The effect of platelet transfusion on functional independence and mortality after antiplatelet therapy associated spontaneous intracerebral hemorrhage: A systematic review and meta-analysis
Journal of the neurological sciences. 2020;417:117075
INTRODUCTION The practice of platelet transfusion to mitigate the deleterious effects of antiplatelet agents on spontaneous intracerebral hemorrhage (ICH) remains common. However, the effect of antiplatelet agents on patients with ICH is still controversial and transfusing platelets is not without risk. We performed a meta-analysis in order to determine the effect of platelet transfusion on antiplatelet agent associated ICH. METHODS We queried PubMed, Embase, and Scopus databases to identify cohort studies, case-control studies, and randomized control trials. Study quality was graded by the Newcastle-Ottawa Scale and Cochrane Risk of Bias tool, as appropriate. Outcomes of interest included functional independence as measured by the modified Rankin Scale and mortality. We compared patients with antiplatelet agent associated ICH who received platelet transfusion to those that did not. RESULTS We identified 625 articles. After reviewing 44 full text articles, 5 were deemed appropriate for meta-analysis, including 4 cohort studies and one randomized control trial. Considerable heterogeneity was present among the studies (I(2) > 81% for all analyses). We did not find a significant effect of platelet transfusions on functional independence (Odds Ratio [OR] 1.3, 95% CI.0.45-3.9) or mortality (OR 0.58, 95% Confidence Interval [CI] 0.12-2.6). CONCLUSION We found no evidence for an effect of platelet transfusions on functional independence or mortality following antiplatelet associated ICH. More randomized trials are needed to evaluate platelet transfusion in patients with ICH and proven reduced platelet activity or those requiring neurosurgical intervention.
Allogeneic umbilical cord blood infusion for adults with ischemic stroke: clinical outcomes from a phase 1 safety study
Stem Cells Translational Medicine. 2018;7((7):):521-529
Stroke is a major cause of death and long-term disability, affecting one in six people worldwide. The only currently available approved pharmacological treatment for ischemic stroke is tissue plasminogen activator; however, relatively few patients are eligible for this therapy. We hypothesized that intravenous (IV) infusion of banked unrelated allogeneic umbilical cord blood (UCB) would improve functional outcomes in patients with ischemic stroke. To investigate this, we conducted a phase 1 open-label trial to assess the safety and feasibility of a single IV infusion of non-human leukocyte antigen (HLA) matched, ABO matched, unrelated allogeneic UCB into adult stroke patients. Ten participants with acute middle cerebral artery ischemic stroke were enrolled. UCB units were matched for blood group antigens and race but not HLA, and infused 3-9 days post-stroke. The adverse event (AE) profile over a 12 month postinfusion period indicated that the treatment was well-tolerated in these stroke patients, with no serious AEs directly related to the study product. Study participants were also assessed using neurological and functional evaluations, including the modified Rankin Score (mRS) and National Institute of Health Stroke Scale (NIHSS). At 3 months post-treatment, all participants had improved by at least one grade in mRS (mean 2.8 +/- 0.9) and by at least 4 points in NIHSS (mean 5.9 +/- 1.4), relative to baseline. Together, these data suggest that a single i.v. dose of allogeneic non-HLA matched human UCB cells is safe in adults with ischemic stroke, and support the conduct of a randomized, placebo-controlled phase 2 study. Stem Cells Translational Medicine 2018.
Platelet transfusion in cerebral haemorrhage (PATCH): a randomised controlled trial
Haematologica. 2016;101((s1)):339-340.. lb2234.
Statistical analysis plan for the PlAtelet Transfusion in Cerebral Haemorrhage (PATCH) trial: a multicentre randomised controlled trial
BACKGROUND Use of antiplatelet therapy shortly before stroke due to spontaneous primary intracerebral haemorrhage (ICH) is associated with higher case fatality in comparison to ICH without prior antithrombotic drug use. The PlAtelet Transfusion in Cerebral Haemorrhage (PATCH) trial aimed to assess the effect of platelet transfusion in patients presenting with ICH while using antiplatelet therapy. The main hypothesis of PATCH was that platelet transfusion would reduce death or dependence by reducing ICH growth. METHODS/DESIGN PATCH was a multicentre prospective, randomised, open, blinded endpoint (PROBE) parallel group trial, conducted at 60 hospitals in The Netherlands, Scotland and France. Forty-one sites enrolled 190 patients with spontaneous supratentorial ICH aged ≥18 years, who had used antiplatelet therapy for ≥7 days preceding ICH, if Glasgow Coma Scale was ≥8. Participants were randomised (1:1, with a secure web-based system using permuted blocks, stratified by study centre and type of antiplatelet therapy pre-ICH) to receive either platelet transfusion within 6 hours of symptom onset and 90 minutes of diagnostic brain imaging, or standard care without platelet transfusion. The primary outcome was modified Rankin Scale (mRS) score assessed blind to treatment allocation at 3 months after ICH. Planned secondary outcomes included ICH growth on brain imaging performed approximately 24 hours after randomisation, survival at 3 months, disability at 3 months scored using the Amsterdam Medical Centre linear disability score, heterogeneity of treatment effect on mRS and ICH growth according to presence of the computed tomography angiography spot sign, causes of poor outcome, and cost-effectiveness. Safety outcomes were transfusion reactions, thromboembolic complications, and serious adverse events occurring during hospitalisation. This statistical analysis plan was written without knowledge of the unblinded data. TRIAL REGISTRATION The trial was registered with the Netherlands Trial Register on 29 April 2008 ( NTR1303 ).
