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Background: As universal leukocyte (WBC) reduction (ULR) is being considered as a new standard, few data are available on the performance of WBC-reduction filtration in routine practice. The performance of WBC-reduction in RBCs, using varied filtration practices, in meeting the current FDA requirement (<5 x 10(6)), Council of Europe (EC) recommendation, the proposed FDA requirement (<1 x 10(6)), and a more stringent proposal (<5 x 10(5)) for residual WBCs per RBC unit was assessed and compared.Study Design and Methods: Participating facilities were the 11 sites of the Viral Activation Transfusion Study (VATS), a prospective study of the impact of transfusion with and without WBC-reduction on survival and HIV viral load in HIV-1-infected patients. Patients randomly assigned to undergo WBC reduction were required to receive RBCs < or =14 days old that had undergone prestorage (within 72 hours of collection) WBC-reduction filtration by a method devised to achieve a postfiltration WBC count of <5 x 10(6). Residual WBC quantitation was performed by PCR in the central VATS laboratory by using frozen WBC-reduced RBC samples obtained at issue for transfusion.Results: A total of 1869 WBC-reduced RBC units were studied. Filtration practices varied within and between sites. There were significant differences in mean residual WBC counts at the 11 sites (p<0.001). Among the WBC-reduced RBC units, 0.8 percent exceeded 5 x 10(6) WBCs per unit, 8.3 percent exceeded 1 x 10(6) WBCs per unit, and 14.3 percent exceeded 5 x 10(5) WBCs per unit.Conclusion: Residual WBCs in WBC-reduced RBC units vary within and between sites. WBC reduction was successful, in that over 99 percent and 91 percent of VATS WBC-reduced RBC units met US and EC thresholds, respectively. However, the small but measurable failure rate indicates that not every unit will meet these guidelines. [ABSTRACT FROM AUTHOR]

Context: Allogeneic blood transfusions have immunomodulatory effects and have been associated with activation of human immunodeficiency virus (HIV) and cytomegalovirus (CMV) in vitro and of HIV in small pilot studies. Retrospective studies suggest that transfusions adversely affect the clinical course of HIV. Data in selected non-HIV-infected patients requiring blood transfusion have suggested clinical benefit with leukocyte-reduced red blood cells (RBCs).Objective: To compare the effects of leukoreduced and unmodified RBC transfusions on survival, complications of acquired immunodeficiency syndrome, and relevant laboratory markers in HIV-infected patients.Design and Setting: Double-blind randomized controlled trial conducted in 11 US academic medical centers from July 1995 through June 1999, with a median follow-up of 12 months (24 months in survivors).Patients: A total of 531 persons infected with HIV and CMV, aged 14 years or older, who required transfusions for anemia; 259 received leukoreduced transfusions and 262 received unmodified transfusions (10 did not receive the planned transfusion).Main Outcome Measures: Survival and change in plasma HIV RNA level 7 days after transfusion, compared by type of transfusion.Results: At entry, the groups were similar in demographic, clinical, and relevant laboratory characteristics. A total of 3864 RBC units were transfused. Two hundred eighty-nine deaths occurred (151 with leukoreduced transfusion; 138 with unmodified transfusion); median survival was 13.0 and 20.5 months, respectively (relative hazard [RH], 1.20; 95% confidence interval [CI], 0.95-1.51; log-rank P =.12). Analyses adjusted for prognostic factors suggested possible worse survival with leukoreduction (RH, 1.35; 95% CI, 1.06-1.72). There was no difference in time to new opportunistic event/death or frequency of transfusion reactions. No changes in plasma HIV RNA level were seen in either group at days 7, 14, 21, or 28, even in patients not taking antiretroviral drugs. There were no differences in trends between groups in CMV DNA, CD4 cell counts, activated (CD38% or human leukocyte antigen-DR) CD8 cell counts, or plasma cytokine levels.Conclusions: We found no evidence of HIV, CMV, or cytokine activation following blood transfusion in patients with advanced HIV infection. Leukoreduction provided no clinical benefit in these patients. These data demonstrate the importance of conducting controlled studies of effects of leukoreduction in different patient populations, since smaller studies in other patient populations have suggested leukoreduction may be beneficial. [ABSTRACT FROM AUTHOR]

Report on research to determine the mechanisms of an increase in the platelet count after therapy for autoimmune thrombocytopenic purpura. Determination of survival time and localization of radiolabeled autologous platelets and measured platelet-associated immunoglobulin levels before and after prednisone therapy or splenectomy in 19 patients.

