Haemostatic therapy in spontaneous intracerebral haemorrhage patients with high-risk of haematoma expansion by CT marker: a systematic review and meta-analysis of randomised trials.
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ABSTRACT: Background and purpose
Current randomised controlled trials (RCTs) showed an uncertain benefit of haemostatic therapy on preventing haematoma expansion and improving the outcome in patients with intracerebral haemorrhage (ICH). This meta-analysis aims to systematically evaluate the effect of haemostatic agents on the prevention of haemorrhage growth in patients with high-risk spontaneous ICH predicted by CT signs in RCTs.Methods
A comprehensive search of PubMed, EMBASE and Cochrane library from 1 January 2005 to 30 June 2021 was conducted. RCTs that compared haemostatic agents with placebo for the treatment of spontaneous patients with ICH with high-risk haemorrhage growth were included. The primary endpoint was haematoma expansion at 24 hours. Other major endpoints of interest included 90-day functional outcome and mortality.Results
The meta-analysis included four RCTs that randomised 2666 patients with ICH with high-risk haemorrhage growth. Haemostatic therapy reduced the rate of haematoma expansion at a marginally statistically significant level when compared with placebo (OR 0.84; 95% CI 0.70 to 1.00; p=0.051). Subgroup analysis for patients with black hole sign on CT revealed a significant reduction of haematoma expansion with haemostatic therapy (OR 0.61; 95% CI 0.39 to 0.94; p=0.03). However, both the primary analysis and subgroup analyses showed that haemostatic therapy could not reduce the rate of poor functional outcome (modified Rankin Scale >3) or death.Conclusions
Haemostatic therapy showed a marginally significant benefit in reducing early haematoma expansion in patients with high-risk spontaneous ICH predicted by markers on CT scan. However, no significant improvement in functional outcome or reduction of mortality was observed.
SUBMITTER: Nie X
PROVIDER: S-EPMC8258086 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundOutcome after spontaneous (non-traumatic) intracerebral haemorrhage (ICH) is influenced by haematoma volume; up to one-third of ICHs enlarge within 24 hours of onset. Early haemostatic therapy might improve outcome by limiting haematoma growth. This is an update of a Cochrane Review first published in 2006, and last updated in 2009.ObjectivesTo examine 1) the effectiveness and safety of individual classes of haemostatic therapies, compared against placebo or open control, in adults with acute spontaneous intracerebral haemorrhage, and 2) the effects of each class of haemostatic therapy according to the type of antithrombotic drug taken immediately before ICH onset (i.e. anticoagulant, antiplatelet, or none).Search methodsWe searched the Cochrane Stroke Trials Register, CENTRAL; 2017, Issue 11, MEDLINE Ovid, and Embase Ovid on 27 November 2017. In an effort to identify further published, ongoing, and unpublished randomised controlled trials (RCT), we scanned bibliographies of relevant articles and searched international registers of RCTs in November 2017.Selection criteriaWe sought randomised controlled trials (RCTs) of any haemostatic intervention (i.e. pro-coagulant treatments such as coagulation factors, antifibrinolytic drugs, or platelet transfusion) for acute spontaneous ICH, compared with placebo, open control, or an active comparator, reporting relevant clinical outcome measures.Data collection and analysisTwo authors independently extracted data, assessed risk of bias, and contacted corresponding authors of eligible RCTs for specific data if they were not provided in the published report of an RCT.Main resultsWe included 12 RCTs involving 1732 participants. There were seven RCTs of blood clotting factors versus placebo or open control involving 1480 participants, three RCTs of antifibrinolytic drugs versus placebo or open control involving 57 participants, one RCT of platelet transfusion versus open control involving 190 participants, and one RCT of blood clotting factors versus fresh frozen plasma involving five participants. We were unable to include two eligible RCTs because they presented aggregate data for adults with ICH and other types of intracranial haemorrhage. We identified 10 ongoing RCTs. Across all seven criteria in the 12 included RCTs, the risk of bias was unclear in 37 (44%), high in 16 (19%), and low in 31 (37%). Only one RCT was at low risk of bias in all criteria.In one RCT of platelet transfusion versus open control for acute spontaneous ICH associated with antiplatelet drug use, there was a significant increase in death or dependence (modified Rankin Scale score 4 to 6) at day 90 (70/97 versus 52/93; risk ratio (RR) 1.29, 95% confidence interval (CI) 1.04 to 1.61, one trial, 190 participants, moderate-quality evidence). All findings were non-significant for blood clotting factors versus placebo or open control for acute spontaneous ICH with or without surgery (moderate-quality evidence), for antifibrinolytic drugs versus placebo (moderate-quality evidence) or open control for acute spontaneous ICH (moderate-quality evidence), and for clotting factors versus fresh frozen plasma for acute spontaneous ICH associated with anticoagulant drug use (no evidence).Authors' conclusionsBased on moderate-quality evidence from one trial, platelet transfusion seems hazardous in comparison to standard care for adults with antiplatelet-associated ICH.We were unable to draw firm conclusions about the efficacy and safety of blood clotting factors for acute spontaneous ICH with or without surgery, antifibrinolytic drugs for acute spontaneous ICH, and clotting factors versus fresh frozen plasma for acute spontaneous ICH associated with anticoagulant drug use.Further RCTs are warranted, and we await the results of the 10 ongoing RCTs with interest.
