Blood Transfusion

Analysis of HLA matching between deceased organ donors and cord blood units from a national bank network as a basis for potential platforms for chimerism-based immune tolerance after solid organ transplantation

Mon, 10 Jun 2024 00:00:00 +0000

We report here the results from a collaborative analysis conducted on 1,427 consecutive deceased organ donors in Italy during January 2021 and July 2022, with the aim of describing the actual HLA match between these donors and over 38,000 cord blood units (CBU) stored in the Italian Cord Blood Network. We found that for 71% of organ donors there is at least one fully HLA-matched CBU or a single-mismatched one at the A, B, and DRB1 loci, providing a basis for potential future applications of combined organ-hematopoietic stem cells (here from CBU) for immune tolerance purposes, through the well-known phenomenon of hematopoietic mixed chimerism. Due to current hurdles in harvesting bone marrow from deceased organ donors, CBU may provide a valuable source of HLA-compatible hematopoietic stem cells as well as other cellular populations potentially suitable in the future for immune tolerance clinical applications.

A "movement" worth making: why and how Transfusion Services can play a role in Fecal Microbiota Transplant programs

Wed, 12 Mar 2025 00:00:00 +0000

Fecal Microbiota Transplantation (FMT) is an innovative therapy with growing applications, particularly for recurrent Clostridioides difficile infections (rCDI). However, the broader use of FMT is challenged by the complexities of donor recruitment, the necessity of stringent screening protocols, and the need for maintaining high-quality stool biobanks. This paper explores the integration of FMT programs within transfusion medicine departments, taking advantage of their expertise in donor management and biological material processing. Despite the complexities of donor screening, including a low eligibility rate, the collaboration between transfusion services and other hospital departments demonstrates a viable model for expanding FMT access. Additionally, the recent EU regulations on substances of human origin (SoHO) offer a framework for standardizing and scaling stool banking, enhancing the safety and efficacy of FMT procedures.

Post-transplant pediatric autoimmune hemolytic anemia: donor vs donor or recipient vs self?

Fri, 29 Nov 2024 00:00:00 +0000

Hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for various blood disorders. However, post-transplant complications such as autoimmune hemolytic anemia (AIHA) can arise, especially in pediatric patients. We present a case of a 7-year-old male with beta-thalassemia major who developed AIHA nine months post-HSCT from an unrelated donor. Despite initial successful treatment with cyclosporine and prednisone, the patient experienced multiple relapses, coinciding with changes in donor-recipient chimerism. This case highlights the complexity of post-transplant immune dysregulation and suggests a recipient-driven autoimmune mechanism.

Warm autoimmune hemolytic anemia: transfusion lessons and therapeutic perspectives learn from a particular patient

Jun Yu Woon, Li-Te Chin, Yu-Ting Lee — Fri, 29 Nov 2024 00:00:00 +0000

The present manuscript is based on an IRB-approved protocol and unveils some necessary points that are often overlooked by clinicians who are responsible in treating warm type autoimmune hemolytic anemia (wAIHA). We think the topics covered have provided the importance in two aspects and may benefit scientists both in fields of basic and practical immunohematology. Firstly, in recent years a much clearer picture of these events has emerged but many questions remain unanswered. One of the major problems still to be clarified is how the adverse reaction related to the treatment is avoided, to which we have some ideas to share. Moreover, in light of the limitations of corticosteroid regimens to account for many aspects of long-term recovery, it will clearly be important to develop greater insight into the mechanisms in the development of wAIHA. With these in mind, the manuscript illustrated the interrelationships between basic and practical aspects of research.

A case of trisomy 9 with mixed-field ABO blood type

Sena Fujii, Yuji Shimura, Keiichi Shigehara, Yuji Sasada, Tohru Inaba — Fri, 07 Jun 2024 00:00:00 +0000

We report the case of a woman with trisomy 9 who showed atypical, mixed-field agglutination of ABO blood type. Her red blood cells showed strong agglutination with anti-A monoclonal antiserum and atypical mixed-field agglutination with anti-B monoclonal antiserum. The results of the genotyping of her father and mother revealed A101/B101 and O01/O02, respectively; however, only B101/O01 was detected in the patient because of the characteristics of the test method used. Multiplex analysis would help in understanding the pathophysiology of abnormal findings; nevertheless, careful data interpretation is required.

