Aneurysmalsubarachnoid hemorrhage (aSAH) caused by rupture of an intracranial aneurysm is a devastating disease. Patients who survive the initial bleeding event remain at risk for secondary complications that have a negative impact on morbidity and mortality. One such complication is aneurysmal rebleed, which is the complication with the largest impact on poor outcome.1,2A rebleed after an initial hemorrhage in aSAH is attributed to high fibrinolytic activity causing instability of the thrombus on the aneurysm, and involves several risk factors.3
Antiplatelet use is one of the factors believed to not only be related to early rebleed, but also to treatment-related complications and worse outcome after aSAH.4,5With the aging of society, the number of patients taking antiplatelet medication is rising as the number of cardiovascular and neurovascular diseases increases with age.6The use of antiplatelet agents carries increased risk for bleeding events in intracranial interventions.7–9Moreover, some studies showed an increased rate of rebleeds in individuals taking antiplatelet medication.10,11
Thrombocyte transfusion overcomes the inhibitory effects of antiplatelet agents by temporarily increasing the number of functioning thrombocytes. Its impact on reducing rebleeds, as well as the impact on mortality and clinical outcome, remains largely unknown. Our team performed an international survey regarding management of prehemorrhage antiplatelet use in aSAH.12The results showed that there is large variability in this management, emphasizing the importance of evidence-based recommendations.
The primary aim of our study was to assess the effect of thrombocyte transfusion on the rebleed rate and clinical outcome in patients with aSAH using antiplatelet agents before initial hemorrhage. We hypothesized that thrombocyte transfusion reduces the rebleed rate and improves the clinical outcome at 6 months’ follow-up in patients with aSAH using antiplatelet agents before initial hemorrhage.
开云体育世界杯赔率
Data Collection
Data on patients with aSAH admitted between January 2005 and December 2022 were extracted from a prospectively managed database of the Department of Neurosurgery and Neuro-Intensive Care Unit of the University Hospital of Zurich, Switzerland. The research ethics board of the Canton Zurich approved use of these data for quality assessment. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Patient Characteristics
We included patients aged 18 years and older with confirmed aSAH on admission CT, or positive lumbar puncture and a proven aneurysm on either CT angiography or digital subtraction angiography, who were using antiplatelet medication (acetylsalicylic acid, acetylsalicylic acid/dipyridamole, clopidogrel, or a combination of these medications) before the onset of aSAH. Patients with non-aSAH, perimesencephalic hemorrhage, or traumatic SAH, as well as patients who had received anticoagulation therapy (alone or in combination with antiplatelet agents), were excluded from the analysis. Patients were divided into two groups, "thrombocyte transfusion" and "nontransfusion," based on whether they did or did not receive any thrombocyte transfusion in the acute stage of aSAH after hospital admission and before the exclusion of the bleeding source.
All clinical and radiological data were prospectively collected by trained staff and verified by an attending vascular neurosurgeon. The following items were collected: patient characteristics, including cardiovascular risk factors, initial clinical severity of aSAH according to the World Federation of Neurosurgical Societies (WFNS) scale grade, and radiological aSAH grade using the Fisher scale; aneurysm location; and aneurysm treatment modality. To reduce the number of variables in the regression analysis, we dichotomized the WFNS into WFNS grades 1–3 and 4–5, and the Fisher grade into grade 3 or grade 1, 2, and 4.2,13住院并发症(rebleed,脑积水and its treatment modalities [urgent placement of an external ventricular drain or insertion of a ventriculoperitoneal (VP) shunt]), occurrence of delayed cerebral ischemia (DCI) and infarction, treatment modality, thrombocyte transfusion, and clinical outcome data at 6 months’ follow-up were collected. Rebleed was defined as a second (or third, etc.) bleeding from the causative aneurysm after the initial bleeding, according to clinical suspicion combined with an increase of SAH on consecutive CT scans. DCI was defined according to Vergouwen et al.31Clinical outcome was assessed using the Glasgow Outcome Scale (GOS) and dichotomized into favorable (GOS score 4–5) and poor outcome (GOS score 1–3).
