Red Blood Cell Ratio Research Articles

Platelet to erythrocyte ratio and mortality in massively transfused trauma patients.

BackgroundThe optimal transfusion ratio of platelets (PLT), plasma and red blood cells (RBC) in trauma patients with massive haemorrhage is still a subject of discussion. The objective of this study is to assess the effect of platelet transfusion on mortality in trauma patients who received massive transfusion. MethodsData were collected from four Dutch level-1 trauma centres. All trauma patients aged ≥ 16 years who received ≥ 6 RBC / 6 hours from the time of injury were included. Patients were divided based on PLT:RBC ratio (no platelets, low (<1:5) and high (≥1:5)). Primary outcome measure was 6-hour mortality and secondary outcomes included mortality at other time points and transfusion characteristics. ResultsA total of 292 patients were included. Patients in the high PLT ratio group had lower mortality rates at six and 12 hours as compared to the low PLT ratio and no PLT group. In the high PLT group mortality as a result of exsanguination (12%) was significantly lower as compared to the low PLT group (23%). High PLT ratio had lower probability for 6-hour mortality multivariable analysis. Higher plasma:RBC ratios were associated with lower mortality at all time points. ConclusionsAlthough the optimal patient specific transfusion strategy in patients with traumatic haemorrhage is still not resolved, these results show that higher PLT to RBC ratios are associated with lower early mortality.

Utility of cell index in the diagnosis of healthcare-associated ventriculitis and meningitis: an analytical cross-sectional study

BackgroundThe diagnosis of healthcare-associated ventriculitis and meningitis (HCAVM) can be complex because multiple factors confound the interpretation of cerebrospinal fluid (CSF) tests. The cell index (CI) may help in the diagnosis of HCAVM. It does not incur additional medical cost and it avoids delays from the turnaround time of CSF cultures. It is derived by calculating the ratio of CSF white blood cell (WBC) and red blood cell (RBC) divided by the ratio of peripheral WBC and RBC. This study aimed to evaluate the diagnostic utility of this parameter.MethodsAn analytic, observational, cross-sectional study was conducted at the University of the Philippines – Philippine General Hospital. All admitted pediatric and adult patients from 2015 to 2022 who underwent external ventricular drain (EVD) insertion for hydrocephalus secondary to intracranial hemorrhage (ICH), acute ischemic stroke, intracranial neoplasms, traumatic brain injury, or congenital hydrocephalus were screened. Records of patients fulfilling the inclusion criteria were then reviewed.ResultsA total of 363 patients underwent EVD insertion from 2015 to 2022. Of these, 161 were included in the study. Two-thirds (66.5%) were adults ≥ 19 years old whereas the remaining were pediatric patients 1 to < 19 years old. There were no patients < 12 months old as they fulfilled at least one exclusion criteria. Forty-nine of them were later confirmed to have HCAVM based on the CDC/NHSN criteria. A CI cut-off of ≥ 1.21 gave a maximum sensitivity of 30.6% and specificity of 86.4%. Receiver operating characteristic area under the curve (AUC-ROC) analysis was 0.585. Subgroup analysis by age showed sensitivity of 52.9% in the pediatric age group and 3.13% in adults. Subgroup analysis by neurologic indication showed sensitivity of 27.6% for ICH and 35.0% for neoplasms. Subsequent AUC-ROC analyses, however, showed that CI failed to adequately diagnose HCAVM in these subgroups.ConclusionsIn our population of neurologic patients who underwent EVD insertion, the cell index is not a reliable parameter in the diagnosis of HCAVM.

Effective Boundary Correction for Deterministic Lateral Displacement Microchannels to Improve Cell Separation: A Numerical and Experimental Study.

