Abstract
The European Haematology Association annual meeting is the second largest conference organized specifically for hematologists. This meeting report gives an overview of one particular session within this meeting, that of the transfusion medicine subject speciality, which included two speakers from the USA and one from the UK. The following lectures will be reviewed here Jo-Ann Moulds – Transfusion policies and practices in alloimmunized sickle cell patients; Derwood Pamphilon – Transfusion problems in stem cell transplant patients; and Naomi Luban – Transfusion issues in neonatal and pediatric hematology. The session, therefore, included a significant discourse in clinical practice of transfusing the difficult to transfuse patient.
The Congress of the European Haematology Association (EHA) is one of two ‘must attend’ meetings per year for hematologists. It is outside the remit of this report to describe the whole meeting; however, I have chosen to review the education section for which I was responsible for organising – transfusion medicine. For me personally, attendance at EHA provides a valuable opportunity to be updated on developments in conventional hematology, and this years major story for me was the increasing knowledge surrounding the JAK2 V617F mutation in hematological malignancy (eminently presented by William Vainchencker). I was also particularly enthralled by the talk presented by Mike Stratton of the Wellcome Trust Sanger Centre (Cambridge, UK) who described the post-genomic efforts focussed in understanding the molecular biology of leukemia and other cancers.
The transfusion medicine education session at EHA traditionally includes a broad mix of topics of contemporary interest in the field. This year, the theme of the session was the vulnerable transfusion patient, notably those suffering from sickle cell disease requiring stem cell transplants and neonatal transfusions. There were two repeated sessions, the first chaired by myself and the second by Narla Mohandas of the New York Blood Center. I describe in this article a brief overview of each speaker’s presentation;the interested reader may refer to the supplementary educational handbook, in which the speakers provided excellent review articles that summarize their presentations Citation[1].
Transfusion policies & practices in alloimmunized sickle cell patients
Jo Ann Moulds (Lifeshare Blood Centers, LA, USA) gave an in-depth analysis of the care of multi-transfused sickle cell disease (SCD) patients, which amount to over 80,000 individuals in the USA Citation[2]. The management of such cases represents a significant workload for her blood center at Shreveport. Blood transfusion has been a significant factor in the management of SCD patients, and has received special attention since the Stroke Prevention Trial in Sickle Cell Anaemia clinical trial (STOP), in which it clearly demonstrated a reduction in the incidence of stroke – a significant complication and cause of mortality in SCD. Such was the success of the treatment that the STOP trial was terminated early. Moulds stressed that blood transfusion is of critical importance in the management of SCD patients, and work needs to be done to standardize approaches across centers specializing in such treatment.
Unfortunately, routine blood transfusion of mismatched blood products results in alloimmunization and other complications (infections and iron overload), which can be life threatening. Moulds explained that the true rate of alloimmunization in SCD patients may be underestimated and reports have appeared describing the frequency in the USA as being between 4 and 40%! Factors that influence such a disparity may include that many alloantibody specificities may not be detected by all centers, especially of the clinically significant Rhesus (Rh) system where enzyme treatment of red cells prior to antibody detection is a procedure that is not universally adopted.
Moulds then described the situation in the USA where serological matching of blood group units is performed in the management of SCD patients, and stressed the disparity in methods of achieving this. Ideally, SCD patients should be minimally matched for Rh C, E and Kell; however, among the Comprehensive Sickle Cell Centers (CSCC) routine phenotype matching is also performed for the ABO, Rh, Kell, Duffy, Kidd, Lewis, Lutheran, P1 and MNS blood group systems. She then described how recent blood group genotyping technology has impacted on the management of SCD. It was stressed that genotyping offers several advantages over serological testing, and that it may be more economic and can be effective if utilized for the typing of 14 clinically significant antigens. Moulds then described several examples of blood group alleles that can only effectively be typed by genotyping techniques, the incompatibility of which has caused problems in several SCD patients.
Transfusion problems in stem cell transplant patients
Derwood Pamphilon (NHS Blood and Transplant, Bristol, UK) described a variety of factors that represent a significant threat for stem cell transplant patients who are very often heavily reliant on blood components for survival Citation[3]. He stressed that European Commission (EC) directives (especially 2002/98/EC) have been of fundamental importance in the standardization of measures imposed on blood components anticipated for transfusion into stem cell transplant (SCT) patients. The first line of threat discussed was microbial contamination of blood products. The EC directive stipulates that hepatitis B and C, HIV-1 and 2, human T-lymphotropic virus-1 and 2, cytomegalovirus, and syphilis must be tested for, and thus seronegative components must be transfused to SCT patients. The high proportion of SCT patients requiring platelet transfusions presents a potential problem with bacterial contamination of platelet concentrates estimated at 0.05–0.5% of components. Pamphilon described the current methods of minimizing bacterial contamination of platelet concentrates, and also the current policies relating to platelet transfusion Citation[4]. The major emphasis was that prophylactic, rather than therapeutic (i.e., when less than 10 × 109), platelet transfusion is much preferred, and that ABO and RhD matching is crucial.
