| 1. |
- Ahlen, Maria Therese, et al.
(författare)
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The Development of Severe Neonatal Alloimmune Thrombocytopenia due to Anti-HPA-1a Antibodies Is Correlated to Maternal ABO Genotypes
- 2012
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Ingår i: Clinical & Developmental Immunology. - : Hindawi Limited. - 1740-2530 .- 1740-2522.
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Tidskriftsartikel (refereegranskat)abstract
- Background. Maternal alloantibodies against HPA-1a can cross placenta, opsonize foetal platelets, and induce neonatal alloimmune thrombocytopenia (NAIT). In a study of 100, 448 pregnant women in Norway during 1995-2004, 10.6% of HPA-1a negative women had detectable anti-HPA-1a antibodies. Design and Methods. A possible correlation between the maternal ABO blood group phenotype, or underlying genotype, and severe thrombocytopenia in the newborn was investigated. Results. We observed that immunized women with blood group O had a lower risk of having a child with severe NAIT than women with group A; 20% with blood group O gave birth to children with severe NAIT, compared to 47% among the blood group A mothers (relative risk 0.43; 95% CI 0.25-0.75). Conclusion. The risk of severe neonatal alloimmune thrombocytopenia due to anti-HPA-1a antibodies is correlated to maternal ABO types, and this study indicates that the observation is due to genetic properties on the maternal side.
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| 2. |
- Axfors, Cathrine, et al.
(författare)
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Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
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Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Forskningsöversikt (refereegranskat)abstract
- Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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| 3. |
- 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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| 4. |
- Benediktsson, Sigurdur, et al.
(författare)
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Linear decline of corrected platelet count increment within 24 hours after platelet transfusion in haematological patients : a prospective observational study
- 2017
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Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; , s. 559-568
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of the present study was to prospectively explore the detailed longitudinal development of platelet increments in patients with chemotherapy-induced bone marrow aplasia during the first 24 hours after platelet transfusion.METHODS: Patients admitted to the Haematology department during 7 months and fulfilled inclusion criteria were divided into 4 groups: Group 1, patients with acute leukaemia; Group 2, patients after autologous stem cell transplantation (SCT); Group 3, patients after allogeneic SCT; Group 4, patients given platelet transfusion prior to intervention. We used frequent blood sampling within 24 hours after platelet transfusion to investigate the kinetics of platelet counts following transfusion.RESULTS AND CONCLUSIONS: 54 platelet transfusion occasions in patients with chemotherapy-induced bone marrow aplasia were included. The decrease of corrected count increment (CCI) 1-24 hours after platelet transfusions in all groups could be described as linear functions. For patients in the aggregated Groups 1-3, the decline was 2.0%± 0.6% (mean± standard deviation) per hour. For patients in Group 4, the decline of CCI was 2.8%± 1.2% per hour. We found no differences between the groups, either in the rate of platelet elimination from the bloodstream or in the mean CCI, in the first 24 hours post-transfusion. This article is protected by copyright. All rights reserved.
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| 5. |
- Bjurström, Martin F., et al.
(författare)
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Adherence to a restrictive red blood cell transfusion strategy in critically ill patients : An observational study
- 2024
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Ingår i: Acta Anaesthesiologica Scandinavica. - : John Wiley & Sons. - 0001-5172 .- 1399-6576.
