anti-D Ig Research Articles

Risk Factors for RhD Immunisation Despite Antenatal and Postnatal Anti-D Prophylaxis

Despite routine antenatal and postnatal administration of anti-D immunoglobulin (Ig) during pregnancy and delivery in a previous pregnancy, 0.1% to 0.3% of women are found to have Rhesus D (RhD) antibodies in their next pregnancy. The primary aim of this case-control study was to identify causative risk factors for rhesus D (RhD) immunization in the next pregnancy among women who had received adequate antenatal and postnatal anti-D prophylaxis in the previous pregnancy. A second aim was to evaluate the preventive effect of additional administration of anti-D Ig in such women with risk factors. Data obtained from the nationwide Dutch antenatal anti- D-prophylaxis program identified 42 new cases of RhD-immunized parae-1, detected with first-trimester screening, despite documented evidence of adequate antenatal and postnatal prophylaxis during the previous pregnancy. The controls were 339 parae-1 without red cell antibodies. Data on risk factors and other information was provided by the obstetric care worker and/or telephone interviews with the women. The primary study outcome measures were risk factors for RhD immunization. Multivariate analysis showed that statistically significant independent risk factors for RhD immunization were postmaturity (≥42 weeks of completed gestation) (odds ratio [OR], 3.07; 95% confidence interval [CI], 1.02-9.02), nonspontaneous delivery (assisted vaginal delivery or cesarean section) (OR, 2.23; 95% CI, 1.04-4.74), and age (OR, 0.89/yr; 95% CI, 0.80-0.98). Pregnancy-related red blood cell transfusion was almost significant; the OR was 3.51, with a 95% CI of 0.97 to 12.7. A condition related to increased feto-maternal hemorrhage and/or insufficient levels of anti-D Ig was observed in at least half of the failures of anti-D Ig prophylaxis. These findings provide direct evidence of causative risk factors for RhD immunization in the next pregnancy of women who had received adequate antenatal and postnatal anti-D prophylaxis in their previous pregnancy. The data show that RhD immunization may be further reduced by routine administration of extra anti-D Ig in these women.

Risk factors for RhD immunisation despite antenatal and postnatal anti-D prophylaxis.

ObjectiveTo identify risk factors for Rhesus D (RhD) immunisation in pregnancy, despite adequate antenatal and postnatal anti-D prophylaxis in the previous pregnancy. To generate evidence for improved primary prevention by extra administration of anti-D Ig in the presence of a risk factor.DesignCase–control study.SettingNation-wide evaluation of the Dutch antenatal anti-D-prophylaxis programme.PopulationCases: 42 RhD-immunised parae-1, recognised by first-trimester routine red cell antibody screening in their current pregnancy, who received antenatal and postnatal anti-D Ig prophylaxis (gifts of 1000 iu) in their first pregnancy. Controls: 339 parae-1 without red cell antibodies.MethodsData were collected via obstetric care workers and/or personal interviews with women.Main outcome measureSignificant risk factors for RhD immunisation in multivariate analysis.ResultsIndependent risk factors were non-spontaneous delivery (assisted vaginal delivery or caesarean section) (OR 2.23; 95% CI:1.04–4.74), postmaturity (≥42 weeks of completed gestation: OR 3.07; 95% CI:1.02–9.02), pregnancy-related red blood cell transfusion (OR 3.51; 95% CI:0.97–12.7 and age (OR 0.89/year; 95% CI:0.80–0.98). In 43% of cases, none of the categorical risk factors was present.ConclusionsIn at least half of the failures of anti-D Ig prophylaxis, a condition related to increased fetomaternal haemorrhage (FMH) and/or insufficient anti-D Ig levels was observed. Hence, RhD immunisation may be further reduced by strict compliance to guidelines concerning determination of FMH and accordingly adjusted anti-D Ig prophylaxis, or by routine administration of extra anti-D Ig after a non-spontaneous delivery and/or a complicated or prolonged third stage of labour.

