Systemic response of coated-platelet and peripheral blood inflammatory cell indices after aneurysmal subarachnoid hemorrhage and long-term clinical outcome.
Ontology highlight
ABSTRACT: Purpose
Post-hemorrhage period after aneurysmal subarachnoid hemorrhage (aSAH) has several systemic manifestations including prothrombotic and pro-inflammatory states. Inter-relationship between these states using established/routine laboratory biomarkers and its long-term effect on clinical outcome is not well-defined.Materials and methods
Retrospective analysis of prospective cohort of 44 aSAH patients. Trend of procoagulant biomarkers [coated-platelets, mean platelet volume to platelet count (MPV:PLT)] and peripheral inflammatory biomarkers [platelet-lymphocyte ratio (PLR), neutrophil-platelet ratio (NLR)] were analyzed using regression analysis. Occurrence of delayed cerebral ischemia (DCI), modified Rankin score (mRS) of 3-6 and Montreal cognitive assessment (MoCA) of <26 at 1-year defined adverse clinical outcome.Results
Patients with worse mRS and MoCA score had higher rise in coated-platelet compared to those with better scores [20.4 (IQR: 15.6, 32.9) vs. 10.95 (IQR: 6.1, 18.9), p = 0.003] and [16.9 (IQR: 13.4, 28.1) vs. 10.95 (IQR: 6.35, 18.65), p = 0.02] respectively. NLR and PLR trends showed significant initial decline followed by a gradual rise in NLR among those without DCI as compared to persistent low levels in those developing DCI (0.13 units/day vs. -0.07 units/day, p = 0.06).Conclusions
Coated-platelet rise after aSAH is associated with adverse long-term clinical outcome. NLR and PLR trends show an early immune-depressed state after aSAH.
SUBMITTER: Ray B
PROVIDER: S-EPMC8663918 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Aneurysmal subarachnoid hemorrhage (aSAH) is one of the most severe neurological disorders, with a high mortality rate and severe disabling functional sequelae. Systemic inflammation following hemorrhagic stroke may play an important role in mediating intracranial and extracranial tissue damage. Previous studies showed that various systemic inflammatory biomarkers might be useful in predicting clinical outcomes. Anti-inflammatory treatment might be a promising therapeutic approach for improving the prognosis of patients with aSAH. This review summarizes the complicated interactions between the nervous system and the immune system.
| S-EPMC10342051 | biostudies-literature
Project description:BackgroundCerebral edema (CE) at admission is a surrogate marker of 'early brain injury' (EBI) after subarachnoid hemorrhage (SAH). Only recently has the focus on the changes in CE after SAH such as delayed resolution or newly developed CE been examined. Among several factors, an early systemic inflammatory response has been shown to be associated with CE. We investigate inflammatory markers in subjects with early CE which does not resolve, i.e., persistent CE after SAH.MethodsComputed tomography scans of SAH patients were graded at admission and at 7 days after SAH for CE using the 0-4 'subarachnoid hemorrhage early brain edema score' (SEBES). SEBES ≤ 2 and SEBES ≥ 3 were considered good and poor grade, respectively. Serum samples from the same subject cohort were collected at 4 time periods (at < 24 h [T1], at 24 to 48 h [T2]. 3-5 days [T3] and 6-8 days [T4] post-admission) and concentration levels of 17 cytokines (implicated in peripheral inflammatory processes) were measured by multiplex immunoassay. Multivariable logistic regression analyses were step-wisely performed to identify cytokines independently associated with persistent CE adjusting for covariables including age, sex and past medical history (model 1), and additional inclusion of clinical and radiographic severity of SAH and treatment modality (model 2).ResultsOf the 135 patients enrolled in the study, 21 of 135 subjects (15.6%) showed a persistently poor SEBES grade. In multivariate model 1, higher Eotaxin (at T1 and T4), sCD40L (at T4), IL-6 (at T1 and T3) and TNF-α (at T4) were independently associated with persistent CE. In multivariate model 2, Eotaxin (at T4: odds ratio [OR] = 1.019, 95% confidence interval [CI] = 1.002-1.035) and possibly PDGF-AA (at T4), sCD40L (at T4), and TNF-α (at T4) was associated with persistent CE.ConclusionsWe identified serum cytokines at different time points that were independently associated with persistent CE. Specifically, persistent elevations of Eotaxin is associated with persistent CE after SAH.