Particle separation and sorting techniques based on microfluidics have found extensive applications and are increasingly gaining prominence. This research presents the design and fabrication of a microfluidic device for separating cells using deterministic lateral displacement (DLD), enabling accuracy and continuity while being size-based. Nevertheless, it remains demanding, to completely reverse the detrimental effects of the boundaries that disturb the fluidic flow in the channel and reduce particle separation efficiency. This study introduces a novel approach to enhance the boundary structure of channels. By using this design, separation efficiency is boosted, and the fluid behavior around the walls is improved. The boundary correction (BC) enhances the operation of the microchannel and is very effective in microchannels. With boundary correction, the device exhibited improved separation efficiencies, but in its absence, separation efficiencies dropped. The collected microscopic images of the isolation of prostate cancer cell lines and red blood cells revealed promising outcomes. The efficiency of circulating tumor cell (CTC) throughput in the microfluidic channel, quantified as the ratio or proportion of tumor cells exiting the channel to cells entering it, exceeds 93%. Moreover, the efficiency of CTC isolation, expressed as the proportion of tumor cells from the upper outlet of the microfluidic channel to all cells, is over 89%. Additionally, the efficiency of red blood cell isolation, evaluated as the ratio of red blood cells from the lower outlet of the microfluidic channel to all cells, surpasses 77%. While using the same DLD separator without boundary correction reduced the separation efficiency by around 5%.

Ultra-Massive Transfusion: Predictors of Occurrence and In-Hospital mortality From the Australian and New Zealand Massive Transfusion Registry (ANZ-MTR)

Few data exist on patient clinical characteristics, predictors of occurrence and short- and long-term outcomes of ultra-massive transfusion (UMT), defined as receiving 20 units or more of red blood cells (RBCs) within 48h. This study analyses UMT events from the Australian and New Zealand Massive Transfusion Registry (ANZ-MTR). The ANZ-MTR captured all patients at 29 participating sites receiving a massive transfusion (MT), defined as ≥5 units of RBCs within 4h. Of 9028 patients, 803 (8.9%) received an UMT. UMT patients were younger than other MT patients (median age 57y vs 62y; P < .001). In UMT and MT, males predominated (66.3% and 62.9%, respectively); and context was predominantly trauma (28.8% and 23%) and cardiothoracic surgery (CTS) (21.7% and 20.3%). Median RBC units received within 4h were 16 (UMT) and 6 (MT). In UMT, 4h FFP:RBC ratio (0.6 vs 0.4, P < .001), and 4h cryoprecipitate use (72.9% vs 39.9%, P < .001) were higher. Independent predictors of UMT (Odds Ratio; 95% CI) were age <60y (1.52; 1.28-1.79), baseline Hb >100g/L (1.31; 1.08-1.59), INR >1.5 (1.56; 1.24-1.96), and APTT >60s (4.49; 3.40-5.61). Predictors of in-hospital mortality in UMT included Charlson Comorbidity Index score ≥3 (11.20, 0.60 - 25.00) and bleeding context, with mortality less likely in liver transplant (0.07, 0.01-0.41) and more likely in vascular surgery (8.27, 1.54-72.85), compared with CTS. In-hospital mortality was higher in the UMT group compared with MT group (20.5% vs 44.2%, P < .001), however 5y survival following discharge was not significantly different between the groups (HR=0.87 [95%CI 0.64-1.18], P = .38). UMT patients are more commonly younger, with baseline coagulopathy, and have higher in-hospital mortality compared with MT. However, UMT is not futile: 55.8% survived to discharge, without significant difference in survival postdischarge between the groups.

High Fresh Frozen Plasma to Red Blood Cell Ratio and Survival Outcomes in Blunt Trauma