Profilaxia antenatal da Isoimunização RH com imunoglobulina anti-d: Efectividade e riscos

Introduction: routine after delivery administration of immunoglobulin (Ig) anti-D, as well as its administration in risk events for transplacental bleeding, decreased the incidence of Rh isoimmunization of 17% to 0,83-1,5%.To minimize this risk it is now suggested its routine administration at antenatal period. Since this is derived from blood, it is necessary to consider the risks involved in its administration. Objectives: to review the available evidence on the Effectiveness and Risks of the routine anti-D Ig administration during pregnancy for prophylaxis of Rh Isoimmunization. Methods: search for articles from systematic review, meta-analyses, clinical trials, randomized controlled clinical studies and practice guidelines in Medline, MEB sites and index of RMP, published in Portuguese, English and Spanish, in the last 10 years. Conclusions: antenatal prophylaxis with Anti-D Ig (1.500 UI at 28 weeks or 500 UI at 28 and 34 weeks of gestation) is effective in preventing Rh Isoimmunization (SORT C).The doses used are insufficient to cause anaemia or clinical hemolysis in newborns and the risk of transmission of infectious diseases is low (SORT C). It would be advisable to do new studies with patient focused end-point to evaluate the impact of this measure on fetus/newborn mortality and morbidity.

Introduction

Introduction

Autoimmune thrombocytopenia related to chronic hepatitis C virus infection

Since the identification of hepatitis C virus (HCV) in 1989 as a causative agent for a number of the extrahepatic alterations related to HCV infection an underlying immune mediated pathogenetic mechanism has been postulated. HCV-associated thrombocytopenia may be considered complex and multifactorial in origin, since different mechanisms have been implicated in its pathophysiology. With respect to autoimmune thrombocytopenia in chronic HCV infection, the detection of specific antibodies against platelet glycoproteins have been reported only in a few studies, but no systematic study has been carried out. We examined the clinical, laboratory, and virological characteristics of a case series of 10 patients with autoimmune thrombocytopenia (platelet count <150·0 × 109/L) related to chronic HCV infection. Cases, six males and four females, aged 57·1 ± 12·6 years, presented high titers of antibodies against platelet glycoprotein (GP) IIb/IIIa, GP Ia/IIa, and/or GP Ib/IX, and no other mechanism involved in the pathogenesis of HCV-associated thrombocytopenia was identified. Furthermore, cases were not associated with particular HCV genotype. Complete platelet response was observed in two patients treated with pegylated interferon plus ribavirin, and partial platelet response was seen in two patients treated with anti-D Ig and one patient treated with corticosteroids. These findings indicate that an autoimmune mechanism may play a role in the pathogenesis of HCV-associated thrombocytopenia in a proportion of these patients.

Growth-Promoting Effect of Rh(D) Antibody on Human Pancreatic Islet Cells

Hyperinsulinism with islet cell hyperplasia is a frequent complication, of unknown cause, in hemolytic disease of the newborn, occurring in Rh(D)-positive infants of Rh-isoimmunized Rh(D)-negative mothers, but not in infants with other hemolytic disorders. We investigated the possibility that trans-placentally acquired anti-D Ig is the cause of both conditions. Monolayer cultures of human islet cells were exposed to sera from Rh-isoimmunized mothers and newborns, where jaundice, hyperinsulinism, and hypoglycemia in the infant had ensued. Parallel cultures with anti-D, specific anti-D monoclonal antibodies, normal human Ig (15 microg/ml), and serum controls were also undertaken. Islet cell proliferation was determined by [3H]thymidine incorporation. Insulin storage and chronic and acute insulin secretion to glucose were analyzed by RIA. Rh(D) surface antigen expression was determined on islet cells by flow cytometric analysis. Islet cell proliferation and insulin secretion were significantly greater in coculture with test sera (P < 0.01; n = 8) and with anti-D (P < 0.001; n = 8), compared with either controls or Ig. After 8 d of growth, the static incubation experiment showed a 3.5-fold response to glucose stimulus in all sera. Rh(D) antigen expression was detected on the islet cell surface by flow cytometry, and islet cell morphology was normal. Colocalization of the proliferation marker Ki67 with insulin by immunofluorescent staining further indicated that Rh(D) antibody promoted islet growth. The anti-Rh(D) islet cell proliferative effect generates neonatal hyperinsulinism in Rh isoimmunization. Anti-Rh(D) may have application for islet cell proliferation in diabetes mellitus treatment for Rh(D)-positive subjects. Further analysis is required.

