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Platelet transfusions in preterm infants: current concepts and controversies-a systematic review and meta-analysis
Ribeiro HS, Assunção A, Vieira RJ, Soares P, Guimarães H, Flor-de-Lima F
European journal of pediatrics. 2023
Abstract
Platelet transfusions (PTx) are the principal approach for treating neonatal thrombocytopenia, a common hematological abnormality affecting neonates, particularly preterm infants. However, evidence about the outcomes associated with PTx and whether they provide clinical benefit or harm is lacking. The aim of this systematic review and meta-analysis is to assess the association between PTx in preterm infants and mortality, major bleeding, sepsis, and necrotizing enterocolitis (NEC) in comparison to not transfusing or using different platelet count thresholds for transfusion. A broad electronic search in three databases was performed in December 2022. We included randomized controlled trials, and cohort and case control studies of preterm infants with thrombocytopenia that (i) compared treatment with platelet transfusion vs. no platelet transfusion, (ii) assessed the platelet count threshold for PTx, or (iii) compared single to multiple PTx. We conducted a meta-analysis to assess the association between PTx and mortality, intraventricular hemorrhage (IVH), sepsis, and NEC and, in the presence of substantial heterogeneity, leave-one-out sensitivity analysis was performed. We screened 625 abstracts and 50 full texts and identified 18 reports of 13 eligible studies. The qualitative analysis of the included studies revealed controversial results as several studies showed an association between PTx in preterm infants and a higher risk of mortality, major bleeding, sepsis, and NEC, while others did not present a significant relationship. The meta-analysis results suggest a significant association between PTx and mortality (RR 2.4, 95% CI 1.8-3.4; p < 0.0001), as well as sepsis (RR 4.5, 95% CI 3.7-5.6; p < 0.0001), after a leave-one-out sensitivity analysis. There was also found a significant correlation between PTx and NEC (RR 5.2, 95% CI 3.3-8.3; p < 0.0001). As we were not able to reduce heterogeneity in the assessment of the relationship between PTx and IVH, no conclusion could be taken. Conclusion: Platelet transfusions in preterm infants are associated to a higher risk of death, sepsis, and NEC and, possibly, to a higher incidence of IVH. Further studies are needed to confirm these associations, namely between PTx and IVH, and to define the threshold from which PTx should be given with less harm effect. What is Known: • Platelet transfusions are given to preterm infants with thrombocytopenia either to treat bleeding or to prevent hemorrhage. • Lack of consensual criteria for transfusion. What is New: • A significant association between platelet transfusions and mortality, sepsis, and NEC.
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Thrombocytopenia in intensive care unit patients: A scoping review
Jonsson, A. B., Rygård, S. L., Hildebrandt, T., Perner, A., Møller, M. H., Russell, L.
Acta Anaesthesiologica Scandinavica. 2021;65(1):2-14
Abstract
BACKGROUND Thrombocytopenia is frequent in intensive care unit (ICU) patients and may be associated with adverse outcomes. We aimed to assess the incidence, risk factors, and outcomes associated with thrombocytopenia in adult ICU patients. METHODS We conducted a scoping review in accordance with the Preferred Reporting Items for Systematic Review and Meta-analyses extension for Scoping Reviews (PRISMA-ScR) and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. We included study reports on adult ICU patients with thrombocytopenia and assessed patient-important outcomes, including mortality and health-related quality-of-life. RESULTS We included a total of 70 studies comprising a total of 215 098 patients; 57 were cohort studies. The incidence of thrombocytopenia varied from 8 to 56 per 100 admissions (very low quality of evidence). We identified several risk factors including age, sepsis, and higher disease severity (low quality of evidence). Thrombocytopenia was associated with bleeding, use of life support, length of stay in the ICU, and increased mortality (low/very low quality of evidence). Data on platelet transfusion before invasive procedures and transfusion thresholds were limited. No studies assessed the benefits and harms of thromboprophylaxis in ICU patients with thrombocytopenia. CONCLUSIONS Thrombocytopenia is common and associated with increased morbidity and mortality in adult ICU patients. Several risk factors for thrombocytopenia exists, but the evidence-base on management strategies, including transfusion thresholds and thromboprophylaxis in ICU patients is very limited.