| S-EPMC6494564 | biostudies-literature
Project description:IntroductionThe role of intracerebral haemorrhage location in haematoma expansion remains unclear. Our objective was to assess the effect of lobar versus non-lobar haemorrhage on haematoma expansion and clinical outcome.Patients and methodsWe analysed data from the prospective PREDICT study where patients with intracerebral haemorrhage presenting to hospital under 6 h of symptom onset received baseline computed tomography (CT), CT angiogram, 24 h follow-up CT, and 90-day mRS. Intracerebral haemorrhage location was categorised as lobar versus non-lobar, and primary outcomes were significant haematoma expansion (>6 ml) and poor clinical outcome (mRS > 3). Multivariable regression was used to adjust for relevant covariates. The primary analysis population was divided by spot sign status and the effect of haemorrhage location was compared to haematoma expansion in exploratory post hoc analysis.ResultsAmong 302 patients meeting the inclusion criteria, lobar haemorrhage was associated with increased haematoma expansion >6 ml (p = 0.003), poor clinical outcome (p = 0.011) and mortality (p = 0.017). When adjusted for covariates, lobar haemorrhage independently predicted significant haematoma expansion (aOR 2.2 (95% CI: 1.1-4.3), p = 0.021) and poor clinical outcome (aOR 2.6 (95% CI: 1.2-5.6), p = 0.019). Post hoc analysis showed that patients who were spot sign negative had a higher degree of haematoma expansion with baseline lobar haemorrhage (lobar 26% versus deep 11%; p = 0.01). No significant associations were observed in spot-positive patients (lobar 52% versus deep 47%; p = 0.69).Discussion and conclusionHaematoma expansion is more likely to occur with lobar intracerebral haemorrhage and haemorrhage location is associated with poor clinical outcome. As expansion is a promising therapeutic target, hemorrhage location may be helpful for prognostication and as a selection tool in future ICH clinical trials.
| S-EPMC6454825 | biostudies-literature
Project description:ObjectivesTo test radiomics-based features extracted from noncontrast CT of patients with spontaneous intracerebral haemorrhage for prediction of haematoma expansion and poor functional outcome and compare them with radiological signs and clinical factors.Materials and methodsSeven hundred fifty-four radiomics-based features were extracted from 1732 scans derived from the TICH-2 multicentre clinical trial. Features were harmonised and a correlation-based feature selection was applied. Different elastic-net parameterisations were tested to assess the predictive performance of the selected radiomics-based features using grid optimisation. For comparison, the same procedure was run using radiological signs and clinical factors separately. Models trained with radiomics-based features combined with radiological signs or clinical factors were tested. Predictive performance was evaluated using the area under the receiver operating characteristic curve (AUC) score.ResultsThe optimal radiomics-based model showed an AUC of 0.693 for haematoma expansion and an AUC of 0.783 for poor functional outcome. Models with radiological signs alone yielded substantial reductions in sensitivity. Combining radiomics-based features and radiological signs did not provide any improvement over radiomics-based features alone. Models with clinical factors had similar performance compared to using radiomics-based features, albeit with low sensitivity for haematoma expansion. Performance of radiomics-based features was boosted by incorporating clinical factors, with time from onset to scan and age being the most important contributors for haematoma expansion and poor functional outcome prediction, respectively.ConclusionRadiomics-based features perform better than radiological signs and similarly to clinical factors on the prediction of haematoma expansion and poor functional outcome. Moreover, combining radiomics-based features with clinical factors improves their performance.Key points• Linear models based on CT radiomics-based features perform better than radiological signs on the prediction of haematoma expansion and poor functional outcome in the context of intracerebral haemorrhage. • Linear models based on CT radiomics-based features perform similarly to clinical factors known to be good predictors. However, combining these clinical factors with radiomics-based features increases their predictive performance.
