Donor Platelets Research Articles

Effect of the added plasma rinseback on residual cell types in plateletpheresis leukoreduction systems.

Platelets collected by the Trima Accel apheresis device (Terumo BCT) are automatically leukoreduced through a leukoreduction system (LRS) where WBCs are trapped in a conical-shaped LRS chamber. The content has been used as a valuable source of mononuclear cells for research purposes. In frequent, long-term platelet apheresis donors, lymphopenia has been associated with the use of LRS chambers, and implementation of plasma rinseback at the end of the procedure has been shown to mitigate the depletion of lymphocytes. In this report, the cellular content of the LRS chamber and remaining disposable was characterized with and without plasma rinseback. Trima disposable sets were obtained from apheresis platelet collections in 100% plasma or 35% plasma/65% PAS with or without plasma rinseback at the end of the collections. Cellular content was drained from the LRS chamber and the disposable and was characterized using a hematology analyzer and flow cytometer to establish total cell counts and proportions of RBC, platelet, and WBC subpopulations. LRS chambers contained approximately 109 WBCs, with the majority being lymphocytes and monocytes. The addition of plasma rinseback significantly decreased the number of WBCs remaining in the disposable, thereby increasing the number of WBCs returned to the donor. However, rinseback did not impact the WBC content of the LRS chamber itself. Blood Centers using the Trima Accel instrument may reduce lymphopenia in regular platelet donors by implementing plasma rinseback, while ensuring the cellular content of the LRS chamber intended for research purposes remains unaffected.

RESULTS OF LONG-TERM THERAPY WITH A BIOSIMILAR OF ECULIZUMAB IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA.

The study aimed to assess the safety, immunogenicity, and efficacy of long-term therapy with biosimilar of eculizumab (Elizaria®) in PNH patients. The study included 30 patients with PNH who had completed previous clinical trials. Of these, 25 patients continued receiving the biosimilar product, and 5 patients switched from the originator product Soliris. The maximum duration of follow-up was 104 weeks, during which the investigational product was administered 52 times at a standard dose. Throughout the study, the levels of LDH, hemoglobin, reticulocytes, and PNH clone remained stable compared to baseline, regardless of the previous therapy (p > 0.05). There were no significant differences in the number of patients with chronic kidney disease at different visits, as well as in the number of patients who received donor red blood cell and platelet transfusions during the study (p > 0.05). There were two cases of adverse reactions reported in two patients (6.6%): elevated aspartate aminotransferase (3.3%) and alopecia (3.3%). Immunogenicity analysis showed no significant differences in the frequency of anti-drug antibody detection compared to baseline (p > 0.05). The study findings confirm the long-term efficacy and safety of biosimilar in patients with PNH.

Hematological Changes in Platelet Apheresis Donors: An Observational Study.

Background The demand for platelet concentrates is increasing for treating patients in clinics such as oncology. Single donor platelets (SDPs) collected through apheresis offer a lower risk of transfusion-related complications. Aim This observational study aims to evaluate hematological changes in donors before and after platelet donation via apheresis, shedding light on donor safety and eligibility criteria. Methods This was a pilot study involving 30 plateletpheresis procedures. Hematological parameters were measured before and after donation, including platelet count and hematocrit. Results All donors were male, with an age range of 18-45 years. Blood group distribution among donors was O+ve (12), A+ve (6), B+ve (5), AB+ve (4), B-ve (1), O-ve (1), and AB-ve (1). The mean fall in platelet count after donation was 50,833/mm3. The overall mean fall in hematocrit was 1.16%, with a range of 0.5-2%. For donors with a platelet yield of 3.0x1011, the average hematocrit reduction was 1.13%, whereas for donors with a yield of 3.5x1011, the reduction was 1.56%. Conclusion Automated cell separators have significantly improved SDP quality and collection efficiency. The correlation between platelet yield and pre-donation platelet count underlines the importance of personalizing collection parameters.

Mobilization and Apheresis Collection Strategies to Reduce Platelet Loss in G-CSF Mobilized Healthy Adult Donors.