Clinical Management
Patients were treated according to our standardized protocol, which is consistent with the international and European guidelines for the management of aSAH.15,16Ruptured aneurysms were treated as early as feasible, preferably within 24 hours after onset of the initial SAH. If patients had a positive history for using antiplatelet medication before hemorrhage onset, a thrombocyte function test was performed at admission, if possible. If this test showed evidence for a reduced thrombocyte function and patients underwent any surgical intervention, a minimum of one thrombocyte unit was transfused. In cases of only endovascular treatment, the decision to transfuse thrombocytes was left to operator discretion. Due to organizational reasons, thrombocyte function testing could not be performed outside of working hours. In those cases, if a surgical intervention was needed, a pragmatic approach was used with transfusion of thrombocytes.
Data Analysis
病人特点、治疗方法和disease-associated complications were compared between the thrombocyte transfusion and nontransfusion groups. The data were investigated for sparsity and missing data. Baseline data were presented as numbers and proportions (percentage) and group differences were compared using the chi-square test. Continuous data were assessed for normality with the skewness and kurtosis tests for normality and normal distribution plot. Normally distributed variables were expressed as means with standard deviations and tested with the Student t-test, whereas nonnormally distributed variables were presented as medians with interquartile ranges (IQRs) and tested with the Mann-Whitney U-test. A two-sided p value < 0.05 was considered significant.
The association between thrombocyte transfusion and rebleed, as well as between thrombocyte transfusion and clinical outcome at 6 months, were assessed using logistic regression analysis to calculate crude ORs and adjusted ORs (aORs). In case of an unequal distribution in a baseline variable and an association with the outcome measure (rebleed or clinical outcome), both defined as a p value < 0.1, the corresponding variable was assessed for confounding by univariable analysis. In this case, the crude association between baseline variables and rebleed rate was assessed. Subsequently, estimates were adjusted for the corresponding variable using the Mantel-Haenszel test. If an estimate difference between crude and adjusted risk ratio was approximately 10% or more, this variable was defined as a confounder and included in the regression analysis. Finally, a multivariable logistic regression analysis was developed with age and sex as fixed variables and including other confounders. Analyses were performed using Stata software (version 16.1, StataCorp LP 2015).
Results
Baseline Characteristics, Treatment Modalities, and Outcome Data
From 1094 patients with aSAH who were treated, 157 (14.4%) consecutive patients had a positive history of antiplatelet medication use (134 patients with acetylsalicylic acid, 3 patients with acetylsalicylic acid/dipyridamole, 9 patients with clopidogrel, and 11 patients under combined treatment with acetylsalicylic acid and clopidogrel) before the onset of aSAH. The study flowchart is given inFig. 1. The proportion of female patients was higher in the nontransfusion group (thrombocyte transfusion vs nontransfusion: 58.6% vs 78.6%, p = 0.01). All other baseline characteristics were equally divided between groups (Table 1). Disease-associated complications and patient outcomes are reviewed inTable 2.
Study flowchart. Between January 2005 and December 2022, 1094 patients with aSAH were treated at the Department of Neurosurgery of the University Hospital Zurich. Of these 1094 patients, 157 with aSAH and prehemorrhage antiplatelet use (use of acetylsalicylic acid, acetylsalicylic acid/dipyridamole, clopidogrel, or a combination of these medications prior to aSAH occurrence) were available for inclusion in this prospective cohort study. Patients with use of anticoagulant agents were excluded from the study. In the final analysis, 157 patients were included: 87 received thrombocyte transfusions and 70 did not.