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRandomized controlled trials relatively consistently show that restrictive red blood cell (RBC) transfusion strategies are safe and associated with similar outcomes compared to liberal transfusion strategies in critically ill patients. Based on these data, the general threshold for RBC transfusion was changed to 70 g/L at a 9-bed tertiary level intensive care unit in September 2020. Implementation measures included lectures, webinars and feedback during clinical practice. The aim of this study was to investigate how implementation of a restrictive transfusion strategy influenced RBC usage, haemoglobin trigger levels and adherence to prescribed trigger levels.MethodsIn this registry-based, observational study, critically ill adult patients without massive bleeding were included and divided into a pre-cohort, with admissions prior to the change of transfusion strategy, and a post-cohort, with admissions following the change of transfusion strategy. These cohorts were compared regarding key RBC transfusion-related variables.ResultsIn total 5626 admissions were included in the analyses (pre-cohort n = 4373, post-cohort n = 1253). The median volume (interquartile range, IQR) of RBC transfusions per 100 admission days, in the pre-cohort was 6120 (4110–8110) mL versus 3010 (2890–4970) mL in the post-cohort (p < .001). This corresponds to an estimated median saving of 1128 € per 100 admission days after a restrictive RBC transfusion strategy was implemented. In total, 26% of the admissions in the pre-cohort and 19% in the post-cohort (p < .001) received RBC transfusion(s) during days 0–10. Both median (IQR) prescribed trigger levels (determined by intensivist) and actual haemoglobin trigger levels (i.e., levels prior to actual administration of transfusion) were higher in the pre- versus post-cohort (90 [80–100] vs. 80 [72–90] g/L, p < .001 and 89 [82–96] g/L vs. 83 [79–94], p < .001, respectively). Percentage of days without compliance with the prescribed transfusion trigger was higher in the pre-cohort than in the post-cohort (23% vs. 14%, p < .001). Sensitivity analyses, excluding patients with traumatic brain injury, ischemic heart disease and COVID-19 demonstrated similar results.ConclusionsImplementation of a restrictive transfusion trigger in a critical care setting resulted in lasting decreased RBC transfusion use and costs, decreased prescribed and actual haemoglobin trigger levels and improved adherence to prescribed haemoglobin trigger levels.
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| 6. |
- Ernstsen, Siw L., et al.
(författare)
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Antenatal intravenous immunoglobulins in pregnancies at risk of fetal and neonatal alloimmune thrombocytopenia : comparison of neonatal outcome in treated and nontreated pregnancies
- 2022
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378. ; 227:3, s. 1-506
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Tidskriftsartikel (refereegranskat)abstract
- Background: Maternal alloantibodies to human platelet antigen-1a can cause severe intracranial hemorrhage in a fetus or newborn. Although never evaluated in placebo-controlled clinical trials, most Western countries use off-label weekly administration of high-dosage intravenous immunoglobulin in all pregnant women with an obstetrical history of fetal and neonatal alloimmune thrombocytopenia. In Norway, antenatal intravenous immunoglobulin is only recommended in pregnancies wherein a previous child had intracranial hemorrhage (high-risk) and is generally not given in other human platelet antigen-1a alloimmunized pregnancies (low-risk). Objective: To compare the frequency of anti-human platelet antigen-1a-induced intracranial hemorrhage in pregnancies at risk treated with intravenous immunoglobulin vs pregnancies not receiving this treatment as a part of a different management program. Study Design: This was a retrospective comparative study where the neonatal outcomes of 71 untreated human platelet antigen-1a-alloimmunized pregnancies in Norway during a 20-year period was compared with 403 intravenous-immunoglobulin-treated pregnancies identified through a recent systematic review. We stratified analyses on the basis of whether the mothers belonged to high- or low-risk pregnancies. Therefore, only women who previously had a child with fetal and neonatal alloimmune thrombocytopenia were included. Results: Two neonates with brain bleeds were identified from 313 treated low-risk pregnancies (0.6%; 95% confidence interval, 0.2–2.3). There were no neonates born with intracranial hemorrhage of 64 nontreated, low-risk mothers (0.0%; 95% confidence interval, 0.0–5.7). Thus, no significant difference was observed in the neonatal outcome between immunoglobulin-treated and untreated low-risk pregnancies. Among high-risk mothers, 5 of 90 neonates from treated pregnancies were diagnosed with intracranial hemorrhage (5.6%; 95% confidence interval, 2.4–12.4) compared with 2 of 7 neonates from nontreated pregnancies (29%; 95% confidence interval, 8.2–64.1; P=.08). Conclusion: The most reliable data hitherto for the evaluation of intravenous immunoglobulins treatment in low-risk pregnancies is shown herein. We did not find evidence that omitting antenatal intravenous immunoglobulin treatment in low-risk pregnancies increases the risk of neonatal intracranial hemorrhage.
