Blood Transfusion

Multicenter evaluation of soluble CD38: neutralizing anti-CD38 pan-reactivity to enable alloantibody detection

Charlotte Engström — 2025-09-19

Background - Anti-CD38 is a monoclonal antibody treatment for multiple myeloma, B-cell malignancies, and autoimmune diseases that targets CD38 antigens on the cell surface. Red blood cells are CD38+, therefore anti-CD38 causes panagglutination, hindering immunohematology testing such as antibody screen, antibody identification, and crossmatch. This interference masks detection of clinically significant alloantibodies in pre-transfusion testing.

Materials and methods - To assess the effectiveness of soluble CD38 (sCD38) in neutralizing anti-CD38 in the clinical setting and user satisfaction, plasma samples from patients receiving anti-CD38 therapy were collected between 0 and 150 days after the last infusion and tested according to routine laboratory procedures with an established sCD38 neutralization method (15 minutes incubation at 37°C with up to 6 µL of sCD38 per 25 µL of plasma). Neutralization was evaluated using antibody screening or crossmatching, by tube or gel card. Some samples were spiked with irregular antibodies to evaluate the impact of sCD38 on antibody detection. A survey assessed user satisfaction.

Results - In total, 273 patient samples were evaluated (263 patients treated with daratumumab and 10 with isatuximab). sCD38 completely neutralized anti-CD38 present in 79.8% of samples tested using either 2 or 4 µL of sCD38. When either 2-4 or 6 µL of sCD38 was used, 98.5% of samples were neutralized. Except for anti-Fy^a and anti-Fy^b, all spiked alloantibodies (anti-D, -c, -E, -K, -Jk^a, -Kp^a, -Lu^a, -S) were detected. The mean score for general satisfaction with sCD38 was 4.44 (with 5 [very satisfied] the highest score).

Discussion - sCD38 has demonstrated strong potential in neutralizing anti-CD38 drugs in the clinical setting. While tested against isatuximab and daratumumab, it could be a potentially universal solution. By mimicking CD38 antigen on red blood cells, sCD38 is likely to interact with a broad range of anti-CD38 antibodies, suggesting its possible applicability across various settings.

ICU-acquired infections and thrombo-embolic events in critically ill patients receiving platelet transfusion: a prospective multicenter observational study

Florian Reizine — 2025-12-17

Background - Platelet transfusion is relatively common in patients hospitalized in intensive care units (ICU). Both ICU-acquired infections and thromboembolic events have been reported after platelet transfusion. We sought to explore risk-factors of these complications.

Materials and methods - We conducted a ancillary analysis of a multicenter prospective observational study including critically ill patients who received at least one platelet transfusion in one of the 9 participating ICUs. Patients' characteristics were compared according to the occurrence of post platelet transfusion
ICU-acquired infections (blood stream infections and ventilator-associated pneumonia) and thromboembolic events. Factors associated with those outcomes were assessed by univariable and multivariable Fine and Gray regression.

Results - Of the 310 included patients, 64 patients (20.6%) and 14 patients (4.5%) experienced at least one ICU-acquired infection and a thromboembolic event after platelet transfusion, respectively. Fifty patients (78.1%) developed blood stream infection (BSI), 32 (50%) experienced ventilator associated pneumonia (VAP) and 18 (28.1%) had both VAP and BSI. Independent risk factors for post platelet transfusion ICU-acquired infection included a platelet count at ICU admission <10⁹/L (protective) (subdistribution Harard Ratio (sHR) 0.52 95% CI [0.31-0.89] p=0.016), multiple platelet transfusion prior to infection occurrence (sHR 2.15 [1.25-3.71] p=0.005) and a Simplified Acute Physiology Score (SAPS) II>50 (sHR 3.67 [2.16-6.25] p<0.001). While, the unique variable independently associated with thrombotic event occurring after platelet transfusion in adjusted Fine-Gray regression was a SAPS II >50 (sHR 4.27 [1.18-15.39] p=0.027).