Baseline characteristics of the 157 study patients
| Variable | Whole Cohort, n (%) | Thrombocyte Transfusion Group, n (%) | Nontransfusion Group, n (%) | p Value* |
|---|---|---|---|---|
| No. of patients | 157 | 87 | 70 | — |
| Mean age ± SD, yrs | 62.1 ± 13.4 | 62.9 ± 13.0 | 61.2 ± 14.0 | 0.44† |
| Female sex | 106 (67.5) | 51 (58.6) | 55 (78.6) | 0.01 |
| Hypertension | 91 (58.0) | 51 (58.6) | 40 (57.1) | 0.85 |
| Hypercholesterolemia | 33 (21.0) | 21 (24.1) | 12 (17.1) | 0.29 |
| Diabetes mellitus | 17 (10.8) | 11 (12.6) | 6 (8.6) | 0.41 |
| Smoking | 62 (39.5) | 34 (39.1) | 28日(40.0) | 0.91 |
| Heart disorder | 48 (30.6) | 29 (33.3) | 19 (27.1) | 0.40 |
| Fisher grade 3 | 44 (28.0) | 25 (28.7) | 19 (27.1) | 0.83 |
| WFNS grade | 0.30 | |||
| 1 | 54 (34.4) | 27 (31.0) | 27 (38.6) | |
| 2 | 36 (22.9) | 21 (24.1) | 15 (21.4) | |
| 3 | 13 (8.3) | 6 (6.9) | 7 (10.0) | |
| 4 | 27 (17.2) | 21 (24.1) | 6 (8.6) | |
| 5 | 27 (17.2) | 12 (13.8) | 15 (21.4) | |
| Posterior circulation aneurysm | 23 (14.6) | 14 (16.1) | 9 (12.9) | 0.57 |
| Aneurysm clip placement | 80 (51.0) | 43 (49.4) | 37 (52.9) | 0.67 |
| Aneurysm coil placement | 68 (43.3) | 39 (44.8) | 29 (41.4) | 0.67 |
Boldface type indicates statistical significance.
Chi-square test.
t-test.
Disease-associated complications and outcomes of 157 patients
| Variable | Whole Cohort, n (%) | Thrombocyte Transfusion Group, n (%) | Nontransfusion Group, n (%) | p Value* |
|---|---|---|---|---|
| No of patients | 157 | 87 | 70 | — |
| Poor outcome, GOS score 1–3 | 57 (36.3) | 31 (35.6) | 26 (37.1) | 0.85 |
| Mortality | 36 (22.9) | 21 (24.1) | 15 (21.4) | 0.44 |
| Rebleed | 18 (11.5) | 6 (6.9) | 12 (17.1) | 0.05 |
| DCI | 32 (20.4) | 19 (21.8) | 13 (18.6) | 0.61 |
| Infarction, not posttreatment | 34 (21.7) | 21 (24.1) | 13 (18.6) | 0.43 |
| Acute hydrocephalus | 106 (67.5) | 65 (74.7) | 41 (58.6) | 0.03 |
| VP shunt dependency | 46 (29.3) | 25 (28.7) | 21 (30.0) | 0.86 |
Boldface type indicates statistical significance.
Chi-square test.
Thrombocyte Transfusions and Rebleed Risk
At least one thrombocyte transfusion was administered to 87 (55.4%) of 157 patients. In 76 of the 87 patients, thrombocytes were applied only once before aneurysm treatment. Eleven patients received a second thrombocyte transfusion after the aneurysm was treated. In the total study cohort, 18 (11.5%) of 157 patients experienced a rebleed during the hospital stay. Among those 18 patients, 6 (33.3%) received a thrombocyte transfusion and 12 (67.7%) did not, resulting in a rebleed risk of 6 (6.9%) of 87 in the thrombocyte transfusion group and 12 (17.1%) of 70 in the nontransfusion group. All patients with a rebleed received their thrombocyte transfusion before the rebleed and all rebleeds occurred before the aneurysm was treated. The median time interval of thrombocyte transfusion was 4.00 (IQR 2.00–7.00) hours after hospital admission.
The following parameters were assessed as confounders and were included in the multivariable analysis (Table 3): age, sex, WFNS grade ≤ 3, and acute hydrocephalus. Thrombocyte transfusion was independently associated with a reduced rebleed rate (aOR 0.29, 95% CI 0.10–0.87). None of the patients who received thrombocyte transfusion experienced an intermediate transfusion complication or transfusion-related acute lung injury.