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| 7. |
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| 8. |
- 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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| 9. |
- Holm, Karin, et al.
(författare)
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Convalescence plasma treatment of COVID-19 : results from a prematurely terminated randomized controlled open-label study in Southern Sweden
- 2021
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Ingår i: BMC Research Notes. - : BioMed Central. - 1756-0500. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Convalescent plasma has been tried as therapy for various viral infections. Early observational studies of convalescent plasma treatment for hospitalized COVID-19 patients were promising, but randomized controlled studies were lacking at the time. The objective of this study was to investigate if convalescent plasma is beneficial to hospitalized patients with COVID-19.Results: Hospitalized patients with confirmed COVID-19 and an oxygen saturation below 94% were randomized 1:1 to receive convalescent plasma in addition to standard of care or standard of care only. The primary outcome was number of days of oxygen treatment to keep saturation above 93% within 28 days from inclusion. The study was prematurely terminated when thirty-one of 100 intended patients had been included. The median time of oxygen treatment among survivors was 11 days (IQR 6–15) for the convalescent plasma group and 7 days (IQR 5–9) for the standard of care group (p = 0.4, median difference -4). Two patients in the convalescent plasma group and three patients in the standard of care group died (p = 0.64, OR 0.49, 95% CI 0.08–2.79). Thus no significant differences were observed between the groups.
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| 10. |
- Kander, Thomas, et al.
(författare)
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Bleeding complications after central line insertions: relevance of pre-procedure coagulation tests and institutional transfusion policy.
- 2013
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 57:5, s. 573-579
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study was to map pre-procedural variables for insertion of a central venous catheter, prophylactic blood component use and to investigate whether any independent variable could be identified as an independent risk factor for associated bleeding complications in patients outside the intensive care unit. METHODS: In this retrospective study, we investigated 1737 consecutive insertions of central venous catheters in 1444 patients in a large university hospital during 2009-2010. Pre-procedural coagulation status, blood component use, type of catheter, insertion site and complications during insertion were recorded and compared with bleeding complications documented on electronic charts. RESULTS: No serious bleeding complications were recorded in connection with the insertion of central venous catheters. Sixteen of 1769 (0.9%) insertions caused grade 2 bleeding, defined as bleeding requiring prolonged compression at the insertion site. Insertion of a large bore central dialysis catheter was found to be an independent risk factor for bleeding complications. Neither conventional coagulation tests nor accidental arterial puncture or the number of needle passes could predict bleeding complications in this study. CONCLUSION: This retrospective study, in non-ICU patients, shows that serious bleeding complications in association with central line insertions are uncommon and that insertion of a large bore catheter is likely to be an independent risk factor for mild-bleeding complications in this population.
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| 11. |
- 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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| 12. |
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| 13. |
- 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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| 14. |
- Kjeldsen-Kragh, Jens, et al.
(författare)
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Foetal and neonatal alloimmune thrombocytopenia – The role of the HLA-DRB3*01:01 allele for HPA-1a-immunisation and foetal/neonatal outcome
- 2020
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Ingår i: Transfusion and Apheresis Science. - : Elsevier BV. - 1473-0502. ; 59:1
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Forskningsöversikt (refereegranskat)abstract
- Foetal and neonatal alloimmune thrombocytopenia (FNAIT) is the platelet counterpart of haemolytic disease of the foetus and newborn. Among Caucasians, around 80 % of FNAIT cases and some of the most severe cases, are caused by alloantibodies against the human platelet antigen 1a (HPA-1a). For around 3 decades it has been known that almost all HPA-1a-immunised women are HLA-DRB3*01:01 positive. The HLA molecule encoded by the HLA-DRA/DRB3*01:01 genes seems to be of crucial importance for initiating the immune response against HPA-1a. The HLA-DRB3*01:01 carrier status is not only important as a risk factor for immunisation, but does also have a significant impact on foetal/neonatal outcome. The possible role of HLA-DRB3*01:01 typing as tool for risk stratification is discussed.
