RH genotypes and red cell alloimmunization rates in chronically transfused patients with sickle cell disease: A multisite study in the USA.

BACKGROUND: Red cell alloimmunization remains a challenge for individuals with sickle cell disease (SCD) and contributes to increased risk of hemolytic transfusion reactions and associated comorbidities. Despite prophylactic serological matching for ABO, Rh, and K, red cell alloimmunization persists, in part, due to a high frequency of variant RH alleles in patients with SCD and Black blood donors. STUDY DESIGN AND METHODS: We compared RH genotypes and rates of alloimmunization in 342 pediatric and young adult patients with SCD on chronic transfusion therapy exposed to >90,000 red cell units at five sites across the USA. Genotyping was performed with RHD and RHCE BeadChip arrays and targeted assays. RESULTS: Prevalence of overall and Rh-specific alloimmunization varied among institutions, ranging from 5% to 41% (p = .0035) and 5%-33% (p = .0002), respectively. RH genotyping demonstrated that 33% RHD and 57% RHCE alleles were variant in this cohort. Patients with RHCE alleles encoding partial e antigens had higher rates of anti-e identified than those encoding at least one conventional e antigen (p = .0007). There was no difference in anti-D, anti-C, or anti-E formation among patients with predicted partial or altered antigen expression compared to those with conventional antigens, suggesting that variant Rh on donor cells may also stimulate alloimmunization to these antigens. DISCUSSION: These results highlight variability in alloimmunization rates and suggest that a molecular approach to Rh antigen matching may be necessary for optimal prevention of alloimmunization given the high prevalence of variant RH alleles among both patients and Black donors.

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.

Variant RHD alleles and Rh immunization in patients with sickle cell disease.

RH diversity among patients and donors contributes to Rh immunization despite serologic Rh-matched red cell transfusions. Anti-D can occur in D+ patients with RHD variants that encode partial D antigens. Anti-D has also been reported in patients with conventional RHD transfused primarily with units from Black donors who frequently have variant RHD. We report 48 anti-D in 690 D+ transfused individuals with sickle cell disease, categorized here as expressing conventional D, partial D or D antigen encoded by RHD*DAU0. Anti-D formed in a greater proportion of individuals with partial D, occurred after fewer D+ unit exposures, and remained detectable for longer than for those in the other categories. Among all anti-D, 13 had clinical or laboratory evidence of poor transfused red cell survival. Most individuals with anti-D were chronically transfused, including 32 with conventional RHD who required an average of 62 D- units/year following anti-D. Our findings suggest that patients with partial D may benefit from prophylactic D- or RH genotype-matched transfusions to prevent anti-D. Future studies should investigate whether RH genotype-matched transfusions can improve use of valuable donations from Black donors, reduce D immunization and minimize transfusion of D- units to D+ individuals with conventional RHD or DAU0 alleles.

Audit of blood product utilization in the care of injured children.

BACKGROUND: Blood product utilization in injured children is poorly characterized; the decision to prepare products or transfuse patients can be difficult due to a lack of reliable evidence of transfusion needs across pediatric age-groups and injury types. We conducted an audit of transfusion practices in pediatric trauma based on age, injuries, and mechanism of injury. METHODS: We reviewed and cross-referenced blood product transfusion practice data from the trauma registry and the anesthesia transfusion record database at a level 1 pediatric trauma center over a 10-year period. Demographic data, injury severity scores, and survival statistics were obtained from the trauma registry. Transfusion rates are reported separately for hospital admission and for intraoperative transfusions for procedures performed during the first two hospital days. Descriptive statistical analysis was used to compare specific groups based on age, injury type, and mechanism of injury. RESULTS: We report 14 569 trauma admissions of 14 606 patients. The transfusion rate during the admission was 1.56% (227/14 569). 4591 (30.9%) admissions had surgical interventions in first two days of hospitalization with an intraoperative transfusion rate of 2.98%. Patients younger than one year had the highest transfusion rate during admission (2.8%), and the highest transfusion rate during surgical procedures performed in the first two days of the admission (18.87%). Admissions due to vascular injuries had the highest transfusion rates in infancy followed by hollow visceral injuries in adolescents (71.4% and 25%, respectively). Vascular injuries in most age-groups also had high transfusion rates ranging from 11% in 5- to 9-year age-group to 71% in infants. Mechanisms with the highest transfusion rates were firearm wounds in patients older than one year and vehicular accidents for patients younger than one year. CONCLUSIONS: The overall blood product needs in the pediatric trauma population are low (1.56%). Selected populations requiring higher rates of need include infants younger than one year, and children with thoracic and vascular injuries. Understanding transfusion patterns is important to optimize resource allocation.

