Anti-D immunization after D positive platelet transfusions in D negative recipients: A systematic review and meta-analysis.

BACKGROUND: Anti-D can be formed after D-incompatible platelet transfusions due to contaminating D+ red blood cells. These antibodies are of particular importance in women of childbearing potential, because anti-D is most often involved in severe cases of hemolytic disease of the fetus and newborn. This systematic review determined the frequency of anti-D after D+ platelet transfusions and risk factors for D alloimmunization. STUDY DESIGN AND METHODS: Relevant literature was searched using PubMed, Embase and Web of Science until December 2022. Overall anti-D frequency and risk factors were estimated using a random effects meta-analysis. RESULTS: In 22 studies, a total of 3028 D- patients received a mean of six D+ platelet transfusions. After a mean follow-up of seven months 106 of 2808 eligible patients formed anti-D. The pooled anti-D frequency was 3.3% (95% CI 2.0-5.0%; I2 71%). After including only patients with an undoubtable follow-up of at least 4 weeks, 29 of 1497 patients formed anti-D with a pooled primary anti-D rate of 1.9% (95% CI 0.9-3.2%, I2 44%). Women and patients receiving whole blood derived platelets had two and five times higher anti-D rates compared with men and patients receiving apheresis derived platelets, respectively. DISCUSSION: Anti-D immunization is low after D incompatible platelet transfusions and dependent on recipients' sex and platelet source. We propose anti-D prophylaxis in girls and women, capable of becoming pregnant in the future, that received D+ platelets, regardless of platelet source, to reduce the risk of anti-D induced hemolytic disease of the fetus and newborn.

Should HLA and HPA-matched platelet transfusions for patients with Glanzmann Thrombasthenia or Bernard-Soulier syndrome be standardized care? A Dutch survey and recommendations.

BACKGROUND: Glanzmann thrombasthenia (GT) and Bernard-Soulier syndrome (BSS) patients require frequent platelet transfusions and hence have an increased risk for alloimmunization against donor Human Leukocyte Antigens (HLA) when no HLA-matching is performed. Knowing that Human Platelet Antigens (HPA) are located on the platelet glycoproteins that can be absent in these patients, preventive HPA-matching may also be considered. Uniform recommendations on this topic lack in transfusion guidelines making standard practice unclear, therefore, we aimed to provide a framework for matched platelet transfusions. STUDY DESIGN AND METHODS: We conducted a targeted literature search and a national survey of Dutch (pediatric) hematologists from July to September 2021. RESULTS: We found 20 articles describing platelet transfusion policies in 483 GT-patients and 29 BSS-patients, both adults and children. Twenty surveys were returned for full analysis. All responders treated patients with platelet disorders, including GT (n = 36 reported) and BSS (n = 29 reported). Of respondents, 75% estimated the risk of antibody formation as "likely" for HLA and 65% for HPA. Formation of HLA antibodies was reported in 5 GT and in 5 BSS-patients, including one child. Fifteen respondents gave preventive HLA-matched platelets in elective setting (75%). Three respondents additionally matched for HPA in GT-patients (15%). Main argument for matched platelet transfusions was preventing alloimmunization to safeguard the effectivity of 'random' donor-platelets in acute settings. CONCLUSION: Elective HLA-matching for GT and BSS-patients is already conducted by most Dutch (pediatric) hematologists. HPA-matching is mainly applied when HPA-antibodies are formed. Based on the current literature and the survey, recommendations are proposed.

Demand forecasting for platelet usage: From univariate time series to multivariable models.

Platelet products are both expensive and have very short shelf lives. As usage rates for platelets are highly variable, the effective management of platelet demand and supply is very important yet challenging. The primary goal of this paper is to present an efficient forecasting model for platelet demand at Canadian Blood Services (CBS). To accomplish this goal, five different demand forecasting methods, ARIMA (Auto Regressive Integrated Moving Average), Prophet, lasso regression (least absolute shrinkage and selection operator), random forest, and LSTM (Long Short-Term Memory) networks are utilized and evaluated via a rolling window method. We use a large clinical dataset for a centralized blood distribution centre for four hospitals in Hamilton, Ontario, spanning from 2010 to 2018 and consisting of daily platelet transfusions along with information such as the product specifications, the recipients' characteristics, and the recipients' laboratory test results. This study is the first to utilize different methods from statistical time series models to data-driven regression and machine learning techniques for platelet transfusion using clinical predictors and with different amounts of data. We find that the multivariable approaches have the highest accuracy in general, however, if sufficient data are available, a simpler time series approach appears to be sufficient. We also comment on the approach to choose predictors for the multivariable models.