Abstract: Up to a third of patients with hemato-oncologic conditions who have received multiply transfusions develop immune-mediated platelet transfusion refractoriness. Yet factors that influence posttransfusion platelet corrected count increments (CCI) in patients with HLA-alloimmune platelet transfusion refractoriness remain less well elucidated. Recent advances in HLA antibody characterization using fluorescent bead-based platforms enable the study of donor-specific antibody (DSA) avidity (as measured by mean fluorescence intensity [MFI]) and its impact on HLA-alloimmune platelet transfusion refractoriness. In this large retrospective study of 2012 platelet transfusions among 73 HLA-alloimmunized patients, we evaluated the impact of cumulative HLA DSA-MFI alongside other donor, platelet component, and patient characteristics on CCI at 2 and 24 hours after transfusion. As part of a quality improvement initiative, we also developed and tested a computerized algorithm to optimize donor-recipient histocompatibility based on cumulative DSA-MFI and sought other actionable predictors of CCI. In multivariate analyses, cumulative HLA DSA-MFI of ≥10 000, major/bidirectional ABO-mismatch, splenomegaly, transfusion reactions, and platelet storage in additive solution negatively affected 2-hour but not 24-hour posttransfusion CCI. The DSA-MFI threshold of 10 000 was corroborated by greater antibody-mediated complement activation and significantly more CCI failures above this threshold, suggesting the usefulness of this value to inform "permissive platelet mismatching" and to optimize CCI. Furthermore, DSA-MFI decreases were deemed feasible by the computer-based algorithm for HLA-platelet selection in a pilot cohort of 8 patients (122 transfusions) evaluated before and after algorithm implementation. When HLA-selected platelets are unavailable, ABO-identical/minor-mismatched platelet concentrates may enhance 2-hour CCI in heavily HLA-alloimmunized patients with platelet transfusion refractoriness., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Bleeding is a primary outcome for many transfusion-related trials in acute leukaemia (AL) patients, typically graded using the World Health Organisation (WHO) bleeding scale (clinically significant bleed (CSB) is ≥grade 2). This composite outcome fails to differentiate minor bleeds that may not be significant, poorly represents the total burden of bleeding and lacks input from healthcare providers (HCPs) and patients. As part of a multi-step project to create a better bleeding tool for trials, our objective was to identify HCPs' perspectives on the components of CSB in AL patients., Study Design and Methods: Using qualitative description, we interviewed 19 physicians and nurses who care for AL patients undergoing induction chemotherapy. Participants were recruited from professional organisations, networks and social media. An inductive approach to conventional content analysis was used., Results: HCPs identified features of CSB as the anatomical site of bleeding, amount of bleeding, need for intervention and changes in vital signs. Using these characteristics, bleeding events were categorised into three groups: clinically significant, could evolve into a CSB and not clinically significant. HCPs considered the patient's condition, bleeding history and clinical intuitions when deciding whether a bleed could escalate into serious bleeding., Discussion: Using data from HCPs, we categorised bleeds as clinically significant, could evolve into a CSB, and not significant. A study of patients' perspectives on the importance of different kinds of bleeding is the next step to creating a bleeding definition that is informed by evidence, clinicians and patients., (© 2024 The Author(s). Transfusion Medicine published by John Wiley & Sons Ltd on behalf of British Blood Transfusion Society.)

