How anti-c in a D- patient prompted lifesaving work between a transfusion service and a blood center reference laboratory.

This case report showcases an extraordinary collaboration to support the transfusion needs of a patient with a rare phenotype and long-standing anemia due to gastrointestinal bleeding. This report describes the Immunohematology Reference Laboratory testing and logistics of rare blood provision over an 11-year period, as well as a summary of the hematologic, gastroenterologic, and surgical interventions. This case illustrates how a strong collaboration among the clinical team, laboratory, blood center, and the rare donor community facilitated successful management of this patient's anemia until the patient could receive life-changing treatment.

Meeting the transfusion needs of a patient with anti-Ena requires an international effort.

This extraordinary case showcases the identification of a rare anti-Ena specificity that was assisted by DNA-based red blood cell antigen typing and collaboration between the hospital blood bank in the United States, the home blood center in Qatar, the blood center Immunohematology Reference Laboratory, as well as the American Rare Donor Program (ARDP) and the International Society for Blood Transfusion (ISBT) International Rare Donor Panel. Ena is a high-prevalence antigen, and blood samples from over 200 individuals of the extended family in Qatar were crossmatched against the patient's plasma with one compatible En(a-) individual identified. The ISBT International Rare Donor Panel identified an additional donor in Canada, resulting in a total of two En(a-) individuals available to donate blood for the patient.

An international effort and use of social media to save a young girl.

BACKGROUND AND OBJECTIVES: A 2-year-old female with neuroblastoma needed In(b-), E- red blood cells (RBCs). No units were available at the blood centre (BC) nor in the rare donor programme member's inventories. BC's Immunohematology Reference Laboratory (IRL) and its marketing department concentrated on recruiting and testing those donors more likely to be antigen negative based on ethnicity. MATERIALS AND METHODS: The BC's communication plan utilized social and traditional media to assist in the search for In(b-) blood. Media strategies directed donors in the United States (US) and Canada to go to their nearest BC for collection, tagging and testing of units. Two segments from each donation were shipped overnight to the BC's IRL (associated with the patient) for testing. Diluted anti-Inb sera was tested by microtechniques to conserve resources. Additionally, the American Rare Donor Program (ARDP) facilitated the international searches and acted as a liaison to the Food and Drug Administration (FDA). RESULTS: More than 25 000 people responded to the appeal. Seventy-seven BCs submitted segments from 4197 units. Two donors were In(b-) but E+ and thus not compatible with the patient but were submitted to ARDP for future needs. The prevalence of In(b-) units identified in the search was 0·048%. In total, five known In(b-) donors, two from the US and three from international sources, provided units for this patient. CONCLUSION: Social media sparked a viral response to the rare blood need. While a match was not found among the units tested, domestic and international searches were able to meet the patient's blood needs.

A review of in vitro methods to predict the clinical significance of red blood cell alloantibodies.

CONCLUSIONS: This review was derived from a presentation made on September 2, 2016, for the first Academy Day presented by the Working Party on Immunohematology at the International Society of Blood Transfusion (ISBT) Congress in Dubai. The focus of this review is on the clinical significance of alloimmunization in transfusion-specifically, the parameters that contribute to a clinically significant alloantibody. The areas of focus were as follows: Introduction, Technical Aspects, and Indications and Limitations. Each section contains a brief review of selected literature and experiential knowledge. Case reports are needed to collect data on current outcomes of incompatible transfusion. The ISBT Working Party on Rare Donors has developed a form to capture case-specific information.

Strategies to identify candidates for D variant genotyping.

BACKGROUND: RhD variants have altered D epitopes and/or decreased antigen copies per red cell. Individuals carrying these variants may test antigen negative, weakly positive, or positive by serology, and may or may not be at risk of alloimmunisation after exposure. There have been recommendations to perform RHD genotyping of patients, pregnant women and females of childbearing potential with serological weak D phenotype, to guide prophylactic use of Rh immune globulin (RhIG), and better conserve D-negative blood products. The purpose of this study was to evaluate the performance of a set of empirical criteria to identify such patients. MATERIALS AND METHODS: A two-method strategy of gel testing (GT) and tube testing (TT) was used for Rh typing of patients with no historical blood type in the present institution. A monoclonal-polyclonal blend anti-D was used for Rh typing by TT at immediate spin. Three empirical criteria were used to identify candidates for genotyping: C1: discrepancy between the two test methods and a GT reaction strength >2+ stronger than TT; C2: weak serological reaction, defined as reaction strength ≤2+ regardless of testing method if both GT and TT were performed or reaction strength ≤2+ if only GT was performed, or reaction strength ≤1+ if only TT was performed; C3: presence of anti-D in D-positive patients with no history of RhIG use in the preceding 3 months and in whom alloanti-D is suspected. RESULTS: Overall, 50 patients, ranging from newly born to 93 years old, were identified. Genomic testing confirmed D variants in 49/50 cases with a positive predictive value of 98%. DISCUSSION: This two-method strategy is a powerful screening tool for identifying candidates for RHD genotyping. This strategy meets the current requirements of two blood type determinations/two specimens in pre-transfusion testing while simultaneously identifying candidates for RHD genotyping with a minimal increase in work load and cost.

