-
1.
Two-year outcomes following a randomised platelet transfusion trial in preterm infants
Moore CM, D'Amore A, Fustolo-Gunnink S, Hudson C, Newton A, Santamaria BL, Deary A, Hodge R, Hopkins V, Mora A, et al
Archives of disease in childhood. Fetal and neonatal edition. 2023
-
-
-
Free full text
-
-
Editor's Choice
Abstract
OBJECTIVE Assess mortality and neurodevelopmental outcomes at 2 years of corrected age in children who participated in the PlaNeT-2/MATISSE (Platelets for Neonatal Transfusion - 2/Management of Thrombocytopenia in Special Subgroup) study, which reported that a higher platelet transfusion threshold was associated with significantly increased mortality or major bleeding compared to a lower one. DESIGN Randomised clinical trial, enrolling from June 2011 to August 2017. Follow-up was complete by January 2020. Caregivers were not blinded; however, outcome assessors were blinded to treatment group. SETTING 43 level II/III/IV neonatal intensive care units (NICUs) across UK, Netherlands and Ireland. PATIENTS 660 infants born at less than 34 weeks' gestation with platelet counts less than 50×10(9)/L. INTERVENTIONS Infants were randomised to undergo a platelet transfusion at platelet count thresholds of 50×10(9)/L (higher threshold group) or 25×10(9)/L (lower threshold group). MAIN OUTCOMES MEASURES Our prespecified long-term follow-up outcome was a composite of death or neurodevelopmental impairment (developmental delay, cerebral palsy, seizure disorder, profound hearing or vision loss) at 2 years of corrected age. RESULTS Follow-up data were available for 601 of 653 (92%) eligible participants. Of the 296 infants assigned to the higher threshold group, 147 (50%) died or survived with neurodevelopmental impairment, as compared with 120 (39%) of 305 infants assigned to the lower threshold group (OR 1.54, 95% CI 1.09 to 2.17, p=0.017). CONCLUSIONS Infants randomised to a higher platelet transfusion threshold of 50×10(9)/L compared with 25×10(9)/L had a higher rate of death or significant neurodevelopmental impairment at a corrected age of 2 years. This further supports evidence of harm caused by high prophylactic platelet transfusion thresholds in preterm infants. TRIAL REGISTRATION NUMBER ISRCTN87736839.
PICO Summary
Population
Preterm infants enrolled in the PlaNeT-2/MATISSE trial, at 43 neonatal intensive care units across UK, Netherlands and Ireland (n= 660).
Intervention
Higher platelet transfusion threshold (n= 296).
Comparison
Lower platelet transfusion threshold (n= 305).
Outcome
The prespecified long-term follow-up outcome was a composite of death or neurodevelopmental impairment (developmental delay, cerebral palsy, seizure disorder, profound hearing or vision loss) at 2 years of corrected age. Follow-up data were available for 601 of 653 (92%) eligible participants. Of the 296 infants assigned to the higher threshold group, 147 (50%) died or survived with neurodevelopmental impairment, as compared with 120 (39%) of 305 infants assigned to the lower threshold group (OR: 1.54; 95% CI [1.09, 2.17]).
-
2.
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.
-
3.
Prophylactic platelet transfusions versus no prophylaxis in hospitalized patients with thrombocytopenia: A systematic review with meta-analysis
Anthon CT, Granholm A, Sivapalan P, Zellweger N, Pène F, Puxty K, Perner A, Møller MH, Russell L
Transfusion. 2022
-
4.
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
-
-
-
Free full text
-
-
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.
-
5.
Effect of platelet storage duration on clinical outcomes and incremental platelet change in critically ill children
Nellis, M. E., Spinella, P. C., Tucci, M., Stanworth, S. J., Steiner, M. E., Cushing, M. M., Davis, P. J., Karam, O.
Transfusion. 2020;60(12):2849-2858
-
-
Free full text
-
Abstract
The safety of platelet (PLT) concentrates with longer storage duration has been questioned due to biochemical and functional changes that occur during blood collection and storage. Some studies have suggested that transfusion efficacy is decreased and immune system dysfunction is worsened with increased storage age. We sought to describe the effect of PLT storage age on laboratory and clinical outcomes in critically ill children receiving PLT transfusions. STUDY DESIGN AND METHODS We performed a secondary analysis of a prospective, observational point-prevalence study. Children (3 days to 16 years of age) from 82 pediatric intensive care units in 16 countries were enrolled if they received a PLT transfusion during one of the predefined screening weeks. Outcomes (including PLT count increments, organ dysfunction, and transfusion reactions) were evaluated by PLT storage age. RESULTS Data from 497 patients were analyzed. The age of the PLT transfusions ranged from 1 to 7 days but the majority were 4 (24%) or 5 (36%) days of age. Nearly two-thirds of PLT concentrates were transfused to prevent bleeding. The indication for transfusion did not differ between storage age groups (P = .610). After patient and product variables were adjusted for, there was no association between storage age and incremental change in total PLT count or organ dysfunction scoring. A significant association between fresher storage age and febrile transfusion reactions (P = .002) was observed. CONCLUSION The results in a large, diverse cohort of critically ill children raise questions about the impact of storage age on transfusion and clinical outcomes which require further prospective evaluation.
