[Clinical applications of iPS cell-derived platelets].

The COVID-19 pandemic has cast a shadow over transfusion medicine based on the blood donation system. However, managing alloimmune platelet transfusion refractoriness (allo-PTR) has already been difficult. As a first step toward resolving this issue using induced pluripotent stem cell-derived platelet products (iPSC-PLTs), a clinical trial of autologous products (iPLAT1) was conducted in a patient with allo-PTR caused by anti-HPA-1a antibodies who had no compatible donor, and safety was confirmed. To produce iPSC-PLTs, a master cell bank (MCB) of expandable megakaryocyte lines (imMKCLs) is established from iPSCs. From this MCB, iPSC-PLTs are manufactured using a newly developed turbulent-type bioreactor and various compounds. Their quality, safety, and efficacy are confirmed by extensive preclinical studies. Based on the findings of the iPLAT1 study, a clinical trial of allo-transfusion of HLA homozygous iPSC-PLTs is currently ongoing and HLA class I-deficient O-type universal iPSC-PLTs are also being developed. iPSC-PLTs are expected to solve various problems, including allo-PTR in platelet transfusion, and greatly contribute to the advancement of transfusion medicine.

Implementation of a dual platelet inventory in a tertiary hospital during the COVID-19 pandemic enabling cold-stored apheresis platelets for treatment of actively bleeding patients.

BACKGROUND: To increase preparedness and mitigate the risk of platelet shortage without increasing the number of collections, we introduced a dual platelet inventory with cold-stored platelets (CSP) with 14-days shelf life for actively bleeding patients during the COVID-19 pandemic. STUDY DESIGN AND METHODS: We collected apheresis platelet concentrates with blood type O or A. All patients receiving CSP units were included in a quality registry. Efficacy was evaluated by total blood usage and laboratory analysis of platelet count, hemoglobin, and TEG 6s global hemostasis assay. Feasibility was evaluated by monitoring inventory and a survey among laboratory staff. RESULTS: From 17 March, 2020, to 31 December, 2021, we produced 276 CSP units and transfused 186 units to 92 patients. Main indication for transfusion was surgical bleeding (88%). No transfusion reactions were reported. 24-h post-transfusion patient survival was 96%. Total outdate in the study period was 33%. The majority (75%) of survey respondents answered that they had received sufficient information and training before CSP was implemented. Lack of information about bleeding status while issuing platelets, high workload, and separate storage location was described as main reasons for outdates. DISCUSSION: CSP with 14-days shelf life is a feasible alternative for the treatment of patients with bleeding. Implementation of a dual platelet inventory requires thorough planning, including information and training of clinical and laboratory staff, continuous follow-up of practice and patients, and an easy-to-follow algorithm for use of CSP units. A dual platelet inventory may mitigate the risk of platelet shortage during a pandemic situation.

Home Delivery: Transfusion Services When and Where They Are Needed.

Home blood product transfusion has been utilized around the world in various forms over the past few decades. There is current interest in decentralizing hospital care to improve patient independence and convenience, minimize cost to the health service, and to prevent nosocomial infection, especially with the recent COVID-19 pandemic. The transition to "hospital in the home" is occurring across the healthcare sector driven by aims to improve patient outcomes and patient satisfaction, capacity pressures in the acute care sector, and most recently due to concerns regarding infectious disease transmission in hospital settings. This review explores the published literature on home red cell and platelet transfusions, and where the literature is limited, also considered data from subcutaneous immunoglobulin studies. Current published experience on red cell and platelet transfusion at home has identified benefits to the patient and health service, with further studies needed to quantify improvement in quality of life and health-related outcomes. Safety concerns may be a perceived barrier to implementation of home transfusion, however current published data suggests serious adverse reactions are rare. Cost-effectiveness data for home transfusion are very limited and a key area for future research. Home transfusion has the potential to benefit from newer technologies, such as portable/remote monitoring and electronic patient identifiers.

There and back again: the once and current developments in donor-derived platelet products for hemostatic therapy.