Logistic regression analysis for rebleed in the whole cohort and adjusted for age, sex, WFNS grade ≤ 3, and acute hydrocephalus
| Risk | Univariable Analysis | Multivariable Analysis | ||||
|---|---|---|---|---|---|---|
| OR | 95% CI | p Value | aOR | 95% CI | p Value | |
| Thrombocyte transfusion | 0.36 | 0.12–1.03 | 0.05 | 0.29 | 0.10–0.87 | 0.03 |
| Age > 70 yrs | 0.92 | 0.31–2.75 | 0.88 | 0.64 | 0.20–2.05 | 0.45 |
| Sex | 0.56 | 0.17–1.81 | 0.32 | 0.81 | 0.24–2.78 | 0.74 |
| Posterior circulation aneurysm | 1.19 | 0.31–4.51 | 0.80 | |||
| Fisher grade 3 | 0.71 | 0.22–2.29 | 0.56 | |||
| WFNS grade ≤ 3 | 0.48 | 0.18–1.30 | 0.14 | 0.51 | 0.18–1.48 | 0.22 |
| Acute hydrocephalus | 2.64 | 0.72–9.69 | 0.13 | 3.02 | 0.76–11.96 | 0.12 |
| Heart disorder | 0.86 | 0.27–2.57 | 0.79 | |||
| Hypertension | 2.82 | 0.87–9.14 | 0.07 | |||
| Diabetes | 0.45 | 0.06–3.67 | 0.45 | |||
| Hypercholesterolemia | 1.08 | 0.33–3.56 | 0.89 | |||
| Smoking | 2.09 | 0.77–5.69 | 0.14 | |||
Boldface type indicates statistical significance.
Thrombocyte Transfusions and Poor Clinical Outcome
Fifty-seven patients (36.3%) had a poor outcome at 6 months’ follow-up. Among those 57 patients, 31 (54.4%) underwent at least one thrombocyte transfusion. The following parameters were assessed as confounders and were included in the multivariable analysis (Table 4): age, sex, WFNS grade ≤ 3, acute hydrocephalus, and rebleed. Thrombocyte transfusion was not associated with poor clinical outcome at 6 months’ follow-up as defined by GOS score 1–3 (aOR 0.91, 95% CI 0.39–2.15). Thirty-six patients (22.9%) died; among those, 21 underwent at least one thrombocyte transfusion and 15 received no thrombocytes. Thrombocyte transfusion was not associated with mortality (unadjusted OR 1.17, 95% CI 0.55–2.48).
Logistic regression analysis for poor outcome (GOS score 1–3) for the whole cohort and adjusted for age, sex, WFNS grade ≤ 3, acute hydrocephalus, and rebleed
| Risk | Univariable Analysis | Multivariable Analysis | ||||
|---|---|---|---|---|---|---|
| OR | 95% CI | p Value | aOR | 95% CI | p Value | |
| Thrombocyte transfusion | 0.94 | 0.91–1.85 | 0.85 | 0.91 | 0.39–2.15 | 0.84 |
| Age > 70 yrs | 3.35 | 1.59–7.07 | <0.001 | 3.32 | 1.39–7.91 | 0.01 |
| Sex | 0.42 | 0.19–0.90 | 0.02 | 0.57 | 0.23–1.42 | 0.22 |
| Posterior circulation aneurysm | 0.93 | 0.36–2.35 | 0.87 | |||
| Fisher grade 3 | 0.41 | 0.18–0.93 | 0.03 | |||
| WFNS grade ≤ 3 | 0.11 | 0.05–0.26 | <0.001 | 0.12 | 0.05–0.27 | <0.001 |
| Acute hydrocephalus | 3.27 | 1.44–7.39 | 0.003 | 1.54 | 0.58–4.08 | 0.38 |
| Rebleed | 4.18 | 1.43–12.23 | 0.005 | 3.57 | 1.08–11.78 | 0.04 |
| Infarction, not posttreatment | 4.02 | 1.75–9.23 | <0.001 | |||
| Heart disorder | 2.62 | 1.27–5.37 | 0.007 | |||
| Hypertension | 2.00 | 1.00–4.00 | 0.05 | |||
| Diabetes | 1.65 | 0.60–4.58 | 0.33 | |||
| Hypercholesterolemia | 1.18 | 0.54–2.61 | 0.68 | |||
| Smoking | 0.75 | 0.38–1.47 | 0.40 | |||
| Clip placement | 1.24 | 0.64–2.39 | 0.52 | |||
| Coil placement | 0.46 | 0.23–0.93 | 0.03 | |||
Boldface type indicates statistical significance.