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 (London, England). 2016;387((10038):):2605-2613. 2605
BACKGROUND Platelet transfusion after acute spontaneous primary intracerebral haemorrhage in people taking antiplatelet therapy might reduce death or dependence by reducing the extent of the haemorrhage. We aimed to investigate whether platelet transfusion with standard care, compared with standard care alone, reduced death or dependence after intracerebral haemorrhage associated with antiplatelet therapy use. METHODS We did this multicentre, open-label, masked-endpoint, randomised trial at 60 hospitals in the Netherlands, UK, and France. We enrolled adults within 6 h of supratentorial intracerebral haemorrhage symptom onset if they had used antiplatelet therapy for at least 7 days beforehand and had a Glasgow Coma Scale score of at least 8. With use of a secure web-based system that concealed allocation and used biased coin randomisation, study collaborators randomly assigned participants (1:1; stratified by hospital and type of antiplatelet therapy) to receive either standard care or standard care with platelet transfusion within 90 min of diagnostic brain imaging. Participants and local investigators giving interventions were not masked to treatment allocation, but allocation was concealed from outcome assessors and investigators analysing data. The primary outcome was shift towards death or dependence rated on the modified Rankin Scale (mRS) at 3 months, and analysed by ordinal logistic regression, adjusted for stratification variables and the Intracerebral Haemorrhage Score. The primary analysis was done in the intention-to-treat population and safety analyses were done in the intention-to-treat and as-treated populations. This trial is registered with the Netherlands Trial Register, number NTR1303, and is now closed. FINDINGS Between Feb 4, 2009, and Oct 8, 2015, 41 sites enrolled 190 participants. 97 participants were randomly assigned to platelet transfusion and 93 to standard care. The odds of death or dependence at 3 months were higher in the platelet transfusion group than in the standard care group (adjusted common odds ratio 2.05, 95% CI 1.18-3.56; p=0.0114). 40 (42%) participants who received platelet transfusion had a serious adverse event during their hospital stay, as did 28 (29%) who received standard care. 23 (24%) participants assigned to platelet transfusion and 16 (17%) assigned to standard care died during hospital stay. INTERPRETATION Platelet transfusion seems inferior to standard care for people taking antiplatelet therapy before intracerebral haemorrhage. Platelet transfusion cannot be recommended for this indication in clinical practice. FUNDING The Netherlands Organisation for Health Research and Development, Sanquin Blood Supply, Chest Heart and Stroke Scotland, French Ministry of Health.
Red blood cell transfusion and mortality effect in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis protocol
Systems Review. 2015;4((1)):41.
BACKGROUND Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease that leads to important morbidity and mortality in a young patient population. Anemia following aSAH is common and may be exacerbated by the treatments instituted by clinicians as part of standard care. The role and optimal thresholds for red blood cell (RBC) transfusion in this patient population remains unknown. METHODS/DESIGN We will conduct a systematic review of the literature using MEDLINE, EMBASE, and EBM Reviews (including Cochrane Central databases) using a comprehensive search strategy for observational and interventional studies of RBC transfusion in aSAH. Our primary objective is to evaluate the association of RBC transfusion with mortality in aSAH patients. Secondary objectives include a) determining associations between RBC transfusion and poor neurologic outcome, b) defining an optimal RBC transfusion threshold in aSAH patients, and c) describing complications associated with RBC transfusion in aSAH patients. We plan a descriptive reporting of all included citations including study characteristics, methodological quality, and reported outcomes. Clinical and statistical heterogeneity observed between studies will be described. If appropriate, meta-analyses of suitable studies and interpretation of their results will be performed. Effect measures will be converted to obtain relative risks and odds ratios (RR and ORs) with 95% confidence intervals and pooled according to study design (randomized trials and observational studies respectively) using a random effects model. DISCUSSION This review will summarize the existing observational and trial evidence regarding RBC transfusion in aSAH patients. The analytical plan has made considerations for different study designs, both observational and interventional in nature, and will summarize the best available evidence to inform the end user and policy and guideline producers and to highlight areas in need of further study. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42014014806.
Effect of acetylsalicylic acid usage and platelet transfusion on postoperative hemorrhage and activities of daily living in patients with acute intracerebral hemorrhage
Journal of Neurosurgery. 2013;118((1):):94-103.