Current trauma-care protocols advocate early administration of fresh frozen plasma (FFP) in a ratio close to 1:1 with red blood cells (RBCs) to manage trauma-induced coagulopathy in patients with severe blunt trauma. However, the benefits of a higher FFP to RBC ratio have not yet been established. To investigate the effectiveness of a high FFP to RBC transfusion ratio in the treatment of severe blunt trauma and explore the nonlinear relationship between the ratio of blood products used and patient outcomes. This was a multicenter cohort study retrospectively analyzing data from the Japan Trauma Data Bank, including adult patients with severe blunt trauma without severe head injury (Injury Severity Score ≥16 and head Abbreviated Injury Scale <3) between 2019 and 2022. Patients were categorized into 2 groups based on the ratio of FFP to RBC: the high-FFP group (ratio >1) and the low-FFP group (ratio ≤1). All-cause in-hospital mortality was the primary outcome. Additionally, the occurrence of transfusion-related adverse events was evaluated. Among the 1954 patients (median [IQR] age, 61 [41-77] years; 1243 male [63.6%]) analyzed, 976 (49.9%) had a high FFP to RBC ratio. Results from logistic regression, weighted by inverse probability treatment weighting, demonstrated an association between the group with a high-FFP ratio and lower in-hospital mortality (odds ratio, 0.73; 95% CI, 0.56-0.93) compared with a low-FFP ratio. Nonlinear trends were noted, suggesting a potential ceiling effect on transfusion benefits. In this cohort study, a high FFP to RBC ratio was associated with favorable survival in patients with severe blunt trauma. These outcomes highlight the importance of revising the current transfusion protocols to incorporate a high FFP to RBC ratio, warranting further research on optimal patient treatment.

Fresh Frozen Plasma to Red Blood Cell Ratios and Survival Benefit

Fresh Frozen Plasma to Red Blood Cell Ratios and Survival Benefit

Predictors of Clinical Outcomes and the Need for Massive Transfusion Protocols in Geriatric Trauma Patients With Hemorrhagic Shock: A Systematic Review.

The current literature lacks a clear consensus on the predictors of mortality and outcomes of geriatric trauma patients in hemorrhagic shock. This systematic review aims to investigate predictors of clinical outcomes and the need for massive transfusion protocol in the geriatric trauma population with hemorrhagic shock. PubMed, EMBASE, Cochrane, ProQuest, and Google Scholar were searched for studies evaluating geriatric trauma patients in hemorrhagic shock or receiving MTP. Outcomes of interest included the effect of advanced age on clinical outcomes, the accuracy of SI and other variables in predicting mortality and need for MTP, and associations between blood product ratio and clinical outcomes. Fifteen studies were included in this systematic review. In most studies, advanced age was an accurate predictor of mortality and complication rates in geriatric patients undergoing management of shock with MTP. SI along with other variables such as systolic blood pressure (SBP) were sensitive predictors of mortality and the need for MTP. Studies evaluating blood product ratio found an increased incidence of complications with higher plasma: red blood cell ratios. Advanced age among geriatric patients is associated with increased mortality and complications when undergoing MTP. Shock Index and age x Shock Index are accurate and reliable predictors of mortality and need for MTP in the geriatric trauma population with hemorrhagic shock suffering blunt and/or penetrating injuries. An increased plasma: RBC ratio was associated with more complications in geriatric patients.

FINDING THE SWEET SPOT: THE ASSOCIATION BETWEEN WHOLE BLOOD TO RED BLOOD CELLS RATIO AND OUTCOMES OF HEMORRHAGING CIVILIAN TRAUMA PATIENTS.

Purpose: To evaluate the dose-dependent effect of whole blood (WB) on the outcomes of civilian trauma patients with hemorrhagic shock. Methods: We performed a 2-year (2020-2021) retrospective analysis of the ACS-TQIP dataset. Adult (≥18) trauma patients with a shock index (SI) >1 who received at least 5 units of PRBC and one unit of WB within the first 4 h of admission were included. Primary outcomes were 6-h, 24-h, and in-hospital mortality. Secondary outcomes were major complications and hospital and intensive care unit length of stay. Results: A total of 830 trauma patients with a mean (SD) age of 38 (16) were identified. The median [IQR] 4-h WB and PRBC requirements were 2 [2-4] U and 10 [7-15] U, respectively, with a median WB:RBC ratio of 0.2 [0.1-0.3]. Every 0.1 increase in WB:RBC ratio was associated with decreased odds of 24-h mortality (aOR: 0.916, P = 0.035) and in-hospital mortality (aOR: 0.878, P < 0.001). Youden's index identified 0.25 (1 U of WB for every 4 U of PRBC) as the optimal WB:PRBC ratio to reduce 24-h mortality. High ratio (≥0.25) group had lower adjusted odds of 24-h mortality (aOR: 0.678, P = 0.021) and in-hospital mortality (aOR: 0.618, P < 0.001) compared to the low ratio group. Conclusions: A higher WB:PRBC ratio was associated with improved early and late mortality in trauma patients with hemorrhagic shock. Given the availability of WB in trauma centers across the United States, at least one unit of WB for every 4 units of packed red blood cells may be administered to improve the survival of hemorrhaging civilian trauma patients.

