Evaluating automated titre score as an alternative to continuous flow analysis for the prediction of passive anti-D in pregnancy.

OBJECTIVES: To evaluate the potential of the automated titre score (TS) as an alternative method to continuous flow analysis (CFA) for the prediction of the nature of anti-D in pregnancy. BACKGROUND: The 2016 revised British Society for Haematology (BSH) antenatal guidelines recommended a measurement of anti-D concentration by CFA to ensure the detection of potential immune anti-D. Due to high referral costs and resource pressures, uptake has been challenging for hospital laboratories. Serious Hazards of transfusion (SHOT) data have previously shown that this has contributed to missed antenatal follow ups for women with immune anti-D and neonates affected by haemolytic disease of the fetus/newborn. METHODS/MATERIALS: In this multicentre comparative study, samples referred for CFA quantification were also tested by an ORTHO VISION automated anti-D indirect antiglobulin test (IAT) serial dilution and then converted to TS. CFA results and history of anti-D prophylaxis were used to categorise samples as passive or immune, with the aim of determining a potential TS cut-off for CFA referral of at risk patients. RESULTS: Five UK National Health Service (NHS) trusts generated a total of 196 anti-D TS results, of which 128 were classified as passive and 68 as immune. Diagnostic testing of CFA and TS values indicated a TS cut-off of 35 to assist in distinguishing the nature of anti-D. Using this cut-off, 175 (89%) results were correctly assigned into the passive or immune range, giving a specificity of 92.19% and a negative predictive value of 91.47%. CONCLUSION: TS in conjunction with clinical and anti-D prophylaxis history can be used as a viable and cost-effective alternative to CFA in a hospital laboratory setting.

Noninvasive fetal RHD genotyping of RhD negative pregnant women for targeted anti-D therapy in Australia: A cost-effectiveness analysis.

OBJECTIVE: To undertake a cost-effectiveness analysis of noninvasive fetal RHD genotyping to target pregnant women for antenatal anti-D prophylaxis therapy. METHOD: A decision-analytic model was constructed to compare RHD testing and targeted anti-D prophylaxis, with current universal anti-D prophylaxis among pregnant women with RhD negative blood type. Model estimates were derived from national perinatal statistics, published literature, donor program records, and national cost sources. One-way sensitivity analyses addressed the uncertainty of variables on the main findings. RESULTS: The unit cost for RHD genotyping was estimated at AU$45.48 (US$31.84). The "mean cost per healthy baby" was AU$7495 (US$5247) for universal prophylaxis and AU$7471 (US$5230) for targeted prophylaxis. The findings were sensitive to the unit costs of anti-D 625 IU (AU$59-AU$88) (US$41-US$62), the genetic test (AU$36-AU$55) (US$25-US$39), and packaging/transport costs of the samples for testing (AU$15-AU$40, US$11-US$28 per sample). With RHD genotyping, 13 938 women would avoid antenatal anti-D prophylaxis at a total cost savings to the National Blood Authority of AU$2.1 million (US$1.5 million) per year. To the health system, net cost savings of AU$159 701 (US$111 791) per year (0.05%) were predicted for total health care costs. CONCLUSIONS: Given the vulnerable supply of donor plasma and other health concerns, RHD genotyping is an economically sound option for Australia.

Financial implications of RHD genotyping of pregnant women with a serologic weak D phenotype.

BACKGROUND: Hemolytic disease of the fetus and newborn, classically caused by maternal-fetal incompatibility of the Rh blood group D antigen, can be prevented by RhIG prophylaxis. While prophylactic practices for pregnant women with serologic weak D phenotypes vary widely, RHD genotyping could provide clear guidance for management. This analysis evaluated the financial implications of using RHD genotyping to guide RhIG prophylaxis among pregnant females. STUDY DESIGN AND METHODS: A Markov-based model was constructed to evaluate the costs of RHD genotyping for pregnant females with serologic weak D phenotypes to inform RhIG prophylaxis. Using a comparison strategy of managing these women conservatively as D-, direct medical costs were assessed over 10- and 20-year periods for a simulated population of US women. One-way and probabilistic sensitivity analyses were used to assess the robustness of conclusions. RESULTS: Using base-case variables, RHD genotyping for pregnant women with serologic weak D phenotypes is expected to marginally reduce overall costs. RHD genotyping these patients, rather than conservatively managing them as D-, would be cost-saving when the cost of genotyping is below $256. Genotyping would decrease net costs among non-Hispanic Caucasian females (-$0.17/pregnancy), but would increase costs among non-Hispanic African Americans (+$0.51/pregnancy), non-Hispanic American Indian/Alaskans (+$0.10/pregnancy), and Hispanics (+$0.37/pregnancy). Incorporating RHD genotyping would not significantly impact costs among Asians and Hawaiians/Pacific Islanders. CONCLUSIONS: Using RHD genotyping to guide RhIG prophylaxis among pregnant women with serologic weak D phenotypes may be clinically beneficial without increasing overall costs.

