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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
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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]).
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Thrombelastography (TEG(®) 6s) early amplitudes predict maximum amplitude in severely injured trauma patients
Vigstedt M, Baksaas-Aasen K, Henriksen HH, Maegele M, Stanworth S, Juffermans NP, Kolstadbråten KM, Naess PA, Brohi K, Gaarder C, et al
Scandinavian journal of clinical and laboratory investigation. 2022;:1-5
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Editor's Choice
Abstract
Severely injured trauma patients are often coagulopathic and early hemostatic resuscitation is essential. Previous studies have revealed linear relationships between thrombelastography (TEG(®)) five- and ten-min amplitudes (A5 and A10), and maximum amplitude (MA), using TEG(®) 5000 technology. We aimed to investigate the performance of A5 and A10 in predicting low MA in severely injured trauma patients and identify optimal cut-off values for hemostatic intervention based on early amplitudes, using the cartridge-based TEG(®) 6s technology. Adult trauma patients with hemorrhagic shock were included in the iTACTIC randomized controlled trial at six European Level I trauma centers between 2016 and 2018. After admission, patients were randomized to hemostatic therapy guided by conventional coagulation tests (CCT) or viscoelastic hemostatic assays (VHA). Patients with available admission-TEG(®) 6s data were included in the analysis, regardless of treatment allocation. Low MA was defined as <55 mm for Kaolin TEG(®) and RapidTEG(®), and <17 mm for TEG(®) functional fibrinogen (FF). One hundred eighty-seven patients were included. Median time to MA was 20 (Kaolin TEG(®)), 21 (RapidTEG(®)) and 12 (TEG(®) FF) min. For Kaolin TEG(®), the optimal Youden index (YI) was at A5 < 36 mm (100/93% sensitivity/specificity) and A10 < 47 mm (100/96% sensitivity/specificity). RapidTEG(®) optimal YI was at A5 < 34 mm (98/92% sensitivity/specificity) and A10 < 45 mm (96/95% sensitivity/specificity). TEG(®) FF optimal YI was at A5 < 12 mm (97/93% sensitivity/specificity) and A10 < 15 mm (97/99% sensitivity/specificity). In summary, we found that TEG(®) 6s early amplitudes were sensitive and specific predictors of MA in severely injured trauma patients. Intervening on early amplitudes can save valuable time in hemostatic resuscitation.
PICO Summary
Population
Adult trauma patients with haemorrhagic shock enrolled in the iTACTIC study at six European trauma centers (n= 187).
Intervention
Haemostatic therapy guided by conventional coagulation tests (CCT).
Comparison
Viscoelastic haemostatic assays (VHA).
Outcome
The study aimed to investigate the performance of A5 and A10 in predicting low maximum amplitude (MA), and to identify optimal cut-off values for haemostatic intervention based on early amplitudes, using the cartridge-based TEG® 6s technology. Patients with available admission-TEG® 6s data were included in the analysis, regardless of treatment allocation. Low MA was defined as <55 mm for Kaolin TEG® and RapidTEG®, and <17 mm for TEG® functional fibrinogen (FF). Median time to MA was 20 (Kaolin TEG®), 21 (RapidTEG®) and 12 (TEG® FF) min. For Kaolin TEG®, the optimal Youden index (YI) was at A5 < 36 mm (100/93% sensitivity/specificity) and A10 < 47 mm (100/96% sensitivity/specificity). RapidTEG® optimal YI was at A5 < 34 mm (98/92% sensitivity/specificity) and A10 < 45 mm (96/95% sensitivity/specificity). TEG® FF optimal YI was at A5 < 12 mm (97/93% sensitivity/specificity) and A10 < 15 mm (97/99% sensitivity/specificity).
