The impact of these outcome predictors’ results in greater mortality rates and larger numbers of patients left in functionally dependent states after ICH. Yet, evidence on treatment options for these severely affected patients remains limited, resulting in weak recommendations by international and European guidelines. Minimization of hematoma enlargement constitutes the main focus of acute care, possibly achieved by blood pressure and reversal management. In all OAC-ICH patients irrespective of anticoagulation agent, immediate and aggressive blood pressure reductions as fast as possible targeting systolic blood pressure levels of 140 mmHg (at least within 4–6 h) seems reasonable. Specifically, in vitamin-K-associated ICH, blood pressure reductions have been shown to be associated with reduced rates of hematoma enlargement. Reversal management in OAC-ICH should be carried out as quickly as possible, though accounting for the different anticoagulation agents used. In vitamin-K-associated ICH, recent large-sized multicenter investigations contributed to refining reversal strategies. One German-wide cohort study including roughly 1 200 patients identified for the first time beneficial target values to guide reversal treatment. Anticoagulation reversal should achieve INR values of less than 1.3 or 1.2 at least within 4 h after admission. Agents to be used comprise prothrombin complex concentrates (PCC), which may achieve faster and more complete reversal. This combined approach (blood pressure management and INR-reversal) was associated with significant reductions of hematoma enlargement and lower in-hospital mortality rates. For dabigatran-related bleeding complications, most recently an antidote (Idarucizumab) has been approved, which has been prospectively investigated and showed rapid and almost complete reversal as well as sufficient hemostasis. Currently, bleeding under the influence of factor-Xa inhibitors poses great difficulties because no antidote is available and efficacy of commonly used antagonizing agents, i. e., PCC or fresh-frozen plasma (FFP), has not been proven for clinical use. The main aim of the present review focuses on acute-care management of OAC-ICH and tries to depict treatment options based on the most current data. Moreover, current neurocritical-care therapies for ICH will be reviewed to identify relevant implications specific to OAC-ICH treatment.


Neurology ◽  
2017 ◽  
Vol 88 (18) ◽  
pp. 1693-1700 ◽  
Author(s):  
Duncan Wilson ◽  
David J. Seiffge ◽  
Christopher Traenka ◽  
Ghazala Basir ◽  
Jan C. Purrucker ◽  
...  

Objective:In an international collaborative multicenter pooled analysis, we compared mortality, functional outcome, intracerebral hemorrhage (ICH) volume, and hematoma expansion (HE) between non–vitamin K antagonist oral anticoagulation–related ICH (NOAC-ICH) and vitamin K antagonist–associated ICH (VKA-ICH).Methods:We compared all-cause mortality within 90 days for NOAC-ICH and VKA-ICH using a Cox proportional hazards model adjusted for age; sex; baseline Glasgow Coma Scale score, ICH location, and log volume; intraventricular hemorrhage volume; and intracranial surgery. We addressed heterogeneity using a shared frailty term. Good functional outcome was defined as discharge modified Rankin Scale score ≤2 and investigated in multivariable logistic regression. ICH volume was measured by ABC/2 or a semiautomated planimetric method. HE was defined as an ICH volume increase >33% or >6 mL from baseline within 72 hours.Results:We included 500 patients (97 NOAC-ICH and 403 VKA-ICH). Median baseline ICH volume was 14.4 mL (interquartile range [IQR] 3.6–38.4) for NOAC-ICH vs 10.6 mL (IQR 4.0–27.9) for VKA-ICH (p = 0.78). We did not find any difference between NOAC-ICH and VKA-ICH for all-cause mortality within 90 days (33% for NOAC-ICH vs 31% for VKA-ICH [p = 0.64]; adjusted Cox hazard ratio (for NOAC-ICH vs VKA-ICH) 0.93 [95% confidence interval (CI) 0.52–1.64] [p = 0.79]), the rate of HE (NOAC-ICH n = 29/48 [40%] vs VKA-ICH n = 93/140 [34%] [p = 0.45]), or functional outcome at hospital discharge (NOAC-ICH vs VKA-ICH odds ratio 0.47; 95% CI 0.18–1.19 [p = 0.11]).Conclusions:In our international collaborative multicenter pooled analysis, baseline ICH volume, hematoma expansion, 90-day mortality, and functional outcome were similar following NOAC-ICH and VKA-ICH.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Andrea Morotti ◽  
Bart H Brouwers ◽  
Javier M Romero ◽  
Michael J Jessel ◽  
Anastasia Vashkevich ◽  
...  

