Report of the clinical donor case workshop of the European Association of Tissue Banks annual meeting 2012.

The European Association of Tissue Banks (EATB) donor case workshop is a forum held within the program of the EATB annual congress. The workshop offers an opportunity to discuss and evaluate approaches taken to challenging situations regarding donor selection, it promotes consensus development in deciding tissue donor acceptability when donor health issues are not addressed in standards and regulations, and serves to strengthen the professional tissue banking networks across Europe and beyond. This report reflects some of the discussion at the workshop during the annual congress in Vienna in 2012. The cases presented dealt with problems encountered by tissue bank facilities concerning idiopathic thrombocytopenia and auto-immune disorders, hemodilution and blood sample identification, premalignant and malignant lesions, and Huntington's disease. The discussions during the workshop demonstrate that the implications on the safety of tissue transplantation of various tissue donor illnesses, physical findings and behaviours, and the preventive measures taken by tissue facilities, may not always be agreed by tissue facility medical directors and other professionals. Moreover, they reveal that operating procedures, regulations and standards cannot comprehensively cover all tissue donor findings, medical histories and circumstances surrounding the cause of death. For many of the issues raised, there is a need for scientific research to provide a better evidence base for future deliberations about the suitability and eligibility of tissue allograft donors.

Results of the clinical donor case and quality system case workshops of the European Association of Tissue Banks annual meeting 2009.

The European Association of Tissue Banks (EATB) Donor Case Workshop and Quality System Case workshop are forums held within the program of the EATB Annual Congress. These workshops offer an opportunity to discuss and evaluate approaches taken to challenging situations, regarding donor selection and quality issues, and strengthen the professional tissue banking and regulatory networks across Europe. This report reflects some of the discussion at the congress workshops and also subsequent correspondence between the various individuals who submitted cases for discussion. The cases presented to the workshops demonstrate that the findings, their interpretation, deducted actions and preventive measures in tissue banks are not predictable. The varied responses and lack of consensus corroborate this and clearly indicate that operating procedures cannot comprehensively cover or prepare for all eventualities. For many of the issues raised there is a lack of information in the published literature. The workshops actively engage participants, representing a wide array of international expertise, in an informal, secure and enjoyable setting, which facilitates learning from peers and provides potential solutions to those submitting cases. By publishing a summary of the discussions, we hope to reach a wider audience and to stimulate individuals to undertake full literature reviews or research on some of the discussed subjects.

Status of blood banking and the blood supply in Afghanistan.

BACKGROUND: As a result of more than 20 years of war in Afghanistan, its blood supply system has been damaged. We carried out an assessment of that blood supply system to determine the type and extent of assistance needed to increase blood availability and safety. STUDY DESIGN AND METHODS: An assessment tool was developed, daily activities in Afghanistan were observed, and key personnel were interviewed. RESULTS: Because there was no donor recruitment organization, most blood was obtained by the family replacement system. There was an inadequate supply of stored blood, which led to use of blood before screening test results for transfusion-transmitted disease were complete. Whole blood was provided but blood components were not produced. Blood was tested intermittently for human immunodeficiency virus Types 1 and 2, hepatitis B surface antigen, hepatitis C virus, and syphilis using agglutination-based screening methods. CONCLUSIONS: A dedicated staff is in place but to strengthen the blood supply system in Afghanistan, it will be important to address infrastructure and facilities, organization, standard operating methods, supplies and equipment, training, quality assurance, and transfusion medicine education.

Distinguishing between transfusion related acute lung injury and transfusion associated circulatory overload.

PURPOSE OF REVIEW: The purpose of this review is to provide an overview of concepts recently presented in the literature that impact our understanding of transfusion related acute lung injury (TRALI) and transfusion associated circulatory overload (TACO), and how to distinguish between the two disorders. RECENT FINDINGS: An exceptionally clear review article by Brux and Sachs clarified the two-hit model of TRALI pathogenesis. The TRALI definition developed at the 2004 consensus conference helped demonstrate that TRALI is likely underreported. Brain natriuretic peptide can be useful in distinguishing cardiogenic from noncardiogenic pulmonary edema. Blood centers are implementing male predominant plasma programs to limit TRALI, and preliminary evidence suggests that this is a useful intervention. SUMMARY: TACO and TRALI have emerged as important causes of posttransfusion morbidity and mortality. As understanding of their pathogenesis improves, incidence, risk factors, differences, and possible preventive interventions are becoming clearer. There is no sentinel feature that distinguishes TRALI from TACO. Developing a thorough clinical profile including presenting signs and symptoms, fluid status, cardiac status including measurement of brain natriuretic peptide, and leukocyte antibody testing is the best strategy currently available to distinguish the two disorders.

