Blood Transfusion

Toward a definition of immunological risk for patients with anti-HLA antibodies before stem cell transplantation

Roberto Crocchiolo — Thu, 21 Sep 2023 00:00:00 +0000

Due to the negative impact of donor-specific, anti-HLA antibodies (DSAs) on engraftment and outcome after allogeneic hematopoietic stem cell transplantation, screening is now recommended before transplantation in order to select an alternative donor or administer a desensitization treatment in the case of detection of such antibodies. Since the permissive level of DSAs is currently matter of debate, the present Editorial aims at strengthening the message about the importance of looking for their presence before transplantation and at providing a proposal on the definition of immunological risk based not only on the quantity and the spectrum of DSAs but also on other main clinical and transplant variables; indeed, the deleterious effect of DSAs is heterogeneous across the donor type, conditioning regimen, underlying disease, to cite some of the variables.

By relancing a collaborative alliance between clinicians and immunogenetic specialists, this Editorial would contribute to go beyond the case-by-case definition of immunological risk for a determined patient-donor pair and go toward an evidence-based, shared risk stratification based on multiple, but defined, characteristics as outlined in the text. This stratification would allow for the modulation of the desensitization strategies, by adapting the intensity of immunosuppression to the estimated risk of engraftment failure.

Psychological responses to blood donated by men who have sex with men

Lisa A. Williams, Kate Nicholls, James R. W. Williams — Wed, 07 Jun 2023 00:00:00 +0000

Background - Restrictions previously limiting the ability of men who have sex with men to donate blood are being eased in a number of nations worldwide. In the context of these changes, it is important to determine public perceptions of receiving a transfusion of blood donated by men who have sex with men.
Materials and methods - In online surveys, 510 (Study 1) and 1,062 (Study 2) heterosexual participants reported attitudes, anxiety, disgust, and gratitude towards potentially receiving a transfusion of blood donated by a homosexual male donor and a heterosexual male donor. In Study 2, half of the participants were reminded of the safety testing carried out on donated blood samples. Negative attitudes, anxiety, disgust, and gratitude were compared between the two donors using t-tests and within-participants indirect effects analysis.
Results - Stronger negative attitudes, higher anxiety and disgust, and lower gratitude were reported in relation to a potential transfusion of blood donated by the homosexual male donor relative to the heterosexual male donor (|d|=0.26-0.46). This was the case even when participants were reminded of the safety testing completed on donated blood samples in Study 2. In both studies, the effect of donor sexual orientation on attitudes was explained via heightened anxiety and disgust and attenuated gratitude (b=0.05-0.30).
Discussion - Considering receiving a transfusion of blood donated by a homosexual male donor elicits more negative attitudes, anxiety and disgust, and less positive emotion, relative to blood donated by a heterosexual male donor. These attitudes and emotional reactions are not shifted by a reminder of the safety testing carried out on donated blood samples. In the context of changing restrictions on blood donation by men who have sex with men, these findings highlight a challenge to shift public perception to embrace this cohort of donors.

Transfusion in hemoglobinopathies and red blood cell alloimmunization, data from Sicily, Sardinia and Malta

Mon, 22 May 2023 00:00:00 +0000

Background - Hemoglobinopathies are a group of diseases that include those due to globin gene mutations, such as thalassemia major (TM) and thalassemia intermedia (TI) or due to alteration of hemoglobin structure such as sickle cell disease (SCD), as well as a combination of these conditions such as thalasso-drepanocytosis (TD). They constitute the most frequent hereditary anemias requiring blood transfusion.
Materials and methods - In April 2022, a questionnaire was sent to the Transfusion Services (TS) of Sicily, Sardinia and the Maltese National Blood Transfusion (MNBT) service. The questionnaire was divided into a generic part including the number of patients followed and the type of hemoglobinopathy, and a section relating to transfusion therapy, including the number of units transfused, whether red blood cells (RBC) were washed and, finally, a section relating to the presence or absence of alloantibodies and their identification.
Results - Data was retrieved for 2,574 patients: 68.6% TM, 15.4% TI, 10.3% TD, 4.1% SCD, and 1.6% other hemoglobinopathies (OHA). The number of RBC units transfused was 76,974, equivalent to 24.5% of all the RBCU transfused from the total number of patients followed. The number of washed RBCU was 21.1% of all the units used; 337 patients (37%) were diagnosed with alloantibodies, the majority of which were patients with SCD (20.6%). Of the 485 alloantibodies found, 90.3% were identified. The antibodies found most frequently were related to the Kell system (41.7%) followed by antibodies to the Rhesus system (37.9%); 29.7% of patients had more than one antibody.
Discussion - From our study, certain indications can be formulated:
1) complete the National Registry for patients with hemoglobinopathies;
2) create a Registry of alloimmunized patients to ensure transfusion therapy is as safe as possible, considering antibody evanescence; and 3) increase the recruitment of blood donors of diverse ethnicities.