Severe aplastic anemia secondary to immune checkpoint inhibitor: case report and literature review

Wed, 12 Jun 2024 00:00:00 +0000

The anti-PD1 immune checkpoint inhibitor (CPI) pembrolizumab can induce cancer response by restoring immune surveillance. A rare side effect is aplastic anemia (AA), an immune-mediated bone marrow failure. We report the case of a 44-year-old man with metastatic colorectal cancer who developed severe AA after pembrolizumab. Given the need for immune competence to maintain oncological remission, anti-thymocyte globulin was not proposed, and the sequential treatment with cyclosporine, eltrombopag and danazol led to full hematological recovery. Staining of sequential bone marrow biopsies revealed a marked deposition of IgG and complement fractions as compared to idiopathic AA cases. This case and the literature review remark the challenge of treating severe AA after CPIs, balancing immunosuppression against tumor surveillance.

Exploring MSM blood donor profiles: a descriptive analysis of demographics, risk characteristics, and donation behaviors

Koson Tony Sriamporn, Nathan Consedine, Peter Saxton — Thu, 13 Mar 2025 00:00:00 +0000

Background - The importance of addressing the blood donor population among men who have sex with men (MSM) is increasing with the global liberalization of blood donor deferral policies. Effective donor management, especially retaining existing donors and recruiting new donors, is essential for a safe and sufficient blood supply. Strategies to engage the broader blood donation population are well-established. However, the historical exclusion of MSM from blood donation, based on heightened HIV risk, has limited the understanding of MSM's unique behavioral and risk characteristics as potential donors. Characterizing these donors (and non-donors) will be useful for blood services to tailor outreach and engagement strategies effectively as deferral policies continue to evolve.

Materials and methods - Data from a national behavioral surveillance program of MSM in New Zealand were examined. We explored differences in demographic and risk characteristics associated with an increased risk of HIV across three groups (i.e., profiles) sorted by their donation history and recency: non-donors, non-active donors, and active donors.

Results - Clear characteristics associated with each donor profile emerged among the 3,225 MSM participants. Active donors (4.2%) were younger, students, less engaged with the LGBTQI+ community, reported fewer risk behaviors and were less sexually active. Non-active donors (36.9%) typically exhibited more characteristics associated with an increased risk of HIV. However, non-donor profiles (56.7%) were less clear in comparison, sharing demographic similarities with active donors but displaying risk characteristics similar to those of non-active donors.

Discussion - In this first study to describe MSM blood donor profiles, we have identified unique characteristics specific to MSM which blood services can use to pinpoint targets for engaging current, new, and previous donors. Future research should examine the factors affecting non-donor status among MSM, as they do not appear to be solely driven by demographic and recent behavioral risk factors.

ELP protocol: an original approach for the mitigation of anti-CD38 interference

Wed, 26 Jun 2024 00:00:00 +0000

Background - Transfusion medicine is facing new challenges from therapies which interfere with pre-transfusional tests, such as monoclonal antibodies targeting blood-cell antigens. Anti-CD38 monoclonal antibodies, widely used to treat multiple myeloma, cause panreactivity of indirect antiglobulin test; this can be resolved by treating cells with dithiothreitol to disrupt the CD38 disulphide bonds expressed on red blood cell surfaces. Interference mitigation strategy with dithiothreitol, however, has some drawbacks: it entails losing the traceability of results and the denaturation of blood group systems sensitive to reducing agents; it takes time to perform and quality controls are lost.
Materials and methods - Panels were treated with 0.2 mol/L dithiothreitol and stored for 30 days with a commercial preservative solution. On day 30, we measured the hemolysis indices and ability to eliminate daratumumab and isatuximab interference in the treated cells using indirect antiglobulin test. We also tested the stability of erythrocyte antigenic structure by screening 42 samples with known antibodies; tests were repeated on day 1, 7, 15 and 30. All indirect antiglobulin testing was performed on gel card.
Results - After 30 days from treatment, panels preserved in preservative solution showed hemolysis indices comparable to untreated panels: all cases of interference by anti-CD38 in pre-transfusional tests were successfully mitigated. All antibodies were detected after 30 days, except for KEL system antibodies, as expected, although there was a detectability of anti-Kell antibodies in high titer samples (the first detection in dithiothreitol-treated cells since 1983).
Discussion - We propose the Extended Lifetime Protocol; a simple card-based method which is cheap and traceable, that combines the strengths of anti-CD38 mitigation strategies. It makes it possible to treat and store, at the same time, a sufficient volume of red blood cells, that can be used for the following 30 days, to avoid any delay in transfusional requests.

