Hemolytic disease of the fetus and newborn mediated by anti-Dia in a U.S. hospital.

Dia is one of the most clinically significant low-prevalence antigens in the Diego blood group system, since antibodies to Dia have, albeit rarely, been implicated in hemolytic transfusion reactions and hemolytic disease of the fetus and newborn (HDFN). Given the geographical association, most anti-Dia HDFN cases have been reported in Japan, China, and Poland. We describe a case of HDFN in a neonate born to a 36-year-old G4P2012 woman of self-identified Hispanic ethnicity and of South American descent with multiple negative antibody detection tests in a U.S. hospital. Upon delivery, a cord blood direct antiglobulin test was positive (3+ reactivity), and neonatal bilirubin levels were moderately elevated, but phototherapy and transfusion were not required. This case highlights a rare, unexpected cause of HDFN in the United States secondary to anti-Dia, given the near-universal absence of this antigen and antibody in most U.S. patient populations. The case also demonstrates the need for awareness of antibodies to antigens that are considered "low-prevalence" in most populations but that might be encountered more frequently in specific racial or ethnic groups and may require more extensive testing.

Procuring rare (しい)* Japanese red blood cell units for a bleeding patient with anti-K11 requiring a life-saving procedure.

Alloimmunization to K11 is an extremely rare event. However, given the potential clinical significance of K11 alloantibodies, allocating antigen-negative red blood cell (RBC) units is a clinical necessity. In brief, we report a 39-year-old woman with multiple comorbidities including a right lower-extremity, below-the-knee amputation, who developed aggressive osteomyelitis associated with continuous bloody oozing, leading to anemia. To address these issues, the patient required extremity amputation. Surgery required addressing the concomitant critical anemia (hemoglobin <5 g/dL). However, with anti-K11 (in addition to anti-Jka) identified, no compatible units were immediately on hand and transfusing crossmatch-incompatible, antigen-positive units was deemed too high a risk. After a national search by the American Rare Donor Program (ARDP) was unsuccessful, the ARDP identified 2 irradiated, group O, K0 (Kellnull), Jk(a-) RBC units in Japan that were predicted to be crossmatch-compatible with the patient's plasma. The units were successfully procured and infused, without evidence of adverse reactions, and the patient was able to safely undergo amputation to save her life. This case report reviews the complexities of anti-K11 detection and confirmation, as well as the processes by which K11- RBC units may be procured, which could help others in the global transfusion community should they be faced with similar challenging cases.

Development of anti-Jk3 associated with silenced Kidd antigen expression and a novel single nucleotide variant of the JK gene.

Anti-Jk3 is a rare alloantibody to a high-prevalence antigen primarily seen in individuals of Polynesian descent and is associated with a handful of well-established variants of the SLC14A1 gene. We report a case of the Jknull phenotype, associated with formation of anti-Jk3, in a patient of non-Polynesian descent. This patient, a 51-year-old woman self-described as of Jamaican and Scottish ancestry, presented to our hospital for oncologic care. The patient's blood sample typed as blood group A, D+. All screening and panel reagent red blood cells showed reactivity, ranging from 2 to 4+; autocontrol and direct antiglobulin test were both negative. Antigen phenotyping revealed Jk(a-b-), leading to suspicion for anti-Jk3, which was subsequently confirmed by our immunohematology reference laboratory. Given her reported familial background, testing of the SLC14A1 gene was performed, revealing that the patient was heterozygous for the single nucleotide variant (SNV) at c.838G>A in exon 8 and therefore carries both JK*01 and JK*02 alleles that encode Jka and Jkb, respectively. However, the patient was found to be heterozygous for several additional SNVs: c.28G>A in exon 3; c.191G>A, c.226G>A, and c.303G>A in exon 4; and c.757T>C in exon 7. The patient's Jk(b-) phenotype can be explained by coinheritance of c.838A with c.191G>A, which defines null allele JK*02N.09. Coinheritance of SNVs c.28G>A and c.838G with rare SNV c.757C that is predicted to cause a non-conservative amino acid change (p.S253P) likely accounts for the complete serologic absence of Jka and the ability to form anti-Jk3 in this case. This finding would represent a new JK*01 null allele. This evaluation illustrates the importance of genetic analysis in identifying the factors preventing a high-prevalence antigen from being expressed, particularly when discovered outside of an expected racial or ethnic group.Anti-Jk3 is a rare alloantibody to a high-prevalence antigen primarily seen in individuals of Polynesian descent and is associated with a handful of well-established variants of the SLC14A1 gene. We report a case of the Jknull phenotype, associated with formation of anti-Jk3, in a patient of non-Polynesian descent. This patient, a 51-year-old woman self-described as of Jamaican and Scottish ancestry, presented to our hospital for oncologic care. The patient's blood sample typed as blood group A, D+. All screening and panel reagent red blood cells showed reactivity, ranging from 2 to 4+; autocontrol and direct antiglobulin test were both negative. Antigen phenotyping revealed Jk(a­b­), leading to suspicion for anti-Jk3, which was subsequently confirmed by our immunohematology reference laboratory. Given her reported familial background, testing of the SLC14A1 gene was performed, revealing that the patient was heterozygous for the single nucleotide variant (SNV) at c.838G>A in exon 8 and therefore carries both JK*01 and JK*02 alleles that encode Jka and Jkb, respectively. However, the patient was found to be heterozygous for several additional SNVs: c.28G>A in exon 3; c.191G>A, c.226G>A, and c.303G>A in exon 4; and c.757T>C in exon 7. The patient's Jk(b­) phenotype can be explained by coinheritance of c.838A with c.191G>A, which defines null allele JK*02N.09. Coinheritance of SNVs c.28G>A and c.838G with rare SNV c.757C that is predicted to cause a non-conservative amino acid change (p.S253P) likely accounts for the complete serologic absence of Jka and the ability to form anti-Jk3 in this case. This finding would represent a new JK*01 null allele. This evaluation illustrates the importance of genetic analysis in identifying the factors preventing a high-prevalence antigen from being expressed, particularly when discovered outside of an expected racial or ethnic group.