Change of neutrophil count after treatment of intravenous immunoglobulin in children with idiopathic thrombocytopenic purpura

Purpose : The aim of this study was to investigate the incidence and course of neutropenia following intravenous immunoglobulin (IVIG) therapy in children with idiopathic thrombocytopenic purpura (ITP). Methods : From January 2001 to June 2006, fifty-four patients with ITP were enrolled in this study. Forty-two of 54 patients were treated with IVIG, while the other 12 were treated with anti-D immunoglobulin (Anti-D Ig). Post-treatment absolute neutrophil counts (ANC) were compared between patients who received IVIG and those who received Anti-D Ig. Comparison of post-treatment ANC between patients who treated with two different IVIG regimens (400 mg/kg/day for 5 days and 1 g/ kg/day for 2 days) was also performed. Results : Pretreatment ANC were not significantly different between the two treatment groups. After treatment with IVIG, 32 out of 42 patients (76.2%) showed more than 50% decrease of ANC from the baseline. On the other hand, only 2 out of 12 patients (16.7%) showed more than 50% decrease of ANC from the baseline after treatment Anti-D Ig. No significant difference was observed in the decline of ANC between the first IVIG treatment (42 patients) and repeated IVIG treatment groups (7 patients). There was no statistical difference in post-treatment ANC between patients who treated with two different IVIG regimens. The neutropenia induced by IVIG had resolved spontaneously in 38 out of 39 patients (97%) after several days. Conclusion : Neutropenia following IVIG administration may not be an uncommon finding in children with ITP. It seems to be transient and self limited.

Anti-D Immunglobulin in the Treatment of Childhood Chronic Idiopathic Thrombocytopenic Purpura.

Chronic idiopathic (immune) thrombocytopenic purpura (ITP) develops in approximately 20% of children with acute ITP. The therapies for chronic refractory ITP include splenectomy, steroids, intravenous immunoglobulin (Ig), anti-D Ig, monoclonal antibodies, danazol, chemotherapy, plasma exchange, and others. We report five 5 RhD-positive, pediatric, non-splenectomized patients with chronic immune thrombocytopenic purpura (ITP), treated with anti-D. Patients were refractory to steroids and high dose intravenous immunoglobulin (IVIG). The mean age of the patients was 10.5 years, duration of thrombocytopenia was more than 6 months, and the median platelet count was 6x 10(9)/l. Patients received a single intravenous dose of 75 microg/kg anti-D, and were monitored for response to treatment and adverse events. Complete blood cell and renal function tests were assessed at baseline and 1, 7, 14 and 28 days after infusion. By 24 hours after treatment two of patients had achieved a platelet count>20 x 10(9)/l. Mild headache, fever, or chills occurred in one patients and ameliorated with prednisone and acetaminophen premedication. None of the patients had more than 0.5 gm/dl fall in the hemoglobin level and renal dysfunction following anti-D infusion by day 1,7, 14, 28. A single 75 microg/kg dose of anti-D may increase the platelet count in some children with chronic resistant immune thrombocytopenic purpura with an acceptable safety profile. It is a valuable, safe, well tolerated, and cheap alternative to conventional chronic ITP treatments in selected non-splenectomized patients.

