RhIG Administration Research Articles

Economic analysis of foregoing Rh immunoglobulin for bleeding in pregnancy

ObjectivesTo perform cost analyses of foregoing RhD blood type testing and administration of Rh immunoglobulin (RhIg) for bleeding in pregnancy at <12 weeks gestation in the United States. Study DesignWe created a decision-analytic model comparing the current standard treatment pathway for patients who have threatened, spontaneous, or induced abortion in the United States, with a new pathway foregoing RhD testing and administration of RhIg for those who are RhD-negative at <12 weeks gestation, assuming that the risk of sensitization is 0%. We derived population and cost estimates from current literature and calculated the number needed to treat, and number needed to screen, to avoid one case of fatal hemolytic disease of the fetus and newborn. We performed sensitivity analyses assuming Rh-sensitization risks of 1.5% and 3% and varying the subsequent pregnancy rates from 44-100%. ResultsThe annual savings to healthcare payers in the United States of foregoing RhD testing and RhIg administration to RhD-negative patients with bleeding events at <12 weeks is $5.5 million/100,000 total pregnancies, assuming that the risk of sensitization is 0%. In the sensitivity analyses with sensitization risk 1.5% and subsequent pregnancy rate 84.3%, foregoing Rh testing and RhIg administration <12 weeks would save $2.8 million/100,000 pregnancies, with a corresponding number needed to treat of 7,322 and number needed to screen of 48,816. At a 3% sensitization rate, the current standard treatment pathway is the most economical. ConclusionsThere is an opportunity to save the United States healthcare payers as much as $5.5 million/100,000 pregnancies by withholding RhIg in specific situations and conserving it for use later in pregnancy. ImplicationsCost analyses support foregoing RhD blood type screening and RhIg administration at <12 weeks gestation if the sensitization rate is <3%. By de-implementing this low value care, payers in the United States can save as much as $5.5 million/100,000 pregnancies and conserve RhIg for use later in pregnancy.

Society for Maternal-Fetal Medicine Statement: RhD immune globulin after spontaneous or induced abortion at less than 12 weeks of gestation

Guidelines for management of first-trimester spontaneous and induced abortion vary regarding RhD testing and Rho(D) immune globulin administration. These existing guidelines are based on limited data that do not convincingly demonstrate the safety of withholding Rho(D) immune globulin for first-trimester abortions or pregnancy losses. Given the adverse fetal and neonatal outcomes associated with RhD alloimmunization, prevention of maternal sensitization is essential in RhD negative patients who may experience subsequent pregnancies. In care settings where RhD testing and Rho(D) immune globulin administration are logistically and financially feasible and do not hinder access to abortion care, we recommend both RhD testing and RhIg administration for spontaneous and induced abortion at <12 weeks of gestation in unsensitized, RhD-negative individuals.

Rh(D) immune globulin administration in pregnancy: Retrospective audit of patient safety events followed by targeted educational intervention with Bayesian analysis.

To examine local patient safety events related to the administration of anti-Rh(D) immune globin (RhIG) during pregnancy, and to follow-up with targeted educational intervention to improve knowledge of this process. Administration RhIG is established treatment for the prevention of haemolytic disease of the foetus and newborn (HDFN). However, patient safety events in relation to its correct use continue to occur. A retrospective audit of patient safety events related to RhIG administration during pregnancy was performed. Targeted educational intervention in the form of PowerPoint® presentation were given to nursing staff, laboratory staff and physicians and evaluated with pre- and post-tests using multiple-choice questions given immediately before and after the presentation. An annual incidence of 0.24% of patient safety events related to the administration of RhIG during pregnancy was found. These events were mostly in the preanalytical phase, for example mislabelled samples or samples for D-rosette/Kleihauer-Betke testing drawn from the baby, not the mother. Using Bayesian analysis, the probability of positive effect for the targeted educational intervention was 100% with a median improved score of 29%. This was compared with a control group using standard curriculum education intervention based on the current curriculum for nursing, laboratory and medical students which showed a median improved score of only 4.4%. Administration of RhIG during pregnancy is a multistep process involving health care professionals of several disciplines providing opportunities to enhance the curriculum for nursing, laboratory and medical students and to ensure on-going education.

Routine noninvasive prenatal screening for fetal Rh D in maternal plasma-A 2-year experience from a single center in Belgium.