Discussion
In this single-center retrospective observational cohort study with prospectively collected data, thrombocyte transfusion was independently associated with a reduced rebleed rate in patients with aSAH and antiplatelet agent therapy before the aSAH occurrence. This reduction in rebleeds did not result in an improved overall clinical outcome at 6 months’ follow-up.
Impact of Thrombocyte Transfusion on Rebleeds After aSAH
Very limited data exist concerning the impact and safety of thrombocyte transfusion in patients with aSAH receiving prehospital antiplatelet therapy.5此外,到目前为止,没有一项研究调查了impact of thrombocyte transfusion on rebleed risk in this patient population. Because our data show that thrombocyte transfusion may be relevant in preventing rebleeds, further clarifications and large clinical trials are necessary, especially since rebleeding in this generally fragile population may have an even larger impact on functional outcome than in the overall population with aSAH.
In 6 patients with a rebleed and thrombocyte transfusion, the rebleed event occurred after the transfusion and despite thrombocyte transfusion, allowing us to truly investigate the impact of thrombocyte transfusion in preventing rebleeds. This finding raises further important clinical observations and questions. First, these rebleeds could not be prevented by increasing the functional thrombocytes and suggests that additional pathophysiological mechanisms are involved in the risk for rebleed (such as hemostasis and fibrinolysis disturbances after aSAH, and blood pressure disturbances). Second, the slight increase in rebleed risk in the nontransfusion group compared with other studies in the literature17could indicate that only a portion of the patients on antiplatelet therapy have a reduced thrombocyte function. This observation is supported by existing data showing 8%–45% of patients do not respond to aspirin therapy as determined by different laboratory tests,18and aspirin resistance ranges from 5.5% to 60% in the general population.19
The use of antiplatelet agents has been associated with a lower incidence of aSAH and explained by a possible protective effect against chronic inflammation and subsequent aneurysm wall degeneration.20Moreover, a recent systematic review and meta-analysis found that aspirin use, regardless of frequency and duration, was associated with a statistically significantly lower risk of unruptured intracranial aneurysm growth.21Furthermore, one study showed that patients taking aspirin prior to their aSAH and who were responders to aspirin had a lower risk of developing DCI,22whereas other studies identified thrombocyte dysfunction as a risk factor for rebleeding.23,24The reduction in the DCI occurrence could also be a reason to give antiplatelet agents, although no effect was seen in the Magnesium and Acetylsalicylic Acid in Subarachnoid Hemorrhage (MASH) study in which acetylsalicylic acid given after aneurysm treatment did not reduce the occurrence of delayed ischemic neurological deficits.25A recently performed systematic review on hemostasis and fibrinolysis following aSAH26incorporated data from 22 studies with conventional or quantitative assays and 23 studies employing dynamic assays, and showed conflicting results. Data from conventional or quantitative assays indicated increased thrombocyte activation, whereas dynamic assays detected thrombocyte dysfunction, possibly related to an increased risk of rebleed.26As reduced thrombocyte function on admission was associated with a rebleed, this review suggested thrombocyte dysfunction as a possible target of treatment, even when patients were not receiving antiplatelet therapy prior to experiencing aSAH.26
Impact of Thrombocyte Transfusion on Clinical Outcome After aSAH
