Jörg Sigle

A pilot iron substitution programme in female blood donors with iron deficiency without anaemia.

Background and objectives  Blood donation can contribute to iron deficiency. The possibly resulting anaemia importantly affects donor return rate. The determination of serum ferritin levels revealed iron deficiency in many non‐anaemic premenopausal female blood donors at our Institution. We started an iron substitution programme targeting this donor group to prevent anaemia and enhance donor retain.

Transfusion policy in ABO-incompatible allogeneic stem cell transplantation

As a result of the fact that the human leucocyte antigen (HLA) system is inherited independently from the ABOblood group system, approximately 40–50% of all haematopoietic stem cell transplants (HSCT) are performed across the ABO-blood group barrier. There are three kinds of ABO incompatibility: minor incompatibility (in 20–25% of transplants) is characterized by the ability of donor B lymphocytes to produce antirecipient alloantibodies (e.g. group O donor to a group A recipient). In contrast, major incompatibility (in 20–25% of transplants) is characterized by the presence of antidonor alloantibodies (e.g. group A donor to a group O recipient). Bidirectional ABO-incompatibility (up to 5% of transplants) occurs when both donor and recipient produce alloantibodies against each other’s red cell (e.g. group A donor to a group B recipient). Several studies demonstrated that an ABO mismatch does not affect the incidence of graft rejection and does not cause slower engraftment of neutrophils and platelets. However, haemolytic transfusion reactions may occur [1]. A distinction can be made between immediate (during graft infusion) and delayed (during engraftment) immune haemolysis. Another phenomenon that may occur is pure red cell aplasia (PRCA) which is seen in 15–20% of cases after a major ABO-incompatible transplant. This phenomenon is explained as to be due to alloantibody-producing plasma cells which are relatively resistant to chemoand radiotherapy. Antibodies produced by such surviving plasma cells of the recipient are responsible for the inhibition of the growth of RBC precursors in the bone marrow [2]. Recommendations for transfusion policy in cases of ABO-incompatible stem cell transplantation and management of RBC transfusions in cases of PRCA or relapse of the underlying disease are not well defined in the literature. To obtain information on these aspects the following questions were sent to various transplant centres and departments of blood group serology and transfusion medicine. We received 10 contributions for this Forum. The participating centers are listed in Table 1. In Table 2, all answers are summarized.

Platelet transfusion: basic aspects.

Platelet transfusions have been shown to prevent major haemorrhage and improve survival in thrombocytopenic patients. Since then, advances in the preparation of platelet components, including the introduction of pathogen reduction techniques, have been achieved. The number of transfused platelet components is still growing owing to the increasing number of patients treated for haemato-oncological diseases. Additionally, indications have been extended, for example to patients with drug-induced platelet dysfunction. This review focuses on current platelet component production and storage techniques, including pathogen reduction, indications for platelet transfusion and safety issues including alloimmunisation and management of platelet refractoriness.

Anti-leucocyte antibodies in platelet apheresis donors with and without prior immunizing events: implications for TRALI prevention.

Transfusion‐related acute lung injury (TRALI) prevention strategies in platelet (PLT) apheresis donors focus on identifying antileucocyte antibody‐positive donors. The use of microbead based assays for screening purposes is hampered by the lack of a consensus cut‐off for TRALI prevention and the undefined role of anti‐leucocyte antibodies in never‐alloexposed donors. This study evaluated anti‐leucocyte antibody assays in PLT apheresis donors with and without prior immunizing events with special focus on microbead assay cut‐offs, antibody specificities and their potential significance in never‐alloexposed donors.

Epstein-Barr Virus Negativity among Individuals Older than 60 Years Is Associated with HLA-C and HLA-Bw4 Variants and Tonsillectomy

ABSTRACT Epstein-Barr virus (EBV) infects ∼95% of the adult population. The factors that confer protection in the remaining ∼5% remain unknown. In an exploratory study, we assessed immunogenetic factors and tonsillectomy in a cohort of 17 EBV-negative and 39 EBV-positive healthy individuals aged >60 years. Analyses of HLA genotypes revealed an association between EBV negativity and the presence of HLA-C-35T/T and/or HLA-Bw4 alleles. In addition, EBV-negative donors presented with a history of tonsillectomy more often than EBV-positive donors.