Hemolytic disease of the fetus and newborn (HDFN) due to rhesus D (RhD) immunization is a potentially life-threatening situation for which use of Rh Immunoglobulin (RhIg) has decreased risk drastically. Determination of fetal RHD on maternal plasma can be used to restrict prenatal RhIg administration to women carrying an RhD-positive child, avoiding unnecessary administration of blood-derived products. The aim of this study is to determine the performance of fetal RHD typing in our center. We prospectively collected 205 fetal RHD and 127 serological cord blood RhD data from RhD-negative women starting at 11 weeks of pregnancy (from October 2019 to October 2021). Real-time polymerase chain reaction targeting RHD exon 5 and 7 was used, similar to the screening program in The Netherlands, supplemented with an amplification control (beta-actin; ACTB) and a sex determination marker located on the Y-chromosome (SRY gene). Fetal RHD testing reached a sensitivity and specificity of 100%. No false-negative nor false-positive results were reported. Inconclusive results (6%, 13/205) were due to weak amplification in 10 cases, a maternal RHD variant in 2 cases (RHD*01N.71 and partial DVI), and a fetal RHD variant (partial DVI) in 1 case. Unnecessary administration of RhIg prophylaxis was avoided in 33% of cases and on the other hand was administered in one case (fetal partial DVI) which would have been missed with cord blood serology. This study demonstrates the high accuracy of routine prenatal fetal RHD gene screening after 11 weeks of pregnancy, encouraging routine clinical practice.

Risk factors for RhD immunisation in a high coverage prevention programme of antenatal and postnatal RhIg: a nationwide cohort study.

ObjectiveTo evaluate which risk factors for RhD immunisation remain, despite adequate routine antenatal and postnatal RhIg prophylaxis (1000 IU RhIg) and additional administration of RhIg. The second objective was assessment of the current prevalence of RhD immunisations.DesignProspective cohort study.SettingThe Netherlands.PopulationTwo‐year nationwide cohort of alloimmunised RhD‐negative women.MethodsRhD‐negative women in their first RhD immunised pregnancy were included for risk factor analysis. We compared risk factors for RhD immunisation, occurring either in the previous non‐immunised pregnancy or in the index pregnancy, with national population data derived from the Dutch perinatal registration (Perined).ResultsIn the 2‐year cohort, data from 193 women were eligible for analysis. Significant risk factors in women previously experiencing a pregnancy of an RhD‐positive child (n = 113) were: caesarean section (CS) (OR 1.7, 95% CI 1.1–2.6), perinatal death (OR 3.5, 95% CI 1.1–10.9), gestational age >42 weeks (OR 6.1, 95% CI 2.2–16.6), postnatal bleeding (>1000 ml) (OR 2.0, 95% CI 1.1–3.6), manual removal of the placenta (MRP) (OR 4.3, 95% CI 2.0–9.3); these factors often occurred in combination. The miscarriage rate was significantly higher than in the Dutch population (35% versus 12.‐5%, P < 0.001).ConclusionComplicated deliveries, including cases of major bleeding and surgical interventions (CS, MRP), must be recognised as a risk factor, requiring estimation of fetomaternal haemorrhage volume and adjustment of RhIg dosing. The higher miscarriage rate suggests that existing RhIg protocols need adjustment or better compliance.Tweetable abstractComplicated delivery (caesarean section, manual removal placenta, major bleeding) is the most valid risk factor for RhD immunization despite antenatal and postnatal RhIg.

Can We Safely Stop Administering Anti-D Immune Globulin to First Trimester Rh-Negative Mothers Undergoing Abortion? A Systematic Review and Meta-Analysis

Fetal red blood cells can express the D-antigen as early as 52 days after the last menstrual period. However, there is no convincing evidence for the benefit of using anti-D immune globulin (RhIG) in the first trimester. The aim of the current review is therefore to determine whether administration of RhIG to women undergoing first trimester spontaneous or induced abortions prevents subsequent sensitization.