RH genotype matching for transfusion support in sickle cell disease.

Rh alloimmunization remains a challenge for patients with sickle cell disease (SCD) despite transfusion of serologic Rh C, E, and K antigen-matched red cells. Inheritance of altered RH alleles contributes to the prevalence of Rh antibodies after blood transfusion in patients with SCD and explains approximately one-third of cases. The remainder seem to be stimulated by altered Rh proteins on African American donor red cells. Matching patients with donors on the basis of RH genotype may mitigate Rh alloimmunization, but the feasibility and resources required are not known. We compared RH allele frequencies between patients with SCD (n = 857) and African American donors (n = 587) and showed that RH allele frequencies are similar. Overall, 29% of RHD and 53% of RHCE alleles are altered in patients and African American donors. We modeled RH genotype matching compared with serologic Rh D, C, and E, along with K antigen matching, and found that approximately twice the number of African American donors would be required for RH genotype vs Rh serologic matching at our institution. We demonstrated that African American donor recruitment is necessary to maintain an adequate supply of C-, E-, and K-negative donor units to avoid depleting the Rh-negative (RhD-) blood supply. Our results suggest that prophylactic RH genetic matching for patients with SCD is feasible with a donor pool comprised primarily of African-Americans and would optimize the use of our existing minority donor inventory. The current cost of RH genotyping all minority donors and management of the data remain limiting factors.

HO-1hi patrolling monocytes protect against vaso-occlusion in sickle cell disease.

Patients with sickle cell disease (SCD) suffer from intravascular hemolysis associated with vascular injury and dysfunction in mouse models, and painful vaso-occlusive crisis (VOC) involving increased attachment of sickle erythrocytes and activated leukocytes to damaged vascular endothelium. Patrolling monocytes, which normally scavenge damaged cells and debris from the vasculature, express higher levels of anti-inflammatory heme oxygenase 1 (HO-1), a heme degrading enzyme. Here, we show that HO-1-expressing patrolling monocytes protect SCD vasculature from ongoing hemolytic insult and vaso-occlusion. We found that a mean 37% of patrolling monocytes from SCD patients express very high levels of HO-1 (HO-1hi) vs 6% in healthy controls and demonstrated that HO-1hi expression was dependent on uptake of heme-exposed endothelium. SCD patients with a recent VOC episode had lower numbers of HO-1hi patrolling monocytes. Heme-mediated vaso-occlusion by mouse SCD red blood cells was exacerbated in mice lacking patrolling monocytes, and reversed following transfer of patrolling monocytes. Altogether, these data indicate that SCD patrolling monocytes remove hemolysis-damaged endothelial cells, resulting in HO-1 upregulation and dampening of VOC, and that perturbation in patrolling monocyte numbers resulting in lower numbers of HO-1hi patrolling monocyte may predispose SCD patients to VOC. These data suggest that HO-1hi patrolling monocytes are key players in VOC pathophysiology and have potential as therapeutic targets for VOC.

Immediate hypersensitivity reaction to human serum albumin in a child undergoing plasmapheresis.

BACKGROUND: Human serum albumin (HSA) is a commonly used colloid for volume expansion and albumin replacement and during plasmapheresis. Colloids are an uncommon cause of anaphylaxis, and cases of hypersensitivity reactions to HSA are extremely rare. CASE REPORT: A 10-year-old boy with chronic inflammatory demyelinating polyneuropathy was treated with plasmapheresis, with albumin as the replacement fluid. He developed a severe reaction characterized by respiratory, gastrointestinal, and cutaneous symptoms. RESULTS: Skin testing to HSA was positive and resulted in objective systemic symptoms, suggesting an immediate hypersensitivity reaction to HSA. CONCLUSION: While colloids are an uncommon cause of immediate hypersensitivity reactions, they can lead to severe and potentially fatal reactions if not recognized and treated promptly.