Pathogen reduced red blood cells as an alternative to irradiated and washed components with potential for up to 42 days storage

Fri, 14 Jul 2023 00:00:00 +0000

Background - The urgency of maintaining a safe and adequate blood supply is increasing. One approach to ensure a sufficient supply is to limit the outdating frequency of blood components. Pathogen inactivation technology was developed primarily to increase safety by preventing transmission of infectious diseases. The Intercept Blood System for pathogen reduction of red blood cells (RBC) has additional benefits such as inactivation of leucocytes and removal of plasma and storage debris through centrifugation. Irradiation and automated washing are detrimental to the RBC membrane and often implicate shortened shelf-life. We aimed to assess whether pathogen inactivation can replace RBC irradiation and washing to avoid shelf-life reduction.
Materials and methods - RBC concentrates (n=48) were pooled-and-split into four study arms, which underwent pathogen inactivation treatment, irradiation, automated washing or no treatment (reference). RBC quality was evaluated during 42 days by assessment of storage lesion. Washing efficacy was defined by IgA and albumin reduction.
Results - Pathogen reduced RBCs had similar membrane preservation to reference RBCs (hemolysis, microvesicles and extracellular potassium ions), whereas the RBCs were negatively impacted by irradiation or automated washing. ATP increased substantially post-pathogen inactivation, while
2,3-DPG decreased. Pathogen inactivation considerably reduced albumin and IgA, though slightly less efficiently than automated washing.
Discussion - RBCs exhibit superior membrane preservation after pathogen inactivation treatment, compared to both irradiation and automated washing. This suggests that replacement is possible, even though the plasma reduction protocol could be further optimised.
Replacement of irradiated and washed RBC concentrates with pathogen reduced RBC concentrates storable up to 42 days would be advantageous for both the blood supply and patient safety.

Full annotation of viral metagenomics in different components from Chinese blood donors using next-generation sequencing

Jingjing Zhang, Yanmin He, Ji He, Yanling Ying, Faming Zhu — Tue, 11 Jul 2023 00:00:00 +0000

Background - Emerging viruses in the blood of healthy/qualified donors can seriously affect transfusion safety. However, the virus characteristics in different healthy blood donors and blood components are still not fully understood.
Materials and methods - Buffy coat (BC) and plasma specimens were collected from 32 whole blood donors, and platelet (PLT) and BC specimens from 30 apheresis platelet donors to explore the full annotation of viral metagenomics in different blood components from Chinese blood donors using next-generation sequencing technology.
Results - The study detected 56 viruses in the plasma and BC groups of whole blood donors. The plasma group had a significantly higher viral abundance and more types of viruses than the BC group. We detected 20 viruses in the PLT and BC groups of apheresis platelet donors. Viral abundance and types were significantly lower in the BC group than in the PLT group. According to β-diversity analysis, the plasma group had a significantly different community structure and composition than the BC group.
Discussion - Viral nucleic acid is found in the blood of healthy Chinese blood donors, with the highest concentration in plasma, which could explain the distribution of viruses in the blood of healthy individuals.

Collection efficiency of mononuclear cells in offline extracorporeal photopheresis: can processing time be shortened?