Passive Transfer Of Allo-Antibodies Following Rhig Administration Given For Rh-Mismatched Platelets Prophylaxis

Abstract Introduction/Objective Human platelets (PLTs) do not express any Rh system antigens; however, PLT concentrates can be contaminated with small amounts of red blood cells (RBCs), which may induce alloimmunization when transfused to Rh(D)-negative individuals. RhIG has been utilized to prevent Rh(D) alloantibody development following transfusion of Rh mismatched PLTs. RhIG is manufactured using pooled plasma of healthy Rh(D)-negative donors, with the most common Rh haplotype being ce; treated subjects are exposed to Rh (D)-positive RBCs, with the most common Rh haplotype of donors being DCe. In this report, we detail our experiences with recipients of Rh mismatched apheresis PLTs who were noted to develop anti-D + anti-C post-RhIG administration. Methods Retrospective review was conducted of all Rh mismatched PLTs between December, 2018 and May, 2019 at our facility (Yale-New Haven Hospital, New Haven, CT). Inclusion in the study required: Rh(D)-negative donor receiving one or more Rh(D)-positive apheresis PLTs, Receiving RhIG, &amp;gt;1 antibody screen following RhIG administration demonstrating antibodies other than anti-D Results Our retrospective review identified 8 unique recipients of Rh mismatched apheresis PLTs who acquired anti- C, in addition to the expected anti-D, following administration of RhIG. The product (Rhophylac) was administered in all cases intravenously at a dose of 1500 IU (300 mcg) within 72 hours following Rh mismatched PLTs. In all patients, routine screening following RhIG simultaneously detected anti-D and anti-C 1-3 days after administration of Rh mismatched PLTs/RhIG, the antibody screen remained positive for a range of 27-167 days for both antibodies. Conclusion Based on this case series, which represented entirely men and older women, and coupled with emerging evidence about the extremely low likelihood of D-alloimmunization following Rh mismatched apheresis PLTs,2,3,6 we have changed our practice, limiting immunoprophylaxis for Rh mismatched platelets exclusively to women of reproductive age. The blood bank and apheresis communities should be aware that passive transfer of non-D antibodies is possible when RhIG is dosed and could account for newly-detected non-D alloimmunization events. This phenomenon is another compelling reason to limit RhIG exposure to cases where it is only absolutely clinically necessary.7

Anti-D from alloimmunization versus RhIG: detective work in the blood bank and transfusion medicine services.

The blood bank and transfusion medicine services (BBTMS) engages with electronic health records (EHRs), clinicians, and outside hospitals (OHs) to obtain comprehensive patient history to optimize care. Detection of anti-D in a pregnant patient underscores this work. Differentiating passive anti-D due to RhIG administration versus alloanti-D affects clinical decision making. The objectives of this study were to identify the required steps, barriers, and outcomes of anti-D investigations in obstetric patients. This retrospective case series reviewed nine pregnant patients over 24 months, for whom anti-D was identified with no reported RhIG history. Six steps were performed to ascertain anti-D history: 1) review the on-site EHR; 2) contact the on-site obstetrician, 3) review history from the automatic health information exchange (HIE) with OHs using the same EHR platform, 4) request information from OHs with a shared EHR platform and without automatic HIE, 5) contact the OH BBTMS, and 6) communicate with the outside ambulatory practice (OAP). The investigations revealed that eight of nine patients received RhIG before their presentation. Five patients received RhIG at an OH's emergency department and three at an OAP. One patient's history remained unknown after initial investigations; however, a subsequent sample unveiled a confounding alloantibody. In the absence of a national HIE, continuity of care suffers through omission of critical information. Strategies to avoid confusing passive anti-D and alloanti-D include expanding HIE capabilities and use of patient identification cards with critical BBTMS information to include RhIG administration dates.

Major applications and limitations of blood group genotyping in China

Molecular immunohematological techniques have been well applied in the transfusion medicine. Here, we review the major applications for blood group genotyping in China. Its application mainly focuses on the typing of blood group antigens in complex cases, such as ABO subgroups, D variants or the Asian specific and common antigens typing (such as the antigens expressed by the MNS hybrid glycophorins), also because of lacking of the corresponding commercial antibodies. The comprehensive antigens profile in some specific samples could be obtained using medium‐ or high‐throughput genotyping platforms. Although, foetal RHD genotyping in D– pregnant women in Europe is highly relevant to avoid unnecessary antenatal RhIg, it is of comparatively less importance in the Chinese D– pregnant women because of the low probability (3–4%) to have a D– baby. In contrast, the application of routine molecular testing for the ‘Asia type’ DEL, which having a frequency up to 30% in East Asian people serologically typed as D‐negative, is more necessary to avoid unnecessary administration of antenatal RhIg, because there is increasing evidence that individuals carrying the ‘Asia type’ DEL allele (c.1227G&gt;A, p.Lys409Lys) do not produce alloanti‐D after exposure to D+ red blood cells. The molecular methods to detect the RHD*1227A are more accurate and applicable for routine testing of ‘Asia type’ DEL.