In a recent study, we demonstrated that prehemorrhage acetylsalicylic acid use in patients with aSAH was independently associated with poor clinical outcome at 6 months.4The influence of thrombocyte transfusion on complications and outcome in those patients, however, is not well understood. In the subanalysis of the above-mentioned multicenter cohort study, there were signs of an increased rebleed risk in patients who did not receive a thrombocyte transfusion. However, no difference in poor outcome was observed in patients receiving thrombocyte transfusion versus those who did not.4The potential risk of thrombocyte transfusion is reflected in the randomized controlled Platelet Transfusion Versus Standard Care After Acute Stroke Due to Spontaneous Cerebral Haemorrhage Associated With Antiplatelet Therapy(PATCH) trial14that showed that thrombocyte transfusion is inferior to standard care in patients receiving antiplatelet therapy after spontaneous intracerebral hemorrhage.14Moreover, a higher case fatality rate was noted when thrombocytes were acutely transfused. Patients with aSAH were excluded from the PATCH study, but the results opened discussion about the safety of thrombocyte transfusion in patients experiencing any kind of intracranial hemorrhage. A recent study with 38 patients receiving antiplatelet therapy prior to aSAH and thrombocyte transfusion during hospital admission demonstrated an increase in poor clinical outcome (defined as modified Rankin Scale [mRS] score 4–6) at 6 months’ follow-up.5The authors concluded that in patients with aSAH who need surgical treatment and are at low risk of bleeding, the possible benefit of thrombocyte transfusion needs to be carefully weighed against the risks. In contrast, our data showed no impact of thrombocyte transfusion on clinical outcome at 6 months’ follow-up in patients using antiplatelet agents before aSAH. Because our cohort consists of a significantly larger number of patients with aSAH using antiplatelet agents, we were able to compare the impact of thrombocyte transfusion among this subgroup of patients. With these data, we have been able to better assess whether thrombocyte transfusion would be beneficial in aSAH in patients receiving antiplatelet agents before the onset of hemorrhage.
Pathophysiology of Thrombocyte Activation After aSAH
In human studies, thrombocyte activation and inflammation occur acutely after aSAH and are associated with early brain injury, DCI, and poor functional outcome.27Thrombocytes have proinflammatory effects, and transfusion might enhance vascular permeability associated with inflammation and thrombocyte aggregation, which can decrease cerebral blood flow and contribute to ischemic injury after aSAH.27–29此外,急性血小板的参与activation on inflammation with subsequent microthrombosis in the pathogenesis of DCI has also been suggested.27,30Cytokine accumulation occurs during storage time of thrombocyte products in the body, resulting in increased proinflammatory effects, which could imply a more complex inflammatory pathophysiology in these patients with aSAH. Consequently, thrombocyte transfusion may therefore have an impact on clinical outcome. Because currently available data show conflicting results regarding the impact of thrombocyte transfusion on clinical outcome, it may be plausible that one or more of these properties, acting alone or as a combined effect, could lead to poor outcome in select cases.
Limitations of the Study
The main limitation of this study is the retrospective and single-center design. However, because we performed a retrospective analysis of prospectively collected data, and a minority of data were collected retrospectively, we assume that the selection and information bias are in the acceptable range. The true thrombocyte dysfunction was not assessed by thrombocyte function tests consequently, leaving a proportion of antiplatelet nonresponders or noncompliant patients in our population. Finally, the indication for thrombocyte transfusion was based on nonobjective measures, which probably led to a selection bias between groups. Nevertheless, baseline and treatment characteristics were comparable between groups, so the indication for transfusion may have been of minor importance in our analysis.
Conclusions
We have shown evidence for a reduction in rebleed risk (aOR 0.29, 95% CI 0.10–0.87) after thrombocyte transfusion in patients with aSAH who were receiving prehemorrhage antiplatelet therapy. Our data did not show an impact of thrombocyte transfusion on clinical outcome at 6 months’ follow-up. These data merit further investigation of thrombocyte transfusion in patients with aSAH who are taking antiplatelet therapy before the onset of hemorrhage.