Fri, 14 Jul 2023 00:00:00 +0000

Background - Extracorporeal photopheresis (ECP) is a well-established but lengthy and burdensome cell-based therapy for various diseases such as cutaneous T-cell lymphoma, graft-versus-host disease and organ rejection after transplantation. The number of mononuclear cells (MNCs) that needs to be collected to obtain a clinical response to ECP is still under debate. The purpose of this retrospective study was to determine the number of lymphocytes, monocytes and neutrophils in mononuclear cell products (MCP) by flow cytometry and the collection efficiency in the offline ECP setting.
Materials and methods - We collected data from 10 different patients undergoing 162 ECP procedures using the Spectra Optia device for MNC collection. White blood cell (WBC) count of MCP was determined using a hematology analyzer. MNCs were analyzed for CD45 and CD14 expression by flow cytometry to exactly determine the collected lymphocyte and monocyte fractions.
Results - Collected MCP showed high cell yields with 55.3×106/kg MNCs and 41.1×106/kg lymphocytes. MCP were characterized by high MNC (81.3%) and low neutrophils (18.7%) percentage. Mean collection efficiency for WBCs and for MNCs was 23.9% and 62.0%, respectively. The MNC fraction showed a moderate to high correlation between peripheral blood cell count of patients and MCP count.
Discussion - This study is one of a few reports showing the monocyte-to-lymphocyte relation in MCP for ECP determined by flow cytometry. In comparison to historical data from inline ECP, the offline ECP processing one total blood volume results in considerably higher cell yields. For this reason, and to reduce the burden on patients, we propose that the offline ECP processing time can be substantially reduced.

Donor specific anti-HLA antibodies in hematopoietic stem cell transplantation. Single Center prospective evaluation and desensitization strategies employed

Thu, 21 Sep 2023 00:00:00 +0000

Background - In the setting of mismatched-hematopoietic stem cells transplantation, the detection of antibodies directed against donor-specific HLA allele(s) or antigen(s) (DSA) represents a barrier for engraftment. It is thus necessary to plan an immunosuppressive strategy, or to select an alternative donor. This prospective study aimed at evaluating the efficacy of our strategy for testing DSAs and the efficacy of the desensitization strategy (DS) employed between November 2017 and November 2020.

Materials and methods - The anti-HLA antibody search was performed using the Luminex bead assays (Lifecode ID and LSA I/II-Immucor) and expressed as mean fluorescence intensity (MFI >1,000 positive). If the patient had DSAs and no alternative donors, a DS was employed with rituximab (day −15), 2 single volume plasmaphereses (PP; days −9 and −8), intravenous immunoglobulins (day −7) and infusion of HLA selected platelets, if persistent DSAs were directed against class I HLA. DS was scheduled with or without PP, according to the DSA MFI (>1,000 or <5,000) and FCXM (flow cytometry crossmatch).

Results - Twenty-two out of 126 patients (17.46%) showed anti-HLA antibodies, 5 of them DSAs (3.97% of total); 3 patients underwent DS obtaining engraftment. Female gender (p=0.033) and a history of previous pregnancies or miscarriages (p=0.009) showed a statistically significant impact on alloimmunization. Factors associated with a delayed neutrophil engraftment were patient’s female gender (p=0.039), stem cell source (p=0.025), and a high HSCT-specific comorbidity index (p=0.028). None of the analyzed variables, including the DSA detection, influenced engraftment.

Conclusions - Our study confirms the importance to test DSAs in mismatched-hematopoietic stem cells transplantation The DS used proved successful in removing DSAs. Prospective multicenter studies are needed to better define and validate consensus strategies on DSA management in HSCT.

T-TAS® 01 as a new tool for the evaluation of hemostasis in thrombocytopenic patients after platelet transfusion

Wed, 29 Nov 2023 00:00:00 +0000

Background - Current laboratory tests fail to evaluate the hemostatic function of platelets in patients with thrombocytopenia. We investigated the use of the Total Thrombus-Formation Analysis System (T-TAS® 01 [Fujimori Kogyo Co, Tokyo, Japan]) to evaluate hemostasis under conditions of experimental thrombocytopenia, and in patients before and after platelet transfusion.

Materials and methods - Specific T-TAS 01 chips, for thrombocytopenic conditions, were used. The area under the curve (AUC) and occlusion time (OT, min) were measured in: (i) experimentally induced thrombocytopenia (183±15 to 6.3±1.2×10³ platelets/µL) in blood samples from healthy donors (No.=13), and (ii) blood from oncohematological thrombocytopenic patients (No.=48), before and after platelet transfusion. The influences of hematocrit and number of transfusions were analyzed in these patients.

Results - Progressive reductions of AUC and prolongations of OT related significantly to decreasing platelet counts (p<0.05 for all) in experimental thrombocytopenia. In samples from thrombocytopenic patients, platelet counts, AUC and OT were, respectively, 10.8±0.6×10³/µL, 175.2±59, and 27.2±1 min before transfusion; and 22±1.5×10³/µL, 400.8±83 and 22.9±1.5 min after platelet transfusion (p<0.01 for all). A hematocrit below 25% or exposure to ten or more previous platelet transfusions had a negative impact on the T-TAS 01 performance in patients. In vitro correction of the hematocrit improved the hemostatic response in thrombocytopenic patients.