Granulocyte-colony stimulating factor (G-CSF) mobilizes hematopoietic progenitor cells (HPC) into the peripheral blood. Donor peripheral blood platelet loss has been observed during both G-CSF mobilization and apheresis collection. This study evaluates two strategies to reduce donor platelet loss, preserve product CD34+ cell yield and collection efficiency and increase volume of whole blood (WB) processed. One hundred and two adults healthy donors were mobilized with either standard dose G-CSF (9.5-12 mcg/kg/day × 4 days) or lower dose G-CSF (7.5-10 mcg/kg/day × 4 days) according to their pre-mobilization platelet count. Apheresis centrifugal force was adjusted by lowering the packing factor (PF) setting on the apheresis instrument. Between-group differences were observed in absolute donor platelet loss (p = 0.04) favoring lower G-CSF dosing, while percent donor platelet loss trended towards significance (p = 0.10). Lowering PF from the manufacturer's default of 4.5 to 4.0 demonstrated between-group differences in absolute donor platelet loss (p < 0.05), percent donor platelet loss (p < 0.001), and apheresis product platelet content (p < 0.001). No differences were observed in the product CD34+ cell content and CD34+ cell collection efficiency when PF was reduced to 4.0. Additionally, a higher volume of WB could be processed due to reduced donor platelet loss. Together, these two strategies may mitigate the risk of cumulative platelet loss in G-CSF mobilized healthy donors undergoing apheresis collection, thereby increasing the likelihood of completing the target total blood volume to be processed while maintaining donor safety.

Comparative Evaluation of Hematological Parameters and Instrument Performance in Single and Double Plateletpheresis Procedures Using Haemonetics MCS+ and Trima Accel Systems

ObjectivesPlateletpheresis (PP) has become increasingly prevalent due to its cost-effectiveness and fewer immunological and infectious complications for recipients. This study compares hematological indices of platelet donors and instrument-related parameters in high-yield PP donors using Haemonetics MCS+ and Trima Accel. MethodsEligible and healthy PP donors meeting the platelet donation criteria were randomly selected.19 single-dose platelet (SDP), and 26 double-dose platelet (DDP) donors underwent PP using the Haemonetics MCS+, while 21 SDP and 21 DDP donors were processed using the Trima Accel system. Complete Blood Count (CBC) and hematological indices of donors between groups with both devices were measured with the cell counter. Platelet yield, collection efficiency (CE), and collection rate (CR) were evaluated for both devices. Results were reported using R-4.3.2 software and a p-value<0.05 was considered statistically significant ResultsThe Trima Accel processed significantly more blood volume and had shorter procedure times than MCS+. Platelet yield in the SDP group with Trima Accel was significantly higher than the Haemonetics MCS+. The Trima Accel demonstrated a significantly higher CR and CE than the MCS+ in both SDP and DDP groups. Post-PP lymphocyte counts significantly decreased with the Trima compared to the MCS+ in the SDP group. However, post-PP hematocrit (HCT), mean corpuscular volume (MCV), and mean platelet volume (MPV) in the DDP group with the MCS+ were significantly lower than Trima. ConclusionDouble-dose plateletpheresis (DDP) offers advantages in cost-effectiveness and platelet production, and although it reduces some hematological indices, these remain within normal limits. The Trima Accel may offer superior efficiency and processing times compared to the MCS+. However, careful monitoring of DDP donors following AABB standards remains essential.

Donor Parameters and Platelet Yield during Plateletpheresis: A Cross-sectional Prospective Study

Abstract Background: Platelet transfusion can be life-saving in bleeding patients with thrombocytopenia or reduced platelet function. Single donor platelets (SDP) unit use is preferred due to the various advantages like reduction in transfusion-transmitted diseases and transfusion reactions. The quality of SDP is determined by platelet yield. Therefore, we conducted this study to assess the donor parameters affecting platelet yield during plateletpheresis. Materials and Methods: This cross-sectional prospective study included 160 single-donor platelet apheresis procedures done for 1 year. The pre-donation platelet count of the donor was set to 250 × 109/L to get double-dose platelet. Plateletpheresis was performed using Trima Accel single-needle separator apheresis machine. The demographic and hematologic parameters of donors were correlated with their platelet yield. Data obtained were tabulated using version 20 of the Statistical Package for the Social Sciences (SPSS). A relationship between pre-donation donor variables and platelet yield was studied using the Pearson correlation coefficient (r). P &lt; 0.05 was considered statistically significant. Results: There was a significant positive correlation between platelet yield and body mass index (BMI) (r = 1710 and P = 0.0304), total leukocyte count (TLC) (r = 0.2220 and P = 0.0048), and platelet count (r = 0.8880 and P &lt; 0.0001). The mean platelet volume (MPV) showed a negative correlation with platelet yield (r = −0.1910 and P = 0.0156). Age, hemoglobin, hematocrit, and platelet distribution width showed no significant correlation with the platelet yield. Conclusion: Donor parameters such as pre-donation platelet count, BMI, TLC, and MPV need to be considered while recruiting the donors for the SDP procedure for better yield of platelets.