| S-EPMC9354324 | biostudies-literature
Project description:Endovascular techniques have proven beneficial in the treatment of aneurysmal subarachnoid hemorrhage (aSAH), but with high risk of arterial clotting, emboli and dissection. Platelet activation and alterations in hemostasis may contribute to these complications. We investigated platelet activation and aggregation pathways in aSAH patients who underwent endovascular treatment.Two blood samples were taken, in the early days after bleeding and during the period at risk of vasospasm. We studied platelet activation through the expression of GpIIbIIIa and P-selectin as well as aggregation rate in the presence of agonists. Platelets from aSAH patients were compared with those from orthopedic postoperative patients (POSTOP).Platelets in aSAH were initially spontaneously activated and remained so over time. aSAH platelets were further activated with rapid aggregation in the presence of agonists, particularly ADP, with behavior comparable to POSTOP platelets.aSAH platelets showed prolonged increases in activation and aggregation. Therapies targeting the ADP pathway might reduce the risk of clotting and ischemic events in this context among patients requiring multiple endovascular procedures.Not applicable.
| S-EPMC5924502 | biostudies-literature
Project description:Aneurysmal subarachnoid hemorrhage is a neurologic emergency that requires immediate patient stabilization and prompt diagnosis and treatment. Early measures should focus on principles of advanced cardiovascular life support. The aneurysm should be evaluated and treated in a comprehensive stroke center by a multidisciplinary team capable of endovascular and, operative approaches. Once the aneurysm is secured, the patient is best managed by a dedicated neurocritical care service to prevent and manage complications, including a syndrome of delayed neurologic decline. The goal of such specialized care is to prevent secondary injury, reduce length of stay, and improve outcomes for survivors of the disease.
| S-EPMC8147706 | biostudies-literature
Project description:Aneurysmal subarachnoid hemorrhage (SAH) is a worldwide health burden with high fatality and permanent disability rates. The overall prognosis depends on the volume of the initial bleed, rebleeding, and degree of delayed cerebral ischemia (DCI). Cardiac manifestations and neurogenic pulmonary edema indicate the severity of SAH. The International Subarachnoid Aneurysm Trial (ISAT) reported a favorable neurological outcome with the endovascular coiling procedure compared with surgical clipping at the end of 1 year. The ISAT trial recruits were primarily neurologically good grade patients with smaller anterior circulation aneurysms, and therefore the results cannot be reliably extrapolated to larger aneurysms, posterior circulation aneurysms, patients presenting with complex aneurysm morphology, and poor neurological grades. The role of hypothermia is not proven to be neuroprotective according to a large randomized controlled trial, Intraoperative Hypothermia for Aneurysms Surgery Trial (IHAST II), which recruited patients with good neurological grades. Patients in this trial were subjected to slow cooling and inadequate cooling time and were rewarmed rapidly. This methodology would have reduced the beneficial effects of hypothermia. Adenosine is found to be beneficial for transient induced hypotension in 2 retrospective analyses, without increasing the risk for cardiac and neurological morbidity. The neurological benefit of pharmacological neuroprotection and neuromonitoring is not proven in patients undergoing clipping of aneurysms. DCI is an important cause of morbidity and mortality following SAH, and the pathophysiology is likely multifactorial and not yet understood. At present, oral nimodipine has an established role in the management of DCI, along with maintenance of euvolemia and induced hypertension. Following SAH, hypernatremia, although less common than hyponatremia, is a predictor of poor neurological outcome.