Comparison of platelet transfusion effectiveness between Helicobacter pylori-positive and -negative immune thrombocytopenia.

Immune thrombocytopenia (ITP) is characterized by early platelet destruction and impaired platelet production. Helicobacter pylori (H. pylori) infection seems to contribute to the pathogenesis in certain ITP patients in Japan. We compared the effectiveness of platelet transfusion in severe ITP in the presence or absence of H. pylori. The median corrected count increment (CCI) at 24 h after platelet transfusion (CCI-24) of the H. pylori-positive ITP patients was higher than that of the H. pylori-negative ITP patients (6463 vs. 754, p < 0.001), and the CCI-1 was also in the same direction but not significant (23 351 vs. 11 578). Multiple regression analyses showed that H. pylori infection was independently associated with CCI-24. Our study suggests that platelet transfusion may be more effective in H. pylori-positive ITP patients.

The importance of ABO in platelet refractoriness, an often overlooked option.

ABO-non-identical (ni) platelets provide less of an increase in platelet count and may increase the length of patient transfusions. The paper by Han and Badami showed that ABO-ni platelets may be a risk factor for immune platelet transfusion refractoriness. Commentary on: Han et al. ABO non-identical platelet transfusions, immune platelet refractoriness and platelet support. Br J Haematol 2024;204:2097-2102.

Evaluation of platelets componentized with the Reveos Automated Blood Processing System and stored for 7 days at room temperature in a non-Di(2-ethylhexyl) phthalate (DEHP) platelet pooling set.

BACKGROUND: Platelet concentrates (PCs) used for transfusion can be produced by apheresis or derived from whole blood (WB). The Reveos device is the first US Food and Drug Administration-approved automated blood processing system that can produce PCs. In this work, we evaluated the quality and function of Reveos-collected PCs stored for 7 days at room temperature. STUDY DESIGN AND METHODS: WB was collected from healthy donors and componentized on the day of collection (Fresh) or after an overnight hold (Overnight). PCs were produced (n = 7 Fresh; n = 6 Overnight), stored at room temperature in plasma, and evaluated on days 1 and 7 for quality metrics, platelet activation, clot formation, and aggregation response. RESULTS: Platelet count was comparable between Fresh and Overnight PCs. A drop in pH was reported in Fresh day 7 PCs (p < .001, vs. day 1) but not in Overnight. Overnight units displayed the lowest levels of P-selectin expression (p = .0008, vs. day 7 Fresh). Reduced clot strength and increased lysis were observed in both Fresh and Overnight units on day 7 (vs. day 1). Overnight-hold PCs resulted in the highest clot strength on day 7 (p = .0084, vs. Fresh). No differences in aggregation were reported between groups. CONCLUSION: Reveos-processed PCs produced from overnight-hold WB performed better in hemostatic function assays and displayed reduced activation compared to fresh WB-derived PCs, although both PC groups maintained platelet quality throughout storage. Utilization of overnight WB for PC preparation with Reveos holds promise as an alternative method of producing platelets for transfusion purposes.

Increased platelet to red blood cell transfusion ratio associated with acute kidney injury in children with life-threatening bleeding.

INTRODUCTION: Transfusion may increase the risk of organ failure through immunomodulatory effects. The primary objective of this study was to assess for patient or transfusion-related factors that are independently associated with the risk of acute kidney injury (AKI) and acute respiratory distress syndrome (ARDS) in a cohort of children with life-threatening bleeding from all etiologies. METHODS: In a secondary analysis of the prospective observational massive transfusion in children (MATIC) study, multivariable logistic regression was performed in an adjusted analysis to determine if blood product ratios or deficits were independently associated with AKI or ARDS in children with life-threatening bleeding. RESULTS: There were 449 children included with a median (interquartile range, IQR) age of 7.3 years (1.7-14.7). Within 5 days of the life-threatening bleeding event, AKI occurred in 18.5% and ARDS occurred in 20.3% of the subjects. Every 10% increase in the platelet to red blood cell transfusion ratio is independently associated with a 12.7% increase in the odds of AKI (adjusted odds ratio 1.127; 95% confidence interval 1.025-1.239; p-value .013). Subjects with operative or medical etiologies were independently associated with an increased risk of AKI compared to those with traumatic injury. No transfusion-related variables were independently associated with the risk of developing ARDS. CONCLUSION: The use of increased platelet to red blood cell transfusion ratios in children with life-threatening bleeding of any etiology may increase the risk of AKI but not ARDS. Prospective trials are needed to determine if increased platelet use in this cohort increases the risk of AKI to examine possible mechanisms.