Abstract: Immune thrombocytopenia (ITP) is an autoimmune disease associated with autoantibody-mediated platelet destruction and impaired platelet production, resulting in thrombocytopenia and a predisposition to bleeding. The ongoing, global phase 1/2 study showed that rilzabrutinib, a Bruton tyrosine kinase inhibitor specifically developed to treat autoimmune disorders, could be an efficacious and well-tolerated treatment for ITP. Clinical activity, durability of response, and safety were evaluated in 16 responding patients who continued rilzabrutinib 400 mg twice daily in the long-term extension (LTE) study. At LTE entry, the median platelet count was 87 × 109/L in all patients, 68 × 109/L in those who had rilzabrutinib monotherapy (n = 5), and 156 × 109/L in patients who received concomitant ITP medication (thrombopoietin-receptor agonists and/or corticosteroids, n = 11). At a median duration of treatment of 478 days (range, 303-764), 11 of 16 patients (69%) continued to receive rilzabrutinib. A platelet count of ≥50 × 109/L was reported in 93% of patients for more than half of their monthly visits. The median percentage of LTE weeks with platelet counts ≥30 × 109/L and ≥50 × 109/L was 100% and 88%, respectively. Five patients discontinued concomitant ITP therapy and maintained median platelet counts of 106 × 109/L at 3 to 6 months after stopping concomitant ITP therapy. Adverse events related to treatment were grade 1 or 2 and transient, with no bleeding, thrombotic, or serious adverse events. With continued rilzabrutinib treatment in the LTE, platelet responses were durable and stable over time with no new safety signals. This trial is registered at www.clinicaltrials.gov as #NCT03395210 and www.clinicaltrialsregister.eu as EudraCT 2017-004012-19., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Inborn errors of immunity (IEIs) are monogenic disorders that predispose patients to immune dysregulation, autoimmunity, and infection. Autoimmune cytopenias, such as immune thrombocytopenia (ITP) and Evans syndrome (a combination of ITP and autoimmune hemolytic anemia), are increasingly recognized phenotypes of IEI. Although recent findings suggest that IEIs may commonly underlie pediatric ITP and Evans syndrome, its prevalence in adult patients with these disorders remains undefined. This study sought to estimate the prevalence of underlying IEIs among adults with persistent or chronic ITP or Evans syndrome using a next-generation sequencing panel encompassing >370 genes implicated in IEIs. Forty-four subjects were enrolled from an outpatient adult hematology clinic at a tertiary referral center in the United States, with a median age of 49 years (range, 20-83). Fourteen subjects (31.8%) had secondary ITP, including 8 (18.2%) with Evans syndrome. No cases of IEI were identified despite a high representation of subjects with a personal history of autoimmunity (45.5%) and early onset of disease (median age at diagnosis of 40 years [range, 2-77]), including 20.5% who were initially diagnosed as children. Eight subjects (18.2%) were found to be carriers of pathogenic IEI variants, which, in their heterozygous state, are not disease-causing. One case of TUBB1-related congenital thrombocytopenia was identified. Although systematic screening for IEI has been proposed for pediatric patients with Evans syndrome, findings from this real-world study suggest that inclusion of genetic testing for IEI in the routine work-up of adults with ITP and Evans syndrome has a low diagnostic yield., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Avatrombopag is an oral thrombopoietin receptor agonist (TPO-RA) that was approved in the US in 2019 for treatment of chronic immune thrombocytopenia (ITP). This post hoc analysis of the pivotal phase III study (NCT01438840) of avatrombopag in adult patients with ITP evaluated platelet count response to avatrombopag during the core study in different subgroups, and durability of response data in patients who responded to avatrombopag treatment both during the core phase (total population) and during the core and extension phase (total population and by subgroup). Loss of response (LOR [platelet count <30 × 10 9 /L]) was defined as LOR over two consecutive scheduled visits. The response was generally similar between subgroups though a few differences were observed. The durability of response analysis showed that avatrombopag-treated patients maintained their response for 84.5% of time on treatment during the core phase and 83.3% during the core and extension phase; 55.2% of patients in the core phase and 52.3% in the core and extension phase never experienced LOR. We conclude that the initial response to avatrombopag is both stable and durable.