More than 100 years ago, Duke transfused whole blood to a patient with thrombocytopenia to raise the platelet count and prevent bleeding. Since then, platelet transfusions have undergone numerous modifications from whole blood-derived platelet-rich plasma to apheresis-derived platelet concentrates. The storage time and temperature have also changed. The mandate to store platelets for a maximum of 5 to 7 days at room temperature has been challenged by recent clinical trial data, ongoing difficulties with transfusion-transmitted infections, and recurring periods of shortages that were further exacerbated by the COVID-19 pandemic. Alternative platelet storage approaches are as old as the first platelet transfusions. Cold-stored platelets may offer increased storage times (days) and improved hemostatic potential at the expense of reduced circulation time. Frozen (cryopreserved) platelets extend the storage time to years but require storage at -80°C and thawing before transfusion. Lyophilized platelets can be powder-stored for years at room temperature and reconstituted within minutes in sterile water but are probably the least explored alternative platelet product to date. Finally, whole blood offers the hemostatic spectrum of all blood components but has challenges such as ABO incompatibility. We know more than ever before about the in vitro properties of these products, and clinical trial data are accumulating. The purpose of this review is to summarize the findings of recent preclinical and clinical studies on alternative, donor-derived platelet products.

Passive transfer of SARS-CoV-2 antibodies with platelet transfusions.

BACKGROUND: Although over 5000 platelet transfusions occur daily in the United States, the presence of SARS-CoV-2 antibodies in platelet units is not commonly evaluated for. The effects of platelet transfusions with SARS-CoV-2 antibodies remain largely unknown. We evaluated single-donor (apheresis) platelet units for SARS-CoV-2 antibodies and determined if platelet transfusions passively transferred antibodies to seronegative recipients. STUDY DESIGN AND METHODS: We conducted a retrospective analysis as part of a quality assurance initiative during February to March 2021 at a tertiary referral academic center in suburban New York. Platelet units and platelet recipients were evaluated for the presence of SARS-CoV-2 antibodies using the DiaSorin LIASON SARS-CoV-2 S1/S2 IgG assay. There were 47 platelet recipients eligible for study inclusion. The primary outcome was the presence of SARS-CoV-2 spike protein IgG antibodies in the recipient's blood after platelet transfusion. RESULTS: Twenty-three patients received platelets with SARS-CoV-2 spike protein IgG antibodies; 13 recipients had detection of SARS-COV-2 antibodies (56.5%), and 10 recipients did not. The median antibody titer in the platelet units given to the group with passive antibodies detected was significantly higher compared to the median antibody titer in the platelet units given to the group without antibodies detected (median [interquartile range]: 306 AU/ml [132, 400] vs. 96.1 AU/ml [30.6, 186], p = .027). CONCLUSIONS: Our study demonstrated a significant rate of passive transfer of SARS-CoV-2 spike protein IgG antibodies through platelet transfusions. Considering the volume of daily platelet transfusions, this is something all clinicians should be aware of.

Impact of different pathogen reduction technologies on the biochemistry, function, and clinical effectiveness of platelet concentrates: An updated view during a pandemic.

Standard platelet concentrates (PCs) stored at 22°C have a limited shelf life of 5 days. Because of the storage temperature, bacterial contamination of PCs can result in life-threatening infections in transfused patients. The potential of blood components to cause infections through contaminating pathogens or transmitting blood-borne diseases has always been a concern. The current safety practice to prevent pathogen transmission through blood transfusion starts with a stringent screening of donors and regulated testing of blood samples to ensure that known infections cannot reach transfusion products. Pathogen reduction technologies (PRTs), initially implemented to ensure the safety of plasma products, have been adapted to treat platelet products. In addition to reducing bacterial contamination, PRT applied to PCs can extend their shelf life up to 7 days, alleviating the impact of their shortage, while providing an additional safety layer against emerging blood-borne infectious diseases. While a deleterious action of PRTs in quantitative and qualitative aspects of plasma is accepted, the impact of PRTs on the quality, function, and clinical efficacy of PCs has been under constant examination. The potential of PRTs to prevent the possibility of new emerging diseases to reach cellular blood components has been considered more hypothetical than real. In 2019, a coronavirus-related disease (COVID-19) became a pandemic. This episode should help when reconsidering the possibility of future blood transmissible threats. The following text intends to evaluate the impact of different PRTs on the quality, function, and clinical effectiveness of platelets within the perspective of a developing pandemic.

No increase in anti-A isohemagglutinin titer after SARS-CoV-2 infection: A retrospective cohort analysis of group O apheresis platelet donors.

The risk of a hemolytic reaction during the transfusion of ABO non-identical PC is determined by the presence of natural anti-A IgM antibodies, the titer of which may increase after infections. The aim of the study was to evaluate the titer of anti-A isohemagglutinins in platelet concentrate (PC) obtained by apheresis from group O donors who experienced SARS-CoV-2 infection, and to compare the titer before and after infection. A retrospective single-center analysis of 21 PC donors with a previous COVID-19 history was performed. The results showed neither a statistically important increase in the anti-A IgM antibody titers nor a significant correlation between the anti-A IgM antibody level and anti-SARS-CoV-2S1 antibody titer in the donors with an asymptomatic or mild COVID-19. Further population-based studies on anti-A titers are necessary for a comprehensive assessment of this phenomenon.