| S-EPMC8452575 | biostudies-literature
Project description:ObjectiveTo obtain precise estimates of age, haematoma volume, secondary haematoma expansion (HE) and mortality for patients with intracerebral haemorrhage (ICH) taking oral anticoagulants [Vitamin K antagonists (VKA-ICH) or non-Vitamin K antagonist oral anticoagulants (NOAC-ICH)] and those not taking oral anticoagulants (non-OAC ICH) at ICH symptom onset.MethodsWe conducted a systematic review and meta-analysis of studies comparing VKA-ICH or NOAC-ICH or both with non-OAC ICH. Primary outcomes were haematoma volume (in ml), HE, and mortality (in-hospital and 3-month). We calculated odds ratios (ORs) using the Mantel-Haenszel random-effects method and corresponding 95% confidence intervals (95%CI) and determined the mean ICH volume difference.ResultsWe identified 19 studies including data from 16,546 patients with VKA-ICH and 128,561 patients with non-OAC ICH. Only 2 studies reported data on 4943 patients with NOAC-ICH. Patients with VKA-ICH were significantly older than patients with non-OAC ICH (mean age difference: 5.55 years, 95%CI 4.03-7.07, p?<?0.0001, I2?=?92%, p?<?0.001). Haematoma volume was significantly larger in VKA-ICH with a mean difference of 9.66 ml (95%CI 6.24-13.07 ml, p?<?0.00001; I2?=?42%, p?=?0.05). HE occurred significantly more often in VKA-ICH (OR 2.96, 95%CI 1.74-4.97, p?<?0.00001; I2?=?65%). VKA-ICH was associated with significantly higher in-hospital mortality (VKA-ICH: 32.8% vs. non-OAC ICH: 22.4%; OR 1.83, 95%CI 1.61-2.07, p?<?0.00001, I2?=?20%, p?=?0.27) and 3-month mortality (VKA-ICH: 47.1% vs. non-OAC ICH: 25.5%; OR 2.24, 95%CI 1.52-3.31, p?<?0.00001, I2?=?71%, p?=?0.001). We did not find sufficient data for a meta-analysis comparing NOAC-ICH and non-OAC-ICH.ConclusionThis meta-analysis confirms, refines and expands findings from prior studies. We provide precise estimates of key prognostic factors and outcomes for VKA-ICH, which has larger haematoma volume, increased rate of HE and higher mortality compared to non-OAC ICH. There are insufficient data on NOACs.
| S-EPMC6851029 | biostudies-literature
Project description:BackgroundSpontaneous intracerebral haemorrhage (SICH) is a common condition with high morbidity and mortality. Segmentation of haematoma and perihaematoma oedema on medical images provides quantitative outcome measures for clinical trials and may provide important markers of prognosis in people with SICH.MethodsWe take advantage of improved contrast seen on magnetic resonance (MR) images of patients with acute and early subacute SICH and introduce an automated algorithm for haematoma and oedema segmentation from these images. To our knowledge, there is no previously proposed segmentation technique for SICH that utilises MR images directly. The method is based on shape and intensity analysis for haematoma segmentation and voxel-wise dynamic thresholding of hyper-intensities for oedema segmentation.ResultsUsing Dice scores to measure segmentation overlaps between labellings yielded by the proposed algorithm and five different expert raters on 18 patients, we observe that our technique achieves overlap scores that are very similar to those obtained by pairwise expert rater comparison. A further comparison between the proposed method and a state-of-the-art Deep Learning segmentation on a separate set of 32 manually annotated subjects confirms the proposed method can achieve comparable results with very mild computational burden and in a completely training-free and unsupervised way.ConclusionOur technique can be a computationally light and effective way to automatically delineate haematoma and oedema extent directly from MR images. Thus, with increasing use of MR images clinically after intracerebral haemorrhage this technique has the potential to inform clinical practice in the future.