Genotyping to prevent Rh disease: has the time come?

In this review, we analyzed the current literature on noninvasive fetal RHD typing to answer the question whether the administration of RhIg to prevent D-alloimmunization during pregnancy can be safely guided by fetal RHD typing. Recently the first centers that implemented large-scale nationwide fetal RHD typing in the second trimester for targeted RhIg administration have published their studies evaluating the diagnostic accuracy of their screening programs. These data show that fetal RHD typing in a routine setting is, at least in a population of European descent, accurate enough to guide both antenatal and postnatal immunoprophylaxis. Depending on the ethnic background and the organization of pregnancy care the decisions regarding RhIg can be safely and cost-effectively based on fetal RHD typing by a duplex real-time PCR. As a result, the unnecessary administration of 40% of antenatal RhIg can be prevented, and cord blood serology can be omitted.

D antibodies in pregnant women in multiethnic Suriname: the observational RheSuN study.

Maternal antibodies against the D antigen are the most common cause of severe hemolytic disease of the fetus and newborn (HDFN). In high-income countries, the risk of D immunization has been reduced by routine antenatal and postpartum administration of RhIG from 13% to less than 0.5%. In less-resourced countries, such as Suriname, red blood cell (RBC) antibody screening during pregnancy and prophylactic RhIG administration are not routine. Accurate data on D immunization risk is not available. In the RheSuN (Rhesus Surinamese Neonates) study, the prevalence and the hemolytic potential of maternal D antibodies were investigated. A multicenter cross-sectional study in four major hospitals in Paramaribo, Suriname, covering 90% of approximately 10,000 births yearly in Suriname. Included were D- pregnant women of various ethnicities seeking routine prenatal care and/or their newborns. D antibodies were detected in 19 of 214 D- pregnancies (8.9%; 95% confidence interval, 5.1%-12.7%), in 2.0% of primigravid and 11.7% of multigravid women. The direct antiglobulin test was positive in 11 of 13 tested D+ newborns. Determination of D antibody titers and antibody-dependent cell mediated cytotoxicity (ADCC) assay revealed three newborns at high risk for HDFN (ADCC > 50%). D immunization risk in Suriname women is comparable to the pre-anti-D prophylaxis era in high-income countries. Recommended is free-of-charge routine RBC antibody screening and prophylactic RhIG administration for women at risk for D antibody formation as part of standard of ante- and postnatal care.

What is it really? Anti-G or Anti-D plus Anti-C: Clinical Significance in Antenatal Mothers.

G antigen of Rh blood group system is present either along with D and/or C positive red cells. Hence, [serologically anti-G presents with the similar picture as that of multiple antibodies (anti-D + anti-C). Differentiating them is important as anti-D + anti-C causes severe hemolytic disease of the fetus and newborn than anti-G. In pregnancies with anti-G alone, alloimmunization due to D antigen could be prevented by prophylactic administration of RhIg. Differentiating between anti-D+C from anti-G in alloimmunized pregnant mothers becomes essential. Sera from antenatal mothers, whose antibody identification by 11-cell panel gave a pattern for anti-D and anti-C were selected. Extended phenotyping for Rh system was performed for these antenatal cases. Differential adsorption and elution testing using R2R2 cells initially and r'r cells subsequently were performed to distinguish anit-G from anti-D+anti-C. Antibody titers of these antibodies were determined and their clinical outcome in the newborn was followed. A pattern suggestive of anti D and anti C on antibody identification were observed in six antenatal cases. On further workup 50% of them confirmed to have anti G. Antibody titers of anti-G and anti-C were lower than that of Anti-D. All newborns were sensitized in vivo and the antibody specificity in them were confirmed with elution studies. The mothers who had only anti-G were subsequently administered with an appropriate dose of RhIg.Differential adsorption and elution studies help in identifying anti-G and distinguishing it from anti-D plus anti-C, thus helping in better patient management.