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Efficacy and Safety of Intravenous Iron Therapy for Treating Anaemia in Critically ill Adults: A Rapid Systematic Review With Meta-Analysis
Geneen LJ, Kimber C, Doree C, Stanworth S, Shah A
Transfusion medicine reviews. 2021
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Editor's Choice
Abstract
Our objective was to systematically evaluate the efficacy and safety of intravenous (IV) iron therapy for treating anaemia in critically ill adults (>16 years) admitted to intensive care or high dependency units. We excluded quasi-RCTs and other not truly randomised trials. We searched 7 electronic databases (including CENTRAL, MEDLINE, and Embase) using a pre-defined search strategy from inception to June 14, 2021. One reviewer screened, extracted, and analysed data, with verification by a second reviewer of all decisions. We used Cochrane risk of bias (ROB) 1 and GRADE to assess the certainty of the evidence. We reported 3 comparisons across 1198 patients, in 8 RCTs: (1) IV iron vs control (7 RCTs, 748 participants); our primary outcome (hemoglobin (Hb) concentration at 10 to 30 days) was reported in 7 of the 8 included trials. There was evidence of an effect (very-low certainty) in favour of IV iron over control in the main comparison only (6 RCTs, n = 528, mean difference (MD) 0.52g/dL [95%CI 0.23, 0.81], P = .0005). For the remaining outcomes there was no evidence of an effect in either direction (low certainty of evidence for Hb concentration at <10 days; very-low certainty of evidence for hospital duration, ICU duration, hospital readmission, infection, mortality; HRQoL outcomes were not GRADED). (2) IV iron + subcutaneous erythropoietin (EPO) vs control (2 RCTs, 104 participants); reported outcomes showed no evidence of effect in either direction, based on very-low certainty evidence (Hb concentration at 10-30 days, and <10 days, infection, mortality). (3) Hepcidin-guided treatment with IV iron or iron+ EPO vs standard care (1 RCT, 399 participants) reported evidence of an effect in favour of the intervention for 90-day mortality (low certainty of evidence), but no other group differences for the reported outcomes (low certainty evidence for Hb concentration at 10-30 days, hospital duration; HRQoL was not GRADED). The evidence across all comparisons was downgraded for high and unclear ROB for lack of blinding, incomplete outcome data, baseline imbalance, and imprecision around the estimate (wide CIs and small sample size). In conclusion, the current evidence continues to support further investigation into the role for iron therapy in increasing Hb in critically ill patients. Recent, small, trials have begun to focus on patient-centred outcomes but a large, well conducted, and adequately powered trial is needed to inform clinical practice.
PICO Summary
Population
Critically ill adults admitted to intensive care or high dependency units (8 studies, n= 1,198).
Intervention
Intravenous (IV) iron therapy; IV iron and subcutaneous erythropoietin (EPO); Hepcidin and targeted IV iron treatment (with and without EPO).
Comparison
Placebo/no iron therapy, or EPO therapy; Standard care.
Outcome
Seven trials (n= 748) comparing IV vs. control, found evidence of an effect in favour of IV iron in the main comparison only (6 RCTs, n = 528, mean difference (MD) 0.52g/dL). There was no evidence of an effect in either direction for hospital duration, intensive care unit duration, hospital readmission, infection, and mortality. For the two trials (n= 104) comparing IV iron and subcutaneous erythropoietin (EPO) vs. control, the reported outcomes showed no evidence of effect in either direction (Hb concentration at 10-30 days, and <10 days, infection, mortality). One trial (n= 399) comparing hepcidin-guided treatment with IV iron or iron and EPO vs. standard care reported evidence of an effect in favour of the intervention for 90-day mortality, but no other group differences for Hb concentration at 10-30 days, hospital duration, and HRQoL.
