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- Geisen, Christof, et al.
(författare)
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An HPA-1a–positive platelet–depleting agent for prevention of fetal and neonatal alloimmune thrombocytopenia : a randomized, single-blind, placebo–controlled, single-center, phase 1/2 proof-of-concept study
- 2023
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 21:4, s. 838-849
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a rare and potentially life-threatening bleeding disorder of the fetus/newborn. Antibodies against human platelet antigen 1a (HPA-1a) are associated with the most frequent FNAIT cases. There are no approved therapies for FNAIT prevention or treatment. RLYB211 is a polyclonal HPA-1a hyperimmune IgG being developed to prevent FNAIT. Objectives: To investigate whether a single dose of anti–HPA-1a (1000 IU) could markedly accelerate the elimination of HPA-1ab platelets transfused into healthy, HPA-1a–negative participants as compared with placebo. Methods: This randomized, single-blind, placebo–controlled, single-center, phase 1/2 proof-of-concept study (EudraCT: 2019-003459-12) included HPA-1a– and HLA-A2–negative healthy men. Cohort 1 received intravenous RLYB211 or placebo 1 hour after transfusion of HPA-1ab platelets. Cohort 1B received RLYB211 or placebo, followed by platelet transfusion 1 week later. Primary endpoint was the half-life of transfused platelets in circulation after administration of RLYB211 or placebo, determined by flow cytometry. Proof of concept was ≥90% reduction of half-life relative to placebo. Results: Twelve participants were allocated to cohort 1 or 1B and randomized to receive RLYB211 (n = 9) or placebo (n = 3). RLYB211 markedly accelerated the elimination of HPA-1ab platelets in all participants vs placebo. In cohort 1B, this effect was observed 7 days after RLYB211 administration. Two treatment–emergent adverse events were possibly related to treatment, both in RLYB211–treated participants. No participants developed HPA-1a antibodies at 12 or 24 weeks. Conclusion: These data support the hypothesis that anti–HPA-1a could be used as prophylaxis in women at risk of having an FNAIT–affected pregnancy.
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| 3. |
- Kjeldsen-Kragh, Jens, et al.
(författare)
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Risk of HPA-1a–immunization in HPA-1a–negative women after giving birth to an HPA-1a–positive child
- 2019
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Ingår i: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 59:4, s. 1344-1352
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is the platelet counterpart of hemolytic disease of the newborn. Most severe cases of FNAIT are caused by antibodies against human platelet antigen-1a (HPA-1a). HPA-1a–negative women giving birth to an HPA-1a–positive child are at risk of becoming HPA-1a–immunized, particularly women who are HLA-DRB3*01:01–positive. The aim of the study was to estimate the risk of HPA-1a–immunization in both HPA-1a–negative/HLA-DRB3*01:01–positive and HPA-1a–negative/HLA-DRB3*01:01–negative women after delivery of an HPA-1a–positive child. STUDY DESIGN AND METHODS: A literature search was conducted, which identified 10 prospective FNAIT studies. The risk of becoming HPA-1a–immunized postpartum was calculated by Bayes' theorem. The results of HLA-DRB3/4/5 typing of 212,472 European Caucasians from the National Marrow Donor Program were used as estimate of the frequency of the HLA-DRB3*01:01 allele. RESULTS: In HPA-1a–negative/HLA-DRB3*01:01–positive women, the risk of HPA-1a–immunization after delivery of an HPA-1a–positive child was estimated to 12.7% (95% confidence interval, 8.6%–16.8%) as compared to 0.5% (95% confidence interval, 0.1%–0.9%) in women who were HLA-1a–negative/HLA-DRB3*01:01–negative. Potential differences between nulliparous and multiparous and the role of one versus two doses of HLA-DRB3*01:01 could not be determined. CONCLUSION: In HPA-1a–negative/HLA-DRB3*01:01–positive women, the risk of HPA-1a–immunization is 12.7% after delivery of an HPA-1a–positive child, which is 25 times higher than in HPA-1a–negative/HLA-DRB3*01:01–negative women. Thus, the risk of HPA-1a–immunization in high-risk pregnancies is in the same range as the risk of RhD immunization in RhD-negative women after delivery of a RhD-positive child without RhD prophylaxis.
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