Eliminating extracellular autoinducing peptide signals inhibits the Staphylococcus aureus quorum sensing agr system

An accessory gene regulator (agr) in the quorum sensing (QS) system in Staphylococcus aureus contributes to host infection, virulence factor production, and resistance to oxidative damage. Artificially maintaining the inactive state of agr QS impedes the host infection strategy of S. aureus and inhibits toxin production. The QS system performs intercellular signal transduction, which is activated by the mature autoinducer peptide (AIP). It is released from cells after AgrD peptide processing as an intercellular signal associated with increased bacterial cell density. This study evaluated the effectiveness of inhibiting agr QS wherein AIP trap carriers were made to coexist when culturing Staphylococcus aureus. Immersing a nitrocellulose (NC) membrane in Staphylococcus aureus ATCC 12600 culture inhibited QS-dependent α-hemolysin production, which significantly reduced the hemolysis ratio of sheep red blood cells by the culture supernatant. A quartz crystal microbalance analysis supported AIP adsorption onto the NC membrane. Adding the NC membrane during culture was found to maintain the expression levels of the agr QS gene agrA and α-hemolysin gene hla lower than that when it was not added. Eliminating extracellular AIP signals allowed agr QS to remain inactive and prevented QS-dependent α-hemolysin expression. Isolating intercellular signals secreted outside the cell is an effective strategy to suppress gene expression in bacterial cells that collaborate via intercellular signaling.

Preferential whole blood transfusion during the early resuscitation period is associated with decreased mortality and transfusion requirements in traumatically injured patients

IntroductionWhole blood (WB) transfusion represents a promising resuscitation strategy for trauma patients. However, a paucity of data surrounding the optimal incorporation of WB into resuscitation strategies persists. We hypothesized that...

Variation in the relationship between fasting glucose and HbA1c: implications for the diagnosis of diabetes in different age and ethnic groups

IntroductionIdentify non-glycemic factors affecting the relationship between fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c), in order to refine diabetes diagnostic criteria.Research design and methodsRelationship between FPG–HbA1c was assessed in...

Performance Improvement Program Review of Institutional Massive Transfusion Protocol Adherence: An Opportunity for Improvement.

Given the acuity of patients who receive MTPs and the resources they require, MTPs are a compelling target for performance improvement. This study evaluated adherence with our MTP's plasma:red blood cell ratio (FFPR) of 1:2 and platelet:red blood cell ratio (PLTR) of 1:12, to test the hypothesis that ratio adherence is associated with lower inpatient mortality. The registry of an urban level I trauma center was queried for adult patients who received at least 6 units of packed red blood cells within 4 hours of presentation. Patients were excluded for interfacility transfer, cardiac arrest during the prehospital phase or within one hour of arrival, or for head AIS ≥5. Univariate analysis and multiple logistic regressions were performed to identify variables associated with early transfusion protocol noncompliance and the effect on inpatient mortality. Three hundred and eighty-three patients were included, with mean ISS of 25.9 ± 13.3 and inpatient mortality of 28.5%. Increasing age, ISS, INR, and total units of blood product transfused were associated with increased odds of mortality, while an increase in revised trauma score was associated with a decreased odds ratio of mortality. Achieving our goal ratios were protective against mortality, with OR of .451 (P = .013) and .402 (P=.003), respectively. Large proportions of critically injured patients were transfused fewer units of plasma and platelets than our MTP dictated; failure to achieve intended ratios at 4 hours was strongly associated with inpatient mortality. MTP processes and outcomes should be critically assessed on a regular basis as part of a mature performance improvement program to ensure protocol adherence and optimal patient outcome.