A modern overview of the process of platelet formation (thrombocytopoiesis) and its dependence on several factors.

Structural and functional alterations in platelets are an actual problem that requires more attention. The treatment of these illnesses proves challenging, inefficient and heavily relies on platelet donations. A difficult task confronting science is producing platelets in vitro, which calls for meticulous examination of factors affecting platelet generation. It is known that megakaryocytes produce platelets in vitro and in vivo differently: in the laboratory we can get a smaller number of platelets compared to the human body. This review primarily examines the stages of megakaryocyte maturation and the processes involved in platelet formation. The article reflects the results of both fundamental research on the problem and the new results obtained over the past decade. Currently, most scientists accept the pro-platelets theory of platelet formation. This review aims to explore in detail each stage of pro-platelet formation and the platelet formation process. It explains on the processes of polyploidization, endomitosis, and apoptosis, as well as the functions of structural cell components (microtubules, mitochondria, T- and α-granules) and pro-platelet migration. The microenvironment influence is acknowledged for the osteoblastic and vascular niches that affect thrombocytopoiesis. The additional aspect is the contribution of specific proteins to thrombocytopoiesis such as RhoA, β1-tubulin, cytokines IL-6, IL-8, Toll-like receptors, etc.

C1q Binding Ability for Prior Risk Assessment of Acute Antibody-Mediated Rejection in ABO-Incompatible Kidney Transplantation.

In ABO blood group incompatible kidney transplantation (ABO-I), potential issues on acute antibody-mediated rejection (ABMR) remain to be solved. This study aimed to assess the risk factors of acute ABMR using recipient- or donor-derived specimens. Quantitative analysis of A/B antigen expression was conducted in 104 donor kidney tissues (Kt), platelets (Plt), and red blood cells (RBC) by immunohistochemical staining or flow cytometry (FCM). ABO-I pre-transplant recipient serum samples (ABMR = 12, non-ABMR = 27) were extracted by propensity score matching. Anti-A antibody titers of IgM, IgG and IgG subclasses, and C1q binding ability (%) on antibody were measured using RBC-FCM. No association was observed between ABMR and A/B antigen expression levels in donor's Plt, RBC, or Kt. In recipient's sample, C1q-IgG binding ability was significantly higher in the ABMR group than in the non-ABMR group (C1q-IgG: 9.04% vs. 5.93% p = 0.049). Neither the A/B antigen expression level in donors (grafts) nor anti-blood group IgG/IgM antibodies in recipient sera before desensitization seemed to influence ABMR incidence in ABO-I. In contrast, C1q-IgG binding ability could be a potential predictor for ABMR in ABO-I.