Discussion - In this prospective multicenter study, the risk of hospital-acquired infection after platelet transfusion increased in patients receiving multiple platelet transfusions and with patient severity at ICU admission.

Impact of 1- and 2-unit red blood cell transfusions on continuously monitored vital signs: a longitudinal study

Kevin Trentino — 2026-02-17

Background - We measured trends in continuous vital sign parameters and hemoglobin concentration in adult patients before and after 1- and 2-unit red cell (RBC) transfusions.

Materials and methods - A multi-center longitudinal study of 72 patients connected to a remote continuous monitoring service transfused 1 or 2 RBC units. Primary outcome was changes in heart rate (HR), respiratory rate (RR), and oxygen saturation (SpO₂), and secondary outcome was changes in hemoglobin concentration.

Results - Fifty-one patients received 1 RBC unit, 21 received 2 units. During the 10-hour pre-single-unit transfusion period, there were no clinically meaningful trends in HR (0.05, 95% CI, −0.36 to 0.46), RR (0.13, 95% CI, 0.02 to 0.25), or SpO₂ (0.08%, 95% CI, −0.02 to 0.18). There were no clinically meaningful differences in trends in the 24-hour period post-single-unit RBC transfusion when compared to the pre-transfusion trend (HR: 0.03, 95% CI, −0.44 to 0.51; RR: −0.09, 95% CI, −0.22 to 0.05; SpO₂: −0.15%, 95% CI, −0.27 to −0.02). The mean hourly hemoglobin trend 48 hours pre-single-unit transfusion was −0.07 g/dL (95% CI, −0.09 to −0.05) and 0.08 g/dL (95% CI, 0.05 g/dL to 0.10 g/dL) in the 48 hours post transfusion when compared to the pre-transfusion trend. Similar results were observed pre- and post-double-unit RBC transfusion.

Discussion - Despite hemoglobin concentration declines pre-single and double-unit RBC transfusion, and expected increases post-transfusion, there were no clinically meaningful trends in vital signs in the 10 hours before single- or double-unit transfusion or changes in trend in vital signs 24 hours post-transfusion.

Exposure of red blood cell concentrates to temperatures below 0°C for a short period does not alter in vitro quality

Natascha Roser — 2026-02-09

Background - To guarantee the quality of red blood cell (RBC) transfusion, RBC concentrates (RCCs) are stored at 4±2°C. Deviations to this specification can alter the RBCs. Although the exposure to higher temperatures is well documented, the exposition to subzero temperatures has been less investigated.

Materials and methods - RCCs (prepared from top-bottom kits and stored in saline-adenine-glucose-mannitol - SAGM) accidentally exposed to temperatures below 0°C were investigated in two regional blood services in Switzerland; Case 1: 1 h 52 min below 0°C (minimum of −5.7°C), and Case 2: 3 h 19 min below 0°C (minimum of −0.9°C). In case 1, 5 exposed and 5 unexposed RCCs were visually inspected for hemolysis or other alterations. Hemolysis was quantified in the 5 exposed RCCs and one control. In Case 2, 71 RCCs were analyzed at the time of the incident and at day 42 for hematological parameters and hemolysis. Ten RCCs were followed weekly for glucose, lactate, potassium levels and deformability.

Results - Under these conditions no signs of out-of-specification hemolysis or RBC damages were observed. Nevertheless, a higher hemolysis was reported in 4-day-old RCCs exposed to subzero temperature compared to existing and age-matched controls. Storage lesions were equivalent to unexposed RCCs and to literature.

Discussion - The two present real cases of RCCs exposure to temperatures below 0°C did not show damage to RBCs over storage. Even though the present work did not investigate the limits of RBCs sensitivity to cold temperature, it provides indications on the capability of RCCs to resist such type of storage deviation.