The impact of vaccination on RBC alloimmunization in a murine model.

Emerging data in animal models and humans suggest that pathogen-associated and damage-associated molecular patterns variably impact RBC alloantibody formation. In this study, we tested the hypothesis that vaccinations may enhance immune responses to transfused RBCs. The Pneumovax23 vaccine decreased the magnitude of anti-KEL alloimmunization in a murine model, whereas the hepB vaccine did not impact the response; RBC transfusion did not alter immune responses to either vaccine. These data highlight the complexities of the intersection of innate and adaptive immunity and suggest that future studies investigating the pathways through which inflammation impacts alloimmunization are warranted.

A novel network analysis tool to identify relationships between disease states and risks for red blood cell alloimmunization.

We hypothesized that diagnoses may be associated with alloantibody 'responder' status and examined associations between disease states and alloimmunization. Patients with ≥1 alloantibody and non-alloimmunized controls were analysed. Pearson's coefficients were calculated to determine associations between alloimmunization and diseases; significant correlations were selected to construct a network. Inflammatory disorders and diseases requiring chronic transfusion support were associated with responder status. Mitigation steps may be considered in patients with these disorders.

Modelling gas exchange during platelet storage without agitation.

The aim of this study was to create a model of oxygen distribution within platelet storage bags to evaluate implications of reduced agitation approaches. Based on our model, platelet concentration and surface area most affect internal partial pressure of oxygen, while temperature modifications have least effect, indicating primary potential approaches for optimization of platelet storage with reduced or absent agitation.

Clinically significant anti-KEL RBC alloantibodies are transferred by breast milk in a murine model.

BACKGROUND AND OBJECTIVES: Fetuses affected by maternal RBC alloantibodies may have prolonged anaemia after birth, leading one to question whether maternal alloantibody transfer may occur outside the placenta. In response to a recent publication describing breast milk transfer of clinically significant amounts of maternal antiplatelet IgA antibodies from mother to nursing infant, we hypothesized that maternal RBC alloantibodies may also be capable of being transferred in breast milk. MATERIALS AND METHODS: The presence and clinical significance of breast milk alloantibody transfer were tested through a series of pregnancy, fostering and transfusion experiments, using a murine model in which transgenic RBCs express the human KEL glycoprotein. RESULTS: Maternal anti-KEL immunoglobulins, induced through transfusion or pregnancy, were detected in the aqueous phase of breast milk. Further, efficient transfer of maternal anti-KEL IgG and IgA to nursing pups was observed in fostering experiments. The breast milk-acquired alloantibodies were clinically significant in wild-type pups in a transfusion setting, binding to 'incompatible' KEL RBCs and leading to premature clearance from the circulation. Although breast milk-acquired alloantibodies also bound to the RBCs of transgenic KEL-positive fostered pups, no anaemia resulted. CONCLUSIONS: Taking these murine data in combination with recently published human data of maternal antiplatelet IgA antibodies in breast milk leading to sequelae in some infants, it is theoretically possible that maternal anti-RBC IgA alloantibodies may also be transferred in human breast milk and may lead to sequelae in some infants under some circumstances.