A real-world study of immune thrombocytopenia management during the COVID-19 pandemic in the UK.

The COVID-19 pandemic has created many challenges in the management of immune thrombocytopenic purpura (ITP). The recommendation for avoidance of steroids by WHO led to the off-licence use, supported by NHS England, of thrombopoietin mimetics (TPO-RA) for newly diagnosed or relapsed ITP. This is a real-world prospective study which investigated the treatment patterns and outcomes in this setting. Twenty-four hospitals across the UK submitted 343 cases. Corticosteroids remain the mainstay of ITP treatment, but TPO-RAs were more effective. Incidental COVID-19 infection was identified in a significant number of patients (9·5%), while 14 cases were thought to be secondary to COVID-19 vaccination.

Therapeutic plasma exchange (TPE) as a plausible rescue therapy in severe vaccine-induced immune thrombotic thrombocytopenia.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is associated with high titers of immunoglobulin G class antibodies directed against the cationic platelet chemokine platelet factor 4 (PF4). These antibodies activate platelets via FcγIIa receptors. VITT closely resembles heparin-induced thrombocytopenia. Inflammation and tissue trauma substantially increase the risk for forming pathogenic PF4 antibodies. We therefore propose the use of therapeutic plasma exchange as rescue therapy in VITT to deplete antibodies plus factors promoting inflammation such as excess cytokines in the circulation as well as extracellular vesicles derived from activated platelets.

Proteomics: A Tool to Study Platelet Function.

Platelets are components of the blood that are highly reactive, and they quickly respond to multiple physiological and pathophysiological processes. In the last decade, it became clear that platelets are the key components of circulation, linking hemostasis, innate, and acquired immunity. Protein composition, localization, and activity are crucial for platelet function and regulation. The current state of mass spectrometry-based proteomics has tremendous potential to identify and quantify thousands of proteins from a minimal amount of material, unravel multiple post-translational modifications, and monitor platelet activity during drug treatments. This review focuses on the role of proteomics in understanding the molecular basics of the classical and newly emerging functions of platelets. including the recently described role of platelets in immunology and the development of COVID-19.The state-of-the-art proteomic technologies and their application in studying platelet biogenesis, signaling, and storage are described, and the potential of newly appeared trapped ion mobility spectrometry (TIMS) is highlighted. Additionally, implementing proteomic methods in platelet transfusion medicine, and as a diagnostic and prognostic tool, is discussed.

Transition from room temperature to cold-stored platelets for the preservation of blood inventories during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has placed great strain on blood resources. In an effort to extend platelet (PLT) shelf life and minimize waste, our institution transitioned room temperature to cold-stored PLTs for administration to bleeding patients. STUDY DESIGN AND METHODS: We describe the administrative and technical processes involved in transitioning room temperature PLTs to cold storage in April 2020. Additionally, we describe the clinical utilization of cold-stored PLTs in the first month of this practice change, with a focus on changes in PLT counts after transfusion, hemostasis, and safety outcomes. RESULTS: A total of 61 cold-stored PLT units were transfused to 40 bleeding patients, with a median (interquartile range [IQR]) of 1 (1-2) units per patient. The median age was 68 (59-73) years; 58% male. Median pretransfusion and posttransfusion PLTs counts were 88 (67-109) and 115 (93-145). A total of 95% of transfusions were administered in the operating room: 57% cardiac surgery, 20% vascular surgery, 8% general surgery, and 5% solid organ transplantation. Hemostasis was deemed to be adequate in all cases after transfusion. There were no transfusion reactions. One patient (3%) experienced a fever and infection within 5 days of transfusion, which was unrelated to transfusion. Median (IQR) hospital length of stay was 8.5 (6-17) days. Two patients (5%) died in the hospital of complications not related to transfusion. CONCLUSION: Cold-stored PLT utilization was associated with adequate hemostasis and no overt signal for patient harm. Conversion from room temperature to cold-stored PLTs may be one method of reducing waste in times of scarce blood inventories.

Severe immune thrombocytopenia in a critically ill COVID-19 patient.

The novel coronavirus SARS-CoV-2 can cause a severe and even fatal respiratory illness named COVID-19. Apart from respiratory failure, COVID-19 may be associated with various autoimmune complications. We present a case of a critically ill patient with COVID-19 who developed severe immune thrombocytopenia that was successfully treated with a concomitant use of corticosteroids and intravenous immunoglobulins.