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Early platelet transfusion improves platelet activity and may improve outcomes after intracerebral hemorrhage.

ABSTRACT: BACKGROUND:In patients with acute intracerebral hemorrhage (ICH), reduced platelet activity on admission predicts hemorrhage growth and poor outcomes. We tested the hypotheses that platelet transfusion improves measured platelet activity. Further, we hypothesized that earlier treatment in patients at high risk for hemorrhage growth and poor outcome would reduce follow-up hemorrhage size and poor clinical outcomes. METHODS:We prospectively identified consecutive patients with ICH who had reduced platelet activity on admission and received a platelet transfusion. We defined high-risk patients as per a previous publication, reduced platelet activity, or known anti-platelet therapy (APT) and the diagnostic CT within 12 h of symptom onset. Platelet activity was measured with the VerifyNow-ASA (Accumetrics, CA), ICH volumes on CT with computerized quantitative techniques, and functional outcomes with the modified Rankin Scale (mRS) at 3 months. RESULTS:Forty-five patients received a platelet transfusion with an increase in platelet activity from 472 ± 50 (consistent with an aspirin effect) to 561 ± 92 aspirin reaction units (consistent with no aspirin effect, P < 0.001). For high-risk patients, platelet transfusion within 12 h of symptom onset, as opposed to >12 h, was associated with smaller follow-up hemorrhage size (8.4 [3-17.4] vs. 13.8 [12.3-62.5] ml, P = 0.04) and increased odds of independence (mRS < 4) at 3 months (11 of 20 vs. 0 of 7, P = 0.01). There were similar results for patients with known APT. CONCLUSIONS:In patients at high risk for hemorrhage growth and poor outcome, early platelet transfusion improved platelet activity assay results and was associated with smaller final hemorrhage size and more independence at 3 months.

SUBMITTER: Naidech AM

PROVIDER: S-EPMC6211165 | biostudies-other | 2012 Feb

REPOSITORIES: biostudies-other

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Early platelet transfusion improves platelet activity and may improve outcomes after intracerebral hemorrhage.

Naidech Andrew M AM Liebling Storm M SM Rosenberg Neil F NF Lindholm Paul F PF Bernstein Richard A RA Batjer H Hunt HH Alberts Mark J MJ Kwaan Hau C HC

Neurocritical care 20120201 1

<h4>Background</h4>In patients with acute intracerebral hemorrhage (ICH), reduced platelet activity on admission predicts hemorrhage growth and poor outcomes. We tested the hypotheses that platelet transfusion improves measured platelet activity. Further, we hypothesized that earlier treatment in patients at high risk for hemorrhage growth and poor outcome would reduce follow-up hemorrhage size and poor clinical outcomes.<h4>Methods</h4>We prospectively identified consecutive patients with ICH w ...[more]

PMID: 21837536

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Project description:ImportanceRecent reports have suggested that cerebral amyloid angiopathy, a common cause of multiple spontaneous intracerebral hemorrhages (ICHs), may be transmissible through parenteral injection of contaminated cadaveric pituitary hormone in humans.ObjectiveTo determine whether spontaneous ICH in blood donors after blood donation is associated with development of spontaneous ICH in transfusion recipients.Design, setting, and participantsExploratory retrospective cohort study using nationwide blood bank and health register data from Sweden (main cohort) and Denmark (validation cohort) and including all 1 089 370 patients aged 5 to 80 years recorded to have received a red blood cell transfusion from January 1, 1970 (Sweden), or January 1, 1980 (Denmark), until December 31, 2017.ExposuresReceipt of red blood cell transfusions from blood donors who subsequently developed (1) a single spontaneous ICH, (2) multiple spontaneous ICHs, or (3) no spontaneous ICH.Main outcomes and measuresSpontaneous ICH in transfusion recipients; ischemic stroke was a negative control outcome.ResultsA total of 759 858 patients from Sweden (median age, 65 [IQR, 48-73] years; 59% female) and 329 512 from Denmark (median age, 64 [IQR, 50-73] years; 58% female) were included, with a median follow-up of 5.8 (IQR, 1.4-12.5) years and 6.1 (IQR, 1.5-11.6) years, respectively. Patients who underwent transfusion with red blood cell units from donors who developed multiple spontaneous ICHs had a significantly higher risk of a single spontaneous ICH themselves, compared with patients receiving transfusions from donors who did not develop spontaneous ICH, in both the Swedish cohort (unadjusted incidence rate [IR], 3.16 vs 1.12 per 1000 person-years; adjusted hazard ratio [HR], 2.73; 95% CI, 1.72-4.35; P < .001) and the Danish cohort (unadjusted IR, 2.82 vs 1.09 per 1000 person-years; adjusted HR, 2.32; 95% CI, 1.04-5.19; P = .04). No significant difference was found for patients receiving transfusions from donors who developed a single spontaneous ICH in the Swedish cohort (unadjusted IR, 1.35 vs 1.12 per 1000 person-years; adjusted HR, 1.06; 95% CI, 0.84-1.36; P = .62) nor the Danish cohort (unadjusted IR, 1.36 vs 1.09 per 1000 person-years; adjusted HR, 1.06; 95% CI, 0.70-1.60; P = .73), nor for ischemic stroke as a negative control outcome.Conclusions and relevanceIn an exploratory analysis of patients who received red blood cell transfusions, patients who underwent transfusion with red blood cells from donors who later developed multiple spontaneous ICHs were at significantly increased risk of spontaneous ICH themselves. This may suggest a transfusion-transmissible agent associated with some types of spontaneous ICH, although the findings may be susceptible to selection bias and residual confounding, and further research is needed to investigate if transfusion transmission of cerebral amyloid angiopathy might explain this association.