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| 15. |
- Kjeldsen-Kragh, Jens, et al.
(författare)
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HLA-DRB3*01:01 exhibits a dose-dependent impact on HPA-1a antibody levels in HPA-1a–immunized women
- 2019
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 3:7, s. 945-951
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Tidskriftsartikel (refereegranskat)abstract
- HLA-DRB3*01:01 is a predisposing factor for human platelet antigen 1a (HPA-1a) immunization, which is responsible for most cases of fetal and neonatal alloimmune thrombocytopenia. The aim of this study was to investigate if the HLA-DRB3*01:01 allele imposes a dose-dependent effect on anti-HPA-1a levels and neonatal platelet counts. One hundred and thirty HPA-1a–immunized women were divided into 3 groups: HLA-DRB3*01:01 negative, HLA-DRB3*01:01 hemizygous or heterozygous, and HLA-DRB3*01:01 homozygous. The dose of the HLA-DRB3*01:01 allele was determined by sequencing exon 2 of the HLA-DRB3 gene followed by HLA-DRB3 and HLA-DRB1 typing of selected samples. Anti-HPA-1a levels at time of delivery and neonatal platelet counts were compared among groups. There was a significant dose-dependent effect of the HLA-DRB3*01:01 allele on anti-HPA-1a levels (global P value [Pglobal] 5 .0032). Median (range) anti-HPA-1a levels were 1.5 IU/mL (0.0-19.0 IU/mL), 21.1 IU/mL (0.0-1967 IU/mL), and 43.7 IU/mL (1.0-980 IU/mL) in women with 0, 1, and 2 copies of the HLA-DRB3*01:01 allele, respectively. There was also a significant, but opposite, dose-dependent effect of the mother’s HLA-DRB3*01:01 allele on the platelet count of the newborn (Pglobal 5 .0155). Median (range) neonatal platelet counts were 241 3 109/L (59 3 109/L to 393 3 109/L), 107 3 109/L (4 3 109/L to 387 3 109/L) and 32 3 109/L (4 3 109/L to 352 3 109/L) for newborns of mothers with 0, 1, and 2 copies of the HLA-DRB3*01:01 allele, respectively. Thus, the HLA-DRB3*01:01 allele exhibits a dose-dependent impact on maternal anti-HPA-1a levels in HPA-1a–immunized women.
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| 16. |
- Kjeldsen-Kragh, Jens, et al.
(författare)
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Mechanisms and prevention of alloimmunization in pregnancy.
- 2013
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Ingår i: Obstetrical and Gynecological Survey. - 0029-7828. ; 68:7, s. 526-532
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Tidskriftsartikel (refereegranskat)abstract
- Transfusion only occasionally gives rise to antibody production, because blood cells per se are not markedly immunogenic. However, the immunological changes that occur during pregnancy increase the risk of alloimmunization against red blood cells, platelets, and/or leukocytes. Fetal-maternal bleeding during pregnancy or in relation to delivery is the antigenic stimuli for immunization against red blood cells, whereas other mechanisms, such as trophoblast-derived microparticles, may also play a role in the production of antibodies against platelets. Antibody-mediated immune suppression has for 4 decades successfully been used for prevention of RhD immunization. Result from a mouse model of fetal and neonatal alloimmune thrombocytopenia (FNAIT) suggests that the same principle may be applied for the prevention of FNAIT. A European Union-funded consortium is presently in the process of developing a hyperimmune anti-human platelet antigen 1a (HPA-1a) immunoglobulin G. The idea is to prevent HPA-1a immunization by administering the drug to nonimmunized HPA-1a-negative women after delivery of an HPA-1a-positive child. The anti-HPA-1a will be purified from plasma collected from women who previously have given birth to a child with FNAIT caused by anti-HPA-1a. If the results of the planned phase III trial are favorable, it is possible that a product for prevention of FNAIT will be available within this decade.
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| 17. |
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| 18. |
- 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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| 19. |
- Kjeldsen-Kragh, Jens, et al.
(författare)
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Towards a prophylactic treatment of HPA-related foetal and neonatal alloimmune thrombocytopenia.
