| 1. |
- Baker, Jillian M., et al.
(författare)
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Postnatal intervention for the treatment of FNAIT : a systematic review
- 2019
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Ingår i: Journal of Perinatology. - : Springer Science and Business Media LLC. - 0743-8346 .- 1476-5543. ; 39:10, s. 1329-1339
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Forskningsöversikt (refereegranskat)abstract
- Objective: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is associated with life-threatening bleeding. This systematic review of postnatal management of FNAIT examined transfusion of human platelet antigen (HPA) selected or unselected platelets, and/or IVIg on platelet increments, hemorrhage and mortality. Study design: MEDLINE, EMBASE and Cochrane searches were conducted until 11 May 2018. Result: Of 754 neonates, 382 received platelet transfusions (51%). HPA-selected platelets resulted in higher platelet increments and longer response times than HPA-unselected platelets. However, unselected platelets generally led to sufficient platelet increments to 30 × 10 9 /L, a level above which intracranial hemorrhage or other life-threatening bleeding rarely occurred. Platelet increments were not improved with the addition of IVIg to platelet transfusion. Conclusion: Overall, HPA-selected platelet transfusions were more effective than HPA-unselected platelets but unselected platelets were often effective enough to achieve clinical goals. Available studies do not clearly demonstrate a benefit for addition of IVIg to platelet transfusion.
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| 2. |
- Kjær, Mette, et al.
(författare)
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Maternal HPA-1a antibody level and its role in predicting the severity of Fetal/Neonatal Alloimmune Thrombocytopenia : a systematic review
- 2019
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Ingår i: Vox Sanguinis. - : Wiley. - 0042-9007. ; 114:1, s. 79-94
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: In Caucasians, fetal/neonatal alloimmune thrombocytopenia (FNAIT) is most commonly due to maternal HPA-1a antibodies. HPA-1a typing followed by screening for anti-HPA-1a antibodies in HPA-1bb women may identify first pregnancies at risk. Our goal was to review results from previous published studies to examine whether the maternal antibody level to HPA-1a could be used to identify high-risk pregnancies. Materials and Methods: The studies included were categorized by recruitment strategies: screening of unselected pregnancies or samples analyzed from known or suspected FNAIT patients. Results: Three prospective studies reported results from screening programmes, and 10 retrospective studies focused on suspected cases of FNAIT. In 8 studies samples for antibody measurement, performed by the monoclonal antibody immobilization of platelet antigen (MAIPA) assay, and samples for determining fetal/neonatal platelet count were collected simultaneously. In these 8 studies, the maternal antibody level correlated with the risk of severe thrombocytopenia. The prospective studies reported high negative predictive values (88–95%), which would allow for the use of maternal anti-HPA-1a antibody level as a predictive tool in a screening setting, in order to identify cases at low risk for FNAIT. However, due to low positive predictive values reported in prospective as well as retrospective studies (54–97%), the maternal antibody level is less suited for the final diagnosis and for guiding antenatal treatment. Conclusion: HPA-1a antibody level has the potential to predict the severity of FNAIT.
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| 3. |
- Kjeldsen-Kragh, Jens, et al.
(författare)
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Fetal/neonatal alloimmune thrombocytopenia : A systematic review of impact of HLA-DRB3∗01:01 on fetal/neonatal outcome
- 2020
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 4:14, s. 3368-3377
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Forskningsöversikt (refereegranskat)abstract
- The most common, severe cases of fetal and neonatal alloimmune thrombocytopenia among whites are caused by antibodies against human platelet antigen 1a (HPA-1a). The aims of this systematic review and meta-analysis are to determine the association between maternal HLA-DRB3∗01:01 and: (1) HPA-1a-alloimmunization and (2) neonatal outcome in children born of HPA-1a-immunized women. A systematic literature search identified 4 prospective and 8 retrospective studies. Data were combined across studies to estimate pooled odds ratios (ORs) and the associated 95% confidence intervals (CIs). The population represented by the prospective studies was more than 150 000. In the prospective studies, there were 64 severely thrombocytopenic newborns (platelet count < 50 × 109/L) of whom 3 had intracranial hemorrhage. The mothers of all 64 children were HLA-DRB3∗01:01+. The number of severely thrombocytopenic children born of HPA-1a-alloimmunized women in the retrospective studies was 214; 205 of whom were born of HLA-DRB3∗01:01+ women. For HLA-DRB3∗01:01- women, the OR (95% CI) for alloimmunization was 0.05 (0.00-0.60), and for severe neonatal thrombocytopenia 0.08 (0.02-0.37). This meta-analysis demonstrates that the risk of alloimmunization and of having a child with severe thrombocytopenia are both very low for HPA-1a- women who are HLA-DRB3∗01:01-.
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| 4. |
- Kappos, Ludwig, et al.
(författare)
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Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study
- 2018
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 391, s. 1263-1273
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Tidskriftsartikel (refereegranskat)abstract
- © 2018 Elsevier Ltd Background: No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor 1,5 modulator, on disability progression in patients with SPMS. Methods: This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatme nt arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings: 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. Interpretation: Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. Funding: Novartis Pharma AG.
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| 5. |
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| 6. |
- Winkelhorst, Dian, et al.
(författare)
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Antenatal management in fetal and neonatal alloimmune thrombocytopenia : A systematic review
- 2017
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 129:11, s. 1538-1547
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Forskningsöversikt (refereegranskat)abstract
- Several strategies can be used to manage fetal or neonatal alloimmune thrombocytopenia (FNAIT) in subsequent pregnancies. Serial fetal blood sampling (FBS) and intrauterine platelet transfusions (IUPT), as well as weekly maternal IV immunoglobulin infusion (IVIG), with or without additional corticosteroid therapy, are common options, but optimal management has not been determined. The aim of this systematic review was to assess antenatal treatment strategies for FNAIT. Four randomized controlled trials and 22 nonrandomized studies were included. Pooling of results was not possible due to considerable heterogeneity. Most studies found comparable outcomes regarding the occurrence of intracranial hemorrhage, regardless of the antenatal management strategy applied; FBS, IUPT, or IVIG with or without corticosteroids. There is no consistent evidence for the value of adding steroids to IVIG. FBS or IUPT resulted in a relatively high complication rate (consisting mainly of preterm emergency cesarean section) of 11% per treated pregnancy in all studies combined. Overall, noninvasive management in pregnant mothers who have had a previous neonate with FNAIT is effective without the relatively high rate of adverse outcomes seen with invasive strategies. This systematic review suggests that first-line antenatal management in FNAIT is weekly IVIG administration, with or without the addition of corticosteroids.
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