Background: Immune thrombocytopenia (ITP) is characterized by primarily autoantibody-mediated platelet destruction and impaired platelet production resulting in thrombocytopenia and an increased risk of bleeding. Other manifestations include increased risk of thrombosis and diminished quality of life. Current treatment approaches are directed toward lowering the rate of platelet destruction or stimulating platelet production to prevent bleeding. Rilzabrutinib is an oral, reversible, potent Bruton tyrosine kinase inhibitor that was specifically designed to treat immune-mediated diseases and mediates its therapeutic effect through a dual mechanism of action: (1) inhibiting B-cell activation and (2) interrupting antibody-coated cell phagocytosis by Fc gamma receptor in spleen and liver. A 24-week dose-finding phase I/II study of rilzabrutinib in patients with ITP showed a 40% platelet response (⩾2 consecutive platelet counts of ⩾50 × 10 9 /L and increase from baseline ⩾20 × 10 9 /L without rescue medication use) and a well-tolerated safety profile with only grade 1/2 transient adverse events across dose levels., Objectives: Assess the efficacy and safety of oral rilzabrutinib in adult and adolescent patients with persistent or chronic ITP., Design: Rilzabrutinib 400 mg BID is being evaluated in the ongoing LUNA 3 multicenter, double-blind, placebo-controlled phase III study., Methods and Analysis: The primary endpoint is durable platelet response, defined as achieving platelet counts of ⩾50 × 10 9 /L for at least two-thirds of ⩾8 available weekly scheduled platelet measurements during the last 12 weeks (including ⩾2 available measurements within the last 6 weeks) of the 24-week blinded treatment period in the absence of rescue therapy., Ethics: Ethical guidelines and informed consent are followed., Discussion: The LUNA 3 trial will further investigate rilzabrutinib's safety and efficacy in adult and adolescent patients, with the primary goal of addressing a major objective in treating patients with ITP: durability of platelet response., Trail Registration: ClinicalTrials.gov NCT04562766: https://clinicaltrials.gov/ct2/show/NCT04562766; EU Clinical Trials Register EudraCT 2020-002063-60: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-002063-60., Competing Interests: DJK: Research: Alnylam, BioCryst, Novartis, Rigel Pharmaceuticals, Sanofi (Principia), Takeda (Bioverativ), UCB. Consulting: AIRx, Alexion (Syntimmune), Alnylam, Alpine Immune Sciences, Amgen, Argenx, BioCryst, Bristol Myers Squibb (BMS), Caremark, Cellularity, Cellphire Therapeutics, Chugai, CRICO, Daiichi Sankyo, Dianthus Therapeutics, Electra Therapeutics, Fujifilm Diosynth Biotechnologies, Hemopure, Hengrui, Immunovant, Incyte, Inmagene Bio, Kezar Life Sciences, Kyowa-Kirin, Merck Sharp & Dohme, Momenta, Novartis, Nuvig Therapeutics, Pfizer, Platelet BioGenesis, Platelet Disorder Support Association, Principia Biopharma (Sanofi), Protagonist Therapeutics, Rigel Pharmaceuticals, Sanofi (Bioverativ), Sanofi (Genzyme), Sanofi, Sobi (Dova Pharmaceuticals), Takeda, UCB, UpToDate, Zafgen; and stock ownership: Rubius Therapeutics. JBB: Reports consulting for Amgen, Argenx, AstraZeneca, Janssen, Novartis, Pfizer, Rally Bio, Rigel, Sobi, and UCB; and honoraria from Up-to-Date. WG: Reports fees for participation in the advisory board from Amgen, Argenx, Grifols, Novartis, Pfizer, Principia Biopharma Inc. – a Sanofi Company, Sanofi, Sobi (Dova), UCB/Cellphire Therapeutics; lecture honoraria from Amgen, Bayer, Bristol Myers Squibb, Grifols, Novartis, Pfizer, Sanofi, and Sobi (Dova); and research grants from Bayer, Bristol Myers Squibb/Pfizer, and UCB. NC: Reports consulting fees and support for traveling from Principia Biopharma (Sanofi) and Sanofi; honoraria for presenting at and support for traveling to educational events and honoraria for participating in advisory boards from Amgen, Argenx, Novartis, Principia Biopharma (Sanofi), Sanofi, Takeda, and UCB. TG: Reports consulting for Cellphire; payment for lectures from Amgen and Sanofi; Data Safety and Monitoring Board for Palisade; and advisory board for Dova and Novartis. MPL: Reports grants/contracts to the institution from Dova, FWGBD, Momenta, Novartis, Octapharma, PDSA, Principia (now Sanofi), and Sysmex; consulting fees from Argenx, Dova, Janssen, Novartis, Octapharma, Principia (now Sanofi), and Shionogi; payment for expert testimony from the DOJ; unpaid participation on a Data Safety Monitoring Board or Advisory Board from Sirolimus in Castleman’s Baricitinib ACS; and unpaid leadership or fiduciary role in board, society, committee or advocacy group from 22g Society, CdLS, ClinGen, ICON, Platelet Disorder Support Association (medical advisor). HAL: Reports research funding for clinical trial from Janssen and Sanofi; consulting fees from Novartis and Sobi; payment for lecture to Mexican Hematology Association from Amgen; participation on a Data Safety Monitoring Board/advisory board for apixaban for antithrombotic prophylaxis in cancer for the AVERT trial; planning committee for the International Conference on Thrombosis and Haemostasis issues in cancer; and guidelines committee for the American Society of Clinical Oncology for thromboembolism in cancer. MDT: Reports consulting fees from Amgen, BioMarin, Dova Pharmaceuticals, Genentech, Novo Nordisk, Octapharma, Pfizer, Sanofi, Sobi, Takeda, and UCB Biosciences; payment or honoraria for lectures, presentations, speakers bureau, manuscript writing, or educational events from Amgen, BioMarin, Genentech, Novartis, Sanofi, and Sobi; and participation on a Data Safety Monitoring Board/advisory board for Octapharma and Takeda. ML, HG, and AD: Current employment and current equity holder in publicly held company Sanofi., (© The Author(s), 2023.)