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Platelet-to-red blood cell ratio and mortality in bleeding trauma patients: A systematic review and meta-analysis
Kleinveld DJB, van Amstel RBE, Wirtz MR, Geeraedts LMG, Goslings JC, Hollmann MW, Juffermans NP
Transfusion. 2021;61 Suppl 1:S243-s251
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Editor's Choice
Abstract
BACKGROUND In traumatic bleeding, transfusion practice has shifted toward higher doses of platelets and plasma transfusion. The aim of this systematic review was to investigate whether a higher platelet-to-red blood cell (RBC) transfusion ratio improves mortality without worsening organ failure when compared with a lower ratio of platelet-to-RBC. METHODS Pubmed, Medline, and Embase were screened for randomized controlled trials (RCTs) in bleeding trauma patients (age ≥16 years) receiving platelet transfusion between 1946 until October 2020. High platelet:RBC ratio was defined as being the highest ratio within an included study. Primary outcome was 24 hour mortality. Secondary outcomes were 30-day mortality, thromboembolic events, organ failure, and correction of coagulopathy. RESULTS In total five RCTs (n = 1757 patients) were included. A high platelet:RBC compared with a low platelet:RBC ratio significantly improved 24 hour mortality (odds ratio [OR] 0.69 [0.53-0.89]) and 30- day mortality (OR 0.78 [0.63-0.98]). There was no difference between platelet:RBC ratio groups in thromboembolic events and organ failure. Correction of coagulopathy was reported in five studies, in which platelet dose had no impact on trauma-induced coagulopathy. CONCLUSIONS In traumatic bleeding, a high platelet:RBC improves mortality as compared to low platelet:RBC ratio. The high platelet:RBC ratio does not influence thromboembolic or organ failure event rates.
PICO Summary
Population
Bleeding trauma patients receiving platelet transfusion (5 studies, n= 1,757).
Intervention
Higher platelet-to-red blood cell (RBC) transfusion ratio.
Comparison
Lower ratio of platelet-to-RBC.
Outcome
A high platelet:RBC compared with a low platelet:RBC ratio significantly improved 24 hour mortality (odds ratio (OR) 0.69 (0.53-0.89)) and 30- day mortality (OR 0.78 (0.63-0.98)). There was no difference between platelet:RBC ratio groups in thromboembolic events and organ failure. Correction of coagulopathy was reported in five studies, in which platelet dose had no impact on trauma-induced coagulopathy.
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Are thrombocytopenia and platelet transfusions associated with major bleeding in preterm neonates? A systematic review
Fustolo-Gunnink SF, Huijssen-Huisman EJ, van der Bom JG, van Hout FMA, Makineli S, Lopriore E, Fijnvandraat K
Blood Reviews. 2018
Abstract
Over 75% of severely thrombocytopenic preterm neonates receive platelet transfusions to prevent bleeding, but transfusion guidelines are based mainly on expert opinion. The aim of this review was to investigate whether platelet counts or transfusions are associated with major bleeding in preterm neonates. We performed a systematic search of the EMBASE and MEDLINE databases until December 2017. We included randomized trials, cohort and case control studies. (Prospero: CRD42015013399). We screened 8734 abstracts and 1225 fulltexts, identifying 36 eligible studies. In 30, timing of the platelet counts or transfusions in relation to the bleeding was unclear. Of the remaining six studies, two showed that thrombocytopenia was associated with increased risk of bleeding, two showed no such assocation, and three showed lack of an association between platelet transfusions and bleeding risk. The study results suggest that prophylactic platelet transfusions may not reduce bleeding risk in preterm neonates.
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The use of higher platelet: RBC transfusion ratio in the acute phase of trauma resuscitation: a systematic review
Hallet J, Lauzier F, Mailloux O, Trottier V, Archambault P, Zarychanski R, Turgeon AF
Critical Care Medicine. 2013;41((12):):2800-11.
Abstract
OBJECTIVE With the recognition of early coagulopathy, trauma resuscitation has shifted toward liberal platelet transfusions. The overall benefit of this strategy remains controversial. Our objective was to compare the effects of a liberal use of platelet (higher platelet:RBC ratios) with a conservative approach (lower ratios) in trauma resuscitation. DATA SOURCES We systematically searched Medline, Embase, Web of Science, Biosis, Cochrane Central, and Scopus. STUDY SELECTION Two independent reviewers selected randomized controlled trials and observational studies comparing two or more platelet:RBC ratios in trauma resuscitation. We excluded studies investigating the use of whole blood or hemostatic products. DATA EXTRACTION Two independent reviewers extracted data and assessed the risk of bias. Primary outcomes were early (in ICU or within 30 d) and late (in hospital or after 30 d) mortality. Secondary outcomes were multiple organ failure, lung injury, and sepsis. DATA SYNTHESIS From 6,123 citations, no randomized controlled trials were identified. We included seven observational studies (4,230 patients) addressing confounders through multivariable regression or propensity scores. Heterogeneity of studies precluded meta-analysis. Among the five studies including exclusively patients requiring massive transfusions, four observed a lower mortality with higher ratios. Two studies considering nonmassively bleeding patients observed no benefit of using higher ratios. Two studies evaluated the implementation of a massive transfusion protocol; only one study observed a decrease in mortality with higher ratios. Of the two studies at low risk of survival bias, one study observed a survival benefit. Three studies assessed secondary outcomes. One study observed an increase in multiple organ failure with higher ratios, whereas no study demonstrated an increased risk in lung injury or sepsis. CONCLUSIONS There is insufficient evidence to strongly support the use of a precise platelet:RBC ratio for trauma resuscitation, especially in nonmassively bleeding patients. Randomized controlled trials evaluating both the safety and efficacy of liberal platelet transfusions are warranted.