Alloimmunization in patients with sickle cell disease and underrecognition of accompanying delayed hemolytic transfusion reactions.

BACKGROUND: Patients with sickle cell disease (SCD) often require red blood cell (RBC) transfusions but alloimmunization remains a significant complication. Alloantibodies can lead to delayed hemolytic transfusion reactions (DHTRs) days to weeks after a RBC transfusion, but may be underrecognized in patients with chronic hemolysis. STUDY DESIGN AND METHODS: This retrospective study aimed to determine the incidence and severity of DHTRs associated with new antibody detection in a cohort of 624 patients with SCD who received transfusion with C-, E-, and K-matched RBCs from primarily African American donors over a 14-year period. We identified potential DHTRs by the change in hemoglobin (Hb) and %HbS at baseline, before transfusion, and up to 30 days after the transfusion that preceded new antibody identification. RESULTS: Laboratory evidence of a DHTR was associated with 54 of 178 evaluable antibodies at first detection (30%), among which less than half were recognized by the patient or provider at the time of the event. A DHTR was associated with 26% of Rh antibodies identified in patients receiving serologic Rh-matched RBCs, and 38% of non-Rh antibodies. Twenty-one of the 54 DHTRs (39%) were associated with a Hb decline greater than 1 g/dL lower than pretransfusion values. Among these 21 severe DHTRs, Rh specificities were identified in 10 of 12 DHTRs in chronically transfused patients, while non-Rh specificities were associated with seven of nine DHTRs in episodically transfused patients. CONCLUSION: High clinical suspicion and monitoring for DHTRs is warranted, as they may be more common in patients with SCD than previously appreciated.

Critical developments of 2018: A review of the literature from selected topics in transfusion. A committee report from the AABB's Clinical Transfusion Medicine Committee.

BACKGROUND: The AABB compiles an annual synopsis of the published literature covering important developments in the field of transfusion medicine. An abridged version of this work is being made available in TRANSFUSION, with the full-length report available as Appendix S1 (available as supporting information in the online version of this paper). STUDY DESIGN AND METHODS: Papers published in late 2017 and 2018 are included, as well as earlier papers cited for background. Although this synopsis is comprehensive, it is not exhaustive, and some papers may have been excluded or missed. RESULTS: The following topics are covered: "big data" and "omics" studies, emerging infections and testing, platelet transfusion and pathogen reduction, transfusion therapy and coagulation, transfusion approach to hemorrhagic shock and mass casualties, therapeutic apheresis, and chimeric antigen receptor T-cell therapy. CONCLUSION: This synopsis may be a useful educational tool.

The sex parameter in estimation of total blood volume for pediatric erythrocytapheresis.

BACKGROUND AND OBJECTIVES: Estimation of the total blood volume (TBV) is fundamental to the control of automated red cell exchange (RCE). Error in the TBV estimate can produce outcomes that deviate from the prescribed targets, and may endanger the patient. Both the Spectra Optia and the COBE Spectra use the Nadler formulae to estimate TBV. There is a potential for large overestimates of TBV when the Nadler formula for males is applied to prepubertal boys. MATERIALS AND METHODS: This study uses our large clinical experience with RCE to examine procedure outcomes when RCE in prepubertal boys is programed with the female parameter instead of male. We determined the differences between programmed and measured values for three outcomes: (a) Programmed End Hematocrit - Post spun HCT by Hemata Stat II, (b) Programmed End Hematocrit - Post CBC HCT, and (c) Predicted Post Hgb S+C - Measured Post Hgb S+C. We defined the experimental group as Male-Female, where the biological sex was male but programmed sex was female, and two control groups where programmed and biological sex were the same. RESULTS: Small but statistically significant differences were demonstrated between the mean programmed-to-observed deviations of these outcome measures in all but two group and subgroup comparisons; however, the absolute magnitudes of the observed differences were not clinically significant. The suggested weight cutoff to begin programming males as male is 35 kg. CONCLUSION: The study provides experiential validation that performing RCE in prepubertal boys using the female parameter is safe.