Patients with immune thrombocytopenia (ITP) may respond to one thrombopoietin receptor agonist (TPO-RA) but not another. Limited data are available describing outcomes in patients who switched from romiplostim or eltrombopag to avatrombopag, a newer oral TPO-RA. We performed a retrospective observational study of adults with ITP who switched from eltrombopag or romiplostim to avatrombopag at four US tertiary ITP referral centres. Forty-four patients were included, with a mean ITP duration of 8.3 years and a median (range) of four prior ITP treatments. On avatrombopag, 41/44 patients (93%) achieved a platelet response (≥50 × 10 9 /l) and 38/44 patients (86%) achieved a complete response (≥100 × 10 9 /l). In all patients, the median platelet count on eltrombopag or romiplostim was 45 × 10 9 /l vs 114 × 10 9 /l on avatrombopag (p < 0.0001); in patients switched for ineffectiveness of romiplostim/eltrombopag, it was 28 × 10 9 /l on romiplostim/eltrombopag vs 88 × 10 9 /l on avatrombopag (p = 0.025). Fifty-seven percent of patients receiving concomitant ITP medications before switching discontinued them after switching, including 63% of patients receiving chronic corticosteroids. In a heavily pretreated chronic ITP population, avatrombopag was effective following therapy with romiplostim or eltrombopag, with high response rates even in patients with inadequate response to a prior TPO-RA., (© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Rilzabrutinib, an oral, reversible covalent inhibitor of Bruton's tyrosine kinase, may increase platelet counts in patients with immune thrombocytopenia by means of dual mechanisms of action: decreased macrophage (Fcγ receptor)-mediated platelet destruction and reduced production of pathogenic autoantibodies., Methods: In an international, adaptive, open-label, dose-finding, phase 1-2 clinical trial, we evaluated rilzabrutinib therapy in previously treated patients with immune thrombocytopenia. We used intrapatient dose escalation of oral rilzabrutinib over a period of 24 weeks; the lowest starting dose was 200 mg once daily, with higher starting doses of 400 mg once daily, 300 mg twice daily, and 400 mg twice daily. The primary end points were safety and platelet response (defined as at least two consecutive platelet counts of ≥50×10 3 per cubic millimeter and an increase from baseline of ≥20×10 3 per cubic millimeter without the use of rescue medication)., Results: Sixty patients were enrolled. At baseline, the median platelet count was 15×10 3 per cubic millimeter, the median duration of disease was 6.3 years, and patients had received a median of four different immune thrombocytopenia therapies previously. All the treatment-related adverse events were of grade 1 or 2 and transient. There were no treatment-related bleeding or thrombotic events of grade 2 or higher. At a median of 167.5 days (range, 4 to 293) of treatment, 24 of 60 patients (40%) overall and 18 of the 45 patients (40%) who had started rilzabrutinib treatment at the highest dose met the primary end point of platelet response. The median time to the first platelet count of at least 50×10 3 per cubic millimeter was 11.5 days. Among patients with a primary platelet response, the mean percentage of weeks with a platelet count of at least 50×10 3 per cubic millimeter was 65%., Conclusions: Rilzabrutinib was active and associated with only low-level toxic effects at all dose levels. The dose of 400 mg twice daily was identified as the dose for further testing. Overall, rilzabrutinib showed a rapid and durable clinical activity that improved with length of treatment. (Funded by Sanofi; ClinicalTrials.gov number, NCT03395210; EudraCT number, 2017-004012-19.)., (Copyright © 2022 Massachusetts Medical Society.)

Cases of de novo immune thrombocytopenia (ITP), including a fatality, following SARS-CoV-2 vaccination in previously healthy recipients led to studying its impact in preexisting ITP. In this study, 4 data sources were analyzed: the Vaccine Adverse Events Reporting System (VAERS) for cases of de novo ITP; a 10-center retrospective study of adults with preexisting ITP receiving SARS-CoV-2 vaccination; and surveys distributed by the Platelet Disorder Support Association (PDSA) and the United Kingdom (UK) ITP Support Association. Seventy-seven de novo ITP cases were identified in VAERS, presenting with median platelet count of 3 [1-9] ×109/L approximately 1 week postvaccination. Of 28 patients with available data, 26 responded to treatment with corticosteroids and/or intravenous immunoglobulin (IVIG), and/or platelet transfusions. Among 117 patients with preexisting ITP who received a SARS-CoV-2 vaccine, 19 experienced an ITP exacerbation (any of: ≥50% decline in platelet count, nadir platelet count <30 × 109/L with >20% decrease from baseline, and/or use of rescue therapy) following the first dose and 14 of 70 after a second dose. Splenectomized persons and those who received 5 or more prior lines of therapy were at highest risk of ITP exacerbation. Fifteen patients received and responded to rescue treatment. In surveys of both 57 PDSA and 43 UK patients with ITP, prior splenectomy was associated with worsened thrombocytopenia. ITP may worsen in preexisting ITP or be identified de novo post-SARS-CoV2 vaccination; both situations responded well to treatment. Proactive monitoring of patients with known ITP, especially those postsplenectomy and with more refractory disease, is indicated., (© 2022 by The American Society of Hematology.)

A variety of autoimmune disorders have been reported after viral illnesses and specific vaccinations. Cases of de novo immune thrombocytopenia (ITP) have been reported after SARS-CoV-2 vaccination, although its effect on preexisting ITP has not been well characterized. In addition, although COVID-19 has been associated with complement dysregulation, the effect of SARS-CoV-2 vaccination on preexisting complementopathies is poorly understood. We sought to better understand SARS-CoV-2 vaccine-induced recurrence of autoimmune- and complement-mediated hematologic conditions. Three illustrative cases were identified at the University of Washington Medical Center and the Seattle Cancer Care Alliance from January through March 2021. We describe the recrudescence of 2 autoimmune conditions (ITP and acquired von Willebrand Disease [AvWD]/acquired hemophilia A) and 1 complementopathy (paroxysmal nocturnal hemoglobinuria [PNH]). We report the first known case of AvWD/acquired hemophilia A, and describe the first PNH exacerbation in the absence of complement inhibition after SARS-CoV-2 vaccination. Although SARS-CoV-2 vaccine-induced ITP is a known concern, our case clearly depicts how thrombocytopenia in the setting of preexisting ITP can sequentially worsen with each vaccine dose. Based on our experiences and these examples, we provide considerations for how to monitor and assess risk in patients with underlying autoimmune- and complement-mediated hematologic conditions., (© 2021 by The American Society of Hematology.)