Preparation of granulocyte concentrates by apheresis

Bacterial and fungal infections still are life-threatening complications in immunocompromised patients. Transfusion of allogeneic granulocytes, collected by donor-apheresis, may be indicated to control these infections [1]. Sedimentation agents such as highor low molecular weight hydroxyethyl starch (HES) are routinely used to improve the separation of WBCs from RBCs. Administration of steroids (i) cytokines (ii) (recombinant G-CSF) or both (iii) to the donors increases the number of circulating neutrophils in the peripheral blood. This practice allows the collection of about 1 · 10 (i), 5 · 10 (ii) or 8 · 10 (iii) granulocytes per run [2,3]. Granulocyte concentrates still contain significant numbers of red cells and therefore an ABO RhD match with the recipient is mandatory, but they may be transfused across the ABO blood group barrier after red cell and ⁄ or plasma depletion [2]. The modalities of collection of granulocytes for supportive therapy vary from one centre to the next. This international forum addresses these collection modalities. Eight centres responded to the survey. Granulocytes are collected from both, healthy donors and from patients’ relatives in five out of eight centres while in two centres only the patients’ relatives serve as granulocyte donors and 1 centre collects granulocytes exclusively from healthy volunteers. Cytomegaly (CMV)-negative donors are preferred for CMV-negative patients. In one centre the donors (whole blood donors) are not routinely tested for CMV. Mobilization regimens and donation frequencies differ among the centres, but G-CSF is commonly used in all centres. The dose varies between 5 lg ⁄ kg body weight (BW) and 12 lg ⁄ kg ⁄ BW 8–18 hours before donation. In two centres a standard dose of 300 lg is given. Although the combination of cytokines and steroids for donor stimulation is favoured by several authors [3], in only half of the centres this regimen is used. The main reason to refrain from the combination of cytokines and steroids was to minimize cumulative adverse events. In three centres G-CSF is used as the only stimulating agent. Prednisolone is used at a dose of 50 mg and dexamethasone at a dose of 3 or 8 mg, either in combination with G-CSF or alone. Of note, the administration of G-CSF is only allowed for the mobilization of peripheral stem cells in healthy donors in two out of eight centres. Thus, healthy volunteers are pretreated exclusively with steroids in one of these centres, while in the other one the short-term application of G-CSF for granulocyte collection requires an approval from the local ethics committee as well as a donor insurance. The frequency of granulocyte donation is restricted to a few times in all centres. It ranges from once in a lifetime to five times per year. In three centres the number of donations is restricted to three (two centres) or four donations (one centre) in a lifetime, respectively. In one centre the number of donations differs between healthy volunteers (once in a lifetime) and patients’ relatives (twice in a lifetime, if necessary both donations within 1 week]). In two centres the number of donations depends on the mobilization regimen used. In the 1st centre G-CSF primed donors are allowed to donate five times per year and steroid primed donors are allowed to donate only four times a year. These restrictions are in accordance with their national law allowing the exposure of donors to 150 g HES within a year and to 200 mg prednisolone per year. In the second centre, donors, pretreated with G-CSF alone, may donate four times per year, but only twice a year if treatment is combined with steroids. In only three of eight centres high molecular weight HES is still used whereas two centres use low molecular weight HES (130 kD) for granulocyte collection. In one centre there is no preference for either, and in two centres no sedimentation agents are used at all; of the latter, one only provides granulocytes for children. In two centres, in which there was a switch from high molecular weight to low molecular weight HES, the efficiency of collection became less resulting in significantly lower granulocyte yields, and the granulocyte collection modalities of the cell separator were therefore adjusted in one of these centres. In all but one centre ABO compatibility between donor and recipient is respected. In only one centre transfusions are given, even against the blood group barrier. In case of blood group incompatibility the product is either red cellor plasmadepleted or both. Another centre demands absence of haemolysins and an alloagglutinine-titre below 1:128 in case of minor incompatibility. In four centres the RhD status of the patients is respected irrespective of their gender and age. In two centres anti-D prophylaxis is given in case of RhD incompatible granulocyte Vox Sanguinis (2010) 98, 567–575

Switching iron-deficient whole blood donors to plateletpheresis.

BACKGROUND: Iron deficiency is a frequent side effect of whole blood (WB) donation. In contrast, less red blood cell loss and therefore less iron loss results from plateletpheresis.

Low-Frequency Blood Group Antigens in Switzerland

Background: High-frequency blood group antigens (HFA) are present in >90% of the human population, according to some reports even in >99% of individuals. Therefore, patients lacking HFA may become challenging for transfusion support because compatible blood is hardly found, and if the patient carries alloantibodies, the cross-match will be positive with virtual every red cell unit tested. Methods: In this study, we applied high-throughput blood group SNP genotyping on >37,000 Swiss blood donors, intending to identify homozygous carriers of low-frequency blood group antigens (LFA). Results: 326 such individuals were identified and made available to transfusion specialists for future support of patients in need of rare blood products. Conclusion: Thorough comparison of minor allele frequencies using population genetics revealed heterogeneity of allele distributions among Swiss blood donors which may be explained by the topographical and cultural peculiarities of Switzerland. Moreover, geographically localized donor subpopulations are described which contain above-average numbers of individuals carrying rare blood group genotypes.

Iron deficiency and thrombocytosis

According to many textbooks, iron deficiency (ID) is associated with reactive thrombocytosis. In this study, we aimed to investigate the correlation between serum ferritin levels and platelet counts in a large cohort of healthy blood donors. We included all whole blood and apheresis donors aged 18 years or older with at least one ferritin measurement and one platelet count performed at the same visit between 1996 and 2014. A total of 130 345 blood counts and ferritin measurements obtained from 22 046 healthy donors were analysed. Overall, no correlation between serum ferritin and platelet count was observed (r = −0.03, ρ = 0.04 for males, and r = 0.01, ρ = −0.02 for females, respectively). Associations remained clinically negligible after adjusting for age, time since previous blood donation, number of donations and restricting the analysis to ferritin deciles. In this large, retrospective single‐centre study, correlations between low ferritin and platelet count in a large and homogeneous cohort of healthy donors were negligible. Further studies in patients with more severe anaemia and patients with inflammation are warranted.

Extending shelf life of dithiothreitol‐treated panel RBCs to 28 days

Daratumumab (DARA) causes non‐specific results in indirect agglutination testing (IAT). Dithiothreitol (DTT) treatment of panel red blood cells (RBCs) abolishes DARA interference. The objective of our study was to extend stability of DTT‐treated panel RBCs to 28 days through application of a commercially available panel RBC stabilizer.