Repeat Laboratory Testing in the Pediatric Emergency Department: How Often and How Important?

BACKGROUND: Little is known about repeat testing for patients admitted to children's hospitals from the emergency department (ED). OBJECTIVE: The objective of this study was to describe the trend of repeat laboratory testing from a children's hospital ED. METHODS: Laboratory studies were analyzed for July 2002 to June 2010 for complete blood counts (CBCs; 7 years), basic metabolic panels (BMPs; 2.5 years), and coagulation studies (7 years) ordered and reordered in the ED within 8 hours for patients admitted to the hospital. Results for tests were generated and classified into high, low, and normal based on reference ranges. To reflect actual practice, we expanded the normal range from 95% of lower bound to 105% of upper bound. RESULTS: A total of 37,035 CBCs, 11,414 BMPs, and 3903 coagulation studies were ordered. Proportions of these tests repeated were 0.9%, 1.9%, and 1.9%, respectively. Mean time to repeat was 2 hours. For CBCs, 25% of repeats were for a missing component; 35% were for low platelet counts. Sixty-eight percent of initial BMPs were repeated for high potassium. Half of coagulation studies were repeated for high prothrombin time; 36% were repeated for a missing component. On repeat, 75% of BMPs with high potassium levels and 65% of CBCs with low platelet count returned normal values, but 16% of coagulation studies repeated for high prothrombin time returned normal values. CONCLUSIONS: Repeat ED laboratory testing occurs infrequently at a children's hospital, and a large proportion of repeats is attributed to missing results. When repeated, abnormal results on initial studies are often returned as normal.

Critical developments of 2017: a review of the literature from selected topics in transfusion. A committee report from the AABB Clinical Transfusion Medicine Committee.

BACKGROUND: The AABB compiles an annual synopsis of the published literature covering important developments in the field of Transfusion Medicine. For the first time, an abridged version of this work is being made available in TRANSFUSION, with the full-length report available as an Appendix S1 (available as supporting information in the online version of this paper). STUDY DESIGN AND METHODS: Papers published in 2016 and early 2017 are included, as well as earlier papers cited for background. Although this synopsis is comprehensive, it is not exhaustive, and some papers may have been excluded or missed. RESULTS: The following topics are covered: duration of red blood cell storage and clinical outcomes, blood donor characteristics and patient outcomes, reversal of bleeding in hemophilia and for patients on direct oral anticoagulants, transfusion approach to hemorrhagic shock, pathogen inactivation, pediatric transfusion medicine, therapeutic apheresis, and extracorporeal support. CONCLUSION: This synopsis may be a useful educational tool.

RBC Transfusions Are Associated With Prolonged Mechanical Ventilation in Pediatric Acute Respiratory Distress Syndrome.

OBJECTIVES: Blood products are often transfused in critically ill children, although recent studies have recognized their potential for harm. Translatability to pediatric acute respiratory distress syndrome is unknown given that hypoxemia has excluded pediatric acute respiratory distress syndrome patients from clinical trials. We aimed to determine whether an association exists between blood product transfusion and survival or duration of ventilation in pediatric acute respiratory distress syndrome. DESIGN: Retrospective analysis of prospectively enrolled cohort. SETTING: Large, academic PICU. PATIENTS: Invasively ventilated children meeting Berlin Acute Respiratory Distress Syndrome and Pediatric Acute Lung Injury Consensus Conference Pediatric Acute Respiratory Distress Syndrome criteria from 2011 to 2015. INTERVENTIONS: We recorded transfusion of RBC, fresh frozen plasma, and platelets within the first 3 days of pediatric acute respiratory distress syndrome onset. Each product was tested for independent association with survival (Cox) and duration of mechanical ventilation (competing risk regression with extubation as primary outcome and death as competing risk). A sensitivity analysis using 1:1 propensity matching was also performed. MEASUREMENTS AND MAIN RESULTS: Of 357 pediatric acute respiratory distress syndrome patients, 155 (43%) received RBC, 82 (23%) received fresh frozen plasma, and 92 (26%) received platelets. Patients who received RBC, fresh frozen plasma, or platelets had higher severity of illness score, lower PaO2/FIO2, and were more often immunocompromised (all p < 0.05). Patients who received RBC, fresh frozen plasma, or platelets had worse survival and longer duration of ventilation by univariate analysis (all p < 0.05). After multivariate adjustment for above confounders, no blood product was associated with survival. After adjustment for the same confounders, RBC were associated with decreased probability of extubation (subdistribution hazard ratio, 0.65; 95% CI, 0.51-0.83). The association between RBC and prolonged ventilation was confirmed in propensity-matched subgroup analysis. CONCLUSIONS: RBC transfusion was independently associated with longer duration of mechanical ventilation in pediatric acute respiratory distress syndrome. Hemoglobin transfusion thresholds should be tested specifically within pediatric acute respiratory distress syndrome to establish whether a more restrictive transfusion strategy would improve outcomes.