Because up to 12% of obstetric patients meet criteria for the diagnosis of thrombocytopenia in pregnancy, it is not infrequent that the anesthesiologist must decide whether to proceed with a neuraxial procedure in an affected patient. Given the potential morbidity associated with general anesthesia for cesarean delivery, thoughtful consideration of which patients with thrombocytopenia are likely to have an increased risk of spinal epidural hematoma with neuraxial procedures, and when these risks outweigh the relative benefits is important to consider and to inform shared decision making with patients. Because there are substantial risks associated with withholding a neuraxial analgesic/anesthetic procedure in obstetric patients, every effort should be made to perform a bleeding history assessment and determine the thrombocytopenia etiology before admission for delivery. Whereas multiple other professional societies (obstetric, interventional pain, and hematologic) have published guidelines addressing platelet thresholds for safe neuraxial procedures, the US anesthesia professional societies have been silent on this topic. Despite a paucity of high-quality data, there are now meta-analyses that provide better estimations of risks. An interdisciplinary taskforce was convened to unite the relevant professional societies, synthesize the data, and provide a practical decision algorithm to help inform risk-benefit discussions and shared decision making with patients. Through a systematic review and modified Delphi process, the taskforce concluded that the best available evidence indicates the risk of spinal epidural hematoma associated with a platelet count ≥70,000 × 106/L is likely to be very low in obstetric patients with thrombocytopenia secondary to gestational thrombocytopenia, immune thrombocytopenia (ITP), and hypertensive disorders of pregnancy in the absence of other risk factors. Ultimately, the decision of whether to proceed with a neuraxial procedure in an obstetric patient with thrombocytopenia occurs within a clinical context. Potentially relevant factors include, but are not limited to, patient comorbidities, obstetric risk factors, airway examination, available airway equipment, risk of general anesthesia, and patient preference., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2021 International Anesthesia Research Society.)

Approximately 80% of adult patients with immune thrombocytopenia (ITP) have treatment failure with corticosteroids or become dependent on them and require second-line therapy. Several new and effective therapies have been introduced during the past decade and our understanding of disease burden and its effect on quality of life has expanded. It is now recommended that splenectomy, the standard second-line therapy for decades, be delayed for at least 12 to 24 months, allowing for more patients to achieve remission on medical therapies before considering surgery. It is highly recommended that medical therapies be used that have abundant clinical trial evidence, such as the thrombopoietin receptor agonists (TPO-RAs) rituximab and fostamatinib. Unfortunately, there are no reliable biomarkers that help in treatment selection. These therapeutic medical options have variable efficacy, safety profiles, mechanisms of action, and modes of administration. This enables and mandates an individualized approach to treatment, where patient involvement, preferences and values have become central to the process of choosing the appropriate therapy. Both TPO-RAs and fostamatinib are maintenance therapies, whereas rituximab is given for a limited number of doses. Although the response is usually maintained while receiving a TPO-RA or fostamatinib therapy, half of rituximab responders will no longer respond 1 to 2 years after administration and require retreatment or other therapy., (© 2021 by The American Society of Hematology.)

Background: The purpose of our studies was to determine if fecal blood loss can provide a quantitative measure of bleeding at platelet counts of 20 000/μL or less in patients with hypoproliferative thrombocytopenia and to document the effects of different prophylactic platelet transfusion triggers on fecal blood loss., Methods and Materials: Patients had an aliquot of their autologous red blood cells (RBCs) labeled with 51 Cr. Following reinjection of their radiolabeled RBCs, all feces and a daily blood sample were collected to determine fecal blood loss per day. Three different studies were performed in patients with thrombocytopenia: The first was in patients with thrombocytopenia with aplastic anemia who were not receiving platelet transfusions, and the other two trials involved thrombocytopenic patients with cancer who were receiving prophylactic platelet transfusions at platelet transfusion triggers of 5000/μL, 10 000/μL, or 20 000/μL., Results: In patients with thrombocytopenia not receiving platelet transfusions, fecal blood loss does not increase substantially until platelet counts are 5000/μL or less. When platelet transfusions are given prophylactically to patients with cancer with chemotherapy-induced thrombocytopenia at platelet counts of 5000/μL or less, fecal blood loss and red cell transfusion requirements are the same as those for patients transfused prophylactically at higher transfusion triggers of 10 000 platelets/μL or 20 000 platelets/μL. However, the total number of platelet transfusions needed increases significantly, and the duration of the patient's thrombocytopenia tends to be longer at the higher platelet transfusion thresholds., Conclusion: A prophylactic platelet transfusion threshold of 5000/μL or greater is sufficient to maintain hemostasis in patients with thrombocytopenia., (© 2020 AABB.)

