Anti-D Alloimmunization in Index Pregnancy after Appropriate Rho(D) Immune Globulin Injection in Two Obese Rh-Negative Patients.

Background The rhesus factor D (RhD)-negative patients who give birth to an RhD-positive newborn or who are otherwise exposed to RhD-positive red blood cells are at risk of developing anti-D antibodies. These antibodies may cause hemolytic disease of the fetus and newborn (HDFN). During pregnancy, prevention of alloimmunization is completed with a Rho(D) immune globulin (RhIg). Cases We report two cases, where obese patients developed alloimmunization, with high neonatal titers, after appropriate RhIG prophylaxis during the index pregnancy. Conclusion Our cases demonstrate cases of anti D-alloimmunization in an index pregnancy, with high neonatal titers. Both patients are obese, with BMI > 35 mg/m 2 . Key Points RhIG can be administered via intramuscular or intravenous formulations. Overall, it appears that both formulations are equally effective. The optimal administration, especially with obese women, is not clearly established.Our cases demonstrate that obesity is a risk factor for failure of RhIG, and could lead to an increase in HDFN.

Case report: Double filtration plasmapheresis (DFPP) for severe rhesus-D alloimmunization in two pregnant patients.

Maternal erythrocyte alloimmunization is one of the most important causes of fetal anemia. The standard treatment for anemic fetuses is intrauterine blood transfusion (IUT). However, IUT may have adverse effects, particularly before 20 weeks of gestation. In this report, two women who had previously had severely affected alloimmunized pregnancy developed high titers of anti-D antibodies before 20 weeks of gestation. Ultrasound Doppler showed severe fetal anemia, and intrauterine transfusion was expected to be unavoidable. To prolong pregnancy to a gestation in which intravascular IUT was possible, we used repeated double filtration plasmapheresis (DFPP) as a rescue therapy. The titers of IgG-D, IgG-A, and IgG-B decreased after DFPP treatment. One woman successfully prolonged pregnancy until 20 weeks of gestation. Subsequently, she underwent four cycles of IUTs and delivered at 30 weeks of gestation by emergency cesarean section due to fetal bradycardia during the fifth intrauterine transfusion. The other woman successfully delayed intrauterine transfusion until 26 weeks of gestation. The favorable results of the two patients indicate that DFPP may be an effective and safe treatment modality for RhD immunity in pregnant women. Moreover, DFPP is potentially helpful for reducing the occurrence of ABO hemolytic disease in neonates due to the clearance of IgG-A and IgG-B antibodies (e.g., O pregnant women harbored A/B/AB neonates). However, more clinical trials are needed to verify the results.

Anti-D Antibodies in Pregnant D Variant Antigen Carriers Initially Typed as RhD.

BACKGROUND: To evaluate the incidence, the consequences, and the prevention strategy of anti-D alloimmunizations of D variant carriers in the obstetric population of Split-Dalmatia County, Croatia. METHODS: RhD immunization events were evaluated retrospectively for the period between 1993 and 2012. Women were tested for RhD antigen and irregular antibodies. Those with anti-D antibody who were not serologically D- were genotyped for RHD. They were evaluated for their obstetric and transfusion history and their titer of anti-D. The neonates were evaluated for RhD status, direct antiglobulin test (DAT), hemoglobin and bilirubin levels, transfusion therapy as well as phototherapy and outcome. RESULTS: Out of 104,884 live births 102,982 women were tested for RhD antigen. Anti-D immunization occurred in 184 women which accounts for 0.9% of individuals at risk of anti-D formation. 181 cases occurred in women serologically typed as D-. Three women were partial D carriers (DVa n = 2, DNB n = 1), initially typed RhD+, and recognized as D variant carriers after the immunization occurred. Anti-D titer varied from 1:1 to 1:16. Six children were RhD+, four had positive DAT, and two underwent phototherapy. CONCLUSION: Anti-D immunization occurred in pregnant partial D carriers (DVa, DNB). RhD+ children had serologic markers of hemolytic disease of the fetus and newborn (HDFN), with no cases of severe HDFN.

Weak D and partial D in Slovenian population through serology and genotyping.

Weak D red cell phenotype (formerly Du) exhibits weaker serological reaction with anti-D antibodies. Weak D occurs in 0.2% to 1% of whites and is caused by qualitatively altered RhD proteins called partial D or normal, only weakly expressed RhD proteins that are called weak D. Partial D genes are hybrid alleles between RHD an RHCE genes. 23 partial RHD alleles are described. Weak D phenotypes with reduced expression are likely to posses the normal RHD gene, but the latest findings indicate that weak D alleles carry at least one point mutation. The aim of the present work was to answer an important question how to approach partial and weak D identification in diagnostic use and if it is possible to distinguish between partial D and weak D using commercially available anti-D reagents for routine use. We also wanted to evaluate D-screen kit for partial D identification. We compared phenotypes identified by serological testing and genotypes identified by RHD Multiplex PCR and DVII specific ASPA PCR. Our results showed that it is not possible to distinguish between partial and weak D using commercially available anti-D reagents for routine use. D-screen proved to be useful for DVI and DVII identification, whereas for partial DDFR identification we must look for another set of monoclonal antibodies or simply use genotyping methods. In 44 samples with not interpretable serological results out of 80 we found all RHD specific exons present and we classified the samples as weak D. Fourteen types of weak D with at least one point mutation were recently proposed. Designing of allele specific PCRs for identification of proposed types of weak D is in progress.

The Evaluation of Biological Activity of Anti-Rh (D) Antibodies / 中国医师杂志

Objective To evaluate the biological activity of anti-Rh(D) antibodies in vitro. Methods The titres of plasma Anti-Rh (D) antibodies in the RH(-) patients uncorrectly infused RH(+) blood were detected by various methods. The anti-D antibodies were evaluated for their capacity to sensitize erythrocytes, trigger monocyte and K-cell mediated antibody-dependent cellular cytotoxicity (ADCC), mediate binding to monocyte and lymphocyte Fc gamma R, and stimulate phagocytosis by monocytes. The synergistic effect of anti-D antibodies in promoting hemolysis was detected by complement fixation test (CFT). Results The titre of plasma anti-D antibodies measured by micro-column gel indirect anti-globulin technique(MGIAT) was the highest compared with the other detection methods. When red cells were sensitized with anti-D antibodies, the binding and phagocytosis of red cells by monocytes and the lysis of red cells by monocytes or lymphocytes were great, and the hemolysis of red cells by alexin was great too. Conclusion Anti-Rh (D) antibodies had great biological activity in vitro, and MGIAT had the highest sensitivity for detecting anti-Rh(D) antibodies.