The issue of Anti-D: An integrated seamless approach from recognition of need to bedside administration

The appropriate and timely administration of Anti-D immunoglobulin to Rhesus (D) negative women who have delivered Rhesus (D) positive babies is a vital part of obstetric care. Anti-D has an especially high profile in Ireland because of the tragic inadvertent transmission of Hepatitis C to Irish women in past decades. We have reviewed our policy and procedures pertaining to the administration of Anti-D for sensitising events during pregnancy and postnatally, in the Mid-Western Health Board in 1999/2000. As a result, major changes were made in the storage, issue, recording and administration of Anti-D. New procedures in the transfusion laboratory and in the maternity hospital have been accepted by scientists and midwives and supported by haematology and obstetric medical staff. The pharmacy and haematology laboratory no longer have a role in this programme. IMPLEMENTATION OF MULTI-DISCIPLINARY CHANGE MANAGEMENT: As a result of these changes, the storage, issuing and tracking of Anti-D has become the responsibility of the hospital blood bank. Measurement offoeto-maternal haemorrhage (FMH) is now the responsibility of bio medical scientists in blood bank, utilising both flow cytometry (increasingly recognised as the gold standard method) and the Kleihauer method (Kleihauer-Betke). The programme has moved from a doctor-administered IV Anti-D Ig, to a midwife-administered IM preparation. Prescription remains the responsibility of the doctor. These changes are facilitated by the protocol guided issue of the appropriate dose of Anti-D Ig by bio medical scientists to midwives. The issue of the Anti-D Ig occurs simultaneously with issue of results of mother and baby's serology testing and estimation of volume of FMH. These major changes have been guided by audit and needs assessment and require close liaison between medical, nursing and laboratory scientific staff in haematology, transfusion and obstetrics. CRITICAL INCIDENT AUDIT-CASE REPORT: Before new procedures became official policy, a critical incident audit allowed us to pilot our protocol and to revise it using draft new procedures. In this critical incident we describe successful management of a patient with a large foeto-maternal haemorrhage. This incident supported the need for the procedural enhancements already underway. This critical incident re-emphasised the need for the planned systems improvements to be introduced quickly.

Treatment, outcome, and cost of care in children with idiopathic thrombocytopenic purpura

Data were reviewed on treatment patterns, outcome, and hospital charges for children with idiopathic thrombocytopenic purpura (ITP). Records of 186 children with ITP, seen between January 1997 and April 2001, were reviewed. Hospital charges for initial management and first re-treatment were calculated by combining physician, hospital, and pathology charges. Anti-D immune globulin [anti-D IG] was used in 32.3%, intravenous immune globulin [IVIG] in 22.6%, steroids in 22.6%, combination therapies in 8%, and 14.5% were observed. Two patients had CNS bleeding, one with intraventricular hemorrhage at diagnosis, and the other with a parietal bleed 1 year from diagnosis. There was no significant differences in time to reach platelet counts of 20, 50, or 150 (x 10(9)/L) across different treatment groups. There was no significant difference in median charges for the IVIG and anti-D IG groups for the initial treatment of ITP. However, the IVIG was significantly more expensive than steroids or observation. Charges for the anti-D IG group were higher than the observation group but not the steroid group. After drug charges were excluded, patients in the IVIG group had statistically higher charges compared to patients in anti-D IG group. Almost half the patients were re-treated. There was no significant difference between anti-D IG, IVIG, and steroid groups when initial and re-treatment charges were combined. The observation group remained least expensive. Outcome for children with ITP is similar regardless of initial management. There is not a statistically significant difference in hospital charges between patients treated with anti-D IG and IVIG. The IVIG-treated group tends to be more costly, but this is not due to drug charges. Re-treatment is common and decreases the difference in patient charges among initial therapies.