Perinatal outcome in pregnant women: the impact of blood transfusion

Tue, 21 Jan 2025 00:00:00 +0000

Background - Obstetric hemorrhage is a life-threatening complication of pregnancy. Systematic collection of data on transfusion practice during pregnancy and post-partum period are scarce, as well as data on fetal or neonatal outcomes of women transfused during pregnancy.

We examined the prevalence of obstetric hemorrhage and outcome of pregnancies in hospitalized transfused women.

Materials and methods - This is a retrospective cohort study collecting clinical and laboratory data of women transfused from 2015 to 2017 in three Italian Tertiary level Obstetrical Departments. Inclusion criteria were:
1) age >18 years; 2) antepartum or peripartum hospital admission and 3) transfusion during the hospital stay of at least one unit of packed red blood cell (RBC) units. Women below 18 years and/or with transfusion outside pregnancy were excluded.

During the observation period, 18,495 women gave birth across the three Obstetrics Departments: transfusion rate was 1.7%.

Results - 315 women were included in the final analysis. Most (75.2%) needed transfusion from 35 weeks onwards. A percentage higher that that observed in general population of transfused women showed co-morbidities such as hypertensive disorders or diabetes (13.9 vs 5.5%). We recorded 90% of live births and 7.6% of Intra Uterine Fetal Demise or neonatal death. Perinatal outcomes were impacted by the dose of transfusion: logistic regression, correcting for age and assisted conception, showed that women transfused with 3 or more RBC units have about 3-fold higher risk of perinatal death (OR: 2.9, 95% CI: 1.0-8.4).

Discussion - In this series, several known risk factors were associated with adverse feto-neonatal outcome. In addition, the number of RBC units transfused was significantly and independently associated with the perinatal outcome. Present data can be helpful to design prospective studies taking into account timing and dose of transfusion during pregnancy with the objective to improve feto-maternal outcome.

A survey on the implementation of Patient Blood Management programs in Italy

Thu, 28 Mar 2024 00:00:00 +0000

Background - Since 2012, in line with the World Health Organization (WHO) resolution WHA63.12 of 05/21/2010, the Italian National Blood Center has been promoting patient blood management (PBM). In order to verify the level of PBM implementation nationwide, we submitted a survey to all healthcare providers.

Material and methods - In line with what was proposed in the international scientific literature in the field, a series of indicators were used derived from the four main blocks related to PBM strategies: the management of patient anemia; the optimization of hemostasis; blood conservation strategies; patient-centred decision-making. We also added two blocks containing important information on general PBM management and other PBM-related aspects.

Results - The survey showed good implementation of anemia screening programs in accordance with the timelines established by national and international guidelines, and the single unit policy is used in line with national guideline recommendations. However, the survey also revealed limited auditing of PBM programs and reduced monitoring and reporting of clinical outcomes and indicators.

Discussion - The first national survey on the level of PBM implementation in Italy shows widespread adoption of diagnostic-therapeutic care pathways aimed at the diagnosis and treatment of anemia in the perioperative setting.

Patient Blood Management in 2023: a Nationwide Survey of Anesthesiologists in Romania following the 2018 Guidelines

Tue, 15 Oct 2024 00:00:00 +0000

Background - In 2018, Romania established national guidelines for patient blood management (PBM), endorsed by the Romanian Society of Anaesthesia and Intensive Care (SRATI) and approved by the Ministry of Health. These guidelines emphasize managing anemia, coagulation issues, and the cautious use of allogeneic transfusions to improve patient outcomes.

Materials and methods - A national survey was conducted among Romanian anesthesiologists to assess PBM guideline adoption. It included 38 questions addressing PBM strategies, resources, transfusion practices, and barriers to implementation. The survey was distributed via email to the SRATI database.

Results - Out of 512 professionals who opened the survey, 74% had adopted some PBM measures, and 97% recognized PBM's efficacy in improving outcomes. However, only 33% of anesthesiologists worked in hospitals with formal PBM groups, and 39% had attended PBM-related educational events. Preoperative anemia management was inconsistent, with only 33.5% routinely treating anemia. Access to diagnostic and therapeutic tools was limited; transferrin saturation testing was available in 27% of cases, and erythropoietin was used in 24%. Despite these limitations, 72% of respondents treated anemia with intravenous iron.

