Rh immune globulin immunoprophylaxis after RhD-positive red cell exposure in RhD-negative patients via transfusion: A survey of practices.

BACKGROUND: Current Association for the Advancement of Blood & Biotherapies (AABB) standards require transfusion services to have a policy on Rh immune globulin (RhIG) immunoprophylaxis for when RhD-negative patients are exposed to RhD-positive red cells. This is a survey of AABB-accredited transfusion services in the United States (US) regarding institutional policies and practices on RhIG immunoprophylaxis after RhD-negative patients receive RhD-positive (i.e., RhD-incompatible) packed red blood cell (pRBC) and platelet transfusions. RESULTS: Approximately half of the respondents (50.4%, 116/230) have policies on RhIG administration after RhD-incompatible pRBC and platelet transfusions, while others had policies for only pRBC (13.5%, 31/230) or only platelet (17.8%, 41/230) transfusions, but not both. In contrast, 18.3% (42/230) report that their institution has no written policies on RhIG immunoprophylaxis after RhD-incompatible transfusions. Most institutions (70.2%, 99/141) do not have policies addressing safety parameters to mitigate the risk of hemolysis associated with the high dose of RhIG required to prevent RhD alloimmunization after RhD-incompatible pRBC transfusions. DISCUSSION: With approximately half of US AABB-accredited institutions report having policies on RhIG immunoprophylaxis after both RhD-incompatible pRBC and platelet transfusions, some institutions may not be in compliance with AABB standards. Further, most with policies on RhIG immunoprophylaxis after RhD-incompatible pRBC transfusion do not have written safeguards to mitigate the risk of hemolysis associated with the high dose of RhIG required. CONCLUSION: This survey underscores the diverse and inadequate institutional policies on RhIG immunoprophylaxis after RhD exposure in Rh-negative patients via transfusion. This observation identifies an opportunity to improve transfusion safety.

Prevalence of red blood cell alloantibodies in pregnant women with sickle cell disease in Bamako.

BACKGROUND AND OBJECTIVES: Pregnancy in women with sickle cell disease (SCD) is associated with severe complications. Red blood cell (RBC) alloimmunisation is a worrying situation in pregnant women with SCD. This could increase the difficulty in finding a pheno-compatible red blood product. Our study aimed to determine the prevalence of RBC alloantibodies in pregnant women with SCD and to determine the risk factors for alloantibodies formation. METHODS/MATERIALS: We conducted a prospective study at the "Centre National de Transfusion Sanguine de Bamako" from August 2022 to January 2023. For each participant, we collected important information, including obstetrical and transfusion histories. We performed ABO group, Rh and Kell phenotyping, and antibody screening in all study participants. We performed statistical analysis. RESULTS: We recruited 95 pregnant women with SCD. In our study, 62% of our participant had a history of blood transfusion. Only 23% of our pregnant women with SCD had a history of miscarriage. The prevalence of RBC alloantibodies was 14%. The main antibodies detected were anti-E (38%) and pan-agglutinins (23%). Miscarriage history, blood transfusion history, and pregnancy number were the main risk factors for RBC alloimmunisation. CONCLUSION: The care of pregnant women with SCD is complex and requires collaboration between haematologists, clinicians and gynaecologists. National guidelines should be implemented to make ABO and D typing, Rh and Kell phenotyping and antibody screening routine for all pregnant women. This would facilitate early detection of high-risk situations. Particular attention should be paid to SCD pregnant women with miscarriage and blood transfusion histories.

Hemolytic disease of the fetus and newborn in the sensitizing pregnancy where anti-D was incorrectly identified as RhIG.

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is a potentially fatal complication in Rh-incompatible pregnancies and rarely occurs in the sensitizing pregnancy. Distinguishing RhIG from true anti-D identified is challenging. A case of severe HDFN in which a sample drawn at 28 weeks showed anti-D antibody (3+ strength) attributed to RhIG is described. RBC antibody testing early in pregnancy was negative. At birth, the infant was severely anemic and maternal anti-D titer was 1:256. This case represents a clinically significant anti-D in the sensitizing pregnancy that was missed due to confusion with RhIG. METHODS: To determine if agglutination strength could be helpful, a retrospective chart-review using both electronic and paper medical records was performed on 348 samples identified as RhIG and 52 true anti-D samples. The agglutination strength of antibody was recorded for each sample. RESULTS: For RhIG, there was an even distribution between the weak to moderate agglutination strength (w+, 1+, and 2+) results (35%, 26%, and 33%, respectively) and just 6% had a 3+ strength. Agglutination strength in patients with high titer (≥1:16) anti-D showed they often (44.4%) have 1+ or 2+ agglutination reactivity. CONCLUSIONS: These results show that agglutination strength alone does not provide reliable evidence to distinguish RhIG from high titer anti-D antibodies. We recommend that in cases where there is any uncertainty about whether the anti-D reactivity is due to RhIG, titers should be performed to rule out clinically significant anti-D antibody.