Indications of neutralising anti-idiotypic antibodies and selective proteolytic fragmentation in polyclonal anti-D IgG preparations

Proteolytic fragmentation is the only suggested cause of potency losses during storage of liquid human polyclonal anti-D Ig. Besides the effect of fragmentation, we have investigated the potential contribution of neutralising anti-idiotypic antibodies (anti-Ids). Potency changes during storage and/or upon pH reduction in anti-D IgG batches with or without addition of plasminogen and urokinase were quantitatively analysed by the autoanalyser (AA) method or by a special procedure of flow cytometry (FC). Moreover, simultaneous changes of the molecular size distribution pattern have been determined by size exclusion chromatography. In contrast to the AA procedure, the particular FC methodology was found to be almost insensitive to proteolysis comprising up to 30% of total IgG. Data interpretation was based on the assumption that both assays cannot detect Ids with neutralised paratopes. In the absence of detectable neutralisation (functional absence of anti-Ids), it could be demonstrated that the anti-D IgG subpopulation is more sensitive to fragmentation by endogenous protease as compared to the unrelated bulk. However, both methods detected batch- and assay-dependently variable potency losses during storage. Moreover, the increase of potency induced by pH reduction correlated with the increase of monomeric IgG, essentially on the expense of dimers. This finding was interpreted to indirectly indicate the neutralising action of anti-Ids known to be the major driving force of dimer formation in polyclonal IgG. A more or less pronounced pH-dependent potency increase was also detectable in three arbitrarily selected batches of two other manufacturers. The data allows to assume that anti-Id-mediated neutralisation can significantly contribute to losses of anti-D potency. In addition, it turned out that anti-D plasma itself can be the source of anti-Ids.

Competitive enzyme-linked immunoassay of monoclonal immunoglobulin G anti-D preparations.

The development of monoclonal immunoglobulin G (IgG) anti-D for prophylaxis necessitates estimation of their potency in terms of their red cell-binding ability, but it is unclear which quantification methodology is most suitable for this. The aim of this study was to assess 50 monoclonal anti-D from the 4th International Workshop for quantitative and qualitative binding to red cells in a competitive enzyme-linked immunoassay (EIA) in which varying amounts of monoclonal antibodies (MoAbs) and a constant amount of biotinylated monoclonal anti-D (BRAD-5) compete for red cell binding. The potencies of the MoAb were estimated against the International Reference Preparation (IRP) for anti-D Ig. Two MoAbs as supplied were insufficiently inhibitory of biotinylated BRAD-5 binding to be quantified; the potencies of the remainder ranged from 4 to 343 IU mL-1 and included 11 MoAbs showing dose-responses that were nonparallel to those of other MoAb and the IRP. Estimation of the concentration of antibody in the supernatants by radial immunodiffusion ranged from 0.5 to 61 micro g mL-1, giving specific activities of <1-24 IU micro g-1. The results show that competitive EIA is suitable for quantitating most monoclonal anti-D for development and quality control purposes, regardless of their D epitope reactivity.

Rh-prophylaxis in early abortion

Rh-prophylaxis in early abortion

The Treatment of Patients with Autoimmune Thrombocytopenia with Intravenous IgG‐Anti‐D

Salama et al. [1] noticed that in patients with autoimmune thrombocytopenia (AITP) treated with high-dose i.v. Ig, the red cells became weakly sensitized with IgG antibodies, present in the i.v. Ig preparation. They concluded that the effect of i.v. Ig on the platelet count is due to a competition between sensitized red cells and platelets sensitized with auto-antibodies, for Fc-receptors (FcR) on splenic macrophages. This observation was the basis of their treatment of patients with AITP with i.v. anti-D IgG. Since the first publication of Salama et al. [2] on the subject, many patients have been treated in several centres. There is controversy concerning the question whether the effect of i.v. anti-D IgG is indeed due to a competition between sensitized red cells and sensitized platelets for FcR and therefore to the RhD antibodies themselves, or to other factors, also present in the anti-D preparation. This question is interesting from a theoretical but also from a practical point of view. There is a general shortage of anti-D Ig for immunoprophylaxis in D-negative women. If not the anti-D but other factors are responsible for the effect in AITP, anti-D Ig should not be used to treat patients with this disease. These considerations led us to devote an International Forum to this subject. The questions listed below were sent to 18 experts of whom 7 have contributed to the Forum. Questions (1) Do you, or your colleagues, treat patients with AITP with i.v. anti-D Ig or have you done so in the past? (2) If so, what have the results of this treatment been? (3) If treatment with anti-D causes an increase in the platelet count (a) do you think that this effect is due to a competition between anti-D IgG sensitized red cells and auto-antibody-sensitized platelets for FcR on macrophages? If so, how do you explain the simultaneous, often severe, destruction of red cells by IgG warm auto-antibodies and of platelets by auto-antibodies in Evans’ syndrome? (b) do you think that any effect on the platelet count is not due to anti-D but, e.g, to other antibodies present in the anti-D preparation? (c) do you have experience with anti-D treatment of Rh-D-negative patients with AITP? (d) do you have experience with anti-D treatment of patients with IgA platelet autoantibodies?