Recombinant Human Thrombopoietin Promotes Platelet Engraftment in Severe Aplastic Anemia Patients Following Treatment With Haploid Hematopoietic Stem Cell Transplantation using Modified Post-Transplantation Cyclophosphamide.

BACKGROUND: Recombinant human TPO (rhTPO) promotes platelet engraftment in patients after allogeneic HSCT (allo-HSCT). However, the effects of rhTPO on platelet recovery after Haplo-HSCT in patients with severe aplastic anemia (SAA) have not been intensively studied. OBJECTIVE: We aimed to evaluate the efficacy of rhTPO on platelet engraftment in patients with SAA who were treated with Haplo-HSCT using post-transplantation cyclophosphamide (PTCy). STUDY DESIGN: SAA patients who received Haplo-HSCT plus PTCy regimen were divided into the rhTPO group (with subcutaneous injection of rhTPO, n = 28) and Control group (no rhTPO administration, n = 27). The engraftment of platelet/neutrophil, platelet infusion amount, and transplant-related complications between the 2 groups were compared. RESULTS: All 55 patients showed successful hematopoietic reconstitution. The median time of platelet engraftment was 11 (9 to 29) days in the rhTPO group and 14 (9 to 28) days in the Control group (P = .003). The rhTPO group had a significantly reduced amount of infused platelets compared to the Control group (2 (1 to 11.5) versus 3 (1 to 14) therapeutic doses; P = .004). There was no significant difference between the 2 groups regarding median time of neutrophil engraftment, incidence of acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD), incidence of cytomegalovirus or Epstein-Barr virus reactivation, 3-yr overall survival rate, and failure-free-survival rate. No obvious adverse reactions were observed in the rhTPO group. CONCLUSION: rhTPO promoted platelet engraftment, reduced the amount of transfused platelets, and demonstrated good safety profiles without evidence of adverse reactions in patients with SAA who received Haplo-HSCT using PTCy regimen.

Acute pulmonary injury in hematology patients supported with pathogen-reduced and conventional platelet components.

ABSTRACT: Patients treated with antineoplastic therapy often develop thrombocytopenia requiring platelet transfusion, which has potential to exacerbate pulmonary injury. This study tested the hypothesis that amotosalen-UVA pathogen-reduced platelet components (PRPCs) do not potentiate pulmonary dysfunction compared with conventional platelet components (CPCs). A prospective, multicenter, open-label, sequential cohort study evaluated the incidence of treatment-emergent assisted mechanical ventilation initiated for pulmonary dysfunction (TEAMV-PD). The first cohort received CPC. After the CPC cohort, each site enrolled a second cohort transfused with PRPC. Other outcomes included clinically significant pulmonary adverse events (CSPAE) and the incidence of treatment-emergent acute respiratory distress syndrome (TEARDS) diagnosed by blinded expert adjudication. The incidence of TEAMV-PD in all patients (1068 PRPC and 1223 CPC) was less for PRPC (1.7 %) than CPC (3.1%) with a treatment difference of -1.5% (95% confidence interval [CI], -2.7 to -0.2). In patients requiring ≥2 PCs, the incidence of TEAMV-PD was reduced for PRPC recipients compared with CPC recipients (treatment difference, -2.4%; 95% CI, -4.2 to -0.6). CSPAE increased with increasing PC exposure but were not significantly different between the cohorts. For patients receiving ≥2 platelet transfusions, TEARDS occurred in 1.3% PRPC and 2.6% CPC recipients (P = .086). Bayesian analysis demonstrated PRPC may be superior in reducing TEAMV-PD and TEARDS for platelet transfusion recipients compared with CPC recipients, with 99.2% and 88.8% probability, respectively. In this study, PRPC compared with CPC demonstrated high probability of reduced severe pulmonary injury requiring assisted mechanical ventilation in patients with hematology disorders dependent on platelet transfusion. This trial was registered at www.ClinicalTrials.gov as #NCT02549222.

Platelet dysfunction reversal with cold-stored vs room temperature-stored platelet transfusions.

