Transfusion最新文献

Background: KEL1 antigen expression is routinely tested in blood donors in Switzerland. A donor sample with an apparent rare KEL:1,-2 phenotype was genotyped KEL*01.01/KEL*02. A series of detailed molecular analyses were performed to solve this discrepancy, and a novel variant KEL*02 allele was identified.

Materials and methods: Standard serological column agglutination and in-house adsorption-elution testing were used for the detection of KEL antigens. Genomic DNA was isolated and analyzed by commercial sequence-specific primer (SSP)-PCR, in-house multiplex SSP-PCR, and KEL exon sequencing. Total RNA was isolated from blood samples; polyadenylated RNA was reverse-transcribed, and cDNA was amplified with allele-specific primers and sequenced. SpliceAI and PolyPhen-2 were used to evaluate the impact of nucleotide variations and amino acid changes on splice effects and protein function, respectively.

Results: The donor sample was initially typed KEL:1,-2. However, SSP-PCR revealed the genotype KEL*01.01/KEL*02 and subsequent adsorption-elution testing indicated very weak KEL2 expression. Exon sequencing showed the heterozygous missense mutation c.139C>T leading to the amino acid substitution p.(Arg47Trp). PolyPhen-2 predicted this change to be benign, whereas SpliceAI analysis indicated a putative change in splice sites. Allele-specific amplification and sequencing revealed that the KEL*02 derived transcript lacks a significant portion of exon 3, causing a frameshift.

Conclusion: We identified a novel missense mutation c.139C>T in KEL*02. Although the variant nucleotide locates in the center of exon 3, far away from the exon/intron boundary, it leads to variant splicing of the transcript, resulting in very weak expression of a truncated protein only detectable by adsorption-elution testing.

Background: Diversity Equity and Inclusion initiatives in blood donation have progressed for priority groups such as ethnic minorities, men who have sex with men, and trans and diverse donors. However, advocacy for persons with disabilities (PWDs) in healthcare, especially in blood donation, remains slow. This study sought international perspectives on how Blood Collection Agencies (BCAs) define and engage with PWDs.

Methods: A survey was circulated to members of the Alliance of Blood Operators (ABO) and the Asia Pacific Blood Network (APBN). Responses were received from 13/15 members, with 12 consenting for their data to be published.

Results: All respondents reported including information about at least one form of disability in donor information, most commonly vision impairment, hearing, and mobility-related disabilities. Physical and sensory disabilities were more frequently recognized than cognitive disabilities. Most BCAs did not collect disability data. More than half reported having standard operating procedures about disability, but most lacked disability access and inclusion plans (DAIPS). Only three BCAs allowed PWDs to donate in wheelchairs.

Conclusion: This study provides foundational insights into how BCAs conceptualize and respond to disability. Findings reveal discrepancies in definitions, accessibility implementations, and inclusion protocols. Despite some facilitating access for donors with mobility challenges or offering staff inclusion education, gaps remain in DAIPs, donor data on PWDs, and research. To promote equity and expand the donor pool, increased research focus on inclusive data tools and exploration of PWDs' lived experiences is recommended.

Background: The deferral period for men who have sex with men (MSM) in the US decreased over time from indefinite deferral to 12 to 3 months. In 2023, the US Food and Drug Administration permitted individual donor assessment (IDA), shifting from categorical exclusions to risk behavior-based screening.

Methods: Trends in HIV risk-based behavior deferrals in a large US collector over similar periods with indefinite MSM, 12-month, and 3-month deferrals versus IDA were analyzed. Rates of confirmed HIV, hepatitis B virus (HBV), and syphilis testing during corresponding pre- and post-IDA periods are reported.

Results: Among males, a significant decrease in HIV risk-based behavior deferrals occurred from indefinite deferral (0.150%) to 12-month (0.114%) to 3-month (0.085%) periods, to IDA (0.067%). For females, MSM contact deferrals significantly decreased from 12-month deferral periods (0.015-0.033%) to 3-month deferral periods (0.007%); post-IDA, rates significantly increased to 0.049%. IDA increased overall deferrals from 0.04% to 0.06% (p < 0.01) compared to the 3-month deferral period. Higher deferrals were seen in males (adjusted odds ratio [aOR] = 1.45 [95% CI = 1.24-1.69]), first-time versus active donors (aOR  = 2.54 [2.12-3.03]), and at ages 19-22 (aOR = 2.73 [2.12-3.52]) compared to 30- and 39-year-olds. IDA implementation did not increase the rates of confirmed HIV, HBV, or active syphilis; however, rates of RPR-negative confirmed syphilis reactivity rose significantly post-IDA.