| S-EPMC4463029 | biostudies-other
Project description:Aneurysmal subarachnoid hemorrhage is a life-threatening disease requiring neurocritical care. Delayed cerebral ischemia is a well-known complication that contributes to unfavorable neurological outcomes. Cerebral vasospasm has been thought to be the main cause of delayed cerebral ischemia, and although several studies were able to decrease cerebral vasospasm, none showed improved neurological outcomes. Our target is not cerebral vasospasm but improving neurological outcomes. The purpose of this review is to discuss what intensivists should know and can do to improve clinical outcomes in subarachnoid hemorrhage patients.Delayed cerebral ischemia is thought to be due to not only vasospasm but also multifactorial mechanisms. Additionally, the concept of early brain injury, which occurs within the first 72 h after the hemorrhage, has become an important concern. Increasing sympathetic activity after the hemorrhage is associated with cardiopulmonary complications and poor outcomes. Serum lactate measurement may be a valuable marker reflecting the severity of sympathetic activity. The transpulmonary thermodilution method will bring about an advanced understanding of hemodynamic management. Fever is a well-recognized symptom and targeted temperature management is an anticipated intervention. To avoid hyperglycemia and hypoglycemia, performing moderate glucose control and minimizing glucose variability are important concepts in glycemic management, but the optimal target range remains unknown. Dysnatremia seems to be associated with negative outcomes. It is not clear yet that maintaining normonatremia actively improves neurological outcomes. Optimal duration of intensive care management has not been determined.Although we have an advanced understanding of the pathophysiology and clinical characteristics of subarachnoid hemorrhage, there are many controversies in the intensive care unit management of subarachnoid hemorrhage. With an awareness of not only delayed cerebral ischemia but also early brain injury, more attention should be given to various aspects to improve neurological outcomes.
| S-EPMC5941608 | biostudies-other
Project description:ObjectiveTo analyze the impact of inflammation and negative nitrogen balance (NBAL) on nutritional status and outcomes after subarachnoid hemorrhage (SAH).MethodsThis was a prospective observational study of SAH patients admitted between May 2008 and June 2012. Measurements of C-reactive protein (CRP), transthyretin (TTR), resting energy expenditure (REE), and NBAL (g/day) were performed over 4 preset time periods during the first 14 postbleed days (PBD) in addition to daily caloric intake. Factors associated with REE and NBAL were analyzed with multivariable linear regression. Hospital-acquired infections (HAI) were tracked daily for time-to-event analyses. Poor outcome at 3 months was defined as a modified Rankin Scale score ≥ 4 and assessed by multivariable logistic regression.ResultsThere were 229 patients with an average age of 55 ± 15 years. Higher REE was associated with younger age (p = 0.02), male sex (p < 0.001), higher Hunt Hess grade (p = 0.001), and higher modified Fisher score (p = 0.01). Negative NBAL was associated with lower caloric intake (p < 0.001), higher body mass index (p < 0.001), aneurysm clipping (p = 0.03), and higher CRP:TTR ratio (p = 0.03). HAIs developed in 53 (23%) patients on mean PBD 8 ± 3. Older age (p = 0.002), higher Hunt Hess (p < 0.001), lower caloric intake (p = 0.001), and negative NBAL (p = 0.04) predicted time to first HAI. Poor outcome at 3 months was associated with higher Hunt Hess grade (p < 0.001), older age (p < 0.001), negative NBAL (p = 0.01), HAI (p = 0.03), higher CRP:TTR ratio (p = 0.04), higher body mass index (p = 0.03), and delayed cerebral ischemia (p = 0.04).ConclusionsNegative NBAL after SAH is influenced by inflammation and associated with an increased risk of HAI and poor outcome. Underfeeding and systemic inflammation are potential modifiable risk factors for negative NBAL and poor outcome after SAH.
| S-EPMC4336106 | biostudies-literature
Project description:This study aims to investigate the characteristics of patients with mild aneurysmal and non-aneurysmal perimesencephalic and non-perimesencephalic subarachnoid hemorrhage (aSAH, pmSAH, npmSAH) with emphasis on admission biomarkers, clinical course, and outcome. A prospective cohort of 115 patients with aSAH (Hunt and Hess 1-3) and of 35 patients without aneurysms (16 pmSAH and 19 npmSAH) admitted between January 2014 and January 2020 was included. Demographic data, blood samples on admission, complications (hydrocephalus, shunt dependency, delayed cerebral ischemia DCI, DCI-related infarction, and mortality), and outcome after 6 months were analyzed. Demographic data was comparable between all groups except for age (aSAH 55 [48-65] vs. npmSAH 60 [56-68] vs. pmSAH 52 [42-60], p = 0.032) and loss of consciousness (33% vs. 0% vs. 0%, p = 0.0004). Admission biomarkers showed poorer renal function and highest glucose levels for npmSAH patients. Complication rate in npmSAH was high and comparable to that of aSAH patients (hydrocephalus, shunt dependency, DCI, DCI-related infarction, mortality), but nearly absent in patients with pmSAH. Favorable outcome after 6 months was seen in 92.9% of pmSAH, 83.3% of npmSAH, and 62.7% of aSAH (p = 0.0264). In this prospective cohort of SAH patients, npmSAH was associated with a complicated clinical course, comparable to that of patients with aSAH. In contrast, such complications were nearly absent in pmSAH patients, suggesting fundamental differences in the pathophysiology of patients with different types of non-aneurysmal hemorrhage. Our findings underline the importance for a precise terminology according the hemorrhage etiology as a basis for more vigilant management of npmSAH patients. NCT02142166, 05/20/2014, retrospectively registered.
