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Anti-platelet antibodies in childhood immune thrombocytopenia: Prevalence and prognostic implications.

ABSTRACT: BACKGROUND:Anti-platelet antibody testing may be useful for the diagnosis and management of childhood immune thrombocytopenia (ITP). OBJECTIVES:Here we aimed to assess the prevalence and prognostic significance of anti-platelet glycoprotein-specific IgM and IgG antibodies. METHODS:Children with newly diagnosed ITP were included at diagnosis and randomized to an intravenous immunoglobulins (IVIg) or careful observation group (TIKI trial). In this well-defined and longitudinally followed cohort (N = 179), anti-platelet glycoprotein-specific IgM and IgG antibodies were determined by monoclonal antibody-immobilization of platelet antigens. RESULTS:The dominant circulating anti-platelet antibody class in childhood ITP was IgM (62% of patients); but IgG antibodies were also found (10%). Children without IgM platelet antibodies were older and more often female. There was weak evidence for an association between IgM anti-GP IIb/IIIa antibodies and an increased bleeding severity (P = .03). The IgM and IgG anti-platelet responses partially overlapped, and reactivity was frequently directed against multiple glycoproteins. During 1-year follow-up, children with IgM antibodies in the observation group displayed a faster platelet recovery compared to children without, also after adjustment for age and preceding infections (P = 7.1 × 10-5 ). The small group of patients with detectable IgG anti-platelet antibodies exhibited an almost complete response to IVIg treatment (N = 12; P = .02), suggesting that IVIg was particularly efficacious in these children. CONCLUSIONS:Testing for circulating anti-platelet antibodies may be helpful for the clinical prognostication and the guidance of treatment decisions in newly diagnosed childhood ITP. Our data suggest that the development of even more sensitive tests may further improve the clinical value of antibody testing.

SUBMITTER: Schmidt DE

PROVIDER: S-EPMC7318215 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Anti-platelet antibodies in childhood immune thrombocytopenia: Prevalence and prognostic implications.

Schmidt David E DE Heitink-Polle Katja M J KMJ Porcelijn Leendert L van der Schoot C Ellen CE Vidarsson Gestur G Bruin Marrie C A MCA de Haas Masja M

Journal of thrombosis and haemostasis : JTH 20200412 5

<h4>Background</h4>Anti-platelet antibody testing may be useful for the diagnosis and management of childhood immune thrombocytopenia (ITP).<h4>Objectives</h4>Here we aimed to assess the prevalence and prognostic significance of anti-platelet glycoprotein-specific IgM and IgG antibodies.<h4>Methods</h4>Children with newly diagnosed ITP were included at diagnosis and randomized to an intravenous immunoglobulins (IVIg) or careful observation group (TIKI trial). In this well-defined and longitudina ...[more]

PMID: 32053276

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Project description:BackgroundThis is a review article on heparin-induced thrombocytopenia, an adverse effect of heparin therapy, and vaccine-induced immune thrombotic thrombocytopenia, occurring in some patients administered certain coronavirus vaccines.Main body/textImmune-mediated thrombocytopenia occurs when specific antibodies bind to platelet factor 4 /heparin complexes. Platelet factor 4 is a naturally occurring chemokine, and under certain conditions, may complex with negatively charged molecules and polyanions, including heparin. The antibody-platelet factor 4/heparin complex may lead to platelet activation, accompanied by other cascading reactions, resulting in cerebral sinus thrombosis, deep vein thrombosis, lower limb arterial thrombosis, myocardial infarction, pulmonary embolism, skin necrosis, and thrombotic stroke. If untreated, heparin-induced thrombocytopenia can be life threatening. In parallel, rare incidents of spontaneous vaccine-induced immune thrombotic thrombocytopenia can also occur in some patients administered certain coronavirus vaccines. The role of platelet factor 4 in vaccine-induced thrombosis with thrombocytopenia syndrome further reinforces the importance the platelet factor 4/polyanion immune complexes and the complications that this might pose to susceptible individuals. These findings demonstrate, how auxiliary factors can complicate heparin therapy and drug development. An increasing interest in biomanufacturing heparins from non-animal sources has driven a growing interest in understanding the biology of immune-mediated heparin-induced thrombocytopenia, and therefore, the development of safe and effective biosynthetic heparins.Short conclusionIn conclusion, these findings further reinforce the importance of the binding of platelet factor 4 with known and unknown polyanions, and the complications that these might pose to susceptible patients. In parallel, these findings also demonstrate how auxiliary factors can complicate the heparin drug development.

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Anti-platelet antibodies in childhood immune thrombocytopenia: Prevalence and prognostic implications.

Publications

Anti-platelet antibodies in childhood immune thrombocytopenia: Prevalence and prognostic implications.

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