Background: This report evaluates hospital blood use trends during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, and identifies factors associated with the need for transfusion and risk of death in patients with coronavirus 2019 (COVID-19)., Methods: Overall hospital blood use and medical records of adult patients with COVID-19 were extracted for two institutions. Multivariate logistic regression models were conducted to estimate associations between the outcomes transfusion and mortality and patient factors., Results: Daily blood use decreased compared to pre-COVID-19 levels; the effect was more significant for platelets (29% and 34%) compared to red blood cells (25% and 20%) at the two institutions, respectively. Surgical and oncologic services had a decrease in average daily use of platelets of 52% and 30%, and red blood cells of 39% and 25%, respectively. A total of 128 patients with COVID-19 were hospitalized, and 13 (10%) received at least one transfusion due to anemia secondary to chronic illness (n = 7), recent surgery (n = 3), and extracorporeal membrane oxygenation (n = 3). Lower baseline platelet count and admission to the intensive care unit were associated with increased risk of transfusion. The blood group distribution in patients with COVID-19 was 37% group O, 40% group A, 18% group B, and 5% group AB. Non-type O was not associated with increased risk of mortality., Conclusion: The response to the SARS-CoV-2 pandemic included changes in routine hospital operations that allowed for the provision of a sufficient level of care for patients with and without COVID-19. Although blood type may play a role in COVID-19 susceptibility, it did not seem to be associated with patient mortality., (© 2020 AABB.)

Background: The first coronavirus (COVID-19) case was reported in United States in the state of Washington, approximately 3 months after the outbreak in Wuhan, China. Three weeks later, the US federal government declared the pandemic a national emergency. The number of confirmed COVID-19 positive cases increased rather rapidly and changed routine daily activities of the community., Study Design and Methods: This brief report describes the response from the hospital, the regional blood center, and the hospital-based transfusion services to the events that took place in the community during the initial phases of the pandemic., Results: In Washington State, the first week of March started with four confirmed cases and ended with 150; by the end of the second week of March there were more than 700 cases of confirmed COVID-19. During the first week, blood donations dropped significantly. Blood units provided from blood centers of nonaffected areas of the country helped keep inventory stable and allow for routine hospital operations. The hospital-based transfusion service began prospective triaging of blood orders to monitor and prioritize blood usage. In the second week, blood donations recovered, and the hospital postponed elective procedures to ensure staff and personal protective equipment were appropriate for the care of critical patients., Conclusion: As community activities are disrupted and hospital activities switch from routine operations to pandemic focused and urgent care oriented, the blood supply and usage requires a number of transformations., (© 2020 AABB.)

Introduction: There is currently no consensus regarding the minimum threshold platelet count to ensure safe neuraxial procedures. Numerous reports describe the safe performance of lumbar punctures in severely thrombocytopenic patients but reports of neuraxial anesthetic procedures in thrombocytopenic patients are limited. To date, the focus on specific populations in contemporary reviews has failed to include any actual hematoma cases. This systematic review aggregates reported lumbar neuraxial procedures from diverse thrombocytopenic populations to best elucidate the risk of spinal epidural hematoma., Methods: MEDLINE, Embase, Cochrane, CINAHL databases were searched for articles about thrombocytopenic patients (<100,000 × 10 6 /L) who received a lumbar neuraxial procedure (lumbar puncture; spinal, epidural, or combined spinal-epidural analgesia/anesthesia; epidural catheter removal), whether spinal epidural hematoma occurred., Results: Of 4167 articles reviewed, 131 met inclusion criteria. 7476 lumbar neuraxial procedures were performed without and 33 procedures with spinal epidural hematoma. Within the platelet count ranges of 1-25,000 × 10 6 /L, 26-50,000 × 10 6 /L, 51-75,000 × 10 6 /L, and 76-99,000 × 10 6 /L there were 14, 6, 9, and 4 spinal epidural hematomas, respectively. An infection point and narrow confidence intervals were observed near 75,000 × 10 6 /L or above, reflecting a low probability of spinal epidural hematoma in this sample. Of the 19 spinal epidural hematoma cases for which the onset of symptoms was reported, 18 (95%) were symptomatic within 48 h of the procedure., Conclusions: Spinal epidural hematoma in thrombocytopenic patients is rare. In this sample of patients, an inflection point and narrow confidence intervals are observed near a platelet count of 75,000 × 10 6 /L or above, reflecting an estimated low spinal epidural hematoma event rate with more certainty given a larger sample size and inclusion of spinal epidural hematoma cases. Thrombocytopenic patients should be monitored, particularly in the first 48 h, and educated about symptoms concerning for spinal epidural hematoma., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Over the last decade, there have been numerous developments and changes in treatment practices for the management of patients with immune thrombocytopenia (ITP). This article is an update of the International Consensus Report published in 2010. A critical review was performed to identify all relevant articles published between 2009 and 2018. An expert panel screened, reviewed, and graded the studies and formulated the updated consensus recommendations based on the new data. The final document provides consensus recommendations on the diagnosis and management of ITP in adults, during pregnancy, and in children, as well as quality-of-life considerations., (© 2019 by The American Society of Hematology.)