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.

Red blood cell alloimmunization in transfused patients with bone marrow failure syndromes.

BACKGROUND: Red blood cell (RBC) alloimmunization is a concern for patients who receive multiple or chronic transfusions. Alloimmunization prevalence in transfused patients with bone marrow failure syndrome (BMFS) is unknown. This study aimed to determine physician practice for RBC antigen matching, immunization rates, and antibody specificities in patients with BMFS. STUDY DESIGN AND METHODS: The clinical records of all patients with BMFS seen at the Children's Hospital of Philadelphia between 2001 and 2015 were reviewed. Immunization rate was determined per 100 units transfused. RESULTS: ABO/D, C, E, and K (CEK) RBC matching was requested for 21.8% of patients. A total of 3782 RBC units were transfused to 87 patients, of which 2551 (67.5%) were CEK matched and 1231 (32.5%) were ABO/D only matched. The majority of units transfused to patients on a chronic transfusion regimen were CEK matched (89.6% of 2728 units). No anti-C, -E, or -K antibodies formed in any patient during the 14-year study period. Two alloantibodies and two autoantibodies formed, resulting in a rate of 0.05 alloantibodies and 0.05 autoantibodies per 100 units transfused. The prevalence of alloimmunization was 2.3%. CONCLUSION: The rate and prevalence of RBC alloimmunization were low in patients with BMFS. CEK matching avoided alloimmunization to these antigens in chronically transfused patients.

Transfusional Iron Overload in a Cohort of Children with Sickle Cell Disease: Impact of Magnetic Resonance Imaging, Transfusion Method, and Chelation.

BACKGROUND: Transfusions prevent a number of complications of sickle cell disease (SCD), but cause inevitable iron loading. With magnetic resonance imaging (MRI), liver iron can be monitored noninvasively. Erythrocytapheresis can limit iron loading and oral chelation provides a more tolerable alternative to subcutaneous administration. The impact of these factors on control of iron burden in SCD has not been well studied. PROCEDURE: Iron monitoring practices, chelation use, and transfusion methods were assessed in our cohort of pediatric patients with SCD receiving chronic transfusion. The impact of these factors on iron burden was assessed. RESULTS: Among 84 subjects, the proportion that underwent appropriate liver iron concentration (LIC) assessment rose from 21% before to 81% after implementation of R2-MRI in 2006. Among subjects with at least two R2-MRI examinations, median LIC improved (13.2-7.9 mg/g dw, P = 0.027) from initial to final study. Most (67.9%) subjects initially received simple transfusions and subsequently transitioned to erythrocytapheresis. After switching, LIC improved from 13.1 to 4.3 mg/g dw (P < 0.001) after a median of 2.7 years and ferritin improved (2,471-392 ng/ml, P < 0.001) after a median of 4.2 years. Final serum ferritin and LIC correlated negatively with the proportion of transfusions administered by erythrocytapheresis and chelation adherence. CONCLUSIONS: Routine liver R2-MRI should be performed in individuals with SCD who receive chronic red cell transfusions. Adherence with chelation should be assessed regularly and erythrocytapheresis utilized when feasible to minimize iron loading or reduce iron stores accumulated during periods of simple transfusion.