| S-EPMC8976787 | biostudies-literature
Project description:There remains a proportion of patients with unfavorable outcomes after aneurysmal subarachnoid hemorrhage, of particular relevance in those who present with a good clinical grade. A forewarning of those at risk provides an opportunity towards more intensive monitoring, investigation, and prophylactic treatment prior to the clinical manifestation of advancing cerebral injury.To assess whether biochemical markers sampled in the first days after the initial hemorrhage can predict poor outcome.All patients recruited to the multicenter Simvastatin in Aneurysmal Hemorrhage Trial (STASH) were included. Baseline biochemical profiles were taken between time of ictus and day 4 post ictus. The t-test compared outcomes, and a backwards stepwise binary logistic regression was used to determine the factors providing independent prediction of an unfavorable outcome.Baseline biochemical data were obtained in approximately 91% of cases from 803 patients. On admission, 73% of patients were good grade (World Federation of Neurological Surgeons grades 1 or 2); however, 84% had a Fisher grade 3 or 4 on computed tomographic scan. For patients presenting with good grade on admission, higher levels of C-reactive protein, glucose, and white blood cells and lower levels of hematocrit, albumin, and hemoglobin were associated with poor outcome at discharge. C-reactive protein was found to be an independent predictor of outcome for patients presenting in good grade.Early recording of C-reactive protein may prove useful in detecting those good grade patients who are at greater risk of clinical deterioration and poor outcome.
| S-EPMC4605277 | biostudies-literature
Project description:Objective: Systemic inflammation after subarachnoid hemorrhage (SAH) is implicated in delayed cerebral ischemia (DCI) and adverse clinical outcomes. We hypothesize that early changes in peripheral leukocytes will be associated with outcomes after SAH. Methods: SAH patients admitted between January 2009 and December 2016 were enrolled into a prospective observational study and were assessed for Hunt Hess Scale (HHS) at admission, DCI, and modified Ranked Scale (mRS) at discharge. Total white blood cell (WBC) counts and each component of the differential cell count were determined on the day of admission (day 0) to 8 days after bleed (day 8). Global cerebral edema (GCE) was assessed on admission CT, and presence of any infection was determined. Statistical tests included student's t-test, Chi-square test, and multivariate logistic regression (MLR) models. Results: A total of 451 subjects were analyzed. Total WBCs and neutrophils decreased initially reaching a minimum at day 4-5 after SAH. Monocyte count increased gradually after SAH and peaked between day 6-8, while basophils and lymphocytes decreased initially from day 0 to 1 and steadily increased thereafter. Neutrophil to lymphocyte ratio (NLR) reached a peak on day 1 and decreased thereafter. WBCs, neutrophils, monocytes, and NLR were higher in patients with DCI and poor functional outcomes. WBCs, neutrophils, and NLR were higher in subjects who developed infections. In MLR models, neutrophils and monocytes were associated with DCI and worse functional outcomes, while NLR was only associated with worse functional outcomes. Occurrence of infection was associated with poor outcome. Neutrophils and NLR were associated with infection, while monocytes were not. Monocytes were higher in males, and ROC curve analysis revealed improved ability of monocytes to predict DCI and poor functional outcomes in male subjects. Conclusions: Monocytosis was associated with DCI and poor functional outcomes after SAH. The association between neutrophils and NLR and infection may impact outcomes. Early elevation in monocytes had an improved ability to predict DCI and poor functional outcomes in males, which was independent of the occurrence of infection.
| S-EPMC8350167 | biostudies-literature