Two Concurrent Cases of NAIT in Pregnant Sisters

Abstract Neonatal alloimmune thrombocytopenia (NAIT) is caused by maternal antibodies directed against fetal platelet antigens inherited from the father. Approximately 80% of cases of NAIT are attributed to antibodies against human platelet antigen (HPA)-1a and less commonly to antibodies against HPA-5b. We present two cases of possible NAIT attributed to anti-HPA-5b that were identified in sisters requiring concurrent management. Patient #1 is a 32-year-old G9P4044 woman with one pregnancy complicated by intrauterine growth retardation and partial placental abruption, another pregnancy complicated by fetal anomaly (intracerebral hemorrhage) status post termination of pregnancy at 23 weeks’ gestation and three miscarriages (one with chromosomal abnormality). The patient is homozygous for HPA-1a and HPA-5a, and the partner is homozygous for HPA-5b. HPA-5b antibodies and HLA antibodies were identified in the patient’s serum. Deemed at high risk for subsequent NAIT, she was started on intravenous immunoglobulin twice weekly and steroids during her second trimester until delivery. The patient underwent weekly fetal sonograms during pregnancy which were normal. The patient’s platelet counts were stable. The patient refused caesarean delivery. At 38 weeks’ gestation, the patient gave birth to a healthy female via normal spontaneous vaginal delivery. HPA-5b negative platelets were procured from our blood supplier, but neither the mother nor neonate required transfusion. The neonate showed no signs of bleeding and had normal platelet counts. Ultrasound imaging of the head was unremarkable. The patient and neonate were discharged home. Patient #2 is a 33-year-old G13P6156 woman with a prior pregnancy complicated by stillbirth at 32 weeks’ gestation. Considering her personal and family history, HPA testing was performed and HPA-5b antibodies were identified in the patient’s serum. The patient’s partner is heterozygous for HPA-5b. Crossmatched platelets were procured from our blood supplier. The patient refused caesarean delivery. The patient gave birth at 37 weeks’ gestation to a healthy male via normal spontaneous vaginal delivery. The fetus had mild thrombocytopenia (107 x 103/uL), with no bleeding or bruising identified. Neither the mother nor neonate required transfusion. The patient and neonate were discharged home. Ultrasound imaging of the head was unremarkable, and his thrombocytopenia resolved. While some studies postulate that anti-HPA-5b identification may be coincidental rather contributory to the disease process, these cases re-emphasize the importance of obtaining pregnancy, neonatal and family history to best risk stratify patients and determine management from both the clinical and transfusion medicine perspectives. If transfusion is needed, transfusion options include HPA negative platelets, crossmatched platelets and random donor platelets depending on clinical urgency and platelet availability.

Haplotypes analysis reveals the genetic basis of type I CD36 deficiency

CD36, also known as glycoprotein IV, is classified into two distinct subgroups based on the presence or absence of its expression on monocytes. The CD36 gene spans approximately 50,000 base pairs. Historically, research has focused on identifying CD36 mutations through Sanger sequencing and next-generation sequencing (NGS), with limited exploration of haplotypes. In this study, we collected blood samples from donors with type I and type II CD36 deficiencies as well as from healthy controls, and employed single-molecule long-read sequencing (also known as Third-Generation Sequencing) of genomic DNA to analyze the genetic basis of CD36. The study identified 180 genetic variants, 12 of which were found to alter the amino acid sequence. Notably, four of these mutations (c.220 C > T; c.329_330delAC; c.430-1 G > C; c.1006 + 2 T > G) are premature termination mutations that lead to protein truncation. Using Fisher’s exact test, we statistically analyzed a specific haplotype, c.-132A > C and c.329_330delAC, along with their clinical phenotypes, revealing a strong association between these variants in the 5’ block and type I CD36 deficiency. We analyzed the CD36 gene sequences in platelet donors and patients with PTR (platelet transfusion refractoriness) and FNAIT (fetal and neonatal alloimmune thrombocytopenia), conducting a detailed haplotype analysis associated with type I CD36 deficiency and FNAIT.

Maternal Immune Thrombocytopenic Purpura Leading to Severe Neonatal Autoimmune Thrombocytopenia: Report of Two Cases

Introduction: In neonatal intensive care units, neonatal thrombocytopenia is one of the common hematological abnormality seen. Neonatal autoimmune thrombocytopenia should be considered in any neonate who is born to a known case of immune thrombocytopenia purpura (ITP) mother, with early onset thrombocytopenia without any signs of sepsis. Neonatal ITP is a condition of autoantibody mediated platelet destruction. Case details: Two neonates with thrombocytopenia, born to mothers with ITP are described in this report. Lowest platelet count noted was 7000 cells/cmm in one of the neonate. Both neonates received intra venous immunoglobulin (IVIG) while one neonate had persistent and severe thrombocytopenia requiring multiple random donor platelet (RDP) transfusions followed by oral steroid as well. Conclusion: Neonatal thrombocytopenia associated with maternal ITP need close monitoring, early sampling and diagnosis to prevent any possible complications and warrant early initiation of treatment.

A novel approach to simultaneous genotyping of human platelet antigen systems and human leucocyte antigen class I loci using PacBio long-read sequencing.