Evaluation of stored whole blood cellular components treated with bactericidal peptides at a higher concentration than required to assess the peptide compatibility with product quality

Supaksorn Chattagul — 2026-02-11

Background - Despite advancements in screening and pathogen detection, bacterial contamination of whole blood (WB) remains a rare but critical risk, typically originating from donor blood or skin-resident bacteria. While current pathogen reduction technologies (PRT) mitigate this risk, they often compromise blood quality relative to the untreated units. As an alternative, we recently evaluated two synthetic peptides, D-CONGA and D-CONGA-Q7 in WB at a concentration of ~8 μM for bactericidal efficacy and compatibility with WB hemostasis potential. However, evaluation of hemostasis property of WB alone is insufficient to ensure that endogenous red blood cells (RBC) and platelets are maintaining other critical functional parameters that are measurable in vitro.

Materials and methods - We investigated the effects of these peptides on the WB endogenous RBC and platelets at ~2.5 times higher concentration (i.e., 20 μM) than what is required (8 μM) for complete bactericidal activity to test their compatibility limits. We investigated the performance of WB endogenous RBC resident hemoglobin oxygen affinity and glycolytic rate as well as WB endogenous platelet aggregation potential as part of monitoring the safety and compatibility profile of the peptides.

Results - Our results support that even higher peptide concentrations do not significantly affect oxygen dissociation from red blood cells but do cause a slight deviation in P50 values and a marginal difference in glycolytic rate. Further, WB endogenous platelet aggregation is not affected by the peptide treatment with any of the aggregation agonists used.

Discussion - Overall, we conclude that while higher peptide concentrations (20 μM) than required for bactericidal activity (~8 μM) may slightly affect glycolysis and the ability of red blood cells to dissociate from oxygen, platelet aggregation is not affected. This report clearly supports the potential safe use of these peptides for inactivating bacteria in WB without harming the product quality.

Therapeutic plasma exchange-related complications in patients with immune-mediated thrombotic thrombocytopenic purpura

Pasquale Agosti — 2025-12-10

Background - Daily therapeutic plasma exchange (TPE) is the cornerstone of treatment for immune-mediated thrombotic thrombocytopenic purpura (iTTP). However, TPE is not a risk-free procedure and there is scarce evidence regarding its safety in iTTP. This study aims to describe the TPE-related clinical complications occurred in a cohort of patients hospitalized for an acute iTTP episode.

Materials and methods - In this cross-sectional study, patients hospitalized for an acute iTTP episode at the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico (Milan) between January 2016 and April 2022 undergoing a central venous catheter (CVC) placement to start TPE were enrolled.

Results - Thirty-three iTTP episodes from 32 patients were included, 20 (61%) first episodes and 2 (6%) complicated with acute exacerbations.
Twenty-one episodes (64%) were complicated with at least one major
TPE-related complication, 18 (55%) with at least one CVC-related complication, of which 9 (27%) with a major complication. Among major CVC-related complications, 5 were venous thromboses (VTs) requiring heparin treatment and CVC removal, and 3 infections (2 systemic) requiring systemic antibiotic treatment and CVC removal. The 19 CVC-related bleeds (in 16 episodes) were minor bleeds and required only local hemostatic medications. Among the major procedure-related complications, the most common were allergic reactions (present in 16 episodes, 49%), mostly urticarial rashes requiring systemic steroids and antihistamines, and clinical hypocalcemia (in 8 episodes, 24%). The episodes complicated with CVC-related VT or infection required a longer hospitalization and those complicated with CVC-related infection required also a higher number of TPE procedures.

Discussion - TPE procedure was well tolerated in our cohort of acute iTTP patients in the majority of cases, with CVC-related minor bleeds and allergic reactions being the most common complications. The occurrence of
CVC-related major complications, as VT or infections, was associated with a longer hospitalization (medians: 30 vs 11.5 days).

Erratum: Quality and stability studies of red blood cell concentrates from umbilical cord blood compared to their adult counterparts

Luisa Stea — 2026-02-10

n/a

Rare inherited autosomal bleeding disorders in women: sex-related bleeding, pregnancy and delivery. A narrative review

Tiziano Martini — 2026-02-03

Rare inherited autosomal bleeding disorders (RAIBDs) are a heterogeneous group of coagulation diseases including rare bleeding disorders and inherited platelet disorders, characterized by a wide variability in frequency and severity of hemorrhagic symptoms. The management of women suffering from these disorders is very challenging due to sex-related bleeding, such as menstrual flow and hemorrhage events linked to pregnancy and delivery. Furthermore, in this subset of patients, there are open issues regarding the delivery mode, to preserve the newborn who could be affected by the same bleeding disorder.