Recurrent Donath-Landsteiner hemolytic anemia: a pediatric case report.

BACKGROUND: Paroxysmal cold hemoglobinuria (PCH) is a form of autoimmune hemolytic anemia caused by the Donath-Landsteiner antibody (D-L antibody). In children, this is typically a transient immune-mediated hemolysis that follows a viral illness and does not recur. Recurrent acute or chronic PCH due to D-L antibody is very rare. CASE REPORT: We have reported a unique case of recurrent PCH in a 5-year-old boy with two acute episodes of hemolysis separated by 21 months of hematologic remission. Each episode was severe requiring red blood cell transfusions, intravenous methylprednisolone, and intravenous immunoglobulin during the second episode. Testing identified recurrence of the D-L antibody with the classic anti-P biphasic hemolysis. CONCLUSION: This demonstrates that PCH can be a recurrent disease in the pediatric population (in the absence of syphilis) with the classical D-L antibody.

Hyperhemolysis syndrome in a patient without a hemoglobinopathy, unresponsive to treatment with eculizumab.

BACKGROUND: Hyperhemolysis is a serious transfusion reaction, most often described in patients with hemoglobinopathies. Hyperhemolysis is characterized by the destruction of host red blood cells (RBCs), in addition to donor RBCs, via an unknown mechanism. STUDY DESIGN AND METHODS: We present the case of a 58-year-old woman with treated human immunodeficiency virus and a normal hemoglobin (Hb) electrophoresis who developed hyperhemolysis in the setting of a delayed hemolytic transfusion reaction (DHTR). RESULTS: The patient was ABO group B and had a previously identified anti-Fy(b) alloantibody. After transfusion of Fy(b)--RBCs, she developed a DHTR and was found to have anti-E, anti-C(w), anti-s, and an additional antibody to an unrecognized high-frequency RBC alloantigen. Subsequent transfusion of ABO-compatible RBCs that were negative for Fy(b), E, C(w), and s antigens resulted in immediate intravascular hemolysis. In the absence of bleeding, her hematocrit (Hct) decreased to 10.2%. An extensive serologic evaluation failed to identify the specificity of the high-frequency antibody. Severe hemolytic reactions also occurred despite pretransfusion conditioning with eculizumab. The Hct and clinical symptoms slowly improved after the cessation of transfusions and treatment with erythropoietin and steroids. This case demonstrates several noteworthy features including hyperhemolysis in a patient without a Hb disorder, the development of an antibody to an unknown RBC antigen, and the failure of eculizumab to prevent intravascular hemolysis after transfusion. CONCLUSION: Hyperhemolysis is not restricted to patients with hemoglobinopathies. Whether eculizumab offers any benefit in the hyperhemolysis syndrome or in the prevention of intravascular hemolysis due to RBC alloantibodies remains uncertain.

Immune hemolytic anemia with drug-induced antibodies to carboplatin and vincristine in a pediatric patient with an optic pathway glioma.

BACKGROUND: Drug-induced immune hemolytic anemia (DIIHA) is a rare, but important condition requiring specialized laboratory testing for diagnosis. We report a case of DIIHA with antibodies against carboplatin and vincristine (VCR) in a child with an optic pathway glioma. Platinum-based drugs are established to cause DIIHA; to our knowledge, this is the first report implicating VCR. STUDY DESIGN AND METHODS: A 35-month-old girl with an optic pathway glioma developed hemolytic anemia while receiving carboplatin and VCR. Specialized blood bank testing was performed to determine the presence of drug-dependent antibodies and thus DIIHA. RESULTS: Initial direct antiglobulin test (DAT) was negative. A repeat DAT 3 days later was positive, 3+ with polyspecific-antiglobulin sera, weak+ with anti-immunoglobulin (Ig)G, and 2+ with anti-C3d. An eluate from the DAT-positive red blood cells (RBCs) was nonreactive. The patient's serum reacted without specificity to all RBC tested using papain-IgG-antiglobulin test (AGT) and polyethylene glycol-IgG-AGT. No alloantibodies to common RBC antigens were detected. When the serum was evaluated for the presence of drug-specific antibody, reactivity was shown with VCR and carboplatin using the drug addition solution method, but only with carboplatin using the drug-coating method. CONCLUSION: The patient developed hemolytic anemia during chemotherapy. Initial detection of a panagglutinin suggested a warm-type autoimmune process. However, since DIIHA could not be excluded, chemotherapy was discontinued and further work-up was initiated. The findings confirmed the presence of antibodies to carboplatin and VCR. This case highlights the importance for clinicians to maintain a high index of suspicion for DIIHA in patients with unexplained hemolysis and the importance of specialized serologic testing.