Background and Purpose: the computed tomography angiography (CTA) spot sign is a strong predictor of intracerebral hemorrhage (ICH) expansion, and may mark those most likely to benefit from intensive blood pressure (BP) reduction. The Spot Sign score in restricting ICH growth (SCORE-IT) study analyzed whether intensive BP reduction improved outcome in Spot Sign positive patients enrolled in the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) clinical trial. Methods: In ATACH-2, patients with ICH were randomly assigned to intensive (systolic BP target: 110-139 mmHg) versus standard (systolic BP target: 140-179 mmHg) BP treatment within 4.5 h from stroke onset. This analysis included patients with a CTA performed within 8 hours from onset. The association between intensive BP lowering, ICH expansion and functional outcome was investigated with a multivariable logistic regression model. Results: 133 subjects met the inclusion criteria, of whom 53 (39.9%) had a spot sign and 24/123 (19.5%) experienced ICH expansion. A total of 56/123 patients had a 90 day modified Rankin scale (mRS) >3 (45.5%). Among Spot positive patients, 74.1% of those in the intensive BP lowering group had poor outcome, compared with 50.0% of those in the standard group (p=0.31). After adjustment for potential confounders, intensive BP lowering was not associated with a significant reduction of ICH expansion (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.27 - 2.51, p = 0.74) or improved functional outcome (OR for mRS>3 1.24, 95% CI 0.53 - 2.91, p = 0.62) in spot sign positive ICH patients. Conclusions: We found no evidence that ICH patients with a spot sign specifically benefit from intensive BP reduction.


2016 ◽  
Vol 12 (6) ◽  
pp. 623-627 ◽  
Author(s):  
Cláudia Marques-Matos ◽  
José Nuno Alves ◽  
João Pedro Marto ◽  
Joana Afonso Ribeiro ◽  
Ana Monteiro ◽  
...  

Background There is a lower reported incidence of intracranial hemorrhage with non-vitamin K antagonist oral anticoagulants compared with vitamin K antagonist. However, the functional outcome and mortality of intracranial hemorrhage patients were not assessed. Aims To compare the outcome of vitamin K antagonists- and non-vitamin K antagonist oral anticoagulants-related intracranial hemorrhage. Methods We included consecutive patients with acute non-traumatic intracranial hemorrhage on oral anticoagulation therapy admitted between January 2013 and June 2015 at four university hospitals. Clinical and demographic data were obtained from individual medical records. Intracranial hemorrhage was classified as intracerebral, extra-axial, or multifocal using brain computed tomography. Three-month functional outcome was assessed using the modified Rankin Scale. Results Among 246 patients included, 24 (9.8%) were anticoagulated with a non-vitamin K antagonist oral anticoagulants and 222 (90.2%) with a vitamin K antagonists. Non-vitamin K antagonist oral anticoagulants patients were older (81.5 vs. 76 years, p = 0.048) and had intracerebral hemorrhage more often (83.3% vs. 63.1%, p = 0.048). We detected a non-significant trend for larger intracerebral hemorrhage volumes in vitamin K antagonists patients ( p = 0.368). Survival analysis adjusted for age, CHA2DS2VASc, HAS-BLED, and anticoagulation reversal revealed that non-vitamin K antagonist oral anticoagulants did not influence three-month mortality (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.39–1.80, p = 0.638). Multivariable ordinal regression for three-month functional outcome did not show a significant shift of modified Rankin Scale scores in non-vitamin K antagonist oral anticoagulants patients (odds ratio (OR) 1.26, 95%CI 0.55–2.87, p = 0.585). Conclusions We detected no significant differences in the three-month outcome between non-vitamin K antagonist oral anticoagulants- and vitamin K antagonists-associated intracranial hemorrhage, despite unavailability of non-vitamin K antagonist oral anticoagulants-specific reversal agents.


Hypertension ◽  
2015 ◽  
Vol 65 (5) ◽  
pp. 1026-1032 ◽  
Author(s):  
Xia Wang ◽  
Hisatomi Arima ◽  
Emma Heeley ◽  
Candice Delcourt ◽  
Yining Huang ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Jianhua Peng ◽  
Bastian Volbers ◽  
Maximilian I. Sprügel ◽  
Philip Hoelter ◽  
Tobias Engelhorn ◽  
...  

