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

Kumpel, Belinda M.; Hazell, Matthew; Guest, A. R.; Dixey, J.; Mushens, Rosey; Bishop, Debbie; Wreford-Bush, Tim; Lee, Edmond

doi:10.1111/trf.12484

Cited by 9 publications

(9 citation statements)

References 40 publications

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“…In a future pregnancy with a D positive fetus, this could cause significant harm through HDFN. 10,11 The use of immunosuppressants during SOT is common practice. These studies support the potential for D sensitisation in immunosuppressed D negative SOT recipients, although the risk remains low.…”

Section: Follow-up Investigation Of D Positive Rbc Volumes and Prophylactic Anti-d Dose Advicementioning

confidence: 99%

“…This should provide guidance for preliminary investigation, prophylactic treatment and further investigation that reflects advice in D negative women following a D positive sensitising event. The FC test is well suited for this as it is rapid and inexpensive, 11 additionally the related PAD treatment is cost effective and safe. 19 The authors agree with current BSH guidance that samples should be referred for FC within 24 h of the SOT, 8 unfortunately for the referrals presented here, data relating to this characteristic was not available.…”

Section: Follow-up Investigation Of D Positive Rbc Volumes and Prophylactic Anti-d Dose Advicementioning

confidence: 99%

“…10 Anti-D is the most common antibody formed by D negative women and the most likely to cause severe haemolytic disease of the fetus and newborn (HDFN) in D positive babies. 10,11 An investigation by flow cytometry (FC) should be performed 24 h post-transplant for the determination of D positive RBCs. 8 Depending on the FC result the correct dose of prophylactic anti-D (PAD) should be administered to mitigate sensitisation to D antigen.…”

Section: Introductionmentioning

confidence: 99%

“…8 Depending on the FC result the correct dose of prophylactic anti-D (PAD) should be administered to mitigate sensitisation to D antigen. 8,9,11 Karakantza et al 12 suggested that D negative women of childbearing age should receive 500 IU PAD within 72 h of receiving a SOT from a D positive donor. Additionally, a FC test should be performed at the time of PAD administration.…”

Section: Introductionmentioning

confidence: 99%

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Quantitation of residual D positive red cells in D negative recipients of D positive solid organ transplants

Rosa

Hazell

2021

Transfusion Medicine

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Background: Solid organ transplants (SOT) from D positive donors are potentially sensitising events for D negative recipients. For this reason, it is important to quantify the presence of residual D positive red blood cells (RBCs) in the recipient's circulation and calculate the correct dose of prophylactic anti-D (PAD) required to prevent sensitisation. This is especially important in females of child-bearing potential where the presence of allo anti-D can, at worst, cause the death of the fetus in future pregnancies.Objective: This study aimed to identify the patient characteristics of D positive SOT cases referred to Red Cell Immunohaematology, NHSBT for flow cytometry investigation. This information could indicate improvements required in the current testing methodology, as well as to the calculations used to prescribe PAD for this patient group.Methods: Samples were investigated using a Beckman Coulter Navios Flow Cytometer using BRAD3-FITC (anti-D), AEVZ5.3-FITC (isotype matched negative control) and BIRMA17C-PE (granulocyte exclusion reagent). Mollison's calculation was used to estimate the dose of PAD required to prevent sensitisation in the D negative recipients. The calculation was adapted to consider the presence of organ donor D positive adult RBCs in the circulation of recipients instead of, larger, fetal RBCs.Results: Samples from 20 patients, all female, aged 14-53 years (one 2-year-old outlier) were referred from 2016 to September 2020. The transplants were-liver (n = 6), kidney (n = 6) and lung (n = 8). D positive cell populations were identified in 11 cases (0.1-8.0 ml); and required PAD (500-1500 IU). From these 20 patients, 10 sent a follow-up sample, where 8 required PAD top-up due to the detection of residual D positive cells (0.1-2 ml)-liver (n = 1), kidney (n = 1) and lung transplant (n = 6). Conclusion:All patients in the study were D negative females, in which 18 were considered by guidelines to be of childbearing potential (2-42 years old) and 2 were >50 years old. Referrals demonstrate an awareness for the correct calculation of PAD to prevent D sensitisation. The sample size is small, but top up requirement in 8/20 of cases demonstrates accurate quantification is clearly needed to ensure the appropriate dose of PAD is provided.

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Section: Follow-up Investigation Of D Positive Rbc Volumes and Prophylactic Anti-d Dose Advicementioning

confidence: 99%

Section: Follow-up Investigation Of D Positive Rbc Volumes and Prophylactic Anti-d Dose Advicementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Quantitation of residual D positive red cells in D negative recipients of D positive solid organ transplants

Rosa

Hazell

2021

Transfusion Medicine

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“…The efficacy of prophylactic anti-D Ig depends on removal of fetal RBC from the circulation by 72 hours 110 . Clinically, tests for FMH are performed to determine whether fetal D-positive RBC have been cleared by this time 111 . For initial clinical trials, pre-menopausal women are not enrolled because they might become D-immunised which could lead to HDFN in subsequent pregnancies.…”

Section: Analysis Of Data From Previous Clinical Trials Of Rbc Clearamentioning

confidence: 99%

Anti-D monoclonal antibodies from 23 human and rodent cell lines display diverse IgG Fc-glycosylation profiles that determine their clinical efficacy

Kumpel

Saldova

Koeleman

et al. 2020

Sci Rep

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Anti-D immunoglobulin (Anti-D Ig) prophylaxis prevents haemolytic disease of the fetus and newborn. Monoclonal IgG anti-Ds (mAb-Ds) would enable unlimited supplies but have differed in efficacy in fcγRIIIa-mediated ADCC assays and clinical trials. Structural variations of the oligosaccharide chains of mAb-Ds are hypothesised to be responsible. Quantitative data on 12 Fc-glycosylation features of 23 mAb-Ds (12 clones, 5 produced from multiple cell lines) and one blood donor-derived anti-D Ig were obtained by HPLC and mass spectrometry using 3 methods. Glycosylation of mAb-Ds from human B-lymphoblastoid cell lines (B) was similar to anti-D Ig although fucosylation varied, affecting ADcc activity. In vivo, two B mAb-Ds with 77-81% fucosylation cleared red cells and prevented D-immunisation but less effectively than anti-D Ig. High fucosylation (>89%) of mouse-human heterohybridoma (HH) and Chinese hamster ovary (CHO) mAb-Ds blocked ADCC and clearance. Rat YB2/0 mAb-Ds with <50% fucosylation mediated more efficient ADCC and clearance than anti-D Ig. Galactosylation of B mAb-Ds was 57-83% but 15-58% for rodent mAb-Ds. HH mAb-Ds had non-human sugars. These data reveal high galactosylation like anti-D Ig (>60%) together with lower fucosylation (<60%) as safe features of mAb-Ds for mediating rapid red cell clearance at low doses, to enable effective, inexpensive prophylaxis.

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Red cell disorders: anaemia, jaundice, polycythaemia and cyanosis

2022

Neonatal Haematology

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

Abstract: 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.

Cited by 9 publications

References 40 publications

Quantitation of residual D positive red cells in D negative recipients of D positive solid organ transplants

Quantitation of residual D positive red cells in D negative recipients of D positive solid organ transplants

Anti-D monoclonal antibodies from 23 human and rodent cell lines display diverse IgG Fc-glycosylation profiles that determine their clinical efficacy

Red cell disorders: anaemia, jaundice, polycythaemia and cyanosis

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