Disclosures
Dr. Regli reported personal fees from B. Braun Medical, Inc., outside the submitted work.
Author Contributions
Conception and design: Sebök, Germans. Acquisition of data: Sebök, Zaugg, Willms, Regli, Germans. Analysis and interpretation of data: Sebök, Zaugg, Keller, Willms, Germans. Drafting the article: Sebök, Germans. Critically revising the article: all authors. Reviewed submitted version of manuscript: Sebök, Keller, Regli, Germans. Approved the final version of the manuscript on behalf of all authors: Sebök. Statistical analysis: Sebök, Zaugg, Germans. Administrative/technical/material support: Sebök. Study supervision: Regli, Germans.
References
-
1 ↑
GermansMR,CoertBA,VandertopWP,VerbaanD.Time intervals from subarachnoid hemorrhage to rebleed.J Neurol.2014;261(7):1425–1431.
-
2 ↑
StienenMN,GermansM,BurkhardtJK,et al.Predictors of in-hospital death after aneurysmal subarachnoid hemorrhage: analysis of a nationwide database (Swiss SOS [Swiss Study on Aneurysmal Subarachnoid Hemorrhage]).Stroke.2018;49(2):333–340.
-
3 ↑
VergouwenMD,VermeulenM,de HaanRJ,LeviM,RoosYB.Dihydropyridine calcium antagonists increase fibrinolytic activity: a systematic review.J Cereb Blood Flow Metab.2007;27(7):1293–1308.
-
4 ↑
SebökM,HostettlerIC,KellerE,et al.Prehemorrhage antiplatelet use in aneurysmal subarachnoid hemorrhage and impact on clinical outcome.Int J Stroke.2022;17(5):545–552.
-
5 ↑
PostR,TjerkstraMA,MiddeldorpS,et al.Platelet transfusion in patients with aneurysmal subarachnoid hemorrhage is associated with poor clinical outcome.Sci Rep.2020;10(1):856.
-
6 ↑
BenjaminEJ,MuntnerP,AlonsoA,et al.Heart Disease and Stroke Statistics-2019 Update: a report from the American Heart Association.Circulation.2019;139(10):e56–e528.
-
7 ↑
PalmerJD,SparrowOC,IannottiF.Postoperative hematoma: a 5-year survey and identification of avoidable risk factors.开云体育app官方网站下载入口.1994;35(6):1061–1065.
-
8
詹姆斯DN,FernandesJR,CalderI,SmithM.Low-dose aspirin and intracranial surgery. A survey of the opinions of consultant neuroanaesthetists in the UK.Anaesthesia.1997;52(2):169–172.
-
9 ↑
KorinthMC.Low-dose aspirin before intracranial surgery—results of a survey among neurosurgeons in Germany.Acta Neurochir (Wien).2006;148(11):1189–1196.
-
10 ↑
Dorhout MeesSM,van den BerghWM,AlgraA,RinkelGJ.Antiplatelet therapy for aneurysmal subarachnoid haemorrhage.Cochrane Database Syst Rev.2007;2007(4):CD006184.
-
11 ↑
ToussaintLGIII,FriedmanJA,WijdicksEF,et al.Influence of aspirin on outcome following aneurysmal subarachnoid hemorrhage.J Neurosurg.2004;101(6):921–925.
-
12 ↑
SebökM,KellerE,van NiftrikCHB,RegliL,GermansMR.Management of aneurysmal subarachnoid hemorrhage patients with antiplatelet use before the initial hemorrhage: an international survey.World Neurosurg.2018;120:e408–e413.
-
13 ↑
NeidertMC,MaldanerN,StienenMN,et al.The Barrow Neurological Institute Grading Scale as a predictor for delayed cerebral ischemia and outcome after aneurysmal subarachnoid hemorrhage: data from a nationwide patient registry (Swiss SOS).开云体育app官方网站下载入口.2018;83(6):1286–1293.
-
14 ↑
BaharogluMI,CordonnierC,Al-Shahi SalmanR,et al.Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial.Lancet.2016;387(10038):2605–2613.