Resolving variable maternal D typing using serology and genotyping in selected prenatal patients.

RhIG prophylaxis for D- pregnant women prevents hemolytic disease of the newborn and typically depends on results of serologic D typing. Interpretation and follow-up of weak D serology is variable. Recent recommendations promote genotyping for RHD status determination in those with weak D serology. Canadian Blood Services performs comprehensive serologic prenatal testing in four provinces. Genotyping is used to determine D typing in patients with weak D. A serologic algorithm identified which patients require genotyping for RHD determination. Genotyping was performed on one of two commercially available platforms. Only 0.4% of D- patients met criteria for genotyping. Sixty-one percent were weak D Type 1, 2, or 3. Thirty percent had a partial or weak D other than Type 1, 2, or 3. Eleven had variants which remained unresolved. Seventeen were D+ and four were D-. Genotyping of patients with weak D serology led to an identified genotype in most patients. RhIG administration was avoided in 66% who were weak D Type 1, 2, or 3 or were D+. The use of a serologic algorithm to select patients for RHD genotyping identifies a majority of patients with weak D types not at risk for alloimmunization. This approach limits the number of genotyping investigations and the cost of providing classification for weak D types.

763: Intravenous drug use is associated with alloimmunization in pregnancy

Anecdotal evidence has suggested an association of intravenous drug abuse (IVDU) with alloimmunization (AI), however published data are limited to case reports. The objective of this study is to determine if women with a history of IVDU have an increased risk of AI. A retrospective cohort study was performed using data from a single-center perinatal database from 2008-2014. IVDU was ascertained from a comprehensive database capturing all IVDU in pregnancy since 2008. Blood bank data was used to identify women with AI, defined as a positive antibody screen in pregnancy not due to a naturally occurring antibodies, agglutinins, or RhIG administration. Charts were abstracted for cases of AI with clinically significant antibodies. For women contributing more than one pregnancy to the database, only the most recent affected pregnancy was included. The rates of AI in the IVDU and general obstetric populations were compared using chi-squared. The distribution of alloantibody types, proportion of Rh-group alloantibodies, and patient Rh status were assessed for IVDU- and non-IVDU-associated AI. AI was more common in IVDU (11 of 305, 3.6%) compared with non-IVDU women (288 of 16,022, 1.8%, p=0.02). This finding persisted among women with clinically significant alloantibodies, (2.6% vs 0.8%, p<0.001). Needle sharing was documented in 7 and suspected in 3 IVDU women. No IVDU women had a history of transfusion. The distribution of alloantibodies was different between IVDU- and non-IVDU-associated AI (Figure). Rh group alloantibodies and Rh negative status were more common in IVDU women. Among Rh negative IVDU women, 50% of RhD AI cases were in nulliparas. The rate of multiple alloantibodies was not different between IVDU and non-IVDU AI. (Table) Maternal history of IVDU is associated with an increased risk of AI. Approximately 1 in 30 IVDU women will be sensitized in pregnancy. Given the current US opioid epidemic, increased vigilance in screening is required. Needle sharing represents a possible mechanism for IVDU-associated AI, however limited obstetric care, failure to obtain RhIG, or failure to identify early pregnancy loss cannot be excluded.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Hemolytic disease of the fetus and newborn: managing the mother, fetus, and newborn.

Hemolytic disease of the fetus and newborn (HDFN) affects 3/100 000 to 80/100 000 patients per year. It is due to maternal blood group antibodies that cause fetal red cell destruction and in some cases, marrow suppression. This process leads to fetal anemia, and in severe cases can progress to edema, ascites, heart failure, and death. Infants affected with HDFN can have hyperbilirubinemia in the acute phase and hyporegenerative anemia for weeks to months after birth. The diagnosis and management of pregnant women with HDFN is based on laboratory and radiographic monitoring. Fetuses with marked anemia may require intervention with intrauterine transfusion. HDFN due to RhD can be prevented by RhIg administration. Prevention for other causal blood group specificities is less studied.