ABSTRACT: Platelets are stored at room temperature for 5 to 7 days (room temperature-stored platelets [RSPs]). Because of frequent and severe shortages, the US Food and Drug Administration recently approved up to 14-day cold-stored platelets (CSPs) in plasma. However, the posttransfusion function of CSPs is unknown and it is unclear which donors are best suited to provide either RSPs or CSPs. In this study, we sought to evaluate the posttransfusion platelet function and its predictors for platelets stored for the maximum approved storage times (7-day RSPs and 14-day CSPs) in healthy volunteers on acetylsalicylic acid (ASA). We conducted a randomized crossover study in 10 healthy humans. Individuals donated 1 platelet unit, stored at either 22°C or 4°C based on randomization. Before transfusion, participants ingested ASA to inhibit endogenous platelets. Transfusion recipients were tested for platelet function and lipid mediators. Platelet units were tested for lipid mediators only. A second round of transfusion with the alternative product was followed by an identical testing sequence. RSPs reversed platelet inhibition significantly better in αIIbß3 integrin activation-dependent assays. In contrast, CSPs in recipients led to significantly more thrombin generation, which was independent of platelet microparticles. Lysophosphatidylcholine-O species levels predicted the procoagulant capacity of CSPs. In contrast, polyunsaturated fatty acid concentrations predicted the aggregation response of RSPs. In summary, we provide, to our knowledge, the first efficacy data of extended-stored CSPs in plasma. Our results suggest that identifying ideal RSP and CSP donors is possible, and pave the way for larger studies in the future. This trial is registered at www.ClinicalTrials.gov as #NCT0511102.

Rh immune globulin immunoprophylaxis after RhD-positive red cell exposure in RhD-negative patients via transfusion: A survey of practices.

BACKGROUND: Current Association for the Advancement of Blood & Biotherapies (AABB) standards require transfusion services to have a policy on Rh immune globulin (RhIG) immunoprophylaxis for when RhD-negative patients are exposed to RhD-positive red cells. This is a survey of AABB-accredited transfusion services in the United States (US) regarding institutional policies and practices on RhIG immunoprophylaxis after RhD-negative patients receive RhD-positive (i.e., RhD-incompatible) packed red blood cell (pRBC) and platelet transfusions. RESULTS: Approximately half of the respondents (50.4%, 116/230) have policies on RhIG administration after RhD-incompatible pRBC and platelet transfusions, while others had policies for only pRBC (13.5%, 31/230) or only platelet (17.8%, 41/230) transfusions, but not both. In contrast, 18.3% (42/230) report that their institution has no written policies on RhIG immunoprophylaxis after RhD-incompatible transfusions. Most institutions (70.2%, 99/141) do not have policies addressing safety parameters to mitigate the risk of hemolysis associated with the high dose of RhIG required to prevent RhD alloimmunization after RhD-incompatible pRBC transfusions. DISCUSSION: With approximately half of US AABB-accredited institutions report having policies on RhIG immunoprophylaxis after both RhD-incompatible pRBC and platelet transfusions, some institutions may not be in compliance with AABB standards. Further, most with policies on RhIG immunoprophylaxis after RhD-incompatible pRBC transfusion do not have written safeguards to mitigate the risk of hemolysis associated with the high dose of RhIG required. CONCLUSION: This survey underscores the diverse and inadequate institutional policies on RhIG immunoprophylaxis after RhD exposure in Rh-negative patients via transfusion. This observation identifies an opportunity to improve transfusion safety.

Comparable bacterial growth in platelet concentrates suspended in plasma and platelet additive solution and improved detection of bacterial contamination using a new generation automated culture system.

BACKGROUND: Microbial screening of platelet concentrates (PC) with automated culture methods is widely implemented to reduce septic transfusion reactions. Herein, detection of bacterial contamination in PC was compared between units prepared in plasma and a mix of plasma and platelet additive solution (PAS) and between the BACT/ALERT 3D and next generation BACT/ALERT VIRTUO systems. STUDY DESIGN/METHODS: Double apheresis units were split into single units, diluted in either PAS (PAS-PC) or plasma (plasma-PC), and tested for in vitro quality and sterility prior to spiking with ~30 CFU/unit of Staphylococcus epidermidis, Staphylococcus aureus, Serratia marcescens, and Klebsiella pneumoniae or ~10 CFU/mL of Cutibacterium acnes. Spiked PC were sampled for BACT/ALERT testing (36 and 48 h post-spiking) and colony counts (24, 36, and 48 h post-spiking). Times to detection (TtoD) and bacterial loads were compared between PC products and BACT/ALERT systems (N = 3). RESULTS: Bacterial growth was similar in plasma-PC and PAS-PC. No significant differences in TtoD were observed between plasma-PC and PAS-PC at the 36-h sampling time except for S. epidermidis which grew faster in plasma-PC and C. acnes which was detected earlier in PAS-PC (p < .05). Detection of facultative bacteria was 1.3-2.2 h sooner in VIRTUO compared with 3D (p < .05) while TtoD for C. acnes was not significantly different between the two systems. DISCUSSION: Comparable bacterial detection was observed in plasma-PC and PAS-PC with PC sampling performed at 36-h post blood collection. PC sampling at ≤36 h could result in faster detection of facultative pathogenic organisms with the VIRTUO system and improved PC safety.