-
6.
Dynamics of Platelet Counts in Major Trauma: The Impact of Haemostatic Resuscitation and Effects of Platelet Transfusion-A Sub-Study of the Randomized Controlled RETIC Trial
Tauber H, Innerhofer N, von Langen D, Ströhle M, Fries D, Mittermayr M, Hell T, Oswald E, Innerhofer P
J Clin Med. 2020;9(8)
-
-
-
Free full text
-
Editor's Choice
Abstract
Although platelets play a central role in haemostasis, the dynamics of platelet counts during haemostatic resuscitation, the response to platelet transfusion, and effects on clinical outcome are poorly described for trauma patients. As a sub-study of the already published randomized controlled RETIC Study "Reversal of Trauma-induced Coagulopathy using First-line Coagulation Factor Concentrates or Fresh-Frozen Plasma" trial, we here analysed whether the type of first-line haemostatic resuscitation influences the frequency of platelet transfusion and determined the effects of platelet transfusion in coagulopathic patients with major trauma. Patients randomly received first-line plasma (FFP) or coagulation factor concentrates (CFC), mainly fibrinogen concentrate. In both groups, platelets were transfused to maintain platelet counts between 50 and 100 × 10(9) /L. Transfusion rates were significantly higher in the FFP (n = 44) vs. CFC (n = 50) group (FFP 47.7% vs. CFC 26%); p = 0.0335. Logistic regression analysis adjusted for the stratification variables injury severity score (ISS) and brain injury confirmed that first-line FFP therapy increases the odds for platelet transfusion (odds ratio (OR) 5.79 (1.89 to 20.62), p = 0.0036) and this effect was larger than a 16-point increase in ISS (OR 4.33 (2.17 to 9.74), p =0.0001). In conclusion, early fibrinogen supplementation exerted a platelet-saving effect while platelet transfusions did not substantially improve platelet count and might contribute to poor clinical outcome.
PICO Summary
Population
Trauma patients with trauma-induced coagulopathy (TIC) enrolled in the RETIC trial (n= 94).
Intervention
First-line plasma (FFP), (n= 44).
Comparison
Coagulation factor concentrates (CFC), (n= 50).
Outcome
Transfusion rates were significantly higher for FFP 47.7% than CFC 26%. Logistic regression analysis adjusted for the stratification variables injury severity score and brain injury confirmed that first-line FFP therapy increases the odds for platelet transfusion.
-
7.
Elevated Syndecan-1 after Trauma and Risk of Sepsis: A Secondary Analysis of Patients from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) Trial
Wei S, Rodriguez EG, Chang R, Holcomb JB, Kao LS, Wade CE
Journal of the American College of Surgeons. 2018;227((6):):587-595.
-
-
Free full text
-
Abstract
BACKGROUND Endotheliopathy of trauma is characterized by breakdown of the endothelial glycocalyx. Elevated biomarkers of endotheliopathy, such as serum syndecan-1 (Synd-1) ≥ 40 ng/mL, have been associated with increased need for transfusions, complications, and mortality. We hypothesized that severely injured trauma patients who exhibit elevated Synd-1 levels shortly after admission have an increased likelihood of developing sepsis. STUDY DESIGN We analyzed a subset of PROPPR patients that survived at least 72 hours after hospital admission and determined elevated Synd-1 levels (≥ 40 ng/mL) 4 hours after hospital arrival. Sepsis was defined a priori as meeting systemic inflammatory response criteria and having a known or suspected infection. Univariate analysis was performed to identify variables associated with elevated Synd-1 levels and sepsis. Significant variables at a p-value <0.2 in the univariate analysis were chosen by purposeful selection and analyzed in a mixed effects multivariate logistic regression model to account for the 12 different study sites. RESULTS We included 512 patients. Of these, 402 (79%) had elevated Synd-1 levels, and 180 (35%) developed sepsis. Median Synd-1 levels at 4 hours after admission were 70 ng/dL (IQR 36 - 157 ng/dL) in patients who did not develop sepsis, and 165 ng/dL (IQR 67 - 336 ng/dL) in those who did (p < 0.001). Adjusting for treatment arm and site, multivariable analyses revealed that elevated Synd-1 status, injury severity score (ISS), and total blood transfused were significantly associated with an increased likelihood of developing sepsis. CONCLUSIONS Elevated Synd-1 levels 4 hours after admission in severely injured adult trauma patients who survived the initial 72 hours after hospital admission is associated with subsequent sepsis.