Accurate quantitation of D+ fetomaternal hemorrhage by flow cytometry using a novel reagent to eliminate granulocytes from analysis

Quantitation of fetomaternal hemorrhage (FMH) is performed to determine the dose of prophylactic anti-D (RhIG) required to prevent D immunization of D- women. Flow cytometry (FC) is the most accurate method. However, maternal white blood cells (WBCs) can give high background by binding anti-D nonspecifically, compromising accuracy. Maternal blood samples (69) were sent for FC quantitation of FMH after positive Kleihauer-Betke test (KBT) analysis and RhIG administration. Reagents used were BRAD-3-fluorescein isothiocyanate (FITC; anti-D), AEVZ5.3-FITC (anti-varicella zoster [anti-VZ], negative control), anti-fetal hemoglobin (HbF)-FITC, blended two-color reagents, BRAD-3-FITC/anti-CD45-phycoerythrin (PE; anti-D/L), and BRAD-3-FITC/anti-CD66b-PE (anti-D/G). PE-positive WBCs were eliminated from analysis by gating. Full blood counts were performed on maternal samples and female donors. Elevated numbers of neutrophils were present in 80% of patients. Red blood cell (RBC) indices varied widely in maternal blood. D+ FMH values obtained with anti-D/L, anti-D/G, and anti-HbF-FITC were very similar (r = 0.99, p < 0.001). Correlation between KBT and anti-HbF-FITC FMH results was low (r = 0.716). Inaccurate FMH quantitation using the current method (anti-D minus anti-VZ) occurred with 71% samples having less than 15 mL of D+ FMH (RBCs) and insufficient RhIG calculated for 9%. Using two-color reagents and anti-HbF-FITC, approximately 30% patients had elevated F cells, 26% had no fetal cells, 6% had D- FMH, 26% had 4 to 15 mL of D+ FMH, and 12% patients had more than 15 mL of D+ FMH (RBCs) requiring more than 300 μg of RhIG. Without accurate quantitation of D+ FMH by FC, some women would receive inappropriate or inadequate anti-D prophylaxis. The latter may be at risk of immunization leading to hemolytic disease of the newborn.

Acute Hemolytic Reactions Reported in ITP Patients Treated with Rho (D) Immune Globulin: Symptom Onset and Does Prior Exposure Lessen the Risk?

Abstract 4670 BACKGROUND:Acute hemolytic reactions (AHR) associated with administration of Rho (D) Immune Globulin (RhIG; WinRho® SDF, Cangene Corporation, Winnipeg, Canada) have been infrequently reported during the previous 16 years. AHR were defined as any case reported with signs of hemolysis (hemoglobin decrease, haptoglobin decrease, LDH increase, elevation of bilirubin, etc.) occurring within hours to a number of days after RhIG administration irrespective of the degree of change from baseline. Intravascular hemolysis (IVH) was defined as a specific type of AHR in which plasma or urinary hemoglobin were positive. The reporting rate of AHR (including IVH) among RhIG-treated patients was previously estimated as 1/946 doses (0.11%), while the estimated reporting rate of IVH was 1/3,271 doses (0.03%).1 Reports surrounding the clinical monitoring of such patients have led to the analysis of AHR post-marketing data. AIMS/PURPOSE:Identify the onset of AHR/IVH symptoms relative to RhIG and determine if prior exposure to RhIG mitigates the risk of such events. METHODS:Retrospective evaluation of AHR (AEs reported with signs of hemolysis; including IVH) from the Cangene post-marketing surveillance database. RESULTS:Table 1Onset of AHR Symptoms (January 1995 to May 14, 2011)Onset of Symptoms (hr)Definite IVH† (%)Other AHR (%)Total AHR* (%)0–23227282–4813124–65236–85330–85045468–1221112–2413101124–4878848–7221210>7281110Unk181310Totaln=60n=146n=206†Demonstrated plasma hemoglobinemia and/or hemoglobinuria*All serious cases receiving RhIG for the ITP indication, with or without information on receiving their first dose or having previous treatment with RhIG.Table 2Effect of Prior Exposure on Risk of AHR: Prior Use of RhIG (January 1995 to May 14, 2011)IVHAHR*RhIG Treatment Naïve (%)31 (84%)94 (80%)RhIG Treatment Experienced (%)6 (16%)24 (20%)Total Cases†n=37n=118*Including IVH†Consists of serious cases of ITP patients receiving RhIG with history of receiving/not receiving prior dosage of RhIG. Patients for whom no information was provided surrounding prior RhIG were excluded from the analysis. CONCLUSION:Of the ITP patients who developed IVH, 40% reported an onset of symptoms within 4 hours of RhIG infusion; an additional 10% reported symptoms within 8 hours. The symptom onset was unidentified in 18% of IVH cases. In addition, previous uneventful administration of RhIG did not preclude the possibility of an occurrence of IVH and its complications following subsequent administration of RhIG; however, the majority (approx 84%) of reports of IVH were among RhIG naïve patients. Disclosures:Muller:Cangene: Employment. Little:Cangene: Employment. Hess:Cangene: Employment. Sinclair:Cangene: Employment.