- 2012
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Ingår i: Current Opinion in Hematology. - 1531-7048. ; 19:6, s. 469-474
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: The purpose of the review is to show the similarities between haemolytic disease of the foetus and newborn (HDFN) and foetal and neonatal alloimmune thrombocytopenia (FNAIT) and to describe the background and challenges related to the current endeavours of developing a prophylaxis against FNAIT. The rationale for this prophylaxis is similar to the prophylaxis which has been used with great success for the last 40 years against RhD-associated HDFN. The idea is to prevent human platelet antigen (HPA)-1a-associated FNAIT by administering anti-HPA-1a immunoglobulin G (IgG) to nonimmunized HPA-1a-negative women after delivery of an HPA-1a-positive child. RECENT FINDINGS: Results from a Norwegian screening and intervention study on FNAIT have indicated that about 75% of women with antibodies against HPA-1a are immunized in relation to delivery. This observation leads to the possibility of preventing HPA-1a-associated FNAIT in the same way as today's prevention of HDFN. Results from a proof-of-concept study in a murine FNAIT model have shown that the production of alloantibodies against platelets can be suppressed by administrating antiplatelet antibodies after the antigenic challenge. Even more interesting, the prophylactic antiplatelet antibodies could also significantly reduce the clinical consequences of FNAIT in this FNAIT model. SUMMARY: These novel observations have paved the way for clinical studies. Production and testing of anti-HPA-1a IgG for clinical use will be carried out by a European Union-funded consortium. If the results from the clinical trial are favourable, there is a chance that a medicinal product for the prevention of FNAIT will be available within this decade.
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| 20. |
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| 21. |
- Ljungquist, Oskar, et al.
(författare)
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Convalescent plasma treatment in severely immunosuppressed patients hospitalized with COVID-19 : an observational study of 28 cases
- 2022
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Ingår i: Infectious Diseases. - : Taylor & Francis Group. - 2374-4235 .- 2374-4243 .- 1651-1980. ; 54:4, s. 283-291
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Tidskriftsartikel (refereegranskat)abstract
- Background: Immunosuppressed patients are particularly vulnerable to severe infection from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), risking prolonged viremia and symptom duration. In this study we describe clinical and virological treatment outcomes in a heterogeneous group of patients with severe immunosuppression due to various causes suffering from COVID-19 infection, who were all treated with convalescent plasma (CCP) along with standard treatment.Methods: We performed an observational, retrospective case series between May 2020 to March 2021 at three sites in Skåne, Sweden, with a population of nearly 1.4 million people. All patients hospitalized for COVID-19 who received CCP with the indication severe immunosuppression as defined by the treating physician were included in the study (n = 28).Results: In total, 28 severely immunocompromised patients, half of which previously had been treated with rituximab, who had received in-hospital convalescent plasma treatment of COVID-19 were identified. One week after CCP treatment, 13 of 28 (46%) patients had improved clinically defined as a decrease of at least one point at the WHO-scale. Three patients had increased score points of whom two had died. For 12 patients, the WHO-scale was unchanged.Conclusion: As one of only few studies on CCP treatment of COVID-19 in hospitalized patients with severe immunosuppression, this study adds descriptive data. The study design prohibits conclusions on safety and efficacy, and the results should be interpreted with caution. Prospective, randomized trials are needed to investigate this further.
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| 22. |
- Nissen-Meyer, Lise Sofie H, et al.
(författare)
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Paroxysmal nocturnal haemoglobinuria at Oslo University Hospital 2000-2010.