In platelet single donor apheresis, platelet factor 4 levels correlated with donor's age and decreased during storage.

The human population is ageing worldwide. The World Health Organization estimated that the world's population of people aged 60 years and older will increase to at least 30%, coinciding with a growing frequency of cognitive and cardiovascular disease. Recently, in preclinical studies platelet Factor 4 (PF4) was presented as a pro-cognitive factor. This molecule is released by platelets in the circulation and could be present in blood products destined for transfusion. We wondered if PF4 levels are correlated to the age of the blood donor or to the storage time of platelet concentrates (PCs) intended for transfusion? We observed higher levels of PF4 in PCs from elderly donors compared to younger donors, while PC storage time did not determine PF4 levels expression.

[Analysis of transfusion effect of different platelet matching schemes in patients with platelet transfusion refractoriness].

Objective: To analyze the transfusion effect of different platelet matching schemes in patients with platelet transfusion refractoriness (PTR). Methods: A total of 94 patients with PTR received by Taiyuan Blood Center from January to December 2021 were retrospectively analyzed, including 26 males and 68 females, aged 53(34,66) years. Platelet antibody screening was performed by enzyme-linked immunosorbent assay (ELISA). For patients with positive human leukocyte antigen (HLA) class Ⅰ antibodies, Luminex platform liquid chip assay was used to identify the specificity of antibodies, and platelets with missing allelic expression antigen corresponding to their specific antibodies were found in the platelet donor gene database established in our laboratory. For patients with negative class HLA-Ⅰ antibody screening, medium and high-resolution HLA-A and B alleles were genotyped by polymerase chain reaction restriction sequence specific oligonucleotide (PCR-SSO), and the compatible platelets were searched from the platelet donor gene database by HLA cross-reactive group genotype matching scheme or directly selected by serological cross-matching. The PCI compliance rate and total transfusion effective rate of different mismatch site groups and different matching scheme groups were statistically analyzed. Results: Platelet antibody was detected in 39 of 94 PTR patients with a positive rate of 41.5%, and all of them were HLA-Ⅰ antibodies, and 1 case was accompanied by human platelet antigen (HPA) antibody. A total of 134 times of compatible platelets were supplied to 39 patients with HLA-Ⅰ antibody positive by using antibody avoidance matching method. And the total effective rate of transfusion was 97.8% (131/134); The PCI compliance rates of HLA-A antigen mismatch, HLA-B antigen mismatch and HLA-A and B antigen mismatch groups were 81.6% (31/38), 86.5% (32/37) and 78.6% (22/28), respectively. The total effective rate of transfusion was 97.4% (37/38), 94.6% (35/37) and 100% (28/28), respectively, with no statistical significance (all P>0.05). A total of 118 times of compatible platelets were provided by HLA antigen cross-reaction group genotype matching and serological cross-matching, 90 transfusion effects were collected during follow-up, and the total effective rate was 76.7% (69/90). Conclusion: The combination of different platelet matching schemes can improve the PCI compliance rate and the total effective rate of transfusion in PTR patients.

Platelet transfusions in haploidentical haematopoietic stem cell allograft candidates: Protecting HLA-A and HLA-B antigens through eplet analysis.

In patients awaiting an allogeneic haematopoietic stem cell transplantation, platelet transfusion is a risk factor for anti-HLA class I immunization because the resulting donor-specific antibodies complicate the allograft process. The objective of the present study was to determine the feasibility of a novel eplet-based strategy for identifying HLA class I mismatches between potential donors and the recipient when pre-allograft platelet transfusions were required. We included 114 recipient/haploidentical relative pairs. For each pair, we entered HLA-class I typing data into the HLA Eplet Mismatch calculator, defined the list of mismatched eplets (for the recipient versus donor direction) and thus identified the shared HLAs to be avoided. Using this list of HLAs, we defined the theoretical availability of platelet components (PCs) by calculating the virtual panel-reactive antibody (vPRA). We also determined the number of PCs actually available in France by querying the regional transfusion centre's database. The mean ± standard deviation number of highly/moderately exposed eplets to be avoided in platelet transfusions was 5.8 ± 3.3, which led to the prohibition of 38.5 ± 2 HLAs-A and -B. Taking into account the mismatched antigens and the eplet load, the mean ± standard deviation theoretical availability of PCs (according to the vPRA) was respectively 34.49% ± 1.95% for HLA-A and 80% ± 2.3% for HLA-B. A vPRA value below 94.9% for highly or moderately exposed eplets would predict that 10 PCs were actually available nationally. Although epitope protection of HLA molecules is feasible, it significantly restricts the choice of PCs.