RBC antibody persistence.

A person exposed to foreign blood group antigens may produce antibodies. The persistence of antibodies varies among people and among antibodies. A study was performed to investigate the persistence of clinically significant RBC alloantibodies over a period of 20 years. A retrospective examination was performed of all records of RBC antibodies in the transfusion laboratory computer database from 1978 through 1997. Records of patients who underwent at least one antibody investigation after an antibody had been detected were studied. The study included all antibodies against the Rh, K, Fy, Jk, and MNs blood group systems. An antibody was regarded as not persistent if, after previous detection, the screening or panel studies became negative for the antibody under study. Anti-D due to RhIg administration was excluded. An analysis was performed of 480 records consisting of 593 antibodies that fulfilled the criteria. Median antibody follow-up was 10 months (range, 1-240). In 137 patients, 153 (26%) antibodies became undetectable over the course of time. After initial negative screening investigations, 310 antibodies were formed. The antibodies that were still detectable had a median follow-up of 7 months (range, 1-193). A patient's age, sex, and antibody specificity were of no influence on the length of time that antibodies were detectable. Antibodies detected with a more sensitive screening technique were less persistent (p = 0.0002). For 28 patients, detection of antibodies was highly irregular. About 25 percent of all antibodies became undetectable over the course of time. The antibody screening technique used, rather than the antibody specificity, affected these results. To prevent delayed hemolytic transfusion reactions, precise antibody documentation is of great importance.

Antenatal suppression of Rh alloimmunization.

For more than the past decade, attempts have been made to suppress HDN by the administration of drugs or biologic materials to the Rh-immunized pregnant woman. With the possible exceptions of IGIV therapy and plasma exchange substitution of IGIV for maternal IgG, all such attempts have been ineffective. On the other hand, antenatal administration of RhIg (300 micrograms at 28-30 weeks' gestation) to the pregnant, unimmunized Rh-negative woman is very effective in preventing Rh immunization and is now the accepted standard of obstetric care. Physicians who neglect to carry out antenatal prophylaxis neglect to do so at their patient's and their own peril.

Failures of intravenous Rh immune globulin prophylaxis: an analysis of the reasons for such failures.

Universal administration of an ion exchange column prepared Rh immune globulin (RhIG-IV) antepartum at 28 weeks' gestation and postpartum to 9,295 Rh negative women delivering Rh positive babies has reduced the prevalence of Rh immunization from the expected 601 to 25 (a protection rate of 95.9%). Rh immunization, despite universal Rh prophylaxis, developed in 25 women; eight before antenatal prophylaxis was administered, 17 after antenatal prophylaxis was administered. Residual Rh immunization is caused by small fetal transplacental hemorrhages (TPH) (greater than or equal to 0.01 mL of fetal blood) before antenatal prophylaxis (15%) and by significant fetal TPH (greater than or equal to 0.05 mL of fetal blood) between 30 and 38 weeks' gestation (18%); TPH was too great, in some instances, for residual passive Rh antibody to give protection. Although a reduction of 62% (five of eight) of early Rh immunization and 82% (14 of 17) of later Rh immunization might be achieved by addition of 16 weeks' to 20 weeks' gestation and 34 weeks' gestation Rh prophylaxis; and a reduction of 84% overall (21 of 25) might be achieved by universal fetal TPH screening every 2 weeks from 10 weeks' gestation until delivery, with administration of RhIG when a small early fetal TPH or a significant later fetal TPH is detected, all of these programs are costly in terms of prevention of perinatal mortality and in terms of cost per quality adjusted life year gained. We believe that the costs outweigh the benefit that would be achieved. Therefore, a residual Rh immunization prevalence of 0.24% to 0.31% during or after each Rh positive pregnancy in patients at risk is to be expected despite universal 28 weeks' gestation antenatal and postnatal Rh prophylaxis.