Maternal human platelet antigen‐1a antibody level correlates with the platelet count in the newborns: a retrospective study

Killie, Mette Kjær; Husebekk, Anne; Kaplan, C.; Taaning, Ellen; Skogen, Bjøŕn

doi:10.1111/j.1537-2995.2007.01063.x

Cited by 43 publications

(43 citation statements)

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“…[4][5][6][7][8][9] Results from the present work, including 161 non-compatible pregnancies, further substantiate this relationship. The theoretically best antibody cut-off level for predicting an outcome appraises sensitivity and specificity equally, but is not necessarily the optimal level for use in clinical practice since the consequences of false-negative and false-positive results may be very different.…”

Section: Discussionsupporting

confidence: 72%

“…Several prospective studies have shown a correlation between anti-HPA 1a antibody level and severity of thrombocytopenia in the newborn. [4][5][6][7] A correlation was also found in two retrospective studies, 8,9 whereas one other retrospective study did not find such a relationship. 10 In a recent trial, we documented that identification of women with anti-HPA 1a antibodies, close clinical follow-up during pregnancy, elective Cesarean section and transfusion of compatible platelets to neonates with severe thrombocytopenia, reduce NAIT-related morbidity and mortality.…”

Section: Introductionmentioning

confidence: 77%

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A prospective study of maternal anti-HPA 1a antibody level as a potential predictor of alloimmune thrombocytopenia in the newborn

Killie¹,

Husebekk²,

et al. 2008

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Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 77%

A prospective study of maternal anti-HPA 1a antibody level as a potential predictor of alloimmune thrombocytopenia in the newborn

Killie¹,

Husebekk²,

et al. 2008

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“…From the large prospective screening studies in Norway, data have emerged showing that a significant proportion of HPA-1a negative mothers develop HPA-1a alloimmunity postdelivery rather than in the first pregnancy itself. 40,41 It is therefore possible that fetomaternal alloimmunization against HPA-1a is more akin to the pattern of red cell immunization than was suggested from previous retrospective data. This observation has raised the question of the feasibility and potential clinical benefit of prophylactic measures to prevent HPA-1a immunization.…”

Section: Discussionmentioning

confidence: 38%

Recombinant HPA-1a antibody therapy for treatment of fetomaternal alloimmune thrombocytopenia: proof of principle in human volunteers

Ghevaert

Herbert

Hawkins

et al. 2013

Blood

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Key Points• Recombinant antibody B2G1Dnab protects platelets from destruction by anti-HPA-1a in the circulation of HPA-1a1b human volunteers.• B2G1Dnab is a potential therapeutic agent for antenatal treatment of fetomaternal alloimmune thrombocytopenia due to HPA-1a antibodies.Fetomaternal alloimmune thrombocytopenia, caused by the maternal generation of antibodies against fetal human platelet antigen-1a (HPA-1a), can result in intracranial hemorrhage and intrauterine death. We have developed a therapeutic human recombinant high-affinity HPA-1a antibody (B2G1Dnab) that competes for binding to the HPA-1a epitope but carries a modified constant region that does not bind to Fcg receptors. In vitro studies with a range of clinical anti-HPA-1a sera have shown that B2G1Dnab blocks monocyte chemiluminescence by >75%. In this firstin-man study, we demonstrate that HPA-1a1b autologous platelets (matching fetal phenotype) sensitized with B2G1Dnab have the same intravascular survival as unsensitized platelets (190 hours), while platelets sensitized with a destructive immunoglobulin G1 version of the antibody (B2G1) are cleared from the circulation in 2 hours. Mimicking the situation in fetuses receiving B2G1Dnab as therapy, we show that platelets sensitized with a combination of B2G1 (representing destructive HPA-1a antibody) and B2G1Dnab survive 3 times as long in circulation compared with platelets sensitized with B2G1 alone. This confirms the therapeutic potential of B2G1Dnab. The efficient clearance of platelets sensitized with B2G1 also opens up the opportunity to carry out studies of prophylaxis to prevent alloimmunization in HPA-1a-negative mothers. (Blood. 2013;122(3):313-320)