| S-EPMC6382492 | biostudies-literature
Project description:AimsWe assessed the association of prior antiplatelet therapy (APT) at onset of intracerebral haemorrhage (ICH) with haematoma characteristics and outcome.MethodsWe performed a systematic review and meta-analysis of studies comparing ICH outcomes of patients on APT (APT-ICH) with patients not taking APT (non-APT-ICH). Primary outcomes were haematoma volume (mean difference and 95% CI), haematoma expansion (HE), in-hospital 3-month mortality rates and good functional outcome (modified Rankin Scale score 0-2). We provide odds ratios (ORs) from random effects models and subgroup analyses for haematoma expansion and short-term mortality rates.ResultsWe included 23 of 1551 studies on 30,949 patients with APT-ICH and 62,018 with non-APT-ICH. Patients on APT were older (Δmean 6.27 years, 95% CI 5.44-7.10), had larger haematoma volume (Δmean 5.74 mL, 95% CI 1.93-9.54), higher short-term mortality rates (OR 1.44, 95% CI 1.14-1.82), 3-month mortality rates (OR 1.58, 95% CI 1.14-2.19) and lower probability of good functional outcome (OR 0.61, 95% CI 0.49-0.77). While there was no difference in HE in the overall analysis (OR 1.32, 95% CI 0.85-2.06), HE occurred more frequently when assessed within 24 h (OR 2.58, 95% CI 1.18-5.67). We found insufficient data for comparison of single versus dual APT-ICH. Heterogeneity was substantial amongst studies.DiscussionAPT is associated with larger baseline haematoma volume, early (<24 h) haematoma expansion, mortality rates and morbidity in patients with ICH. Data on differences in single and dual APT-ICH are scarce and warrant further investigation. New treatment options for APT-ICH are urgently needed.
| S-EPMC8948504 | biostudies-literature
Project description:IntroductionPatients presenting with acute intracerebral haemorrhage are at a high risk of exhibiting haematoma expansion, a phenomenon that can significantly worsen long-term functioning. Numerous clinical and radiological factors are associated with expansion. In a bid to better select patients at increased risk of expanding, these factors have been collated together into clinical scores. Several clinical scores have been developed, but comparisons of diagnostic potential between these scores are limited and the frequency of use in clinical trial enrolment is unknown.ObjectiveTo perform a scoping review of haematoma expansion scores and explore numerous factors such as the methodology of development and diagnostic capabilities.Methods and analysisMEDLINE, PubMed, EMBASE, CENTRAL and ClinicalTrials.gov will be searched with assistance from an experienced information specialist. Eligible studies will involve adults presenting with spontaneous intracerebral haemorrhage who received baseline assessments, follow-up imaging and risk stratification through a haematoma expansion score. Reviewers will independently extract data from the included studies and will collect data on patient demographics and medical history, details on score development, diagnostic capabilities and usage proportions. Analysis of extracted data will focus on comparing the predictive capability of each score and similarities/differences in score development. The exact analysis technique will be dictated on the type of data extracted.Ethics and disseminationFormal ethics is not required as primary data will not be collected. The findings of this study will be disseminated through conference presentations and peer-reviewed publications.