-
8.
Platelet transfusions improve hemostasis and survival in a substudy of the prospective, randomized PROPPR trial
Cardenas JC, Zhang X, Fox EE, Cotton BA, Hess JR, Schreiber MA, Wade CE, Holcomb JB
Blood Advances. 2018;2((14)):1696-1704.
-
-
Free full text
-
Abstract
Transfusing platelets during massive hemorrhage is debated because of a lack of high-quality evidence concerning outcomes in trauma patients. The objective of this study was to examine the effect of platelet transfusions on mortality in severely injured trauma patients. This work analyzed PROPPR (Pragmatic, Randomized Optimal Platelet and Plasma Ratios) trial patients who received only the first cooler of blood products, which either did or did not contain platelets. Primary outcomes were all-cause mortality at 24 hours and 30 days and hemostasis. Secondary outcomes included cause of death, complications, and hospital-, intensive care unit (ICU)-, and ventilator-free days. Continuous variables were compared using Wilcoxon rank sum tests. Categorical variables were compared using Fisher's exact tests. There were 261 PROPPR patients who achieved hemostasis or died before receiving a second cooler of blood products (137 received platelets and 124 did not). Patients who received platelets also received more total plasma (median, 3 vs 2 U; P < .05) by PROPPR intervention design. There were no differences in total red blood cell transfusions between groups. After controlling for plasma volume, patients who received platelets had significantly decreased 24-hour (5.8% vs 16.9%; P < .05) and 30-day mortality (9.5% vs 20.2%; P < .05). More patients in the platelet group achieved hemostasis (94.9% vs 73.4%; P < .01), and fewer died as a result of exsanguination (1.5% vs 12.9%; P < .01). Patients who received platelets had a shorter time on mechanical ventilation (P < .05); however, no differences in hospital- or ICU-free days were observed. In conclusion, early platelet administration is associated with improved hemostasis and reduced mortality in severely injured, bleeding patients. This trial was registered at www.clinicaltrials.gov as # NCT01545232.
-
9.
Outcomes after concomitant traumatic brain injury and hemorrhagic shock: a secondary analysis from the Pragmatic, Randomized Optimal Platelets and Plasma Ratios trial
Galvagno SM Jr, Fox EE, Appana SN, Baraniuk S, Bosarge PL, Bulger EM, Callcut RA, Cotton BA, Goodman M, Inaba K, et al
The Journal of Trauma and Acute Care Surgery. 2017;83((4)):668-674.
-
-
Free full text
-
Abstract
BACKGROUND Often the clinician is faced with a diagnostic and therapeutic dilemma in patients with concomitant traumatic brain injury (TBI) and hemorrhagic shock (HS), as rapid deterioration from either can be fatal. Knowledge about outcomes after concomitant TBI and HS may help prioritize the emergent management of these patients. We hypothesized that patients with concomitant TBI and HS (TBI + HS) had worse outcomes and required more intensive care compared with patients with only one of these injuries. METHODS This is a post hoc analysis of the Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR) trial. TBI was defined by a head Abbreviated Injury Scale score greater than 2. HS was defined as a base excess of -4 or less and/or shock index of 0.9 or greater. The primary outcome for this analysis was mortality at 30 days. Logistic regression, using generalized estimating equations, was used to model categorical outcomes. RESULTS Six hundred seventy patients were included. Patients with TBI + HS had significantly higher lactate (median, 6.3; interquartile range, 4.7-9.2) compared with the TBI group (median, 3.3; interquartile range, 2.3-4). TBI + HS patients had higher activated prothrombin times and lower platelet counts. Unadjusted mortality was higher in the TBI + HS (51.6%) and TBI (50%) groups compared with the HS (17.5%) and neither group (7.7%). Adjusted odds of death in the TBI and TBI + HS groups were 8.2 (95% confidence interval, 3.4-19.5) and 10.6 (95% confidence interval, 4.8-23.2) times higher, respectively. Ventilator, intensive care unit-free and hospital-free days were lower in the TBI and TBI + HS groups compared with the other groups. Patients with TBI + HS or TBI had significantly greater odds of developing a respiratory complication compared with the neither group. CONCLUSION The addition of TBI to HS is associated with worse coagulopathy before resuscitation and increased mortality. When controlling for multiple known confounders, the diagnosis of TBI alone or TBI+HS was associated with significantly greater odds of developing respiratory complications. LEVEL OF EVIDENCE Prognostic study, level II.
-
10.
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.