Severe bleeding complications other than intracranial hemorrhage in neonatal alloimmune thrombocytopenia: a case series and review of the literature

Winkelhorst, Dian; Kamphuis, M.; Kloet, Liselotte C de; Zwaginga, Jaap Jan; Oepkes, Dick; Lopriore, Enrico

doi:10.1111/trf.13550

Cited by 32 publications

(31 citation statements)

References 21 publications

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“…[3][4][5][6] In the absence of population-based screening programs, the diagnosis of FNAIT is usually made after an incidental finding of neonatal thrombocytopenia or because of bleeding complications ranging from bruising or petechiae to intracranial hemorrhage in the fetus or newborn.…”

Section: Introductionmentioning

confidence: 99%

Antenatal management in fetal and neonatal alloimmune thrombocytopenia: a systematic review

Winkelhorst

Murphy

Greinacher

et al. 2017

Blood

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Key Points• The systematic review suggests that first-line antenatal management in FNAIT is weekly IVIG administration.• Noninvasive management is effective without the relatively high rate of adverse outcomes seen in invasive strategies.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. (Blood. 2017;129(11):1538-1547

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Section: Introductionmentioning

confidence: 99%

Antenatal management in fetal and neonatal alloimmune thrombocytopenia: a systematic review

Winkelhorst

Murphy

Greinacher

et al. 2017

Blood

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“…Comparison with other studies is relatively difficult due to the fact that the majority of authors have calculated FBS-related fetal loss and adverse outcome rates in relation to the total number of treated fetuses, rather than the total number of procedures performed in this population, which, by definition, would result in an higher reported rate of such complications [9, 12, 16, 18-21] (Appendix 1). Two reports did calculate the risk compared to the total number of procedures: Berkowitz et al [21] reported a rate of pregnancy loss similar to our data (0.6 vs. 0.8%) with, however, a rate of other adverse outcomes five times higher than in our series (6 vs. 0.8%), and Overton et al [19] reported a fetal loss rate of 2.4% (2/84 procedures) in a small series of 12 cases, including an unexplained fetal death occurring 7 days after an uncomplicated PLT IUT.…”

Section: Discussionmentioning

confidence: 99%

“…Our single FBS-related fetal loss (0.8%) occurred due to severe abdominal hemorrhage during FBS in a severely thrombocytopenic fetus (PLT count of 1 × 10 9 /L) in an (IVIG) untreated pregnancy. This was also prior to the recognition of the crucial importance of always having PLTs ready for transfusion at any FBS of a potentially thrombocytopenic fetus, which became routine practice following the report of Paidas et al [14-16]. There were no fetal losses in any of the IVIG-treated cases.…”

Section: Discussionmentioning

confidence: 99%

Management and Neonatal Outcomes of Pregnancies with Fetal/Neonatal Alloimmune Thrombocytopenia: A Single-Center Retrospective Cohort Study

et al. 2018

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Background: There is no consensus regarding the optimal antenatal treatment of fetal/neonatal alloimmune thrombocytopenia (F/NAIT). We aimed to review the fetal blood sampling (FBS)-related risk, fetal response to maternal intravenous immunoglobulin (IVIG), and cesarean section (CS) rate in pregnancies with a history of F/NAIT. Methods: Maternal demographics, alloantibodies, pregnancy management, fetal and neonatal outcomes, and index case characteristics were collected. Responders (R) and non-responders (NR) were defined as women treated with IVIG in whom fetal platelets (PLTs) were normal or low (< 50 × 10⁹/L). Results: An FBS-related risk occurred in 1.6% (2/119) of procedures. Maternal characteristics did not differ between responders (n = 21) and non-responders (n = 21). HPA-1a antibody was detected in all non-responders and in 72% of responders (p < 0.01). The index case had a significantly lower PLT count at birth in non-responders versus responders (median PLT count: R = 20 × 10⁹/L [IQR 8–43] vs. NR = 9 × 10⁹/L [IQR 4–18], p < 0.02). No differences were found in IVIG treatment duration or dosage. PLTs at birth were significantly lower in non-responders compared to responders. No intracranial hemorrhages occurred. CSs were performed for obstetric indications only in all but two cases. Conclusion: Maternal IVIG can elicit different fetal responses. The lack of prognostic factors to predict responders or non-responders suggests that there remains a role for FBS in F/NAIT in experienced hands.

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“…It is a rare, but potentially life threatening disorder with intracranial hemorrhage (ICH) as the most severe complication. Severe gastrointestinal and pulmonary hemorrhages have also been reported [1]. Antibodies against human platelet antigen (HPA)-1a are accountable for nearly 85% of FNAIT cases [2].…”

Section: Introductionmentioning

confidence: 99%

Anti-human platelet antigen (HPA)-1a antibodies may affect trophoblast functions crucial for placental development: a laboratory study using an in vitro model

Eksteen

Heide

Tiller

et al. 2017

Reprod Biol Endocrinol

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BackgroundFetal and neonatal alloimmune thrombocytopenia (FNAIT) is a bleeding disorder caused by maternal antibodies against paternal human platelet antigens (HPAs) on fetal platelets. Antibodies against HPA-1a are accountable for the majority of FNAIT cases. We have previously shown that high levels of maternal anti-HPA-1a antibodies are associated with clinically significant reduced birth weight in newborn boys. Chronic inflammatory placental lesions are associated with increased risk of reduced birth weight and have previously been reported in connection with FNAIT pregnancies. The HPA-1a epitope is located on integrin β3 that is associated with integrin αIIb (the fibrinogen receptor) on platelets and megakaryocytes. Integrin β3 is also associated with integrin αV forming the αVβ3 integrin heterodimer, the vitronectin receptor, which is expressed on various cell types, including trophoblast cells. It is therefore thinkable that maternal anti-HPA-1a antibodies present during early pregnancy may affect placenta function through binding to the HPA-1a antigen epitope on invasive throphoblasts. The aim of the study was to examine whether interaction of a human anti-HPA-1a monoclonal antibody (mAb) with HPA-1a on trophoblast cells affect adhesion, migration and invasion of extravillous trophoblast cells.MethodsAn in vitro model with human anti-HPA-1a mAb, clone 26.4, and the first trimester extravillous trophoblast cell line HTR8/SVneo was employed. The xCELLigence system was utilized to assess the possible effect of anti-HPA-1a mAb on adhesion and migration of HTR8/SVneo cells. Specially designed chambers precoated with Matrigel were used to assess the effect on the invasive capacity of cells.ResultsWe found that human anti-HPA-1a mAb 26.4 partially inhibits adhesion and migratory capacity of HTR8/SVneo cells.ConclusionsOur findings suggest that anti-HPA-1a antibodies may affect trophoblast functions crucial for normal placental development. Future studies including primary throphoblast cells and polyclonal anti-HPA-1a antibodies are needed to confirm these results.

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Severe bleeding complications other than intracranial hemorrhage in neonatal alloimmune thrombocytopenia: a case series and review of the literature

Cited by 32 publications

References 21 publications

Antenatal management in fetal and neonatal alloimmune thrombocytopenia: a systematic review

Antenatal management in fetal and neonatal alloimmune thrombocytopenia: a systematic review

Management and Neonatal Outcomes of Pregnancies with Fetal/Neonatal Alloimmune Thrombocytopenia: A Single-Center Retrospective Cohort Study

Anti-human platelet antigen (HPA)-1a antibodies may affect trophoblast functions crucial for placental development: a laboratory study using an in vitro model

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