Detection of platelet autoantibodies to identify immune thrombocytopenia: state of the art

Porcelijn, Leendert; Huiskes, Elly; Oldert, Gonda; Schipperus, Martin R.; Zwaginga, Jaap Jan; Haas, Masja de

doi:10.1111/bjh.15404

Cited by 58 publications

(69 citation statements)

References 15 publications

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“…Different assay configurations detect circulating antiplatelet antibodies (indirect methods) and membrane‐bound, platelet‐associated antibodies (direct, PAIg). Direct assay methods are generally more sensitive than indirect assays; however, platelets constitutively express immunoglobulin receptors that cause nonspecific antibody binding and complicate interpretation of a “positive” test . Assay sensitivity is impeded by the fact that ITP is not always an antibody‐mediated process.…”

Section: Building the Evidence For A Diagnosis Of Itpmentioning

confidence: 99%

“…In human medicine, assay specificity is greatly enhanced by measuring platelet glycoprotein‐specific autoantibodies. Platelet antigens primarily targeted by autoantibodies include GPIIb/IIIa (CD41/CD61, fibrinogen receptor), GPIb/IX (CD42c/CD42a, von Willebrand factor receptor), and GPV (CD42d) . The monoclonal antibody‐specific immobilized platelet antigen assay (MAIPA) and bead‐immobilized monoclonal antibody assays are configured to define each ITP patient's autoantibody specificity.…”

Section: Building the Evidence For A Diagnosis Of Itpmentioning

confidence: 99%

“…The monoclonal antibody‐specific immobilized platelet antigen assay (MAIPA) and bead‐immobilized monoclonal antibody assays are configured to define each ITP patient's autoantibody specificity. The assays are based on detection of trimolecular complexes formed by a monoclonal antibody to a known platelet glycoprotein, the patient's autoantibodies, and the platelet membrane that carries the respective epitopes of each of these antibodies . MAIPA specificity for an ITP diagnosis is reported to be as high as 98% but still lacks sensitivity (81% sensitive), potentially due to T cell as opposed to antibody‐mediated autoimmunity in some patients .…”

Section: Building the Evidence For A Diagnosis Of Itpmentioning

confidence: 99%

“…The assays are based on detection of trimolecular complexes formed by a monoclonal antibody to a known platelet glycoprotein, the patient's autoantibodies, and the platelet membrane that carries the respective epitopes of each of these antibodies . MAIPA specificity for an ITP diagnosis is reported to be as high as 98% but still lacks sensitivity (81% sensitive), potentially due to T cell as opposed to antibody‐mediated autoimmunity in some patients . Surveys of ITP patients reveal that autoantibodies targeting GPIIb/IIIa are the most common; found in approximately 70‐80% of patients, with anti‐GpIb complex antibodies found in 20‐40% of patients .…”

Section: Building the Evidence For A Diagnosis Of Itpmentioning

confidence: 99%

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Immune thrombocytopenia (ITP): Pathophysiology update and diagnostic dilemmas

LeVine

Brooks

2019

Veterinary Clinical Pathol

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Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder. The understanding of ITP pathogenesis is rapidly evolving. We now recognize ITP as a complex and heterogeneous syndrome that results from a combination of humoral and cell-mediated attacks on platelets peripherally and megakaryocytes in the bone marrow. Autoantibody-mediated ITP also varies in the pathway used to clear platelets, which depends on the platelet glycoprotein being targeted. Moreover, ITP patients present with variable bleeding severities and treatment responses that do not closely correlate with platelet count. A gold standard diagnostic test for ITP is lacking, and biomarkers to assess disease severity are in their infancy. This review provides an update on the immunopathogenesis of ITP and summarizes currently available tests for ITP diagnosis, prediction of disease severity, and treatment responses. Given the heterogeneous pathogenesis and clinical presentation of ITP, we highlight the need for the development of diagnostic and prognostic tests that would allow for the individualized management of a complex disease. K E Y W O R D Sautoantibodies/autoimmune disease, bleeding score, dog, hemorrhage, immune thrombocytopenia, immunology, platelet

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Section: Building the Evidence For A Diagnosis Of Itpmentioning

confidence: 99%

Section: Building the Evidence For A Diagnosis Of Itpmentioning

confidence: 99%

Section: Building the Evidence For A Diagnosis Of Itpmentioning

confidence: 99%

Section: Building the Evidence For A Diagnosis Of Itpmentioning

confidence: 99%

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Immune thrombocytopenia (ITP): Pathophysiology update and diagnostic dilemmas

LeVine

Brooks

2019

Veterinary Clinical Pathol

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“…An important limitation of circulating anti‐platelet antibody testing in autoimmune thrombocytopenia is the problem that antibodies with a high affinity and excellent effector functions are likely to have bound to platelets and may have been cleared preferentially in vivo. This is emphasized by a generally higher sensitivity of direct cell‐bound anti‐platelet antibody tests in ITP . In juvenile patients, due to the limited sample volume and the low platelet counts in ITP, we were not able to perform direct anti‐platelet antibody tests on patients’ cells.…”

Section: Discussionmentioning

confidence: 91%

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

Schmidt

Heitink‐Pollé

Porcelijn

et al. 2020

Journal of Thrombosis and Haemostasis

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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. | 1211SCHMIDT eT al. S U PP O RTI N G I N FO R M ATI O NAdditional supporting information may be found online in the Supporting Information section.

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