-
15 ↑
HohBL,KoNU,Amin-HanjaniS,et al.2023guideline for the management of patients with aneurysmal subarachnoid hemorrhage: a guideline from the American Heart Association/American Stroke Association.Stroke.2023;54(7):e314–e370.
-
16 ↑
TreggiariMM,RabinsteinAA,BuslKM,et al.Guidelines for the neurocritical care management of aneurysmal subarachnoid hemorrhage.Neurocrit Care.Published online May 18, 2023. doi:10.1007/s12028-023-01713-5
-
17 ↑
Dorhout MeesSM,RinkelGJ,HopJW,AlgraA,van GijnJ.Antiplatelet therapy in aneurysmal subarachnoid hemorrhage: a systematic review.Stroke.2003;34(9):2285–2289.
-
18 ↑
ChiangJY,LeeSH,ChenYC,et al.Metabolomic analysis of platelets of patients with aspirin non-response.Front Pharmacol.2019;10:1107.
-
19 ↑
FeherG,FeherA,PuschG,LupkovicsG,SzaparyL,PappE.The genetics of antiplatelet drug resistance.Clin Genet.2009;75(1):1–18.
-
20 ↑
HostettlerIC,AlgVS,ShahiN,et al.Characteristics of unruptured compared to ruptured intracranial aneurysms: a multicenter case-control study.开云体育app官方网站下载入口.2018;83(1):43–52.
-
21 ↑
YangS,LiuT,WuY,XuN,XiaL,YuX.The role of aspirin in the management of intracranial aneurysms: a systematic review and meta-analyses.Front Neurol.2021;12:646613.
-
22 ↑
von der BrelieC,SubaiA,LimpergerV,RohdeV,DempfleA,BoströmA.In vitro analysis of platelet function in acute aneurysmal subarachnoid haemorrhage.Neurosurg Rev.2018;41(2):531–538.
-
23 ↑
FujiiY,TakeuchiS,SasakiO,MinakawaT,KoikeT,TanakaR.Ultra-early rebleeding in spontaneous subarachnoid hemorrhage.J Neurosurg.1996;84(1):35–42.
-
24 ↑
HeQ,ZhouY,LiuC,et al.Thromboelastography with platelet mapping detects platelet dysfunction in patients with aneurysmal subarachnoid hemorrhage with rebleeding.Neuropsychiatr Dis Treat.2019;15:3443–3451.
-
25 ↑
van den BerghWM,AlgraA,Dorhout MeesSM,et al.Randomized controlled trial of acetylsalicylic acid in aneurysmal subarachnoid hemorrhage: the MASH Study.Stroke.2006;37(9):2326–2330.
-
26 ↑
HvasCL,HvasAM.Hemostasis and fibrinolysis following aneurysmal subarachnoid hemorrhage: a systematic review on additional knowledge from dynamic assays and potential treatment targets.Semin Thromb Hemost.2022;48(3):356–381.
-
27 ↑
FronteraJA,ProvencioJJ,SehbaFA,et al.The role of platelet activation and inflammation in early brain injury following subarachnoid hemorrhage.Neurocrit Care.2017;26(1):48–57.
-
28
MarcusAJ,BroekmanMJ,DrosopoulosJH,et al.代谢控制细胞外nucle过度otide accumulation by CD39/ecto-nucleotidase-1: implications for ischemic vascular diseases.J Pharmacol Exp Ther.2003;305(1):9–16.
-
29 ↑
SehbaFA,MostafaG,FriedrichVJr,BedersonJB.Acute microvascular platelet aggregation after subarachnoid hemorrhage.J Neurosurg.2005;102(6):1094–1100.
-
30 ↑
YeF,KeepRF,HuaY,GartonHJ,XiG.Acute micro-thrombosis after subarachnoid hemorrhage: a new therapeutic target?J Cereb Blood Flow Metab.2021;41(9):2470–2472.
-
31 ↑
VergouwenMD,VermeulenM,van GijnJ,et al.Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group.Stroke2010;41(10):2391–2395.
