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Summary Tumor-educated platelets (TEPs) are potential biomarkers for cancer diagnostics. We employ TEP-derived RNA panels, determined by swarm intelligence, to detect and monitor glioblastoma . We assessed specificity by comparing the spliced RNA profile of TEPs from glioblastoma patients with multiple sclerosis and brain metastasis patients (validation series, n = 157; accuracy, 80%; AUC, 0.81 [95% CI, 0.74–0.89; p < 0.001]). Second, analysis of patients with glioblastoma versus asymptomatic healthy controls in an independent validation series (n = 347) provided a detection accuracy of 95% and AUC of 0.97 (95% CI, 0.95–0.99; p < 0.001). Finally, we developed the digitalSWARM algorithm to improve monitoring of glioblastoma progression and demonstrate that the TEP tumor scores of individual glioblastoma patients represent tumor behavior and could be used to distinguish false positive progression from true progression (validation series, n = 20; accuracy, 85%; AUC, 0.86 [95% CI, 0.70–1.00; p < 0.012]). In conclusion, TEPs have potential as a minimally invasive biosource for blood-based diagnostics and monitoring of glioblastoma patients.

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Patients with subarachnoid hemorrhage (SAH) who are using antiplatelet drugs prior to their hemorrhage, often receive platelet transfusions to reverse antiplatelet effects prior to life-saving surgical interventions. However, little is known about the effect of platelet transfusion on patient outcome in these patients. The aim of this study is to investigate the effect of platelet transfusion on clinical outcome in patients with aneurysmal SAH (aSAH) who use antiplatelet agents. Consecutive adult patients with an aSAH admitted between 2011 and 2015 to the Academic Medical Center (Amsterdam, the Netherlands) were included. Demographic characteristics and in-hospital complications were compared and clinical outcome was assessed after six months. Multivariable logistic regression analysis was performed to correct for confounding variables. A total of 364 patients with an aSAH were included. Thirty-eight (10%) patients underwent platelet transfusion during admission. Patients receiving platelet transfusion had worse clinical outcome (modified Rankin Scale score 4-6) at six months compared to patients without platelet transfusion (65% versus 32%, odds ratio 4.0, 95% confidence interval:1.9-8.1). Multivariable logistic regression analysis showed that platelet transfusion during admission was associated with unfavorable clinical outcome after six months; adjusted for age, treatment modality, modified Fisher and WFNS on admission (adjusted odds ratio 3.3, 95% confidence interval: 1.3-8.4). In this observational study, platelet transfusion was associated with poor clinical outcome at six months after correcting for confounding influences. In aSAH patients who need surgical treatment at low risk of bleeding, the indication for platelet transfusion needs careful weighing of the risk-benefit-balance. Most patients with a history of thromboembolic vascular disease or ischemic stroke are prescribed antiplatelet therapy, and its use has increased over the last decade 1-3. Although these drugs are certainly beneficial in aforementioned diseases 4 , they also increase the risk of major bleeding. In case of intracranial hemorrhage, platelet transfusions are more frequently used to reverse the effect of antiplatelet agents over the past several years 5,6. The rationale for platelet transfusion is to improve platelet activity in acute bleeding, thereby reducing the extent of the hemorrhage and potentially improving clinical outcome and survival 7-9. The existing literature is controversial when evaluating the role of platelets (platelet transfusion and antiplatelet therapy) in intracerebral hemorrhage (ICH). Studies concerning this subject are either supporting 7,10 , questioning 11,12 or even disapproving 13,14 , and vary in their observed effect on hematoma growth, clinical outcome, mortality, and rates of acute adverse events. Other more specific transfusion-related complications may also arise, such as acute lung injury, thrombosis, hemolytic transfusion reactions and transfusion-associated sepsis 15-19 .