Accurate human leucocyte antigen (HLA) and human platelet antigen (HPA) typing is essential for establishing a blood platelet donor bank to deal with refractoriness in patients undergoing multiple platelet transfusions. Current methods, such as Sanger and next-generation sequencing, encounter difficulties in haplotyping. Herein, the aim of this study was to establish a method for HLA and HPA typing based on the long read sequencing. The HPA and HLA class I genotypes of 268 platelet donors from the Taiyuan Blood Center, China were identified using long-read sequencing on the PacBio platform. Allele frequencies for HPA systems and HLA class I genes were calculated, and genetic variability within HPA system genes was analysed. Polymorphisms were identified in 8 of the 35 HPA systems (HPA-1 to HPA-6w, HPA-15 and HPA-21w), with the frequencies of the 'b' allele at 0.0187, 0.0709, 0.4086, 0.0075, 0.0149, 0.0317, 0.4310 and 0.0019, respectively. The alleles with the highest frequencies at the HLA-A, HLA-B and HLA-C loci are HLA-A02:01, B51:01, B46:01 and C06:02, respectively. Additionally, several genetic patterns in HPA systems were identified, including the c.166-1029C>T variant, which was found exclusively in samples carrying the HPA-1b allele. This study developed a targeted long-read sequencing method characterized by high throughput and simultaneity, capable of resolving allele ambiguities for effective HLA class I genotyping in establishing a platelet donor bank.

Establishment and Application of a Multiplex PCR NGS Method for the Genotyping of HLA-Class I and HPA.

Selecting compatible HLA-Class I and/or HPA platelets based on genotyping could alleviate immune platelet transfusion refractoriness (PTR). A fast and reliable method of HLA-Class I and HPA genotyping is necessary to construct a platelet donor bank with known HLA-Class I and HPA genotypes. Ten pairs of specific primers for HLA-A, HLA-B, HLA-C, HPA-1 through HPA-6w, HPA-15 and HPA-21w were designed. The appropriate fragments were optimised for amplification in a single multiplex reaction. After a cleanup step using paramagnetic beads, the amplicon library was prepared and sequenced. To validate the accuracy of the developed method, commercial NGS kits for the genotyping of HLA-A, HLA-B and HLA-C and the TaqMan real-time PCR method in-house for the genotyping of HPA-1 through HPA-6w, HPA-15 and HPA-21w were used to detect all the specimens in parallel. A total of 386 specimens were detected and the results of genotyping HLA-A, HLA-B, HLA-C and HPA-1 through HPA-6w, HPA-15 and HPA-21w were obtained simultaneously, which is 100% consistent between the two methods. Four new HLA alleles, HLA-A*11:451, HLA-A*30:01:26, HLA-B*39:201 and HLA-B*40:538, were also reconfirmed. Two novel SNVs, c.2671C > T and c.2681T > G, in the coding region of ITGA2B were detected, all of which are heterozygous in individuals. A novel NGS method based on multiplex PCR was established to detect HLA-Class I and HPA simultaneously, which is high-throughput, rapid and accurate and could be applied to build a platelet donor bank.

Identification of the Novel HLA-A*33:03:68 Allele in a Chinese Platelet Donor.

The novel HLA-A*33:03:68 allele differs from HLA-A*33:03:01:01 by 1 variation in exon 3.

Patients with Waldenström macroglobulinemia have impaired platelet and coagulation function

AbstractClinical features in patients with the B-cell lymphoma, Waldenström macroglobulinemia (WM), include cytopenias, immunoglobulin M (IgM)–mediated hyperviscosity, fatigue, bleeding, and bruising. Therapeutics such as Bruton's tyrosine kinase inhibitors (BTKis) exacerbate bleeding risk. Abnormal hemostasis arising from platelet dysfunction, altered coagulation or vascular impairment have not yet been investigated in patients with WM. Therefore, this study aimed to evaluate hemostatic dysfunction in samples from these patients. Whole blood (WB) samples were collected from 14 patients with WM not receiving therapy, 5 patients receiving BTKis and 15 healthy donors (HDs). Platelet receptor levels and reticulation were measured by flow cytometry, plasma thrombin generation with or without platelets by fluorescence resonance energy transfer assay, WB clotting potential by rotational thromboelastometry, and plasma soluble glycoprotein VI (sGPVI) and serum thrombopoietin (TPO) by enzyme-linked immunosorbent assay. Donor platelet spreading, aggregation, and ability to accelerate thrombin generation in the presence of WM-derived IgM were assessed. WM platelet receptor levels, responses to physiological agonists, and plasma sGPVI were within normal ranges. WM platelets had reduced reticulation (P = .0012) whereas serum TPO levels were increased (P = .0040). WM plasma displayed slower thrombin generation (P = .0080) and WM platelets contributed less to endogenous thrombin potential (ETP; P = .0312). HD plasma or platelets incubated with IgM (50-60 mg/mL) displayed reduced spreading (P = .0002), aggregation (P < .0001), and ETP (P = .0081). Thus, alterations to thrombin potential and WB coagulation were detected in WM samples. WM IgM significantly impaired hemostasis in vitro. Platelet and coagulation properties are disturbed in patients with well-managed WM.