Patient blood management guideline for adults with critical bleeding.

The management of patients with critical bleeding requires a multidisciplinary approach to achieve haemostasis, optimise physiology, and guide blood component use. The 2011 Patient blood management guidelines: module 1 - critical bleeding/massive transfusion were updated and published. Systematic reviews were conducted for pre-specified research questions, and recommendations were based on meta-analyses of included studies. The critical bleeding/massive transfusion guideline includes seven recommendations and 11 good practice statements addressing: major haemorrhage protocols (MHPs) facilitating a multidisciplinary approach to haemorrhage control, correction of coagulopathy and normalisation of physiological derangement; measurement of physiological, biochemical and metabolic parameters in critical bleeding/massive transfusion; the optimal ratio of red blood cells to other blood components; the use of tranexamic acid; viscoelastic haemostatic assays; and cell salvage. The new guideline recommends MHPs be established as standard of care in all institutions managing patients with critical bleeding. In addition to routine physiological markers, the new guideline recommends temperature, biochemistry and coagulation profiles be measured early and frequently, providing parameters that define critical derangements. Ratio-based MHPs should include no fewer than four units of fresh frozen plasma and one adult unit of platelets for every eight units of red blood cells. In the setting of trauma and obstetric haemorrhage, administration of tranexamic acid within three hours of bleeding onset is recommended. The use of recombinant activated factor VII (rFVIIa) is not recommended. There was insufficient evidence to make recommendations on the use of viscoelastic haemostatic assays or cell salvage as part of MHPs.

Adherence to balanced transfusion among severely injured patients: A post hoc analysis of the RESTRIC trial.

A balanced transfusion strategy has been a standard resuscitation method for trauma patients, and adherence to a massive transfusion protocol incorporating balanced transfusion is reported to reduce mortality. This study aimed to assess adherence to balanced transfusion among severely injured patients in Japan. This study analyzes RESTRIC (restrictive transfusion strategy for critically injured patients) trial patients who were cluster-randomized based on restrictive or liberal transfusion strategy. We defined two transfusion groups: massive transfusion group 1, which includes RBC transfusions of at least eight units within 6 h; and massive transfusion group 2, which includes RBC transfusions of at least 20 units within 24 h. Adherence to balanced transfusion was assessed as the ratios of fresh frozen plasma (FFP) to red blood cells (RBC) and platelet concentrate (PC) to RBC ratio >0.5. Among 220 eligible patients, 98 (44.5%) were grouped as massive transfusion group 1 and 38 (17.3%) as massive transfusion group 2. The balanced transfusion in terms of the FFP to RBC ratio was nearly 100% for groups 1 and 2 over all periods. However, the balanced transfusion in terms of the PC to RBC ratio within 6 h were 51.0% for group 1 and 68.4% for group 2. This study revealed that while the ratio of FFP to RBC was balanced among patients from the early phase, the ratio of PC to RBC was not fully balanced, particularly in the early phase.