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Background and ObjectivesThe ULTRA-trial showed that ultra-early and short-term tranexamic acid treatment after subarachnoid hemorrhage did not improve clinical outcome at six months. An expected proportion of the included patients had non-aneurysmal subarachnoid hemorrhage In this post-hoc study, we will investigate whether ultra-early and short-term tranexamic acid treatment in patients with aneurysmal subarachnoid hemorrhage improves clinical outcome at six months.MethodsThe ULTRA-trial is a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment, conducted between July 24, 2013 and January 20, 2020. After confirmation of subarachnoid hemorrhage on non-contrast computer tomography, patients were allocated to either ultra-early and short-term tranexamic acid treatment with usual care, or usual care only. In this post-hoc analysis, we included all ULTRA-participants with a confirmed aneurysm on CT angiography and/or digital subtraction angiography. The primary endpoint was clinical outcome at six months, assessed by the modified Rankin Scale, dichotomized into good (0-3) and poor (4-6) outcome.ResultsOf the 813 ULTRA-trial patients who had an aneurysmal subarachnoid hemorrhage, 409 (50%) were assigned to the tranexamic acid group and 404 (50%) to the control group. In the intention-to-treat analysis, 233 of 405 (58%) patients in the tranexamic acid group and 238 of 399 (60%) patients in the control group had a good clinical outcome (adjusted odds ratio (aOR) 0·92; 95% confidence interval (C.I.) 0·69 to 1·24). None of the secondary outcomes showed significant differences between the treatment groups: excellent clinical outcome (mRS 0-2) aOR 0.76, 95% C.I. 0.57-1.03, all-cause mortality at 30 days aOR 0.91, 95% C.I. 0.65-1.28), all-cause mortality at six months aOR 1.10 (95% C.I. 0.80-1.52).DiscussionUltra-early and short-term tranexamic acid treatment did not improve clinical outcome at six months in patients with aneurysmal subarachnoid hemorrhage and therefore, cannot be recommended.Trial Registration:ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24th, 2013).Classification of EvidenceThis study provides Class II evidence that tranexamic acid does not improve outcomes in patients presenting with aneurysmal subarachnoid hemorrhage.

Background: Literature is inconclusive regarding the association between antiplatelet agents use and outcome after aneurysmal subarachnoid hemorrhage (aSAH). Aims: To investigate the association between clinical outcome and prehemorrhage use in aSAH patients as well as the impact of thrombocyte transfusion on rebleed and clinical outcome. Methods: Data were collected from prospective databases of two European tertiary reference centers for aSAH patients. Patients were divided into “antiplatelet-user” and “non-user” according to the use of acetylsalicylic acid (ASA) prior to the hemorrhage. Primary outcome was poor clinical outcome at six months (Glasgow Outcome Scale score 1-3). Secondary outcomes were in-hospital mortality, and impact of thrombocyte transfusion. Results: One hundred and sixty-one of 1,033 patients (15.6%) were antiplatelet users. The antiplatelet users were older with higher incidence of cardiovascular risk factors. Antiplatelet use was associated with poor outcome and in-hospital mortality. After correction for age, sex, WFNS score, infarction and heart disorder, pre-hemorrhage ASA use was only associated with poor clinical outcome at six months (adjusted OR 1.80, 95% CI 1.08 to 3.02). Thrombocyte transfusion was not associated with a reduction in rebleed or poor clinical outcome. Conclusion: In this multicenter study, the prehemorrhage ASA use in aSAH patients was independently associated with poor clinical outcome at six months. Thrombocyte transfusion was not associated with the rebleed rate or poor clinical outcome at six months. Data access statement: The data that support this study are available upon reasonable request.

Delayed cerebral ischemia (DCI) substantially contributes to disability and death in subarachnoid hemorrhage (SAH) patients; however, its pathophysiology is incompletely understood and diagnostic and therapeutic strategies are lacking. Biomarkers may help to elucidate the pathophysiology, optimize early diagnosis, or provide treatment targets. We systematically searched PubMed and Embase on October 13, 2021, for studies that evaluated at least one laboratory biomarker in patients with DCI, using the most up-to-date definition of DCI as proposed by a panel of experts in 2010. Quality of studies was assessed using the Newcastle-Ottawa Scale or Cochrane Collaboration’s risk of bias assessment tool. Biomarkers of clinical and radiological DCI were analyzed separately. Results were meta-analyzed if possible, otherwise narratively reviewed. Biomarkers were classified as significant, inconclusive, or nonsignificant. We defined validated biomarkers as those with significant results in meta-analyses, or in at least two studies using similar methodologies within the same time interval after SAH. The search yielded 209 articles with 724 different biomarkers; 166 studies evaluated 646 biomarkers of clinical DCI, of which 141 were significant and 7 were validated biomarkers (haptoglobulin 2-1 and 2-2, ADAMTS13, vWF, NLR, P-selectin, F2-isoprostane); 78 studies evaluated 165 biomarkers of radiological DCI, of which 63 were significant and 1 was a validated biomarker (LPR). Hence, this review provides a selection of seven biomarkers of clinical DCI and one biomarker of radiological DCI as most promising biomarkers of DCI. Future research should focus on determining the exact predictive, diagnostic, and therapeutic potentials of these biomarkers.