Red cell aplasia and autoimmune hemolytic anemia following immunosuppression with alemtuzumab, mycophenolate, and daclizumab in pancreas transplant recipients.

BACKGROUND AND OBJECTIVES: Acquired red cell aplasia (RCA) is a rare disorder and can be either idiopathic or associated with certain diseases, pregnancy, or drugs. In exceptionally rare cases, it has been reported to co-exist with other autoimmune cytopenias. We report a high incidence of RCA and autoimmune hemolytic anemia (AIHA) in pancreas transplant recipients on alemtuzumab-based maintenance therapy. DESIGN AND METHODS: Between February 2003 and July 2005, 357 pancreas transplant recipients were treated with immunosuppressive regimens containing the lymphocyte-depleting antibody alemtuzumab, the T-cell activation inhibitor daclizumab, and the anti-metabolite mycophenolate mofetil (MMF). We retrospectively reviewed medical records, blood bank data and bone marrow biopsy specimens of patients with a Transplant Information Services database diagnosis of RCA and AIHA from February 2003 to November 2005. RESULTS: Severe RCA, AIHA, and idiopathic thrombocytopenic purpura (ITP) occurred independently or in combination, in 20 out of 357 (5.6%) pancreas transplant recipients, 12 to 24 months following the initiation of the aforementioned immunosuppressive regimens. Severe opportunistic infections developed late in 14/20 (70%) of these patients. Atypical morphologic features, including variable dysgranulopoiesis, variable megakaryocytic hyperplasia with normal or low peripheral platelet counts, and atypical lymphoid aggregates were found in bone marrow trephine sections of 11 patients in whom the diagnosis of RCA was made. INTERPRETATION AND CONCLUSIONS: We hypothesize that the combination of alemtuzumab, daclizumab and MMF can result in immune dysregulation thereby permitting autoantibody formation. Because the use of these three immune suppressants is becoming increasingly common, it is important to recognize the severe hematologic complications that can arise.

Bacterial infection transmitted by human tissue allograft transplantation.

Bacterial contamination of tissue allografts obtained from cadaveric donors has been a serious cause of morbidity and mortality in recipients. Recent cases of fatal and nonfatal bacterial infections in recipients of contaminated articular cartilage (distal femur) and tendon allografts have called attention to the importance of avoiding tissue donors suspected of carrying infectious disease, of not processing donated tissue carrying virulent bacteria, the occurrence of falsely negative final sterility tests, and the need to sterilize tissues. These cases demonstrated that contamination can arise from an infected donor, during tissue removal from cadaveric donors, from the processing environment, and from contaminated supplies and reagents used during processing. Final sterility testing can be unreliable, especially when antibiotics remain on tissues. There is an increasing need for control of microbial contamination in tissue banks, and sterilization of tissue allografts should be recommended whenever possible.

Blood donor and component management strategies to prevent transfusion-related acute lung injury (TRALI).

OBJECTIVE: Discuss the pros and cons of using donor and blood product-management strategies to prevent transfusion-related acute lung injury (TRALI). DATA SOURCE: A review of the literature was performed. RESULTS: Despite therapeutic advances in pulmonary and critical care medicine, TRALI is now considered to be one of the leading causes of transfusion-associated mortality, and thus determining how to prevent TRALI is extremely important. Donor and product-management strategies to prevent this life-threatening condition have been suggested, but because of gaps in our understanding of TRALI, blood-bankers do not know how beneficial these interventions will be, nor the amount of potential harm-such as decreasing the availability of blood-that could arise if they were implemented. This article discusses the advantages and disadvantages of the various preventive measures that have been described in the literature. CONCLUSIONS: Preventing TRALI poses a difficult challenge for blood-banking experts, because it is unknown which measures will be effective in decreasing the incidence of TRALI and which could have significant drawbacks. Only additional research into TRALI prevention will provide the answers on how to best protect patients from this potentially fatal reaction.

Early-onset autoimmune hemolytic anemia after cladribine therapy for Waldenström's macroglobulinemia.

