Progress and development of platelet antibody detection

Porcelijn, Leendert; Huiskes, Elly; Haas, Masja de

doi:10.1016/j.transci.2019.102705

Cited by 27 publications

(26 citation statements)

References 104 publications

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“…Alloantibodies develop without clinical symptoms during pregnancy. Details about diagnostics of these antibodies are published by Porcelijn et al [56] in this issue. The only way to prevent severe complications in first pregnancies is by screening and timely antenatal treatment.…”

Section: Antenatal Managementmentioning

confidence: 99%

Epidemiology and management of fetal and neonatal alloimmune thrombocytopenia

Vos

Winkelhorst

Haas

et al. 2020

Transfusion and Apheresis Science

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Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease in pregnancy characterized by maternal alloantibodies directed against the human platelet antigen (HPA). These antibodies can cause intracranial hemorrhage (ICH) or other major bleeding resulting in lifelong handicaps or death. Optimal fetal care can be provided by timely identification of pregnancies at risk. However, this can only be done by routinely antenatal screening. Whether nationwide screening is cost-effective is still being debated. HPA-1a alloantibodies are estimated to be found in 1 in 400 pregnancies resulting in severe burden and fetal ICH in 1 in 10.000 pregnancies. Antenatal treatment is focused on the prevention of fetal ICH and consists of weekly maternal IVIg administration. In high-risk FNAIT treatment should be initiated at 12-18 weeks gestational age using high dosage and in standard-risk FNAIT at 20-28 weeks gestational age using a lower dosage. Postnatal prophylactic platelet transfusions are often given in case of severe thrombocytopenia to prevent bleedings. The optimal threshold and product for postnatal transfusion is not known and international consensus is lacking. In this review practical guidelines for antenatal and postnatal management are offered to clinicians that face the challenge of reducing the risk of bleeding in fetuses and infants affected by FNAIT.

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Section: Antenatal Managementmentioning

confidence: 99%

Epidemiology and management of fetal and neonatal alloimmune thrombocytopenia

Vos

Winkelhorst

Haas

et al. 2020

Transfusion and Apheresis Science

Self Cite

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“…Among the 35 pregnancies with an incompatibility between the mother and the fetus, 51% (18/35) were incompatible in HPA‐1, including nine with exclusive incompatibility in the HPA‐1 system (Fig 3). The sensitivity of the detection of anti‐HPA‐1 alloantibodies using a MAIPA test is high (> 90%), 38 but we only detected 57% (8/14) HPA‐1a alloimmunized women in this cohort. This is in agreement with previous studies showing that HPA‐1a alloimmunization occurred in some HPA‐1bb women 39 .…”

Section: Discussionmentioning

confidence: 67%

“…This result underscores the high immunogenicity of HPA-5b incompatibility and the importance of HPA-5 genotyping in pregnancies at risk of FNAIT. Although, the presence of anti-HPA-5b alloantibodies is considered to induce a mild thrombocytopenia, 38 a previous report has shown that in addition to being the second most frequent cause of FNAIT, severe haemorrhages may occur in 23% of cases of fetomaternal incompatibility. 11 Fetomaternal HPA-3 incompatibility was described in 37% (13/35) of cases, including two cases with exclusive incompatibility in this system.…”

Section: Discussionmentioning

confidence: 99%

A new efficient tool for non‐invasive diagnosis of fetomaternal platelet antigen incompatibility