| S-EPMC6347899 | biostudies-literature
Project description:Despite the global health burden, treatment of spontaneous intracerebral haemorrhage (ICH) is largely supportive, and translation of specific medical therapies has not been successful. Zebrafish larvae offer a unique platform for drug screening to rapidly identify neuroprotective compounds following ICH. We applied the Spectrum Collection library compounds to zebrafish larvae acutely after ICH to screen for decreased brain cell death and identified 150 successful drugs. Candidates were then evaluated for possible indications with other cardiovascular diseases. Six compounds were identified, including two angiotensin-converting enzyme inhibitors (ACE-Is). Ramipril and quinapril were further assessed to confirm a significant 55% reduction in brain cell death. Proteomic analysis revealed potential mechanisms of neuroprotection. Using the INTERACT2 clinical trial dataset, we demonstrated a significant reduction in the adjusted odds of an unfavourable shift in the modified Rankin scale at 90 days for patients receiving an ACE-I after ICH (versus no ACE-I; odds ratio, 0.80; 95% confidence interval, 0.68-0.95; P=0.009). The zebrafish larval model of spontaneous ICH can be used as a reliable drug screening platform and has identified therapeutics that may offer neuroprotection. This article has an associated First Person interview with the first author of the paper.
| S-EPMC8990924 | biostudies-literature
Project description:ObjectivesAmbient temperature has been reported to play a role in the occurrence of spontaneous intracerebral haemorrhage (ICH). This study aimed to investigate the relation between ambient temperature of onset time and ICH and the effect of hourly temperature within 72 h before ICH.DesignThis is a cross-sectional case-only study and a retrospective analysis of a prospective database.SettingTwo medical centres in Southern Taiwan participating a prospective stroke registry.ParticipantsA total of 933 patients with ICH registered from August 2006 to July 2008.Primary and secondary outcome measuresThe hourly temperature was collected, and patients were grouped according to the deciles of hourly temperature at onset. Primary outcome was the association between the number of ICH cases and mean temperature (or temperature variation). Secondary outcome was the difference of onset temperature and hourly temperature before onset in patients with known onset time.ResultsWinter (n=282) had significant higher ICH cases than other seasons (n=651; p=0.002). Of those patients with an exact time of onset, the results showed 13% patients occurred at the lowest decile temperature group (<17.4°C) and 8% patients occurred at the highest decile temperature group (>30.8°C). It showed a significant temperature change before onset for these patients (p<0.005).ConclusionsThis study showed that lower ambient temperature and variation of temperatures precipitated ICH in southern Taiwan. Better protecting vulnerable people from cold temperatures may prevent the occurrences of ICH.
| S-EPMC3371577 | biostudies-literature
Project description:ObjectiveTo evaluate whether delayed appearance of intraventricular hemorrhage (dIVH) represents an independent entity from intraventricular hemorrhage (IVH) present on admission CT or is primarily related to the time interval between symptom onset and admission CT.MethodsA total of 282 spontaneous intracerebral hemorrhage (ICH) patients, admitted February 2009-March 2014 to the neurological intensive care unit of a tertiary care university hospital, were prospectively enrolled in the ICH Outcomes Project. Multivariate logistic regression was used to determine associations with acute mortality and functional long-term outcome (modified Rankin Scale).ResultsA cohort of 282 ICH patients was retrospectively studied: 151 (53.5%) had intraventricular hemorrhage on initial CT scan (iIVH). Of the remaining 131 patients, 19 (14.5%) developed IVH after the initial CT scan (dIVH). The median times from symptom onset to admission CT were 1.1, 6.0, and 7.4 hours for the dIVH, iIVH, and no IVH groups (Mann-Whitney U test, dIVH vs iIVH, p < 0.001) and median time from onset to dIVH detection was 7.2 hours. The increase in ICH volume following hospital admission was larger in dIVH than in iIVH and no IVH patients (mean 17.6, 0.2, and 0.4 mL). After controlling for components of the ICH score and hematoma expansion, presence of IVH on initial CT was associated with discharge mortality and poor outcome at 3, 6, and 12 months, but dIVH was not associated with any of the outcome measures.ConclusionsIn ICH patients, associated IVH on admission imaging is commonly encountered and is associated with poor long-term outcome. In contrast, dIVH on subsequent scans is far less common and does not appear to portend worse outcome.
| S-EPMC4352099 | biostudies-literature