BACKGROUND: Purine nucleoside analogs are a class of antineoplastic drugs with potent lymphotoxicity against T and B lymphocytes, causing prolonged lymphopenia and linked to delayed immune complications such as opportunistic infections and more recently autoimmune hemolytic anemia (AIHA), seen mostly in patients with chronic lymphocytic leukemia (CLL). A characteristic temporal relation between fludarabine therapy and the appearance of a warm-reactive immunoglobulin G (IgG)-mediated AIHA in patients with CLL has been observed and, in some, the AIHA has been fatal. Whether both fludarabine and cladribine cause AIHA is uncertain because AIHA is commonly seen in patients with CLL without the use of these drugs. In contrast, AIHA is encountered in Waldenström's macroglobulinemia (WM) much less frequently, and the autoantibody is usually cold-reactive and IgM-mediated. In a few reported cases of AIHA arising in patients with WM after cladribine therapy, there was a latency of 24 to 60 months between therapy and the onset of AIHA, three of which were warm-reactive and IgG-mediated. CASE REPORT: A warm-reacting IgG red cell autoantibody and evidence of hemolysis detected 1 month after completing cladribine therapy for WM, with warm antibody AIHA developing 4 months later, are described. CONCLUSIONS: Cladribine, like fludarabine, is possibly able to produce this complication during or early after therapy. Because the use of purine analogs is becoming increasingly common, it is important to have an awareness of the complications that can arise during and after treatment. Further observations of warm AIHA during cladribine therapy are needed to establish it as a distinct complication.

Autoimmune haemolytic anaemia complicating haematopoietic cell transplantation in paediatric patients: high incidence and significant mortality in unrelated donor transplants for non-malignant diseases.

Haemolytic anaemia is a recognized complication of haematopoietic cell transplantation (HCT) and can result from alloimmune- or autoimmune-derived antibodies. Unlike alloimmune haemolytic anaemia, autoimmune haemolytic anaemia (AIHA) is poorly understood, particularly in the paediatric population where only case reports have been published. Between January 1995 and July 2001, 439 consecutive allogeneic HCT were performed in paediatric patients at the University of Minnesota, 31% (n = 136) from related donors (RD) and 69% (n = 303) from unrelated donors (URD). Nineteen cases of AIHA were identified with documented significant haemolysis and a positive direct antiglobulin test. All cases of AIHA occurred in URD transplants, yielding a cumulative incidence of AIHA post-transplant of 6% at 1 year. Patients transplanted for non-malignant disease, particularly metabolic diseases, had a higher incidence of AIHA post-HCT when compared with patients transplanted for malignancies (RR 4.2 95% CI 1.2-15.4, P = 0.01). Mortality was high in our series of 19 patients with 10 (53%) dying following the onset of AIHA, three as a direct consequence of haemolysis. Fifty per cent of deaths occurred from infection while on immunosuppressive therapy to treat haemolysis. Alternative treatment strategies were employed, with the majority of patients demonstrating disease refractory to traditional steroid therapy.

Histologic evaluation of demineralized freeze-dried bone allografts in barrier membrane covered periodontal fenestration wounds and ectopic sites in dogs.

BACKGROUND/AIM: The aim of this study was to investigate healing responses to demineralized freeze-dried bone powder allografts in standardized periodontal fenestration defects, compared with subcutaneous wounds in a dog model. METHODS: Circular periodontal fenestration defects were created buccally at all four canines in 14 mongrel dogs. Each site received one of the following underneath a barrier membrane: (a) ethylene oxide (EO)-sterilized demineralized freeze-dried bone allografts (DFDBA), (b) heat-treated DFDBA, (c) non-sterilized DFDBA and (d) ungrafted control. Twelve of the 14 dogs had three subcutaneous chest wall pouches created and one of the three DFDBA materials placed in each. The animals were necropsied at 4 weeks. Histologic sections were prepared through the center of the fenestration sites in an apico-coronal direction. Quantitative analysis using computer-assisted imaging technique was performed. Subcutaneous implants were evaluated histologically and quantified for associated inflammatory cell infiltrate. RESULTS: Fenestration defects healed by partial osseous fill and cementum regeneration with formation of a periodontal ligament. The graft particles generally appeared isolated from the site of osteogenesis and covered by cementum-like substance. Graft particles incorporated into newly formed bone at a distance from the root surface was the exception. No statistically significant differences in new bone formation were observed between treatment groups within animals, but significant inter-animal variation was found (p<0.01). Quantities of retained graft particles were limited, and without cellular resorption. A bone augmentation effect was associated with the barrier in the majority of sites. No bone formation was evident at the subcutaneous sites where graft particles displayed distinctly modified surface zones and multinucleated giant cell resorption. Significantly more inflammatory infiltrate was associated with EO-sterilized grafts compared with heat-treated grafts (p=0.05). CONCLUSION: Implantation of DFDBA neither enhanced osseous healing in periodontal fenestration defects, nor resulted in ectopic bone induction. DFDBA particles implanted in either periodontal fenestration or subcutaneous wounds evoked distinctly different healing responses.