et al. 2020

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Summary Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the consequence of platelet destruction by maternal alloantibodies against fetal human platelet antigens (HPA). This may result in intracranial haemorrhages (ICH) or even fetal death. Currently, fetal HPA genotyping is performed using invasive procedures. Here, we carried out a proof‐of‐concept study for non‐invasive prenatal diagnosis of fetal platelet genotyping in four HPA systems (HPA‐1, ‐3, ‐5 and‐15) by droplet digital polymerase chain reaction (ddPCR) using cell‐free DNA extracts from the plasma of 47 pregnant women with suspected, or history of, FNAIT. Results showed that 74% (35/47) of pregnant women presented incompatibility in at least one HPA system, and 38% (18/47) of cases presented HPA‐1 incompatibility, including nine women with multiple incompatibilities. ICH occurred in one case of profound fetal thrombocytopenia with HPA‐15 incompatibility, confirming the need for non‐invasive prenatal genotyping in systems other than HPA‐1. Fetal HPA genotypes predicted by ddPCR were confirmed in all FNAIT cases after amniocentesis or delivery. Fetal HPA genotyping on maternal plasma based on ddPCR is a fast, safe and reliable non‐invasive method. This technique will be useful for the early identification of pregnancies at high risk of FNAIT requiring antenatal management to minimize the risk of fetal/neonatal haemorrhage.

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“…All mothers and fathers and/or cases were genotyped for HPA‐1, ‐3, ‐5 and ‐15 to determine possible fetal–maternal incompatibilities. Platelet antibodies were screened and identified with monoclonal antibody‐specific immobilisation of platelet antigens (MAIPA) 13 and the platelet immunofluorescence test (PIFT) including crossmatching between maternal serum and paternal platelets 14 . FNAIT was confirmed if there was clinical suspicion with neonatal thrombocytopenia (<150 × 10 9 /l) and/or fetal/neonatal bleeding, confirmed HPA incompatibility between the mother and child and the presence of an HPA antibody in the maternal blood sample.…”

Section: Methodsmentioning

confidence: 99%

Clinical characteristics of human platelet antigen (HPA)‐1a and HPA‐5b alloimmunised pregnancies and the association between platelet HPA‐5b antibodies and symptomatic fetal neonatal alloimmune thrombocytopenia

et al. 2021

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Summary Fetal neonatal alloimmune thrombocytopenia (FNAIT) is caused by maternal alloantibodies directed against the human platelet antigens (mostly HPA‐1a or HPA‐5b) of the (unborn) child and can lead to severe bleeding. Anti‐HPA‐1a‐mediated FNAIT shows a severe clinical outcome more often than anti‐HPA‐5b‐mediated FNAIT. Given the relatively high prevalence of anti‐HPA‐5b in pregnant women, the detection of anti‐HPA‐5b in FNAIT‐suspected cases may in some cases be an incidental finding. Therefore we investigated the frequency of anti‐HPA‐5b‐associated severe bleeding in FNAIT. We performed a retrospective nationwide cohort study in cases with clinical suspicion of FNAIT. HPA antibody screening was performed using monoclonal antibody‐specific immobilisation of platelet antigens. Parents and neonates were typed for the cognate antigen. Clinical data were collected by a structured questionnaire. In 1 864 suspected FNAIT cases, 161 cases (8·6%) had anti‐HPA‐1a and 60 (3·2%) had anti‐HPA‐5b. The proportion of cases with severe bleeding did not differ between the cases with anti‐HPA‐1a (14/129; 11%) and anti‐HPA‐5b (4/40; 10%). In multigravida pregnant women with a FNAIT‐suspected child, 100% (81/81) of anti‐HPA‐1a cases and 79% (38/48) of anti‐HPA‐5b cases were HPA‐incompatible, whereas 86% and 52% respectively were expected, based on the HPA allele distribution. We conclude that anti‐HPA‐5b can be associated with severe neonatal bleeding symptoms. A prospective study is needed for true assessment of the natural history of anti‐HPA‐5b mediated FNAIT.

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Progress and development of platelet antibody detection

Cited by 27 publications

References 104 publications

Epidemiology and management of fetal and neonatal alloimmune thrombocytopenia

Epidemiology and management of fetal and neonatal alloimmune thrombocytopenia

A new efficient tool for non‐invasive diagnosis of fetomaternal platelet antigen incompatibility

Clinical characteristics of human platelet antigen (HPA)‐1a and HPA‐5b alloimmunised pregnancies and the association between platelet HPA‐5b antibodies and symptomatic fetal neonatal alloimmune thrombocytopenia

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