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A meta-analysis to determine the effect on survival of platelet transfusions in patients with either spontaneous or traumatic antiplatelet medication-associated intracranial haemorrhage
Batchelor JS, Grayson A
BMJ Open. 2012;2((2)):e000588.
Abstract
OBJECTIVES The aim of this study was to evaluate by meta-analysis the current level of evidence in order to establish the impact of a platelet transfusion on survival in patients on pre-injury antiplatelet agents who sustain an intracranial haemorrhage (either spontaneous or traumatic). DESIGN This was a meta-analysis; the MEDLINE Database was searched using the PubMed interface and the Ovid interface. CINAHL and EMBASE Databases were also searched. The search was performed to identify randomised controlled trials (RCT)'s case-controlled studies or nested case-controlled studies. Comparing the outcome (death or survival) of patients with intracranial haemorrhage (ICH) and pre-injury antiplatelet agents who received a platelet transfusion against a similar cohort of patients who did not receive a platelet transfusion. RESULTS 499 citations were obtained from the PubMed search. 31 full articles were reviewed from 34 abstracts. 6 studies were found suitable for the meta-analysis. No randomised controlled studies were identified. 2 of the six studies were in patients with spontaneous ICH. The remaining four studies were in patients with traumatic intracranial haemorrhage. Significant heterogeneity was present between the studies, I(2)=58.276. The random effects model was therefore the preferred model, this produced a pooled OR for survival of 0.773 (95% CI 0.414 to 1.442). CONCLUSIONS The results of this meta-analysis has shown, based upon six small studies, that there was no clear benefit in terms of survival in the administration of a platelet transfusion to patients with antiplatelet-associated ICH. Further work is required in order to establish any potential benefit in the administration of a platelet transfusion in patients with spontaneous or traumatic intracranial haemorrhage who were on pre-injury antiplatelet agents.
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Utility of platelet transfusion in adult patients with traumatic intracranial hemorrhage and preinjury antiplatelet use: A systematic review
Nishijima DK, Zehtabchi S, Berrong J, Legome E
The Journal of Trauma and Acute Care Surgery. 2012;72((6):):1658-63.
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Abstract
BACKGROUND Preinjury use of antiplatelet agents (e.g., clopidogrel and aspirin) is a risk factor for increased morbidity and mortality for patients with traumatic intracranial hemorrhage (tICH). Some investigators have recommended platelet transfusion to reverse the antiplatelet effects in tICH. This evidence-based medicine review examines the evidence regarding the impact of platelet transfusion on emergency department (ED) patients with preinjury antiplatelet use and tICH on patient-oriented outcomes. METHODS The MEDLINE, EMBASE, Cochrane Library, and other databases were searched. Studies were selected for inclusion if they compared platelet transfusion with no-platelet transfusion in the treatment of adult ED patients with preinjury antiplatelet use and tICH and reported rates of mortality, neurocognitive function, or adverse effects. We assessed the quality of the included studies using standard criteria. RESULTS Five retrospective, registry-based studies were identified, which enrolled 635 patients cumulatively. Based on standard criteria, three studies were of low-quality evidence, and two studies were of very low-quality evidence. One study reported higher in-hospital mortality for patients with platelet transfusion (relative risk, 2.42; 95% confidence interval, 1.2-4.9); another showed a lower mortality rate for patients receiving platelet transfusion (relative risk, 0.21; 95% confidence interval, 0.05-0.95). Three studies did not show any statistical difference in comparing mortality rates between the groups. No studies reported intermediate or long-term neurocognitive outcomes or adverse events. CONCLUSION Five retrospective registry studies with suboptimal methodologies provide inadequate evidence to support the routine use of platelet transfusion in adult ED patients with preinjury antiplatelet use and tICH. (J Trauma Acute Care Surg. 2012;72: 1658-1663. Copyright Copyright 2012 by Lippincott Williams & Wilkins). LEVEL OF EVIDENCE Systematic review, level III.