DEL in China: the D antigen among serologic RhD-negative individuals.

BACKGROUND: Providing RhD-negative red cell transfusions is a challenge in East Asia, represented by China, Korea, and Japan, where the frequency of RhD-negative is the lowest in the world. FINDINGS: Among 56 ethnic groups in China, the RhD-negative frequency in Han, the prevalent ethnicity, is 0.5% or less, similar to most other ethnic groups. The Uyghur ethnic group has the highest reported RhD-negative frequency of up to 4.7%, as compared to 13.9% in the US. However, an estimated 7.15 million RhD-negative people live in China. The RhD-negative phenotype typically results from a loss of the entire RHD gene, causing the lack of the RhD protein and D antigen. The DEL phenotype carries a low amount of the D antigen and types as RhD-negative in routine serology. The DEL prevalence in RhD-negative individuals averages 23.3% in the Han, 17% in the Hui and 2.4% in the Uyghur ethnicities. The Asian type DEL, also known as RHD*DEL1 and RHD:c.1227G > A allele, is by far the most prevalent among the 13 DEL alleles observed in China. CONCLUSION: The purpose of this review is to summarize the data on DEL and to provide a basis for practical strategy decisions in managing patients and donors with DEL alleles in East Asia using molecular assays.

Mitigation strategies for anti-D alloimmunization by platelet transfusion in haematopoietic stem cell transplant patients: a survey of NCCN® centres.

BACKGROUND AND OBJECTIVES: D-negative patients are at risk of developing an alloantibody to D (anti-D) if exposed to D during transfusion. The presence of anti-D can lead to haemolytic transfusion reactions and haemolytic disease of the newborn. Anti-D alloimmunization can also complicate allogeneic haematopoietic stem cell transplantation (HSCT) with haemolysis and increased transfusion requirements. The goal of this study was to determine whether cancer centres have transfusion practices intended to prevent anti-D alloimmunization with special attention in patients considered for HSCT. METHODS AND MATERIALS: To understand transfusion practices regarding D-positive platelets in D-negative patients with large transfusion needs, we surveyed the 28 cancer centres that are members of the National Comprehensive Cancer Network® (NCCN® ). RESULTS: Nineteen centres responded (68%). Most centres (79%) avoid transfusing D-positive platelets to RhD-negative patients when possible. Four centres (21%) avoid D-positive platelets only in D-negative women of childbearing age. If a D-negative patient receives a D-positive platelet transfusion, 53% of centres would consider treating with Rh immune globulin (RhIg) to prevent alloimmunization in women of childbearing age. Only one centre also gives RhIg to all D-negative patients who are HSCT candidates including adult men and women of no childbearing age. CONCLUSION: There is wide variation in platelet transfusion practices for supporting D-negative patients. The majority of centres do not have D-positive platelet transfusion policies focused on preventing anti-D alloimmunization specifically in patients undergoing HSCT. Multicentre, longitudinal studies are needed to understand the clinical implications of anti-D alloimmunization in HSCT patients.

Low frequency of anti-D alloimmunization following D+ platelet transfusion: the Anti-D Alloimmunization after D-incompatible Platelet Transfusions (ADAPT) study.

The reported frequency of D alloimmunization in D- recipients after transfusion of D+ platelets varies. This study was designed to determine the frequency of D alloimmunization, previously reported to be an average of 5 ± 2%. A primary anti-D immune response was defined as the detection of anti-D ≥ 28 d following the first D+ platelet transfusion. Data were collected on 485 D- recipients of D+ platelets in 11 centres between 2010 and 2012. Their median age was 60 (range 2-100) years. Diagnoses included: haematological (203/485, 42%), oncological (64/485, 13%) and other diseases (218/485, 45%). Only 7/485 (1·44%; 95% CI 0·58-2·97%) recipients had a primary anti-D response after a median serological follow-up of 77 d (range: 28-2111). There were no statistically significant differences between the primary anti-D formers and the other patients, in terms of gender, age, receipt of immunosuppressive therapy, proportion of patients with haematological/oncological diseases, transfusion of whole blood-derived or apheresis platelets or both, and total number of transfused platelet products. This is the largest study with the longest follow-up of D alloimmunization following D+ platelet transfusion. The low frequency of D alloimmunization should be considered when deciding whether to administer Rh Immune Globulin to D- males and D- females without childbearing potential after transfusion of D+ platelets.