Composition of thrombi in zebrafish: similarities and distinctions with mammals

BackgroundBlood clots are primarily composed of red blood cells (RBCs), platelets/thrombocytes, and fibrin. Despite the similarities observed between mammals and zebrafish, the composition of fish thrombi is not as well known. ObjectivesTo analyze the formation of zebrafish blood clots ex vivo and arterial and venous thrombi in vivo. MethodsTransgenic zebrafish lines and laser-mediated endothelial injury were used to determine the relative ratio of RBCs and thrombocytes in clots. Scanning electron and confocal microscopy provided high-resolution images of the structure of adult and larval clots. Adult and larval thrombocyte spreading on fibrinogen was evaluated ex vivo. ResultsRBCs were present in arterial and venous thrombi, making up the majority of cells in both circulations. However, bloodless mutant fish demonstrated that fibrin clots can form in vivo in the absence of blood cells. Scanning electron and confocal microscopy showed that larval and adult zebrafish thrombi and mammalian thrombi look surprisingly similar externally and internally, even though the former have nucleated RBCs and thrombocytes. Although adult thrombocytes spread on fibrinogen, we found that larval cells do not fully activate without the addition of plasma from adult fish, suggesting a developmental deficiency of a plasma activating factor. Finally, mutants lacking αIIbβ3 demonstrated that this integrin mediates thrombocyte spreading on fibrinogen. ConclusionOur data showed strong conservation of arterial and venous and clot/thrombus formation across species, including developmental regulation of thrombocyte function. This correlation supports the possibility that mammals also do not absolutely require circulating cells to form fibrin clots in vivo.

The ratio of lymphocyte/red blood cells and platelets/lymphocytes are predictive biomarkers for lymph node metastasis in patients with breast cancer.

Axillary lymph node metastasis (LNM) affects the progression of breast cancer. However, it is difficult to preoperatively diagnose axillary lymph node status with high sensitivity. Therefore, we hypothesized that platelets/lymphocytes ratio (PLR) and lymphocytes/ red blood cells ratio (LRR) might help in the prognosis of lymph node metastasis in T1-T2 breast cancer. 166 patients (Chang Ning Maternity & Infant Health Institute) were included in our study, and the associations of PLR and LPR with lymph node metastasis were investigated. Peripheral blood was collected one week before the surgery, and the patients were divided into different categories based on their PLR and LRR. The incidence of LNM was significantly increased in the high PLR group (p= 0.002) compared with the low PLR group; LNM was also significantly increased in the low LRR group (p= 0.036) compared with the high LPR group. Further, our study revealed that high PLR (p< 0.001, OR = 4.397, 95% CI = 2.005-9.645), low LRR (p= 0.017, OR = 0.336, 95%CI = 0.136-0.825) and high clinical T stage (p< 0.001, OR = 3.929, 95%CI = 1.913-8.071) are independent predictors of LNM. PLR and LRR could be identified as predictors of LNM in patients with T1/T2 breast cancer.

Beyond Traditional Treatments: Exploring Cutting-Edge Approaches for Androgenetic Alopecia

Androgenetic Alopecia is a genetically predetermined disorder resulting in hair loss from an excessive sensitivity to androgens. Several treatment options have been investigated for androgenetic alopecia, yet only topical minoxidil and finasteride have received approval from the US Food and Drug Administration. This review article examines and evaluates the efficacy of new, cutting-edge techniques for treating AGA, including Low-Level Laser Therapy, Platelet Rich Plasma Therapy, Micro needling, and Topical Growth Factors and Peptides. Several essential factors are stimulated by minoxidil, including vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and insulin-like growth factor (IGF)-1. IGF-1 also plays a significant role in regulating follicular differentiation, which makes it a vital regulator of hair follicle development and function. Low-level laser therapy (LLLT) uses low-intensity light at red or near-infrared wavelengths to induce changes in cellular activity, which improves blood circulation, reduces inflammation, and boosts cellular energy, ultimately leading to improved hair follicle density and diameter. Platelet-rich plasma therapy (PRP) is used in dermatology for acne scar treatment, lipid transplantation, wound healing, and hair regeneration. It involves a centrifugation process that increases the platelet concentration and reduces the red blood cell ratio. Micro needling is a minimally invasive procedure that stimulates the production of collagen, growth factors, and neovascularization, which promotes tissue rejuvenation. It is most utilized for individuals who are unable to achieve successful results using medical therapy. These approaches have shown positive outcomes in terms of hair regrowth, improved hair density, increased hair shaft thickness, and patient satisfaction.

Achieving balanced transfusion early in critically bleeding trauma patients: an observational study exploring the effect of attending trauma surgical presence during resuscitation

BackgroundAfter 15 years of damage control resuscitation (DCR), studies still report high mortality rates for critically bleeding trauma patients. Adherence to massive hemorrhage protocols (MHPs) based on a 1:1:1 ratio...