Conclusion: Transition from indefinite MSM deferral to 12 and then 3 months significantly decreased deferral rates. Rates rose in female but not male donors with IDA. IDA implementation did not result in higher rates of confirmed HIV, HBV, or active syphilis. An increase in remote/treated syphilis may be confounded by broader epidemiological trends rather than IDA.

Background: Characterization of platelet gel (PG) from different blood sources and preparation methods remains incomplete.

Study design and methods: This study compared the weight, growth factor (GF) content, and gelation dynamics (via rotational thromboelastometry, ROTEM) of allogeneic PG prepared from adult blood (AB) and cord blood (CB) platelet concentrates (PC). ABPC were suspended in 100% plasma or 35% plasma/65% platelet additive solution (PAS), while CBPC were suspended in 100% plasma. PG was prepared in commercial BioNest D mini-bags using a method with calcium gluconate, locally made cryoprecipitate, and thrombin (CT), or a reference method with calcium gluconate and commercial batroxobin (BA). PG was analyzed at 30 min and 6 h.

Results: At 30 min, PG weights were higher with CT than BA across all conditions. With 5 mL ABPC in 100% plasma, weights were 7.20 ± 1.07 g (CT) versus 2.72 ± 0.19 g (BA); with 10 mL ABPC in PAS, 9.49 ± 2.86 g (CT) versus 3.87 ± 3.1 g (BA); and with 4.09 ± 0.45 mL CBPC, 5.62 ± 1.21 g (CT) versus 2.04 ± 0.78 g (BA). All PGs lost mass by 6 h, but CT consistently retained more weight. GF percent retention in the PG at 6 h was higher with CT. ROTEM results showed differences in clotting time and comparable values of maximum clot firmness between PG from AB and CB.

Discussion: The CT method is a promising alternative for producing allogeneic PG using affordable, locally sourced reagents.

Background: Cryoprecipitate Anti-Haemophilic Factor (CRYO-AHF) is enriched for fibrinogen, VWF, FVIII, FXIII and fibronectin, but has short post-thaw expiration due to risk of transfusion-transmitted infection (TTI) limiting availability for rapid treatment. Amotosalen-UVA pathogen reduction treatment (A-PRT) to manufacture pathogen-reduced cryoprecipitated fibrinogen complex (PRCFC) allows 5-day post-thaw expiration, reduces TTI risk, and facilitates early treatment of hemorrhage.

Aims: To evaluate adhesive protein functions in PRCFC and lyophilized PRCFC (LIFC).

Methods: CRYO-AHF, PRCFC, LIFC, and commercial fibrinogen concentrate (CFC) were evaluated for platelet adhesion and aggregation in variable shear microfluidic assays.

Results: Platelet adhesion kinetics to CRYO-AHF, PRCFC, and LIFC, under low shear flow (300 s^-1) were conserved. Platelet adhesion to CFC at low shear was reduced due to absence of functional VWF. αIIbβ3 integrin/fibrinogen and GPIb-IX-V/VWF platelet interactions with CRYO-AHF, PRCFC, and LIFC were confirmed by abciximab and caplacizumab inhibition, respectively. All fibrinogen sources promoted efficient platelet aggregation. Perfusion of reconstituted plasma-free blood (RBC + platelets + various cryoprecipitates) on immobilized VWF-binding peptide (1500 s^-1) showed impaired platelet adhesion to CFC compared to PRCFC and CRYO-AHF. Perfusion of reconstituted blood on collagen (3000 s^-1) indicated CRYO-AHF, PRCFC and LIFC formed thrombi to similar levels. Platelets treated with A-PRT combined with PRCFC or LIFC retained similar activity to CRYO-AHF for platelet aggregation and thrombus formation on collagen.

Conclusions: PRCFC and LIFC retained critical hemostatic functions of VWF and fibrinogen to support platelet adhesion and aggregation during physiologic shear. PRCFC and LIFC represent a therapeutic option for early treatment of massive hemorrhage.