Blood Volume Required for Detection of Low Levels and Ultralow Levels of Organisms Responsible for Neonatal Bacteremia by Use of Bactec Peds Plus/F, Plus Aerobic/F Medium, and the BD Bactec FX System: an In Vitro Study.

We used an in vitro technique to investigate blood volumes required to detect bacteremia and fungemia with low concentrations of an organism. At 1 to 10 CFU/ml, Escherichia coli, Staphylococcus epidermidis, Staphylococcus aureus, Listeria monocytogenes, Candida albicans, and Candida parapsilosis isolates were detected in volumes as low as 0.5 ml. Detection of Streptococcus agalactiae and detection of bacteremia at <1 CFU/ml were unreliable.

High prevalence of red blood cell alloimmunization in sickle cell disease despite transfusion from Rh-matched minority donors.

Red blood cell (RBC) transfusion is a key treatment of patients with sickle cell disease (SCD) but remains complicated by RBC immunization. In the present study, we evaluated the effects of antigen matching for Rh D, C, and E, and K and transfusion from African American donors in 182 patients with SCD. Overall, 71 (58%) chronic and 9 (15%) episodically transfused patients were alloimmunized. Fifty-five (45%) chronic and 7 (12%) episodically transfused patients were Rh immunized. Of 146 antibodies identified, 91 were unexplained Rh antibodies, one-third of which were associated with laboratory evidence of delayed transfusion reactions. Fifty-six antibodies occurred in patients whose RBCs were phenotypically positive for the corresponding Rh antigen and 35 in patients whose RBCs lacked the antigen and were transfused with Rh-matched RBCs. High-resolution RH genotyping revealed variant alleles in 87% of individuals. These data describe the prevalence of Rh alloimmunization in patients with SCD transfused with phenotypic Rh-matched African American RBCs. Our results suggest that altered RH alleles in both the patients and in the donors contributed to Rh alloimmunization in this study. Whether RH genotyping of patients and minority donors will reduce Rh alloimmunization in SCD needs to be examined.

Changing practice: red blood cell typing by molecular methods for patients with sickle cell disease.

BACKGROUND: Extended red blood cell (RBC) antigen matching is recommended to limit alloimmunization in patients with sickle cell disease (SCD). DNA-based testing to predict blood group phenotypes has enhanced availability of antigen-negative donor units and improved typing of transfused patients, but replacement of routine serologic typing for non-ABO antigens with molecular typing for patients has not been reported. STUDY DESIGNS AND METHODS: This study compared the historical RBC antigen phenotypes obtained by hemagglutination methods with genotype predictions in 494 patients with SCD. For discrepant results, repeat serologic testing was performed and/or investigated by gene sequencing for silent or variant alleles. RESULTS: Seventy-one typing discrepancies were identified among 6360 antigen comparisons (1.1%). New specimens for repeat serologic testing were obtained for 66 discrepancies and retyping agreed with the genotype in 64 cases. One repeat Jk(b-) serologic phenotype, predicted Jk(b+) by genotype, was found by direct sequencing of JK to be a silenced allele, and one N typing discrepancy remains under investigation. Fifteen false-negative serologic results were associated with alleles encoding weak antigens or single-dose Fy(b) expression. CONCLUSIONS: DNA-based RBC typing provided improved accuracy and expanded information on RBC antigens compared to hemagglutination methods, leading to its implementation as the primary method for extended RBC typing for patients with SCD at our institution.

Severe hemolytic transfusion reaction due to anti-D in a D+ patient with sickle cell disease.

A 5-year-old male with sickle cell disease presented with pain, dark urine, and fatigue 10 days after a red blood cell (RBC) transfusion. Laboratory evaluation demonstrated severe anemia, blood type O+, and anti-D in the serum. Anti-D in a D+ patient led to RH genotyping, which revealed homozygosity for RHD*DAU4 that encodes partial D antigen. Anti-D in this patient whose RBCs exclusively express partial D caused a delayed hemolytic transfusion reaction after exposure to D+ RBCs. The finding of anti-D in a D+patient should be investigated by molecular methods to help distinguish an alloantibody from an autoantibody.