1210 Network Meta-Analysis of Associated Mortality with Transfusion Strategies for Major Haemorrhage in Adults

Abstract Aim The aetiology of a large proportion of mortality in trauma patients is attributed to acute major haemorrhage. Damage control resuscitation and surgery have been developed as part of management, which often includes large volume blood product transfusion. The aim of this meta-analysis was to investigate differences in mortality between transfusion strategies used in major haemorrhage in adults (18+ years). Method A frequentist random effects network meta-analysis (NMA) using the netmeta package in R 4.0.5 of the eligible papers in the systematic review “Optimal dose, Timing and Ratio of Blood Products in Massive Transfusion: Results from a systematic review” compared a 1:1:1 ratio of red blood cells (RBC), fresh frozen plasma (FFP) and platelets (P) to a ratio of 2:1:1, whole blood, and laboratory-guided replacement. Homogeneity and heterogeneity were assessed with Cochran’s Q. Results Mortality at one month by group was 21.8% (12/55) for whole blood, 17.0% (58/342) for 2RBC:1FFP:1P, 14.3% (5/35) for laboratory-guided transfusion and 22.3% (96/43) for standard 1RBC:1FFP:1P ratio. The NMA showed no significant differences between groups, with relative risk of death when compared to 1RBC:1FFP:1P by one month of 1.42 (0.631; 3.19, p = 0.398) for whole blood, 0.7643 (0.562; 1.04, p = 0.0871) for 2RBC:1FFP:1P and 0.4396 (0.1741; 1.1099, p = 0.0820) for laboratory-guided transfusion. Conclusions The results demonstrated no significant differences in mortality between transfusion strategies in major haemorrhage - however, some arms of the NMA contain few patients and so may be underpowered to detect differences between groups. On this evidence, current use of component therapy is not inferior to another transfusion strategy.

Changes in Immature Reticulocytes Aid the Indirect Detection of Microdose Recombinant Erythropoietin Use in Men and Women.

We investigated whether immature reticulocyte fraction (IRF) and the immature reticulocytes to red blood cells ratio (IR/RBC) are sensitive and specific biomarkers for microdose recombinant human erythropoietin (rHuEPO) and whether the inclusion of reticulocyte percentage (RET%) and the algorithm "abnormal blood profile score (ABPS)" increased the athlete biological passport (ABP) sensitivity compared with hemoglobin concentration ([Hb]) and the OFF-hr score ([Hb]-60 × √RET%). Forty-eight (♀ = 24, ♂ = 24) participants completed a 2-wk baseline period followed by a 4-wk intervention period with three weekly intravenous injections of 9 IU·kg -1 ·bw -1 epoetin β (♀ = 12, ♂ = 12) or saline (0.9% NaCl, ♀ = 12, ♂ = 12) and a 10-d follow-up. Blood samples were collected weekly during baseline and intervention as well as 3, 5, and 10 d after treatment. The rHuEPO treatment increased [Hb] (time-treatment, P < 0.001), RET% (time-treatment, P < 0.001), IRF (time-treatment, P < 0.001) and IR/RBC (time-treatment, P < 0.001). IRF and IR/RBC were up to ~58% ( P < 0.001) and ~141% ( P < 0.001) higher compared with placebo, and calculated thresholds provided a peak sensitivity across timepoints of 58% and 54% with ~98% specificity, respectively. To achieve >99% specificity for IRF and IR/RBC, sensitivity was reduced to 46% and 50%, respectively. Across all timepoints, the addition of RET% and ABPS to the ABP increased sensitivity from 29% to 46%. Identification of true-positive outliers obtained via the ABP and IRF and IR/RBC increased sensitivity across all timepoints to 79%. In summary, IRF, IR/RBC, RET% and ABPS are sensitive and specific biomarkers for microdose rHuEPO in both men and women and complement the ABP.