Discussion - T-TAS 01 measurements were sensitive to low platelet counts in the experimental setting. The technology was sensitive to evaluate the hemostatic capacity of platelet transfusions. Exposure to multiple medications, repeated platelet transfusions and lower hematocrits may interfere with the hemostatic performance in oncohematological patients with thrombocytopenia.

Extract from the 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery - Patient Blood Management

Sigrun Halvorsen, Julinda Mehilli, Suma Choorapoikayil, Kai Zacharowski — Wed, 06 Dec 2023 00:00:00 +0000

The 2022 Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery of the European Society of Cardiology are an update on the previous guidelines reported in 2014. The revised guidelines provide standardized perioperative cardiovascular management of surgical patients and emphasis on risk assessment of the patient combined with the inherent risk of the surgical procedure. One of the novelties in these guidelines is the Patient Blood Management programme, which is based on a three pillar concept: preoperative hemoglobin optimization, minimize iatrogenic blood loss and bleeding, and harness tolerance to anemia in an effort to improve patient outcome. In this review, we highlight the three pillars of Patient Blood Management and recommendations made by the 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery.

Diagnosis and clinical management of thrombotic thrombocytopenic purpura (TTP): a consensus statement from the TTP Catalan group

Mon, 04 Sep 2023 00:00:00 +0000

Thrombotic thrombocytopenic purpura (TTP) is a low prevalence disease characterized by severe deficiency of the enzyme ADAMTS13, leading to the development of thrombotic microangiopathy (TMA) and often resulting in severe organ disfunction. TTP is an extremely serious condition and, therefore, timely and appropriate treatment is critical to prevent life-threatening complications.
Over the past 25 years, significant advances in the understanding of the pathophysiology of immune TTP have led to the development of readily available techniques for measuring ADAMTS13 levels, as well as new drugs that are particularly effective in the acute phase and in preventing relapses. These developments have improved the course of the disease.
Given the complexity of the disease and its various clinical and laboratory manifestations, early diagnosis and treatment can be challenging.
To address this challenge, a group of experienced professionals from the Catalan TTP group have developed this consensus statement to standardize terminology, diagnosis, treatment and follow up for immune TTP, based on currently available scientific evidence in the field. This guidance document aims to provide healthcare professionals with a comprehensive tool to make more accurate and timely diagnosis of TTP and improve patient outcomes.

Use of a recombinant deacetylase to convert A1 red blood cells to the acquired B phenotype for quality control purposes

Wed, 20 Sep 2023 00:00:00 +0000

Background - Correct blood group typing is the cornerstone of transfusion medicine. In patients whose gastrointestinal wall is compromised, bacterial enzymes can cause deacetylation of blood group A, converting N-acetylgalactosamine to galactosamine, which resembles the B-defining galactose. This acquired B (acqB) phenomenon, first described 1959, can lead to blood grouping errors. Herein, we explore the possibility of producing acqB red blood cells (RBCs) by enzymatic conversion, for quality control purposes.
Materials and methods - A₁ RBCs along with group B and O control RBCs were subjected to enzymatic digestion by bacterially derived deacetylase, FpGalNAcDeAc. RBCs were tested with monoclonal anti-A, anti-B, acquired-B-reactive anti-B (ES4 clone), and a panel of donor plasmas. Standard serological techniques were used. RBCs were subsequently frozen by a glycerolisation method, stored at −80 ^oC, and thawed for testing to evaluate stability.
Results - Specific deacetylation of A antigen was achieved at both enzyme concentrations. Enzymatically modified A₁ RBCs reacted 1-3+ with clone ES4 but not with other anti-B reagents. Group B and O RBC controls reacted as expected. Crossmatch testing revealed 1-3+ reactions in 17/26 group A plasma with modified RBCs but not with untreated controls. Furthermore, 2/3 group AB plasmas reacted strongly with the modified RBCs. The acqB phenotype was maintained upon freezing/thawing.
Discussion - Using a recombinant deacetylase, we demonstrated the feasibility of creating acqB RBCs from donor A₁RBCs, thus providing a reagent for quality assurance of monoclonal anti-B. These RBCs can be frozen once treated, providing a reliable source of this unusual but clinically important phenotype.