Transfusion-related acute lung injury induced by human leucocyte antigen-II antibodies: Analysis of antibody typing and source.

To explore transfusion-related acute lung injury (TRALI) induced by human leucocyte antigen (HLA)-II antibodies, and to analyse antibody typing and source. We retrospectively analysed the clinical symptoms and signs of two leukaemia patients with suspected TRALI from the same female donor. HLA phenotyping was performed on the two patients, the platelet donor, her husband and her two children. The HLA and human neutrophil antigenantibodies in the donor's plasma were identified. The clinical manifestations of two leukaemia patients were those of TRALI, and we treated them with timely ventilator support. A high titre of HLA-II antibodies was in the plasma of the platelet donor. The antibodies were directed at HLA-DRB3*03:01, HLA-DRB1*09:01, HLA-DRB1*12:02, HLA-DRB3*01:01 and HLA-DRB1*12:01:01G, which were specific to the HLA antigens of the two patients. High-resolution HLA genotyping suggested that the donor's HLA-II antibodies were derived from immune stimulation by the husband's antigens during pregnancy. This study described two cases of TRALI caused by HLA-II antibodies from the same female donor. Appropriate management of blood donors with a history of multiple pregnancies is crucial.

Categorization of the Inevitable Causes of Blood and Components Wastage Detected in South Indian Urban Blood Centre

Background: Since there is no artificial substitute for human blood, it plays a vital role in the patient management in this era of modern medicine. Therefore the donated blood from a healthy donor is precious and must not be wasted without proper utilization. Blood wastage is a universal phenomenon which needs a careful approach with strict guidelines. The study aims at categorizing the various inevitable causes of wastage with an attempt to determine ways of preventing the loss due to non-utilization. Materials and Methods: A retrospective – cross sectional study was conducted in a newly started Stand-alone Blood Centre in South Indian Urban city between June, 2022 and June 2024.All the components including Whole Blood (WB), Packed Red Blood Cell Concentrate (PRBC), Platelet concentrate (PC) and Fresh Frozen Plasma (FFP) were included in the study. The reasons for blood and component wastage was noted down from the various Registers of the Blood Centre and all the data was analyzed using Microsoft Excel Spread Sheet. Results: A total of 2456 units of blood were collected. 5284 components were prepared from these which includes 42 units of Whole Blood, 2397 Packed Red Blood cells(PRBC), 2393 Fresh frozen Plasma(FFP), 452 Platelet Concentrate(PC).Overall discard rate was found to be 11.90%. PC discard rate was highest (49.34%) followed by WBU (19.04%), PRBC (13.01%) AND FFP (3.59%). The commonest cause for the discarding was expiry of the shelf life of blood bags (74.72%) followed by damaged bags (9.69%) and TTI’s (6.76%). Conclusion: Blood and its components wastage is an inevitable reality which needs to be approached as upmost priority. Zero wastage of blood and components may be targeted by recommendations like appropriate training of the blood bank staff, keeping negative group donors on reserve, strictly following FIFO policy while dispensing blood, whole blood unit collection may be minimized, encouraging Single Donor Platelets (SDP) by apheresis instead of Random Donor Platelets (RDP) preparation, Blood Utilization Committee to be made mandatory and permission for reciprocal sharing of blood components among blood banks.