Project description:BackgroundExacerbated blood-brain barrier (BBB) damage is related with tissue plasminogen activator (tPA)-induced brain hemorrhage after stroke. Platelets have long been recognized as the cellular orchestrators of primary haemostasis. Recent studies have demonstrated further that platelets are required for supporting intact mature blood vessels and play a crucial role in maintaining vascular integrity during inflammation. Therefore, we sought to investigate whether platelets could reduce tPA-induced deterioration of cerebrovascular integrity and lead to less hemorrhagic transformation.MethodsMice were subjected to models of collagenase-induced intracerebral hemorrhage (ICH) and transient middle cerebral artery (MCA) occlusion. After 2 h of MCA occlusion, tPA (10 mg/kg) was administered as an intravenous bolus injection of 1 mg/kg followed by a 9 mg/kg infusion for 30 min. Immediately after tPA treatment, mice were transfused with platelets. Hemorrhagic volume, infarct size, neurological deficit, tight junction and basal membrane damages, endothelial cell apoptosis, and extravascular accumulation of circulating dextran and IgG, and Evans blue were quantified at 24 h.ResultsPlatelet transfusion resulted in a significant decrease in hematoma volume after ICH. In mice after ischemia, tPA administration increased brain hemorrhage transformation and this was reversed by resting but not activated platelets. Consistent with this, we observed that tPA-induced brain hemorrhage was dramatically exacerbated in thrombocytopenic mice. Transfusion of resting platelets ameliorated tPA-induced loss of cerebrovascular integrity and reduced extravascular accumulation of circulating serum proteins and Evans blue, associated with improved neurological functions after ischemia. No changes were found for infarct volume. Inhibition of platelet receptor glycoprotein VI (GPVI) blunted the ability of platelets to attenuate tPA-induced BBB disruption and hemorrhage after ischemia.ConclusionOur findings demonstrate the importance of platelets in safeguarding BBB integrity and suggest that transfusion of resting platelets may be useful to improve the safety of tPA thrombolysis in ischemic stroke.

Project description:OBJECTIVES:Impaired oxygen delivery due to reduced cerebral blood flow is the hallmark of delayed cerebral ischemia following subarachnoid hemorrhage. Since anemia reduces arterial oxygen content, it further threatens oxygen delivery increasing the risk of cerebral infarction. Thus, subarachnoid hemorrhage may constitute an important exception to current restrictive transfusion practices, wherein raising hemoglobin could reduce the risk of ischemia in a critically hypoperfused organ. In this physiologic proof-of-principle study, we determined whether transfusion could augment cerebral oxygen delivery, particularly in vulnerable brain regions, across a broad range of hemoglobin values. DESIGN:Prospective study measuring cerebral blood flow and oxygen extraction fraction using O-PET. Vulnerable brain regions were defined as those with baseline oxygen delivery less than 4.5?mL/100?g/min. SETTING:PET facility located within the Neurology/Neurosurgery ICU. PATIENTS:Fifty-two patients at risk for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage with hemoglobin 7-13?g/dL. INTERVENTIONS:Transfusion of one unit of RBCs over 1 hour. MEASUREMENTS AND MAIN RESULTS:Baseline hemoglobin was 9.7?g/dL (range, 6.9-12.9), and cerebral blood flow was 43?±?11?mL/100?g/min. After transfusion, hemoglobin rose from 9.6?±?1.4 to 10.8?±?1.4?g/dL (12%; p < 0.001) and oxygen delivery from 5.0 (interquartile range, 4.4-6.6) to 5.5?mL/100?g/min (interquartile range, 4.8-7.0) (10%; p = 0.001); the response was comparable across the range of hemoglobin values. In vulnerable brain regions, transfusion resulted in a greater (16%) rise in oxygen delivery associated with reduction in oxygen extraction fraction, independent of Hgb level (p = 0.002 vs normal regions). CONCLUSIONS:This study demonstrates that RBC transfusion improves cerebral oxygen delivery globally and particularly to vulnerable regions in subarachnoid hemorrhage patients at risk for delayed cerebral ischemia across a wide range of hemoglobin values and suggests that restrictive transfusion practices may not be appropriate in this population. Large prospective trials are necessary to determine if these physiologic benefits translate into clinical improvement and outweigh the risk of transfusion.

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Early platelet transfusion improves platelet activity and may improve outcomes after intracerebral hemorrhage.

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Early platelet transfusion improves platelet activity and may improve outcomes after intracerebral hemorrhage.

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