Transfusion management of a Chinese pregnant woman with RHD*DEL1 allele.

We report the case of a 33-year-old pregnant Chinese woman who typed as Rh-negative in routine serology. Two injections of RhIG were given and two Rh-negative red cell units were sourced and put aside then returned with a reduced shelf life. RHD*DEL1 allele was determined in this woman by RHD genotyping two month later after delivery occasionally. In this representative case, a pregnant woman with RHD*DEL1 allele can safely be managed as Rh-positive, avoiding the unnecessary procurement of Rh-negative red cells and payment for RhIG injections. We analyzed the cost benefit of using RHD genotyping to guide transfusion management on the Chinese pregnant woman in Beijing where the average salary level is top-ranked in China. Considering the healthcare condition in China, we recommend molecular analysis of serologic Rh-negative early in pregnancy before the Rh-negative transfusion and administration of RhIG become unnecessarily required.

Relevance and costs of RHD genotyping in women with a weak D phenotype.

OBJECTIVES: For pregnant women, the serologic test results of D antigen will determine the frequency of RBC antibody detection as well as the indication for RhIG prophylaxis. RHD genotyping is the only method that may provide clear guidance on prophylaxis for women with a weak D phenotype. This analysis evaluated the economical implications of using RHD genotyping to guide RhIG prophylaxis among pregnant women with a serological weak D phenotype. METHODS: We compared the costs of 2 strategies in a cohort of 273 women with weak D phenotype. In the first strategy, we did not perform genotyping and all women with weak D phenotypes were treated as if they were D-, thus considered to be a risk of RhD alloimmunization. These women all received the prophylactic follow up. In the second strategy, RHD genotyping was performed on all women with a serologic weak D phenotype. Then, the follow-up will be determined by phenotype deduced from genotype. RESULTS: On the studied cohort, the additional expense occurred by genotyping is 26,536 €. RHD Genotyping has highlighted 162 weak D Type 1, 2 3, that could safely be managed as D+ and 111 partial D to consider as D-. By comparing the 2 strategies, the savings generated by genotyping the patients of our cohort are € 12,046 for the follow up of one pregnancy. Knowing that in France, a woman has on average 2 pregnancies and that the genotyping is carried out only once, the savings generated for the following pregnancies would be € 38,581. CONCLUSIONS: Performing RHD genotyping for pregnant women with a weak D phenotype enables to clearly identify weak D type 1, 2 or 3 from the other variants at risk of alloimmunization. This analysis generates savings in terms of follow-up schedule of pregnant women and RhIG prophylaxis. It also allows saving of D- products for patient with a weak D type 1, 2 or 3 in case of a transfusion need.

Should cell-free DNA testing be used to target antenatal rhesus immune globulin administration?

OBJECTIVE: To compare the rates of alloimmunization with the use of cell-free DNA (cfDNA) screening to target antenatal rhesus immune globulin (RhIG) prenatally, versus routine administration of RhIG in rhesus D (RhD)-negative pregnant women in a theoretic cohort using a decision-analytic model. METHODS: A decision-analytic model compared cfDNA testing to routine antenatal RhIG administration. The primary outcome was maternal sensitization to RhD antigen. Sensitivity and specificity of cfDNA testing were assumed to be 99.8% and 95.3%, respectively. Univariate and bivariate sensitivity analyses, Monte Carlo simulation, and threshold analyses were performed. RESULTS: In a cohort of 10,000 RhD-negative women, 22.6 sensitizations would occur with utilization of cfDNA, while 20 sensitizations would occur with routine RhIG. Only when the sensitivity of the cfDNA test reached 100%, the rate of sensitization was equal for both cfDNA and RhIG. Otherwise, routine RhIG minimized the rate of sensitization, especially given RhIG is readily available in the United States. CONCLUSIONS: Adoption of cfDNA testing would result in a 13.0% increase in sensitization among RhD-negative women in a theoretical cohort taking into account the ethnic diversity of the United States' population.