End of life care for people with a learning disability.

AIM: To explore the experiences of learning disability and district nurses caring for people with a learning disability at the end of their lives. METHOD: A small-scale semi-structured qualitative study involving interviews was carried out to explore the experiences of healthcare professionals from two specialist healthcare settings. FINDINGS: Healthcare professionals felt that formal guidelines and support were needed in this complex area. The study also revealed that successful provision of palliative care for people with a learning disability requires a person-centred approach. CONCLUSION: Modifications to existing palliative care services, involving joint working, improved co-ordination and reasonable adjustments, is recommended. This aims to address any inequalities in care provision for people with a learning disability who are at the end of their lives.

How to find, recruit and maintain rare blood donors.

PURPOSE OF REVIEW: Since the early 1960s, it was recognized that patients with very complex serology may be limited in the availability of rare blood for transfusion. Over the years, there have been publications about the quest to meet those needs. Although the world's literature on how to find, recruit and maintain rare blood donors is not overwhelming, there are quite a few pearls. This review will seek out those pearls published in 2007-2009 and provides some insight from a perspective of having a responsibility for a nation of patients requiring rare blood for over 15 years. RECENT FINDINGS: Most pertinent publications have focused on a particular country and the data gathered by a particular regional area or the national rare donor program. It is clear that the definition of 'rare' varies from country to country. A blood type rare in one country may not be considered rare in another. A few of the publications that will be reviewed are specific to donor recruitment or specific details regarding a particular blood type. Recently, with the advent of semi-automated equipment to assist in DNA analysis, there has been a volley of articles on the use of this equipment.Without effective rare donor programs, there is a risk that transfusion needs may not be met. Hemovigilance concentrates on adverse events related to blood transfusions, and the event that happens when rare blood is not available may be that the patient dies without the transfusion they need. SUMMARY: The need for rare blood has been recognized for nearly 50 years, and there are some very effective programs across the world, but not all the areas of the world are equally supplied. The International Society of Blood Transfusion Working Party for Rare Donors is a vital link in the worldwide goal of providing rare blood to the patients who need it.

A DOB allele encoding an amino acid substitution (Phe62Ser) resulting in a Dombrock null phenotype.

BACKGROUND: The gene polymorphisms responsible for the antigens Doa, Dob, Hy, and Joa in the Dombrock (Do) blood group system have been identified. Four different mutations have been reported to cause the Dombrock null [Gy(a-)] phenotype. These include splice mutations, an eight-nucleotide deletion, and insertion of a stop codon. Here a Dombrock null caused by a single-amino-acid substitution in the full-length protein is reported. STUDY DESIGN AND METHODS: DOA and DOB were determined by polymerase chain reaction-restriction fragment length polymorphism, and DO (ART4) exons and flanking regions were sequenced from genomic DNA. Expression analysis was performed by transfection of wild-type and mutant cDNAs into HEK 293T cells followed by flow cytometry and immunoblotting. Homology modeling was used to map the mutation on the protein structure. RESULTS: The patient's sample carried nt 793G/G, indicating a DOB/DOB background. Exon 2 sequencing showed the sample carried a new mutation, nt 185T>C, causing a Phe62Ser substitution. This variant Do was not expressed on the surface of transfected HEK 293T cells. The mutation maps to a highly conserved FDDQY motif located between the beta1-strand and alpha1-helix near the COOH terminus in the native molecule. CONCLUSIONS: The Dombrock null reported here is due to a single Phe62Ser mutation. The expression data confirmed that 62Ser is responsible for lack of cell surface Do, and protein modeling suggests the mutation disrupts important aromatic side chain interactions between Phe62 and His160. Production of an antibody to a high prevalence Dombrock antigen (anti-Gya) in this patient was consistent with complete absence of Dombrock/ART4 protein.