Background: Adverse events following blood transfusion include allosensitization and generalized immunosuppression, collectively referred to as transfusion-related immune modulation. We evaluated the immunological effects of red blood cell (RBC) and platelet transfusions on alloantibody responses and on immunoregulatory cells in nonimmunosuppressed patients undergoing cardiovascular surgery., Study Design and Methods: Patients were randomized to receive standard unmodified (STD), leukoreduced (LR), or leukoreduced and γ-irradiated (LRγ) RBCs. Patients received only apheresis platelets that were in-process LR and were γ-irradiated for the third arm. Nontransfused patients served as controls for the effects of surgery itself on immunologic changes. Antibodies to HLA were assessed with use of solid-phase assays. The effects of transfusion on adaptive and innate immunity were evaluated by assessing T regulatory cells (Tregs) and invariant natural killer T (iNKT) cells., Results: LR of blood products reduced the development of human leukocyte antigen (HLA) alloantibodies, but only in patients without preexisting HLA antibodies. However, if LR blood products were γ-irradiated, HLA antibody production was not reduced. Compared to nontransfused patients, recipients of STD or LR transfusions showed a significant increase in CD4+CD25 hi T cells expressing FoxP3 or CTLA4 and also of iNKT cells producing interleukin-4. In contrast, recipients of LRγ blood products showed markedly lower increases in all three cellular assays., Conclusion: LR decreased HLA alloantibody production in naïve recipients, but did not reduce the immunosuppressive effects of transfusion. LRγ reduced immunosuppression and was not associated with decreased HLA alloantibody production., (© 2019 AABB.)

Background: It is unknown how pooled platelets (PPs) compare to random apheresis platelets (RAPs) when HLA-selected platelets (PLTs) are unavailable for HLA-sensitized patients. The aim of this study was to compare patient responses to RAPs, HLA-selected PLTs, and PPs in HLA-sensitized patients., Study Design and Methods: This is a single-institution retrospective study of patients from January 2014 to April 2017 with a class I calculated panel-reactive antibody of 60% or more. Response to transfusion was determined by a corrected count increment (CCI) up to 1 hour after completion of transfusion. A CCI of 5 or more was considered successful., Results: Seventy-seven units of RAPs, 412 units of HLA-selected PLT, and 388 units PPs were transfused. Mean CCIs when transfusing RAPs, HLA-selected PLTs, and PPs were 2.82, 11.44, and 4.77, respectively (p < 0.0001). Posttest comparison between RAPs and PPs revealed no significant difference in mean CCI while there was a significant difference between HLA-selected PLTs versus RAPs and HLA-selected PLTs versus PPs. The success rates of RAPs, HLA-selected PLTs, and PPs were 31%, 80%, and 35% respectively. There was no significant association of type of PLT and success rate when comparing RAPs versus PPs (p = 0.51) while there was a significant association between success rate and type of PLT transfusion when comparing HLA-selected PLTs with RAPs and PPs., Conclusion: HLA-selected PLTs resulted in higher mean CCIs and more successful transfusions. There was no significant difference in mean CCI or success rate when transfusing RAPs versus PPs to HLA-sensitized patients. Future studies should assess clinical outcomes in HLA-sensitized patients receiving each type of PLT product., (© 2019 AABB.)

Bleeding remains a significant problem for many thrombocytopenic hematology/oncology patients in spite of platelet transfusions. Factors that might contribute to bleeding were analyzed for 16 320 patient-days on or after their first platelet transfusion in 1077 adult patients enrolled in the Platelet Dose (PLADO) trial. All patients had a greatly increased risk of bleeding at platelet counts of ≤5 × 10 9 /L (odds ratio [OR], 3.1; 95% confidence interval [CI], 2.0-4.8) compared with platelet counts ≥81 × 10 9 /L. Platelet counts between 6 × 10 9 /L and 80  × 10 9 /L were also associated with a somewhat elevated bleeding risk in patients receiving allogeneic stem cell transplants (SCTs) or chemotherapy but not in those undergoing autologous SCTs. Other significant laboratory predictors of bleeding were hematocrit ≤25% (OR, 1.29; 95% CI, 1.11-1.49), activated partial thromboplastin time (aPTT) 30 to ≤50 seconds (OR, 1.40; 95% CI, 1.08-1.81; P = .01), aPTT >50 seconds (OR, 2.34; 95% CI, 1.54-3.56), international normalized ratio (INR) 1.2 to 1.5 (OR, 1.46; 95% CI, 1.17-1.83), and INR >1.5 (OR, 2.05; 95% CI, 1.43-2.95). Transfusion of either platelets or red blood cells (RBCs) on days with bleeding was often not sufficient to change bleeding outcomes on the following day. Because bleeding occurred over a wide range of platelet counts among patients undergoing allogeneic SCT or chemotherapy and because platelet transfusions may not prevent bleeding, other risk factors may be involved. These may include low hematocrit and coagulation abnormalities. This trial was registered at www.clinicaltrials.gov as #NCT00128713., (© 2017 by The American Society of Hematology.)