The estimation of fetomaternal haemorrhage

Prepared by a working party of the BCSH Blood Transfusion (Chairman P. Kelsey) and General Haematology (Chairman J. T. Reilly) Task Forces Working party: J. F. Chapman, B. J. Bain, S. C. Bates, S. M. Knowles, K. H. Shwe, J. Parker-Williams, L. Robson and S. C. Robson Blood Transfusion Task Force: M. Bruce, J. F. Chapman, J. Duguid, S. M. Knowles, M. F. Murphy, L. Williamson, I. Cavill and J. K. Wood Haematology Task Force: R. J. Amos, B. J. Bain, C. Chapman, K. Hyde, E. Matutes, J. Parker-Williams, I. Cavill and J. K. Wood

Production of pigs expressing multiple transgenes for use in xenotransplantation studies

Flow cytometry (FC) has been primarily applied to the diagnosis of hematological malignancies, and thereafter, to detection and quantification of CD34+ cells in bone marrow transplants, and granulocytes in neutropenias and paroxysmal nocturnal hemoglobinuria (PNH). In PNH and hereditary spherocytosis, changes in some of the erythrocyte membrane proteins are tested (CD59, CD55, and band 3). The purpose of this paper is to focus on the use of FC in RBC testing. With anti-D, -HbF, and -CA (carbonic anhydrase), we can detect RhD+, HbF+, and CA- fetal RBCs in the maternal RhD-, HbF-, and CA+ blood sample. Obtained results allow to select the appropriate dose of anti-D Ig in the RhD prophylaxis of feto-maternal incompatibility, or to detect the cause of fetal anemia. Expression of antigens and their weak variants, and concentration of specific antibodies, can also be assessed. It is possible to observe changes in selected CD molecules during storage of RBC units. If RBCs for transfusion are unavailable, due to patient's unusual antibody specificity, some of the available RBCs are opsonised, and then phagocytosis with the recipient monocytes is assessed. The microscopic time-consuming and subjective assay is usually used. Stained CD14+ monocytes and CD235a+ erythrocytes are visible on cytograms as well as their interaction. It makes evaluation of phagocytosis easier and objective. Microparticles of RBCs released during storage are also detected. They are 235a+. In differentiation of hemolysis causes, it is important to measure osmotic fragility, and that can be also achieved using FC. Flow cytometry should be applied to immunohematological testing of red blood cells more often than now.

Kleihauer Testing and Flow Cytometry. A Comparative Study for Assessment of Feto-Maternal Haemorrhage.