The reduction of alloimmunization events in SCT patients (like those of SCD patients) was also considered, and measures to avoid red cell and HLA alloimmunization (especially leukodepletion) were described in depth. Further to leukodepletion, g-irradiation of blood products for SCT patients and the associated side effects (reduced circulation half-lifes) was also discussed. Red cell products must also be ABO and RhD typed, and special treatment of previously alloimmunized patients (e.g., SCD patients requiring SCT) must be considered.
Pamphilon then discussed the merits of granulocyte transfusion in especially vulnerable neutropaenic patients (those with granulocyte counts of less than 0.2 × 109/l), who are highly susceptible to fungal infections. He concluded by stating that SCT patients must be given the highest quality blood products, prepared in a standardized fashion devoid of microbial contaminants and any components that may stress an already challenged immune system.
Transfusion issues in neonatal & pediatric hematology
The presentation by Naomi Luban (George Washington University, Washington DC, USA) considered transfusion complications in the very young Citation[2]. While there were parallels with the treatment of stem cell patients, the transfusion triggers and considerations that must be given to patients of such a young age were stressed throughout the presentation. This is especially the case in premature infants, and the merits of transfusing red cells to very-low birthweight and extremely low birthweight were discussed. Recombinant human erythropoietin had been suggested as a mechanism to reduce the transfusion burden of anemic infants, but Luban carefully reviewed a series of recent studies that showed only marginal benefit of using this approach.
Luban then discussed the inherent difficulties of serological crossmatching of neonates due to the fact that a significant proportion (if not all) blood group-specific antibodies in their blood will be of maternal origin. Thus, in the first 4 months of the babies life, neither antibody screens nor crossmatching are necessary and are not performed after the first antibody screen at birth. Once the baby’s immune system matures (>4 months), then anti-A and anti-B will be formed, and possibly the presence of other blood group specificities as well. If this occurs, then antigen-negative blood will be required for transfusion.
The presentation then considered neonatal platelet transfusions, and again considered the issue of different transfusion triggers, with levels of 30,000 and 50,000/ml being discussed. It was also stressed that platelet transfusions must also consider the condition for which the fetus is being treated – for example, neonatal alloimmune thrombocytopenia is much more likely to have a life-threatening bleeding episode than sepsis. Luban also discussed that single-donation platelets tend to be used for neonatal transfusions (thus avoiding exposure to multiple platelet antigens), and that they should be ABO compatible.
Again, with parallels to the treatment of stem cell transplant patients, Luban described the transfusion of granulocytes for neonates that are at high risk of bacterial infection due to neutropenia. Like SCT patients, the side effects of granulocyte transplantation (for instance transfusion-related acute lung injury) were also discussed. Finally, Luban discussed the merits of processing blood components for example leukodepletion and g-irradiation to prevent alloimmunization and transfusion-associated graft-versus-host disease, respectively.
Conclusion
All three speakers provided a strong insight into the management of the difficult-to-transfuse patient, and their level of expertise and experience in these given areas was of profound benefit to the audience. While there were parallels in the management of all three patient groups it became quite apparent that the one-size-fits-all approach to blood component production does not occur, and modifications to blood products, and their transfusion requires a personalized approach to the patient being treated.
Financial & competing interest disclosure
Neil D Avent has consulted in the past for Progenika Biopharma SA, a producer of a blood group genotyping system. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
References
- Hematology education: The Education Program for the Annual Congress of the European Haematology Association3(1), (2009).
- Hematology education: The Education Program for the Annual Congress of the European Haematology Association3(1), 276–281 (2009).
- Hematology education: The Education Program for the Annual Congress of the European Haematology Association3(1), 282–287 (2009).
- Stanworth SJ, Hyde C, Heddle N, Rebella P, Brunskill S, Murphy MF. Prophylactic platelet transfusion for haemorrhage after chemotherapy and stem cell transplantation. Cochrane Database Syst. Rev.4, CD004269 (2004).