Molecular genetics and clinical applications for RH.

Rhesus is the clinically most important protein-based blood group system. It represents the largest number of antigens and the most complex genetics of the 30 known blood group systems. The RHD and RHCE genes are strongly homologous. Some genetic complexity is explained by their close chromosomal proximity and unusual orientation, with their tail ends facing each other. The antigens are expressed by the RhD and the RhCE proteins. Rhesus exemplifies the correlation of genotype and phenotype, facilitating the understanding of general genetic mechanisms. For clinical purposes, genetic diagnostics of Rhesus antigens will improve the cost-effective development of transfusion medicine.

Cost implications of routine antenatal administration of Rh immune globulin.

Using decision analysis, we estimated the benefits, risks, and costs of a program for routine antepartum administration of Rh immune globulin to Rh-negative primiparous women, who were studied through their second deliveries. The number of births of second-order infants with Rh hemolytic disease of the newborn averted by an antepartum program for 10,000 Rh-negative primiparous women was estimated by race to be white, 14; black, 18; and Asian, 35. For all races, the costs incurred by an antepartum program were more than double the costs averted. Sensitivity analyses showed that the most crucial factor influencing the benefits of routine antepartum administration of Rh immune globulin is the probability of severe chronic disability from hemolytic disease of the newborn. Current data are unavailable for the probability of this event. Another factor affecting the program's benefits is the rate of antepartum Rh sensitization among primiparous women. If the program were restricted to primiparous women at high risk for antepartum Rh sensitization, its benefits might exceed its costs.

The economics of routine antenatal anti-D prophylaxis for pregnant women who are rhesus negative.

OBJECTIVE: To investigate the economics of routine antenatal anti-D prophylaxis in the prevention of haemolytic disease of the newborn, in support of the NICE appraisals process. DESIGN: Cost effectiveness analysis. SETTING: UK NHS. POPULATION/SAMPLE: Pregnant women who are RhD-negative. METHODS: A model was constructed to estimate the incremental cost effectiveness and cost utility of: (1) offering routine antenatal anti-D prophylaxis to all pregnant women who are RhD-negative; (2) offering routine antenatal anti-D prophylaxis to RhD-negative primigravidae, compared with conventional management alone. Effectiveness estimates were derived from a meta-analysis of two UK community-based studies. Costs were derived from published sources and NHS product lists. Threshold analysis was conducted to reflect the social value of routine antenatal anti-D prophylaxis through incorporating valuations of parental grief and fetal/neonatal loss. MAIN OUTCOME MEASURES: Cost per life year gained and cost per quality adjusted life year (QALY) gained. RESULTS: The cost per life year gained is in the range pound 5,000- pound 15,000. The inclusion of long term neurodevelopmental problems results in a cost utility ranging between pound 11,000 and pound 52,000 per QALY gained. Threshold analysis suggests that if fetal loss, parental grief and subsequent high intervention pregnancy are valued at greater than 9 QALYs, the comprehensive policy would be more attractive than the primigravidae policy, assuming a maximum acceptable threshold of pound 30,000 per QALY. CONCLUSION: Routine antenatal anti-D prophylaxis provides a cost effective intervention for preventing haemolytic disease of the newborn in the pregnancies of women who are RhD-negative.

[Clinical aspects of prenatal prevention of rhesus incompatibility]. / Klinische Aspekte der antenatalen Rhesus-Prophylaxe.

The postnatal treatment with anti-D immunoglobulin to prevent rhesus sensitization is successful in about 90% of all rhesus-negative mothers at risk. Failures derive mostly from large fetomaternal hemorrhages during the last months of pregnancy. Studies from Canada, Great Britain and Sweden have shown that the injection of an additional dosage of anti-D during the 28th to 34th week of pregnancy results in a further 90% reduction of the failure rate. Although there is only a limited number of cases of hemolytic diseases in the newborn, the cost-effect ratio of this prophylactic treatment calculated for the Federal Republic of Germany shows not only a medical but also an economic benefit.

Cost-effectiveness of antenatal anti-D prophylaxis.

This paper estimates the incremental cost-effectiveness of providing antenatal anti-D prophylaxis in varying dose sizes to either primigravidae or all Rh D negative women. It presents a model for calculating the net cost per 1000 'at risk' women based on the costs of anti-D prophylaxis and the future NHS costs avoided. Incremental cost-effectiveness is measured in terms of the net cost per Rh D-alloimmunization and the net cost per Rh HD loss prevented. Programmes for Rh D negative primigravidae are more cost-effective than the same dose protocol extended to all Rh D negative women. The 1 x 1250 iu programme is the most cost-effective option.