Genetic engineering of transfusable platelets with mRNA-lipid nanoparticles is compatible with blood banking practices

AbstractPlatelets contribute to a variety of physiological processes, including inflammation, sepsis, and cancer. However, because of their primary role in hemostasis, platelet transfusions are largely restricted to managing thrombocytopenia and bleeding. One way to expand the utility of platelet transfusions would be to genetically engineer donor platelets with new or enhanced functions. We have previously shown that lipid nanoparticles containing mRNA (mRNA-LNP) can be used to genetically modify authentic platelets in a nonclinical crystalloid solution. Currently, platelets collected for transfusion are stored in plasma or in plasma supplemented with platelet additive solution (PAS) at supraphysiological concentrations at room temperature, or at 4°C if intended for use in acute hemorrhage. Here, we describe a new plasma-optimized mRNA-LNP for transfecting platelets directly in plasma and plasma supplemented with PAS that is scalable to physiological and supraphysiological platelet concentrations. Transfecting platelets in clinical solutions with mRNA-LNP does not affect aspects of in vitro physiology, and transfected platelets are storable. The compatibility of this transfection system with current clinical practices could enable future mRNA-LNP–based platelet products and cell therapies.

A rare case of hemolytic disease-associated thrombocytopenia mimicking alloimmune thrombocytopenia: Salvaging a precious baby

Abstract: Thrombocytopenia associated with hemolytic disease of fetus and newborn (HDFN) is usually mild-to-moderate severity. Neonatal alloimmune thrombocytopenia (NAIT) is one of the leading causes of severe thrombocytopenia in neonates. We describe a rare case of very severe thrombocytopenia (5 g/L) with bleeding manifestations associated with HDFN mimicking NAIT. The baby was a preterm female, born to a 34-year-old multiparous mother with a bad obstetric history and multiple alloantibodies (anti-D, anti-C, anti-E, and anti-Jka). She was managed with phototherapy, exchange transfusion with phenotype-matched packed red blood cells, random donor platelets and intravenous immunoglobulin as platelet crossmatching could not provide compatible platelets. NAIT was ruled out with human platelet antigen (HPA) genotyping of the baby, the mother, and the father. It was concluded that the very severe thrombocytopenia might be due to HDFN after ruling out the other causes. HDFN can rarely cause very severe thrombocytopenia. However, when a newborn presents with severe/very severe thrombocytopenia, NAIT is to be ruled out with HPA genotyping, even in resource-limited settings, to plan out subsequent pregnancies.

Indicators of iron metabolism in regular donors of blood platelets and plasma

Introduction. The high frequency of medical withdrawals from donatio ns due to a decrease in hemoglobin levels and the negative impact on the motivation and return to donation of temporarily withdrawn individuals dictates the need to study the effect of exfusion of blood and its components on iron metabolism.Aim: to evaluate the iron metabolism indicators in regular donors of platelets and plasma.Materials and methods. 99 platelet donors and 90 blood plasma donors who regularly participated in donations were examined. The comparison group consisted of 158 healthy individuals who had not previously donated blood and its components. Hemoglobin concentration, hematocrit, erythrocyte count and erythrocyte indices were assessed. The concentration levels of ferritin, iron, transferrin in blood serum as well as the values of total and unsaturated iron-binding capacity of se rum were studied, and the saturation coefficient of transferrin was calculated.Results. In men who donated platelets, a statistically significant decrease in the red blood cells count (p = 0.001), hematocrit (p = 0.014) and ferritin concentration (p &lt; 0.001) were found relative to those in the comparison group: 4.8×1012/l, 42.0 %, 28.9 ng/ml versus 5.0×1012/l, 44.0 %, 74.2 ng/ml respectively. In regular donors a significant increase in the medium of hemoglobin of red blood cells was noted: 30.8 pg (p = 0.008) and 31.4 pg (p &lt; 0.001) in men and 30.2 pg (p = 0.030) and 31.0 pg (p &lt; 0.001) in women with platelet and plasma exfusions respectively compared to 29.4 pg in men and 29.6 pg in women who participated in donation for the first time. In plasma donors of both sexes, the values of hemoglobin and its average concentration in the erythrocyte were significantly higher than in first-time donors: 154.0 g/l (p = 0.008), 35.7 g/dl (p &lt; 0.001) and 138.0 g/l (p &lt; 0.001), 35.2 g/dl (p &lt; 0.001) versus 146.0 g/l, 33.6 g/dl and 129.0 g/l, 33.8 g/dl in men and women, respectively.Conclusion. To prevent the development of iron deficiency in donors of blood components it is necessary to monitor the con-centration of serum ferritin and correct its reduced values by changing the donation regimen or prescribing iron-containing drugs. When selecting donors, attention should be paid to the frequency of apheresis, especially in men who regularly donate platelets.