Hypotensive reaction during staphylococcal protein A column therapy in a patient with anomalous degradation of bradykinin and Des-Arg9-bradykinin after contact activation.

BACKGROUND: Hypotensive reactions have occurred in patients taking angiotensin converting enzyme (ACE) inhibitors after infusion of blood previously in contact with negatively charged surfaces capable of generating kinins, which accumulate when ACE, a kininase, is inhibited. A patient with anomalous bradykinin (BK) metabolism who experienced hypotension during extracorporeal staphylococcal protein A (SPA) therapy while on an ACE inhibitor was studied. CASE REPORT: A patient with mitomycin-associated hemolytic-uremic syndrome received SPA treatments after her ACE inhibitor, lisinopril, was held. Lisinopril was restarted before her 18th SPA treatment, and immediately after return of treated plasma she developed facial redness and hypotension, which resolved after the return stopped and recurred when restarted. To study formation and degradation of kinins, exposed her plasma to glass beads. We found a normal kinin formation rate but an abnormal degradation and accumulation of Des-Arg9-BK. The kinin degradation enzymes ACE, aminopeptidase P (APP), and carboxypeptidase N (CPN) were measured while on an ACE inhibitor, showing absence of ACE activity, low APP, but normal CPN. CONCLUSION: This patient's vasodilation and hypotension during SPA therapy was associated with a pre- existing anomaly of BK metabolism. Her ACE inhibitor shifted degradation toward Des-Arg9-BK formation, and her low APP was associated with a prolonged t50 and accumulation of the vasoactive Des-Arg9-BK.

HLA alloimmunization in patients requiring ventricular assist device support.

BACKGROUND: Ventricular assist devices (VADs) are often necessary to maintain circulation in patients with heart failure prior to cardiac transplantation. However, the use of such devices has been reported to be associated with a high incidence of development of human leukocyte antigen (HLA) antibodies, due perhaps, according to some investigators, to immune-activating properties of the VAD itself. We looked at HLA antibody formation in our patients during VAD support to determine the rate and potential causes of antibody formation. METHODS: Between 1995 and 2000, 54 patients were placed on a VAD at our institution. We reviewed clinical and blood transfusion history and HLA antibody testing of the 29 patients without HLA antibodies prior to implantation. HLA antibody testing was performed by an anti-globulin-augmented cytotoxicity method or by a commercial enzyme-linked immunoassay (ELISA) kit. RESULTS: Eight of 29 patients (28%) developed HLA antibodies. Patients who developed HLA antibodies after VAD implantation received significantly more total peri- and post-operative transfusions than did those who remained negative (99 transfusions vs 34 transfusions, p = 0.0014). Within this small study group, gender, age, etiology of heart failure, previous cardiac surgery and duration of VAD support showed no statistically significant correlation with formation of HLA antibodies. CONCLUSIONS: Our data suggest that HLA alloimmunization during VAD support may be due to extensive blood transfusion. The rate of HLA alloimmunization does not appear to be greater than that reported in other populations of multi-transfused patients. Leukoreduction of cellular components, as well as plasma, or other initiatives is needed to reduce the rate of alloimmunization and, potentially, the wait to transplantation.

Transfusion-related acute lung injury during plasma exchange: Suspecting the unsuspected.

Transfusion-related acute lung injury (TRALI) has been implicated with use of almost all types of blood products that contain variable amounts of plasma. Even though the reported incidence of TRALI is rare, its overall occurrence is thought to be more common, as less severe cases remain unreported. More TRALI cases are unrecognized and misdiagnosed due to lack of suspicion and absence of appropriate investigation. There are exceedingly rare reports of TRALI during plasma exchange despite the fact that liters of plasma may be used for replacement during a single procedure. We describe a mild case of TRALI during plasma exchange for thrombotic thrombocytopenic purpura in a 56-year-old woman, status post autologous hematopoietic stem cell transplant for non-Hodgkin's lymphoma. She developed severe rigors, peripheral cyanosis, hypoxia, and a transient diffuse pulmonary infiltrate. Of the 10 U of plasma used, one was from a multiparous female donor with HLA antibodies reactive with patient's granulocytes in immunofluorescence and agglutination assays. This case emphasizes the fact that the physicians and apheresis staff should consider TRALI in the differential diagnosis for patients developing respiratory distress during or soon after the procedure. Diagnosing TRALI has implications not only for the plasma exchange recipient, but also for the management of donors found to have leukocyte antibodies.