BACKGROUND AND OBJECTIVES Transfusion-transmitted malaria (TTM) is a rare but potentially severe transfusion complication. Increasing global mobility from malaria-endemic regions challenges donor selection policies in non-endemic settings, as asymptomatic parasitaemia may persist for years in previously exposed semi-immune individuals. This review aims to contextualise the residual risk of TTM and critically appraise current and past preventive strategies considering available evidence, with particular attention to policy implications. MATERIALS AND METHODS A literature review of all confirmed cases of TTM reported in Europe and North America between 2005 and 2024 was performed to retrospectively assess the effectiveness and limitations of past and current preventive strategies, with particular reference to the recommendations of the European Directorate for the Quality of Medicines & HealthCare (EDQM) Blood Guide and the U.S. Food and Drug Administration (FDA). RESULTS Eighteen confirmed TTM cases were identified: 11 by Plasmodium falciparum with three fatalities, six by Plasmodium malariae and one by Plasmodium ovale. Sixteen cases were linked to donors born in or long-term residents of malaria-endemic regions, predominantly sub-Saharan Africa; two involved short-term European travellers. Since 2012, no P. falciparum TTM cases have been reported in Europe following the correct implementation of EDQM guidelines. CONCLUSION The residual risk of TTM in Europe and North America appears to be extremely low. However, long-term asymptomatic carriers-particularly of P. falciparum-remain a potential threat. Approaches based on deferral and immunological testing appeared to be effective and sustainable; nevertheless, high-sensitivity nucleic acid testing may represent a valuable alternative, particularly where blood availability is critical.
Background and Objectives Parvovirus B19 (B19V) testing is often not required to release blood components. However, the European Pharmacopoeia requires that plasma pools for fractionation contain no more than 104 IU/mL of B19V DNA. In France, pool B19 nucleic acid testing (NAT) screening was performed by & Eacute;tablissement Fran & ccedil;ais du Sang since 2015. Since June 2024, positive pools are broken down into individual testing, allowing for the identification and management of infected blood donations. Materials and Methods B19V NAT is performed in pools of 96 donations (P96) with the DPX Parvo/hepatitis A virus assay (Roche). A P96 with a viral load >104 IU/mL B19V DNA is considered positive. All individual donations (IDs) testing reactive for B19V by ID-NAT are excluded from plasma-based medicinal products production, and the corresponding blood components are destroyed if not yet transfused. Results From June 2024 to June 2025, 99 of 2,627,678 donations (3.7/100,000) were B19V DNA positive. All blood components related to 90 donations were discarded. Of the remaining nine donations, 13 blood components (9 platelet concentrates [PCs] that had undergone pathogen reduction (PR) and four red blood cell [RBC] concentrates) were transfused before NAT results were obtained. Two B19V transmissions were reported in recipients (0.078/100,000 transfusions) after transfusion of 1 PR-PC and 1 RBC unit. Conclusion B19V DNA testing for plasma intended for fractionation performed in blood services helps in avoiding transmissions by the related blood components, provided positive donations are detected prior to their transfusion. Delayed availability of results may result in transfusion-transmitted B19V infection, which cannot prevented by current PR technology.
Background and Objectives Immune platelet transfusion refractoriness (PTR) is usually mediated by anti-HLA class I antibodies; immunisation against CD36 (platelet glycoprotein IV [GPIV]) is relatively rare. Platelet CD36 deficiency shows marked ethnic variability and is seldom reported in admixed Latin American populations. We describe the diagnostic and transfusional challenges of anti-CD36 alloimmunisation in a Brazilian patient. Materials and Methods A 48-year-old Brazilian woman with a myeloid/lymphoid neoplasm with fibroblast growth factor receptor 1 (FGFR1) rearrangement developed severe PTR. Platelet antibodies were assessed by a Luminex-based Pak-Lx assay, CD36 expression by flow cytometry and CD36 genotyping by Sanger sequencing. Results Platelet counts remained <5 & times; 10(9)/L with absent corrected count increment and recurrent mucocutaneous bleeding. Platelet antibody testing showed isolated anti-GPIV/CD36 reactivity (median fluorescence intensity [MFI] 4388); no additional HLA class I or human platelet antigen (HPA) antibodies were detected. No CD36 expression was detected on the patient's platelets by flow cytometry, and CD36 gene sequencing identified two heterozygous variants (c.975T>G and c.1079T>G) known to be associated with CD36 deficiency. Crossmatches remained incompatible with all available platelet units, including from an HLA-identical brother, reflecting the scarcity of CD36-negative platelet donors. The patient died of disease progression. Conclusion Anti-CD36 alloimmunisation should be considered in severe PTR with negative HLA antibody screening, particularly in heavily transfused patients from admixed populations. To our knowledge, this is the first Brazilian case of anti-CD36 alloimmunisation causing severe PTR; platelet CD36 deficiency has previously been reported in a Brazilian woman with anti-CD36 antibodies in the context of pregnancy, underscoring the importance of considering this antibody specificity in persistent PTR despite negative HLA and HPA antibody screening.
Abstract Background and Objectives Immunoglobulin M (IgM) is a promising therapeutic agent. However, its production is limited by high molecular weight, complex structure and poor stability. This study aimed to develop a novel manufacturing process for high‐purity, stable plasma‐derived IgM while improving plasma utilization. Materials and Methods The flow‐through fraction from first‐step anion‐exchange chromatography (Step 1 AEX) in an intravenous immunoglobulin manufacturing process was used as the starting material. Second‐step AEX (Step 2 AEX) and third‐step mixed‐mode chromatography (Step 3 MMC) were used to remove impurities, including prekallikrein activator (PKA), immunoglobulin G (IgG), immunoglobulin A (IgA) and α2‐macroglobulin. The elution conditions for Step 2 AEX were optimized to improve IgM recovery and purity. Four resins were evaluated for Step 3 MMC, and separation conditions were optimized to increase IgM purity and recovery. Finally, formulation studies were conducted to improve IgM stability. Results The optimized conditions were stepwise elution for Step 2 AEX (0.4 M followed by 1.0 M sodium acetate), Capto Core 400 resin for flow‐through‐mode Step 3 MMC and loading at pH 7.8, conductivity 15.0 mS/cm and protein concentration 1.0% ( w / v ). Key impurities IgA and PKA were reduced to 0.184 ± 0.011 mg/mL and below the limit of detection (<10 IU/mL), respectively, and IgM purity exceeded 90%. Under the final formulation conditions (0.1 M glycine, pH 4.0), the high‐purity IgM showed good stability. Conclusion A novel process was developed to address the critical challenges in plasma‐derived IgM manufacture, achieving high IgM purity (>90%). By optimizing plasma utilization, this process represents a promising platform for next‐generation immunoglobulin therapies.