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Prothrombin complex concentrate vs. fresh frozen plasma in adult patients undergoing heart surgery - a pilot randomised controlled trial (PROPHESY trial)
Green L, Roberts N, Cooper J, Agarwal S, Brunskill SJ, Chang I, Gill R, Johnston A, Klein AA, Platton S, et al
Anaesthesia. 2020
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Editor's Choice
Abstract
There is equipoise regarding the use of prothrombin complex concentrate vs. fresh frozen plasma in bleeding patients undergoing cardiac surgery. We performed a pilot randomised controlled trial to determine the recruitment rate for a large trial, comparing the impact of prothrombin complex concentrate vs. fresh frozen plasma on haemostasis (1 h and 24 h post-intervention), and assessing safety. Adult patients who developed bleeding within 24 h of cardiac surgery that required coagulation factor replacement were randomly allocated to receive prothrombin complex concentrate (15 IU.kg(-1) based on factor IX) or fresh frozen plasma (15 ml.kg(-1) ). If bleeding continued after the first administration of prothrombin complex concentrate or fresh frozen plasma administration, standard care was administered. From February 2019 to October 2019, 180 patients were screened, of which 134 (74.4% (95%CI 67-81%)) consented, 59 bled excessively and 50 were randomly allocated; 25 in each arm, recruitment rate 35% (95%CI 27-44%). There were 23 trial protocol deviations, 137 adverse events (75 prothrombin complex concentrate vs. 62 fresh frozen plasma) and 18 serious adverse events (5 prothrombin complex concentrate vs. 13 fresh frozen plasma). There was no increase in thromboembolic events with prothrombin complex concentrate. No patient withdrew from the study, four were lost to follow-up and two died. At 1 h after administration of the intervention there was a significant increase in fibrinogen, Factor V, Factor XII, Factor XIII, α(2) -antiplasmin and antithrombin levels in the fresh frozen plasma arm, while Factor II and Factor X were significantly higher in the prothrombin complex concentrate group. At 24 h, there were no significant differences in clotting factor levels. We conclude that recruitment to a larger study is feasible. Haemostatic tests have provided useful insight into the haemostatic changes following prothrombin complex concentrate or fresh frozen plasma administration. A definitive trial is needed to ascertain the benefits and safety for each.
PICO Summary
Population
Cardiac surgery patients who developed bleeding within 24 hours of surgery (n= 50).
Intervention
Prothrombin complex concentrate (n= 25).
Comparison
Fresh frozen plasma (n= 25).
Outcome
There were 137 adverse events (75 prothrombin complex concentrate vs. 62 fresh frozen plasma) and 18 serious adverse events (5 prothrombin complex concentrate vs. 13 fresh frozen plasma). There was no increase in thromboembolic events with prothrombin complex concentrate. At 1 h after administration of the intervention there was a significant increase in fibrinogen, Factor V, Factor XII, Factor XIII, α(2) -antiplasmin and antithrombin levels in the fresh frozen plasma arm, while Factor II and Factor X were significantly higher in the prothrombin complex concentrate group. At 24 h, there were no significant differences in clotting factor levels.
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Viscoelastic haemostatic assay augmented protocols for major trauma haemorrhage (ITACTIC): a randomized, controlled trial
Baksaas-Aasen K, Gall LS, Stensballe J, Juffermans NP, Curry N, Maegele M, Brooks A, Rourke C, Gillespie S, Murphy J, et al
Intensive care medicine. 2020
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Editor's Choice
Abstract
PURPOSE Contemporary trauma resuscitation prioritizes control of bleeding and uses major haemorrhage protocols (MHPs) to prevent and treat coagulopathy. We aimed to determine whether augmenting MHPs with Viscoelastic Haemostatic Assays (VHA) would improve outcomes compared to Conventional Coagulation Tests (CCTs). METHODS This was a multi-centre, randomized controlled trial comparing outcomes in trauma patients who received empiric MHPs, augmented by either VHA or CCT-guided interventions. Primary outcome was the proportion of subjects who, at 24 h after injury, were alive and free of massive transfusion (10 or more red cell transfusions). Secondary outcomes included 28-day mortality. Pre-specified subgroups included patients with severe traumatic brain injury (TBI). RESULTS Of 396 patients in the intention to treat analysis, 201 were allocated to VHA and 195 to CCT-guided therapy. At 24 h, there was no difference in the proportion of patients who were alive and free of massive transfusion (VHA: 67%, CCT: 64%, OR 1.15, 95% CI 0.76-1.73). 28-day mortality was not different overall (VHA: 25%, CCT: 28%, OR 0.84, 95% CI 0.54-1.31), nor were there differences in other secondary outcomes or serious adverse events. In pre-specified subgroups, there were no differences in primary outcomes. In the pre-specified subgroup of 74 patients with TBI, 64% were alive and free of massive transfusion at 24 h compared to 46% in the CCT arm (OR 2.12, 95% CI 0.84-5.34). CONCLUSION There was no difference in overall outcomes between VHA- and CCT-augmented-major haemorrhage protocols.