Measuring the influence of blood component infusion rate on recipient vital signs.

BACKGROUND AND OBJECTIVES: One of the challenges surrounding blood component administration is the determination of an appropriate rate of infusion. There are very few evidence-based guidelines available to guide healthcare providers looking for a 'standard' infusion rate for red blood cells (RBCs), plasma or platelets (PLTs). Our objective was to determine the extent to which blood component infusion rates were associated with changes in transfusion recipient vital signs. MATERIALS AND METHODS: We retrospectively examined records of 3496 component infusions (RBCs, n = 2359; PLTs, n = 478; plasma, n = 659) over a 1-year period at a 362-bed multispecialty hospital. The following data were collected for each transfusion: blood product volume and infusion time, recipient pre- and post-transfusion temperature, blood pressure and pulse rate, and hospital ward where transfusion occurred. RESULTS: Plasma (median 10.4 ml/min) was infused faster than PLTs (median 7.2 ml/min, P < 0.0001) or RBCs (median 2.3 ml/min, P < 0.0001). For all blood components, infusion rates varied based on the hospital unit performing the infusion. No association was found between relatively fast RBC, plasma or PLT infusion rates (>20 ml/min) and clinically significant reported changes in vital signs. CONCLUSIONS: There does not appear to be a strong correlation between infusion rate and significant changes in recipient temperature, blood pressure or pulse rate. Based on these data, a reasonable rate for routine transfusion is 2-3 ml/min for RBCs and 7-10 ml/min for plasma and PLTs. Faster infusion rates (>20 ml/min) likely can be applied with close patient monitoring if there is a more urgent need for transfusion.

Allergic transfusion reactions to platelets are more commonly associated with prepooled than apheresis components.

BACKGROUND AND OBJECTIVES: Transfusions of pooled or apheresis platelets are seen as equally effective in increasing platelet counts with similar rates of transfusion reactions. It has been suggested that allergic transfusion reactions (ATRs) to platelets are associated with recipient and donor factors. In this study, we assessed differences in ATR rates among individuals who received platelet components at two academic medical centres. MATERIALS AND METHODS: A total of 45 189 leukoreduced platelet products were transfused during the study period of which 31 748 were apheresis units and 13 441 were pooled units. RESULTS: Transfusion reactions were reported in 0·6% (277 of 45 189) of platelet transfusions. The reaction rate was significantly higher in pooled (102 of 13 441) than in apheresis (175 of 31 748) (0·76% vs. 0·55%, respectively, P = 0·01) components. However, an analysis of reactions by categories indicated that only the ATR rate was significantly higher in pooled (55 of 13 441) products as compared with apheresis (76 of 31 748) (0·41% vs. 0·24%, respectively, P = 0·0029) platelets. Moreover, there was no difference in the rate of ABO mismatch between pooled and apheresis products. CONCLUSION: Our data indicate that pooled platelet components are associated with higher ATR rates than apheresis platelets, suggesting that these components may not be completely equivalent from the standpoint of adverse events. Further investigation is needed to address whether differences in ATRs are related to the pooling process or the extent of donor antigen exposure.

Delayed intravascular haemolysis following multiple asymptomatic ABO-incompatible red blood cell transfusions in a patient with hepatic failure.

ABO-incompatible red blood cell (RBC) transfusions have rarely been associated with delayed haemolysis. However, we report the case of a 75-year-old man (blood type O) with hepatic disease, who received 5 units of incompatible type B RBCs over 8 days. The patient did not develop symptomatic or biochemical evidence of haemolysis until 7-8 days after the first incompatible RBC unit. The patient had a low anti-B antibody titre (1 : 64) prior to the first transfusion. The onset of haemolysis was temporally associated with an increase in anti-B and the infusion of fresh-frozen plasma. In conclusion, a patient with hepatic failure experienced a delayed haemolytic transfusion reaction after receiving multiple ABO-incompatible RBC transfusions that were initially well-tolerated. We speculate that the delayed haemolysis may have resulted from an anamnestic antibody response to the initial incompatible transfusion, or possibly as a result of the transfusion of fresh-frozen plasma, which might have repleted low complement levels.