OBJECT The authors evaluated the effects of acetylsalicylic acid (ASA) usage and transfusion of previously frozen apheresis platelets on postoperative hemorrhage, activities of daily living (ADL) score, and mortality rate in patients with acute hypertensive basal ganglia hemorrhage undergoing craniotomy. METHODS This was a prospective, double-blind, parallel, randomized controlled trial in patients with acute hypertensive basal ganglia hemorrhage, who had either not received ASA therapy (control) or received ASA therapy. The patients who received ASA therapy were divided according to the results of a platelet aggregation test into ASA-resistant, ASA-semiresponsive, and ASA-sensitive groups. All patients required an emergency craniotomy for hematoma removal after hospitalization. The patients who were sensitive to ASA were randomized to receive one of the following transfusion regimens of previously frozen apheresis platelets: no transfusion, 1 therapeutic dose before surgery, or 2 therapeutic doses (1 before surgery and 1 after 24 hours of hospitalization). The postoperative hemorrhage rate and the average postoperative hemorrhage volume were recorded and the ADL scores and mortality rate were measured during a 6-month follow-up period. RESULTS The rate of postoperative hemorrhage, average postoperative hemorrhage volume, and mortality rate were significantly higher in the ASA-sensitive patients who received ASA therapy compared with patients who did not receive ASA therapy (all p < 0.005). The ADL scores were grouped into different grades and the number of cases in the lower grades was higher and the overall scores were poorer in patients who received ASA therapy compared with those who did not (all p < 0.005). After transfusion of previously frozen apheresis platelets, the postoperative hemorrhage rate, average postoperative hemorrhage volume, and mortality rate of the ASA-sensitive patients were significantly lowered (all p < 0.005), and the ADL scores and their classification level were better than those of patients who did not undergo transfusion (all p < 0.005). CONCLUSIONS Transfusion of previously frozen apheresis platelets reduces the rate of postoperative hemorrhage, average postoperative hemorrhage volume, disability rate, and mortality rate in ASA-sensitive patients with acute hypertensive basal ganglia hemorrhage undergoing craniotomy.
Anemia and transfusion after subarachnoid hemorrhage
Neurocritical Care. 2011;15((2):):342-53.
Delayed cerebral ischemia after subarachnoid hemorrhage (SAH) may be affected by a number of factors, including cerebral blood flow and oxygen delivery. Anemia affects about half of patients with SAH and is associated with worse outcome. Anemia also may contribute to the development of or exacerbate delayed cerebral ischemia. This review was designed to examine the prevalence and impact of anemia in patients with SAH and to evaluate the effects of transfusion. A literature search was made to identify original research on anemia and transfusion in SAH patients. A total of 27 articles were identified that addressed the effects of red blood cell transfusion (RBCT) on brain physiology, anemia in SAH, and clinical management with RBCT or erythropoietin. Most studies provided retrospectively analyzed data of very low-quality according to the GRADE criteria. While RBCT can have beneficial effects on brain physiology, RBCT may be associated with medical complications, infection, vasospasm, and poor outcome after SAH. The effects may vary with disease severity or the presence of vasospasm, but it remains unclear whether RBCTs are a marker of disease severity or a cause of worse outcome. Erythropoietin data are limited. The literature review further suggests that the results of the Transfusion Requirements in Critical Care Trial and subsequent observational studies on RBCT in general critical care do not apply to SAH patients and that randomized trials to address the role of RBCT in SAH are required.
PATCH: platelet transfusion in cerebral haemorrhage: study protocol for a multicentre, randomised, controlled trial
BMC Neurology. 2010;10:19
BACKGROUND Patients suffering from intracerebral haemorrhage have a poor prognosis, especially if they are using antiplatelet therapy. Currently, no effective acute treatment option for intracerebral haemorrhage exists. Limiting the early growth of intracerebral haemorrhage volume which continues the first hours after admission seems a promising strategy. Because intracerebral haemorrhage patients who are on antiplatelet therapy have been shown to be particularly at risk of early haematoma growth, platelet transfusion may have a beneficial effect. METHODS/DESIGN The primary objective is to investigate whether platelet transfusion improves outcome in intracerebral haemorrhage patients who are on antiplatelet treatment. The PATCH study is a prospective, randomised, multi-centre study with open treatment and blind endpoint evaluation. Patients will be randomised to receive platelet transfusion within six hours or standard care. The primary endpoint is functional health after three months. The main secondary endpoints are safety of platelet transfusion and the occurrence of haematoma growth. To detect an absolute poor outcome reduction of 20%, a total of 190 patients will be included. DISCUSSION To our knowledge this is the first randomised controlled trial of platelet transfusion for an acute haemorrhagic disease.
Stroke with transfusions changing to hydroxyurea (SWiTCH): a phase 3 randomized clinical trial for treatment of children with sickle cell anemia, previous stroke, and iron overload
Blood. 2010;116((21):): Abstract No. 844.