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“…Immunization against HPA-1a occurs in ;1:450 random pregnancies. [8][9][10] Although platelet decrement is related to antibody titer in FNAIT, 8,11,12 this correlation is not strict, as cases with low titers and very low platelet counts, as well as cases with high titers and normal platelet counts, are frequently observed. Recently we found that at least some of this discrepancy is due to differences in the functional quality of these antibodies, determined by its Fc glycosylation, in particular the level of core fucosylation.…”

Section: Introductionmentioning

confidence: 99%

C-reactive protein enhances IgG-mediated phagocyte responses and thrombocytopenia

Kapur

Heitink‐Pollé

Porcelijn

et al. 2015

Blood

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Key Points• CRP enhances IgG-mediated respiratory burst and phagocytosis of platelets in vitro and their clearance in vivo.• CRP levels are increased in ITP patients and correlate with platelet counts and bleeding severity and predict time to recovery.Immune-mediated platelet destruction is most frequently caused by allo-or autoantibodies via Fcg receptor-dependent phagocytosis. Disease severity can be predicted neither by antibody isotype nor by titer, indicating that other factors play a role. Here we show that the acute phase protein C-reactive protein (CRP), a ligand for Fc receptors on phagocytes, enhances antibody-mediated platelet destruction by human phagocytes in vitro and in vivo in mice. Without antiplatelet antibodies, CRP was found to be inert toward platelets, but it bound to phosphorylcholine exposed after oxidation triggered by antiplatelet antibodies, thereby enhancing platelet phagocytosis. CRP levels were significantly elevated in patients with allo-and autoantibody-mediated thrombocytopenias compared with healthy controls. Within a week, intravenous immunoglobulin treatment in children with newly diagnosed immune thrombocytopenia led to significant decrease of CRP levels, increased platelet numbers, and clinically decreased bleeding severity. Furthermore, the higher the level of CRP at diagnosis, the longer it took before stable platelet counts were reached. These data suggest that CRP amplifies antibody-mediated platelet destruction and may in part explain the aggravation of thrombocytopenia on infections. Hence, targeting CRP could offer new therapeutic opportunities for these patients. (Blood. 2015;125(11): 1793-1802 IntroductionFetal or neonatal alloimmune thrombocytopenia (FNAIT) and immune thrombocytopenia (ITP) are both antibody-mediated disorders in which platelets are destroyed mainly through activating immunoglobulin (IgG) Fc receptors on phagocytes in the spleen and liver, eventually resulting in thrombocytopenia. 1 In childhood, ITP is characterized by a typical history of acute development of purpura and bruising in an otherwise healthy child, caused by development of platelet autoantibodies, with an incidence of ;5 in 100 000 children.2 Most children with newly diagnosed ITP will not suffer from serious bleeding and will recover within 12 months. In ;60% of ITP, there is a history of a prior infection. [1][2][3] FNAIT is a potentially destructive disease in pregnancies, with intracerebral hemorrhage (ICH) of the fetus or neonate as the most feared complication, resulting in perinatal death in 1% to 7% or in severe neurological impairments in 14% to 26% of affected pregnancies. [4][5][6][7] FNAIT is caused by maternal IgG platelet alloantibodies, in whites mainly directed against human platelet antigen (HPA)-1a (85%), that cross the placenta and destroy the platelets of the fetus or newborn. Immunization against HPA-1a occurs in ;1:450 random pregnancies. [8][9][10] Although platelet decrement is related to antibody titer in FNAIT, 8,11,12 this correlation is not strict, as cas...

show abstract

Maternal human platelet antigen‐1a antibody level correlates with the platelet count in the newborns: a retrospective study

Cited by 43 publications

References 13 publications

A prospective study of maternal anti-HPA 1a antibody level as a potential predictor of alloimmune thrombocytopenia in the newborn

A prospective study of maternal anti-HPA 1a antibody level as a potential predictor of alloimmune thrombocytopenia in the newborn

Recombinant HPA-1a antibody therapy for treatment of fetomaternal alloimmune thrombocytopenia: proof of principle in human volunteers

C-reactive protein enhances IgG-mediated phagocyte responses and thrombocytopenia

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