The purpose of this review is to explore evidence on the management of women suffering from RAIBDs in order to guide physicians taking care of this subset of patients.

Heavy menstrual bleeding (HMB) is often the most frequent reported symptom and the reason for referral: its lack of prompt identification can lead to a delay of diagnosis; HMB often provokes iron-deficiency anemia, with a significant reduction of quality of life. HMB treatments are limited and based on limited efficacy data. The rarity of these coagulation defects poses a challenge in the management of pregnancy and delivery, especially if the bleeding disorder is not diagnosed prior to the physiological pregnancy-associated changes in hemostasis (which make the diagnosis more difficult); a careful collection of the hemorrhagic and family history is essential. Currently, there is only limited evidence about the management of RAIBDs during pregnancy and delivery, and the present clinical practice is often based on the current local policy.

Complete D epitope expression of the most common weak D types 15, 25, 33, and 72 in the Chinese population

Yalin Luo — 2025-10-28

Background - The most common weak D type 1, 2, and 3 individuals in the Caucasian population can be safely treated as D+ patients. However, the management of the common weak D type 15 in the East Asian population and the frequent weak D types 25, 33, and 72 in the Chinese population remains controversial.

Materials and methods - D epitope expression in individuals with weak D types 15, 25, 33, and 72 was assessed using an anti-D panel (D-Screen) via both hemagglutination and sensitive adsorption/elution methods. Furthermore, these four variant RHD constructs and one wild-type (wt) RHD construct were cotransfected with the wt RHAG construct into HEK 293T cells in vitro. After transfection, the surface expression of the RhD antigen was assessed via flow cytometry with a panel of monoclonal anti-Ds.

Results - Routine serological D epitope typing with D-Screen revealed that the red blood cells of weak D types 15 (No.=3), 25 (No.=3), 33 (No.=4), and 72 (No.=3) individuals were negatively agglutinated with one or multiple monoclonal anti-Ds. For the D epitopes undetectable by hemagglutination testing, positive reactions were obtained in the adsorption/elution tests when the corresponding non-reactive monoclonal anti-Ds were used. In vitro expression analyses revealed that all four weak D variant constructs expressed all tested D epitopes comparable to those observed with the wt RHD construct.

Discussion - The complete repertoire of D epitope expression was observed both in weak D types 15, 25, 33, and 72 individuals in vivo and expression analysis in vitro. This provided evidences that individuals with these four weak D types, similar to D+ patients, can receive D+ red blood cell transfusion and do not require Rh immunoglobulin prophylaxis.

Beyond vital signs: oxygen delivery, oxygen utilization, and the limits of physiologic signal after red cell transfusion

Aryeh Shander — 2026-05-04

N/A

Patient autonomy and Patient Blood Management: lessons from the Pindo Mulla v. Spain Case

Antonio Perez-Ferrer — 2026-02-12

The Pindo Mulla v. Spain judgment (European Court of Human Rights, 2024) demonstrates that violations of patient autonomy may arise not from individual clinical decisions, but from inadequate procedural and institutional preparedness. The case involved a competent Jehovah’s Witness who received a blood transfusion despite her explicit refusal. From a transfusion medicine perspective, the judgment makes clear that respect for informed refusal depends on system readiness rather than ad hoc decision-making. The Court’s finding of a violation of Article 8 exposes cumulative failures, including insufficient Patient Blood Management (PBM) optimization, omission of available bloodless alternatives, and the absence of meaningful patient participation before judicial intervention. These shortcomings transformed an ethically manageable situation into a procedural emergency. PBM should be understood as an organizational framework that operationalizes respect for autonomy while fulfilling the duty to protect life, reconciling Articles 2 and 8 through institutional design rather than emergency exception.