PICO Summary
Population
Trauma patients from the ITACTIC trial (n= 396).
Intervention
Empiric major haemorrhage protocols (MHPs) augmented by Viscoelastic Haemostatic Assays (VHA), (n= 201).
Comparison
Interventions guided by Conventional Coagulation Tests (CCTs), (n= 195).
Outcome
At 24 h, there was no difference in the proportion of patients who were alive and free of massive transfusion (VHA: 67%, CCT: 64%). 28-day mortality was not different overall (VHA: 25%, CCT: 28%), nor were there differences in other secondary outcomes or serious adverse events. In pre-specified subgroups which included patients with severe traumatic brain injury (TBI), there were no differences in primary outcomes. In the pre-specified subgroup of 74 patients with TBI, 64% were alive and free of massive transfusion at 24 h compared to 46% in the CCT arm.
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Safety of blood donation from individuals with treated hypertension or non-insulin dependent type 2 diabetes - a systematic review
Stainsby D, Brunskill S, Chapman CE, Doree C, Stanworth S
Vox Sanguinis. 2010;98((3 Pt 2):):431-40.
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Editor's Choice
Abstract
BACKGROUND AND OBJECTIVES This systematic review was aimed at finding evidence for the safety of blood donation by individuals with treated hypertension or type 2 diabetes. It was undertaken as part of a wider project to re-evaluate exclusion criteria for UK blood donors with a view to increasing eligibility. MATERIALS AND METHODS Searches were undertaken in the Cochrane Library to 2008, MEDLINE (1950 onwards), EMBASE (1974 onwards), CINAHL (1982 onwards), BNID (1994 onwards), the NHSBT SRI Handsearching Database and the Web of Science (all years) to February 2008. Planned analysis was largely descriptive. RESULTS We identified only 16 relevant papers. None of the identified studies directly addressed the review questions and methodological appraisal highlighted a number of deficiencies. However all included papers provided contributory data and the findings were consistent. No study found any evidence of increased risk to homologous (allogeneic) or autologous blood donors with treated hypertension or with raised baseline systolic blood pressure up to 200 mmHg. We found very few data relating to blood donation by diabetic subjects. CONCLUSIONS No identified study indicated that raised baseline blood pressure level, treated hypertension or diabetes was predictive of increased adverse reactions in blood donors but the level of overall evidence was limited. This is the first attempt to systematically review a donor area as part of an approach to change longstanding practice recommendations, and may have implications for other recommendations for changes in donor acceptance criteria. [References: 20]
PICO Summary
Population
Blood donors with treated hypertension or type 2 diabetes (16 studies).
Intervention
Systematic review to ascertain the evidence for safety of blood donation by blood donors with treated hypertension or type 2 diabetes.
Comparison
Outcome
None of the identified studies directly addressed the review questions and methodological appraisal highlighted a number of deficiencies. All included papers provided contributory data and the findings were consistent. No study found any evidence of increased risk to homologous (allogeneic) or autologous blood donors with treated hypertension or with raised baseline systolic blood pressure up to 200 mmHg. Very few data relating to blood donation by diabetic subjects was found.