The main challenges to implementation included insufficient time for
pre-surgical assessments, lack of standardized procedures, and difficulties in surgeon-anesthetist collaboration.

Discussion - The survey highlights the need for systemic improvements in PBM adoption. Recommendations include enhancing organizational structures, standardizing protocols, and improving interdisciplinary collaboration to boost PBM implementation in Romania. While progress has been made, a national program with dedicated funding and auditing could facilitate widespread PBM integration into clinical practice.

Efficiency assessment of cord blood banking and compatibility with delayed cord clamping

Mon, 05 Aug 2024 00:00:00 +0000

Background There is debate whether delayed umbilical cord clamping following delivery, the current gold standard, affects the proportion of cord blood units (CBU) suitable for public cord blood banking. This study was designed to assess the impact of delayed cord clamping on the number of CBU suitable for therapeutic uses.

M&M To minimize variability, data from the four most active collection centers within the Programa Concordia (Spain) were included. Data on CBU collected in utero from mothers following normal vaginal deliveries from July 2018 to December 2021 were analyzed. The weight of the collection bags (as a surrogate of volume) and total nucleated cell (TNC) count were analyzed according to three defined clamping times: 30 s, 60 s and ≥120 s. The CBU were stratified as suitable for stem cell transplantation (≥110 g and ≥1,500x10⁶ TNC/unit) or other clinical applications (≥100 g but TNC count below the threshold).

Results There were 131 (18%), 548 (76%), and 40 (5%) CBU collected at 30 s, 60 s and ≥120 s, respectively. The median weight of the CBU decreased gradually with time, with a significant difference between units collected when the cord was clamped at 30 s or 60 s (p=0.036), so significantly fewer CBU met the minimal weight criterion (100 g) at 60 s than at 30 s (p=0.002). However, this was not reflected by the TNC available, resulting in non-statistical differences in CBU eligible for banking between these times. The major predictor of collection success was the neonate’s birth-weight.

Discussion Despite decreases in the volume of cord blood collected when cord clamping at 30 s or 60 s, TNC count is maintained resulting in similar numbers of CBU eligible for banking. The different clamping delays investigated in this study are, therefore, compatible with public cord blood banking needs.

Evaluation of platelet function by Total Thrombus-Formation Analysis System (T-TAS®01) in term and preterm infants and its relationship with patent ductus arteriosus. A prospective observational pilot study

Fri, 25 Oct 2024 00:00:00 +0000

Background - Newborns exhibit a pro-coagulant hemostatic profile despite platelet hyporeactivity and reduced coagulation factors. Assessing infant hemostasis, particularly in preterm infants, is challenging, with inconsistent findings regarding the relationship between platelet count and function in patients with patent ductus arteriosus (PDA).

Materials and methods - This study aims to assess platelet function using the Total Thrombus-Formation Analysis System (T-TAS®01) in term and preterm newborns. T-TAS®01 measures the Occlusion Start Time (OST), Occlusion Time (OT), and the Area Under the Curve (AUC) at the end of thrombus formation. The study includes term and preterm newborns below 30 weeks' gestational age (GA) admitted to the Neonatal Intensive Care Unit. Blood samples were collected from preterm newborns on the 1^st day of life (T0), between 48-72 hours of life (T1), between the 7^th and 10^th day of life (T2), and from term newborns at T0 and T2. Secondary endpoints include the relationship between T-TAS®01 parameters and significant PDA in preterm newborns and the correlation between T-TAS®01 parameters, GA, and complete blood count (CBC).

Results - OST is delayed by 65.5 seconds in preterm infants at T0 (p<0.001) and by 46 seconds at T2 (p=0.041) compared to full-term newborns. OT is delayed by 164 seconds in preterm infants at T0 (p=0.002) and by 352 seconds at T2 (p=0.002). AUC at T0 is lower in preterm infants (p=0.028). There is no significant correlation between T-TAS®01 parameters and GA or CBC. Additionally, OST and OT are delayed, and AUC is reduced in preterm infants with PDA and hemodynamically significant PDA (hsPDA).

Discussion - T-TAS®01 is a reliable tool for evaluating platelet function in term newborns. However, measurements show higher variability in preterm infants, with significantly lower platelet activity observed in preterm infants with PDA and hsPDA.