- 2015
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Ingår i: Tidsskrift for Den Norske Lægeforening. - : Norwegian Medical Association. - 0807-7096 .- 0029-2001. ; 135:11, s. 1039-1043
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Paroxysmal nocturnal haemoglobinuria (PNH) is a rare haematological disease characterised by chronic haemolysis, pancytopenia and venous thrombosis. The condition is attributable to a lack of control of complement attack on erythrocytes, thrombocytes and leukocytes, and can be diagnosed by means of flow cytometry. In this quality assurance study, we have reviewed information from the medical records of all patients tested for PNH using flow cytometry at our laboratory over a ten-year period.MATERIAL AND METHOD In the period 2000-2010 a total of 28 patients were tested for PNH using flow cytometry at the Department of Immunology and Transfusion Medicine, Oslo University Hospital. We have reviewed the results of these examinations retrospectively together with information from medical records and transfusion data for the patients concerned.RESULTS Flow cytometry identified 22 patients with PNH: four with classic disease and 18 with PNH secondary to another bone marrow disease. Five patients had atypical thrombosis. Seventeen patients received antithymocyte globulin or drug treatment; of these, six recovered from their bone marrow disease, while six died and five had a need for long-term transfusion. Five patients with life-threatening bone marrow disease underwent allogeneic stem cell transplantation, three of whom died. Six of 22 patients received eculizumab; the need for transfusion has been reduced or eliminated in three patients treated with eculizumab over a longer period.INTERPRETATION Flow cytometry identified PNH in a majority of patients from whom we obtained samples. Most patients had a PNH clone secondary to bone marrow failure. Atypical thrombosis should be borne in mind as an indication for the test. Treatment with eculizumab is relevant for selected patients with PNH.
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| 23. |
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| 24. |
- Sørensen, Kirsten, et al.
(författare)
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Determination of fetal RHD type in plasma of RhD negative pregnant women
- 2018
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 78:5, s. 411-416
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Tidskriftsartikel (refereegranskat)abstract
- Alloimmunization against the RhD antigen is the most common cause of hemolytic disease of the fetus and newborn. Antenatal anti-D prophylaxis in addition to postnatal anti-D prophylaxis reduces the number of RhD-immunizations compared to only postnatal administration. Cell-free fetal DNA released from the apoptotic trophoblastic placental cells into the maternal circulation can be used to determine the fetal RHD type in a blood sample from an RhD negative mother. Based on this typing, antenatal anti-D prophylaxis can be recommended only to RhD negative women carrying an RhD positive fetus, since only these women are at risk of developing anti-D. The objective was to establish and validate a method for non-invasive fetal RHD typing. The fetal RHD genotype was studied in 373 samples from RhD negative pregnant women (median gestational week 24). DNA extracted from plasma was analyzed for the presence/absence of RHD exon 7 and 10 in a real-time PCR. The RHD genotype of the fetus was compared with the serological RhD type of the newborn. In 234 samples, the fetal RHD test was positive and in 127 samples negative. There was one false positive and no false negative results. In 12 samples, the fetal RHD type could not be determined, in all of them due to a maternal RHD gene. This method gives a reliable detection of fetal RHD positivity in plasma from RhD negative pregnant women. Antenatal anti-D prophylaxis based on the predicted fetal RhD type will avoid unnecessary treatment of pregnant women carrying an RhD negative fetus.
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| 25. |
- Tenje, Maria, et al.
(författare)
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Acoustophoretic removal of proteins from blood components
- 2015
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Ingår i: Biomedical microdevices (Print). - : Springer Science and Business Media LLC. - 1387-2176 .- 1572-8781. ; 17:5
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Tidskriftsartikel (refereegranskat)abstract
- This work presents the development of a miniaturized system for removing plasma proteins and other low-molecular-weight compounds from red blood cell (RBC) concentrate in a simple one-step-process using integrated ultrasound. The technology utilizes the principles of acoustophoresis to transfer the RBCs from the original plasma-containing solution into a protein-free SAG-M additive solution in a continuous flow process. The preparation of protein free RBC concentrate is important for blood transfusion to patients suffering from immunoglobulin A (IgA)-deficiency and developing antibodies against IgA. We show a nearly complete removal of both albumin and IgA from concentrated RBCs via this one-step-processes in samples obtained from RBC concentrate. The cell recovery of our technology is close to 97 %, compared to just above 90 % of the current procedure of repeated dilution and centrifugation steps. This work clearly shows the potential of integrated acoustophoresis in a miniaturized system for clinical applications.
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