The Kleihauer test has been used world-wide for many years to quantify feto-maternal haemorhage, and to ensure that an appropriate dose of anti-D Immunoglobulin (anti-D Ig) is administered both ante-natally and postnatally to RhD negative women to prevent Rh alloimmunisation. Although apparently a simple test to perform, recent reports have suggested that unless meticulous attention is paid to both technique and interpretation, the accuracy of the test cannot be guaranteed. It is suggested that it should be replaced with a flow cytometric test for the presence of fetal RhD positive cells which would give more relevant and accurate results. Flow cytometers are not, however, available to all laboratories performing estimations of feto-matemal haemorrhage (FMH). This study was undertaken to assess the comparability of results obtained using a standardised Kleihauer technique with results obtained using a variety of techniques within hospital laboratories and with flow cytometry. A total of 957 samples were analysed, referring hospitals initially performing a routine Kleihauer test and then forwarding the same sample to the Mersey Transfusion Centre where a standardised Kleihauer test and flow cytometric analysis of FMH were performed. Our results showed that there is variation in Kleihauer results, even when the same sample is used, particularly in quantifying an FMH for which additional anti-D Ig may be required. The tendency however, appears to be to over-estimate the size of FMH and administer unnecessary anti-D Ig. Our results suggest that if careful attention is paid to performing a standardised Kleihauer test, then it is of value in estimating the size of FMH, and that flow cytometry may be of additional value for cases in which the Kleihauer result is equivocal or indicates that a large FMH has occurred which requires the administration of additional anti-D Ig.

Human Rh D Monoclonal Antibodies (BRAD-3 and BRAD-5) Cause Accelerated Clearance of Rh D+ Red Blood Cells and Suppression of Rh D Immunization in Rh D- Volunteers

The use of prophylactic anti-D to prevent Rh D immunization in Rh D- women and subsequent hemolytic disease in Rh D+ infants is widespread, but has led to shortages of the anti-D Ig. With the aim of substituting monoclonal anti-D for Rh D prophylaxis, we have compared the abilities of monoclonal and polyclonal anti-D to clear Rh D+ red blood cells (RBCs) infused into Rh D- male volunteers and to suppress Rh D immunization. Two human monoclonal antibodies (MoAbs), BRAD-3 (IgG3) and BRAD-5 (IgG1), produced from stable Epstein-Barr virus-transformed B-lymphoblastoid cell lines, were selected because of their proven in vitro activity in promoting RBC lysis in antibody-dependent cell-mediated cytotoxicity assays. RBC clearance was assessed by intravenous injection of 3 mL of 51chromium-labeled D+ RBCs into 27 volunteers 48 hours after intramuscular injection of monoclonal or polyclonal anti-D. Further 3-mL injections of unlabeled D+ cells were administered at 6 and 9 months to induce immunization. Blood samples were taken throughout the 12-month period of study for the serologic detection of anti-D. The mean half-life (t50%) of RBCs in 7 recipients of 300 micrograms BRAD-5 (5.9 hours) was similar to that in 8 recipients of 500 IU polyclonal anti-D (5.0 hours), whereas D+ cells were cleared more slowly in some of the 8 subjects injected with 300 micrograms BRAD-3 (mean t50% 12.7 hours) and in 1 individual administered 100 micrograms BRAD-3 (t50% 41.0 hours). The rate of RBC clearance in both groups administered 300 micrograms monoclonal anti-D correlated with the amount of antibody bound per cell, determined by flow cytometry. There was no evidence of primary immunization having occurred in any subject after 6 months of follow-up. Five of 24 subjects produced anti-D after one or two further injections of RBCs, confirming that they were responders who had been protected by the monoclonal or polyclonal anti-D administered initially. Four of these responders were recipients of monoclonal anti-D (3 BRAD-3, 1 BRAD-5). One individual who received BRAD-5 produced accelerated clearance of D+ RBCs at the third unprotected RBC challenge but did not seroconvert. This study shows that the human MoAbs BRAD-3 and BRAD-5 can prevent Rh D immunization, and indicates that they may be suitable replacements for the polyclonal anti-D presently used in prophylaxis of Rh D hemolytic disease of the newborn.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-D Ig for treatment of immune thrombocytopenic purpura [letter; comment

Anti-D Ig for treatment of immune thrombocytopenic purpura [letter; comment

Anti-D IG for Treatment of Immune Thrombocytopenic Purpura

Anti-D IG for Treatment of Immune Thrombocytopenic Purpura