Objective: Early enteral nutrition (EEN) represents the current standard of care for patients treated in general intensive care units (ICU). Specific nutritional recommendations for patients receiving dedicated neurocritical care are not established. This study investigated associations of EEN with clinical outcomes for patients suffering from intracerebral hemorrhage treated at a neurological ICU (NICU).Methods: This retrospective cohort study included patients admitted to the NICU with atraumatic ICH over a 4-year period. Nutritional data, demographic, clinical, radiological, and laboratory characteristics were assessed. EEN was defined as any enteral nutrition within 48 hours after admission. Comparisons were undertaken for patients with EEN vs. those without, further propensity score (PS) matching (caliper 0.2; one: many) was used to account for baseline imbalances. Primary outcome was the modified Rankin Scale (0–3 = favorable, 4–6 = unfavorable) at 12 months, secondary outcomes comprised perihemorrhagic edema (PHE) volume, infectious complications during the hospital stay, and mRS at 3 months, as well as mortality rates at 3 and 12 months.Results: Of 166 ICH-patients treated at the NICU, 51 (30.7%) patients received EEN, and 115 (69.3%) patients received no EEN (nEEN). After propensity score matching, calories delivered from enteral nutrition (EEN 161.4 [106.4–192.3] kcal/day vs. nEEN 0.0 [0.0–0.0], P &lt; 0.001) and the total calories (EEN 190.0 [126.0–357.0] kcal/day vs. nEEN 33.6 [0.0–190.0] kcal/day, P &lt; 0.001) were significantly different during the first 48 h admitted in NICU. Functional outcome at 12 months (mRS 4–6, EEN 33/43 [76.7%] vs. nEEN, 49/64 [76. 6%]; P = 1.00) was similar in the two groups. There were neither differences in mRS at 3 months, nor in mortality rates at 3 and 12 months between the two groups. EEN did not affect incidence of infective complications or gastrointestinal adverse events during the hospital stay; however, EEN was associated with significantly less extent of PHE evolution [maximum absolute PHE (OR 0.822, 95% CI 0.706–0.957, P = 0.012); maximum relative PHE (OR 0.784, 95% CI 0.646–0.952, P = 0.014)].Conclusion: In our study, EEN was associated with reduced PHE in ICH-patients treated at a NICU. However, this observation did not translate into improved survival or functional outcome at 3 and 12 months.


2019 ◽  
Vol 16 (2) ◽  
pp. 123-128 ◽  
Author(s):  
Xianjun Han ◽  
Shoujiang You ◽  
Zhichao Huang ◽  
Qiao Han ◽  
Chongke Zhong ◽  
...  

Background: Experimental animal model studies have shown neuroprotective properties of magnesium. We assessed the relationship between admission magnesium and admission stroke severity and 3-month clinical outcomes in patients with acute intracerebral hemorrhage (ICH). Methods: The present study included 323 patients with acute ICH who were prospectively identified. Demographic characteristics, lifestyle risk factors, National Institute of Health Stroke Scale (NIHSS) score, hematoma volumes, and other clinical features were recorded at baseline for all participants. Patients were divided into three groups based on the admission magnesium levels (T1: <0.84; T2: 0.84-0.91; T3: =0.91 mmol/L). Clinical outcomes were death, poor functional outcome (defined by modified rankin ccale [mRS] scores 3-6) at 3 months. Results: After 3-month follow-up, 40 (12.4%) all-cause mortality and 132 (40.9%) poor functional outcome were documented. Median NIHSS scores for each tertile (T1 to T3) were 8.0, 5.5, and 6.0, and median hematoma volumes were 10.0, 8.05, and 12.4 ml, respectively. There was no significant association between baseline NIHSS scores (P=0.176) and hematoma volumes (P=0.442) in T3 and T1 in multivariable linear regression models. Compared with the patients in T1, those in T3 were associated with less frequency of all-cause mortality [adjusted odds ratio (OR), 0.10; 95% confidence interval (CI), 0.02-0.54; P-trend=0.010] but not poor functional outcome (adjusted OR, 1.80; 95%CI, 0.71-4.56; P-trend=0.227) after adjustment for potential confounders. Conclusion: Elevated admission serum magnesium level is associated with lower odds of mortality but not poor functional outcome at 3 months in patients with acute ICH.


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