Acquired Glanzmann's thrombasthenia caused by glycoprotein IIb/IIIa autoantibodies of the immunoglobulin G1 (IgG1), IgG2 or IgG4 subclass: a study in six cases

Porcelijn, Leendert; Huiskes, Elly; Maatman, R.; Kreuk, Arne de; Haas, Masja de

doi:10.1111/j.1423-0410.2008.01093.x

Cited by 21 publications

(24 citation statements)

References 30 publications

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“…The inhibitory effect of aIIbb3 integrin autoantibodies on platelet aggregation is known for acquired Glanzmann thrombasthenia patients, with a primary coagulation defect in spite of (near) normal platelet counts. 35 This inhibitory effect exists in some immune thrombocytopenic purpura patients that, next to the thrombocytopenia, further impairs the primary coagulation. Clearly, this effect can be characterized by FCA.…”

Section: Fca Allows Testing the Effect Of Platelet Autoantibodies In mentioning

confidence: 99%

A novel flow cytometry–based platelet aggregation assay

Cuyper

Meinders

Vijver

et al. 2013

Blood

139

148

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Section: Fca Allows Testing the Effect Of Platelet Autoantibodies In mentioning

confidence: 99%

A novel flow cytometry–based platelet aggregation assay

Cuyper

Meinders

Vijver

et al. 2013

Blood

139

148

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“…However, the patient's Abs recognized common recognition sites of PA anti‐αIIbβ3 autoAbs detected in chronic ITP patients, suggesting that the difference in epitope does not account for the unique phenotype of the patient's platelets. We identified that IgG subclasses of PA anti‐αIIbβ3 autoAbs of the patient were IgG1 and IgG2, which are usual in reported aGT cases . Because reduction of αIIbβ3 expression was not reported in these cases, it is also unlikely that the differences of IgG subclass affect the phenotype of our patient.…”

Section: Discussionmentioning

confidence: 51%

A unique phenotype of acquired Glanzmann thrombasthenia due to non‐function‐blocking anti‐αIIbβ3 autoantibodies

Akuta

Kashiwagi

Yujiri

et al. 2019

Journal of Thrombosis and Haemostasis

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Acquired Glanzmann thrombasthenia (aGT) is generally caused by function‐blocking antibodies (Abs). We demonstrated a unique aGT case due to marked reduction of αIIbβ3 with anti‐αIIbβ3 Abs. The anti‐αIIbβ3 Abs of the patient did not inhibit platelet function but reduced surface αIIbβ3. Internalization of αIIbβ3 induced by the Abs binding may be responsible for the phenotype. Summary BackgroundAcquired Glanzmann thrombasthenia (aGT) is a bleeding disorder generally caused by function‐blocking anti‐αIIbβ3 autoantibodies. AimWe characterize an unusual case of aGT caused by marked reduction of surface αIIbβ3 with non‐function‐blocking anti‐αIIbβ3 antibodies (Abs). MethodsA 72‐year‐old male suffering from immune thrombocytopenia since his 50s showed exacerbation of bleeding symptom despite mild thrombocytopenia. Platelet aggregation was absent with all agonists but ristocetin. Analysis of αIIbβ3 expression and genetic analysis were performed. We also analyzed effects of anti‐αIIbβ3 Abs of the patient on platelet function and αIIbβ3 expression. ResultsSurface αIIbβ3 expression was markedly reduced to around 5% of normal, whereas his platelets contained αIIbβ3 to the amount of 40–50% of normal. A substantial amount of fibrinogen was also detected in his platelets. There were no abnormalities in ITGA2B and ITGB3 cDNA. These results indicated that reduced surface αIIbβ3 expression caused a GT phenotype, and active internalization of αIIbβ3 was suggested. Anti‐αIIbβ3 IgG Abs were detected in platelet eluate and plasma. These Abs did not inhibit PAC‐1 binding, indicating that the Abs were non‐function‐blocking. Surface αIIbβ3 expression of a megakaryocytic cell line and cultured megakaryocytes tended to be impaired by incubation with the patient's Abs. After 2 years of aGT diagnosis, his bleeding symptom improved and surface αIIbβ3 expression was recovered to 20% of normal with reduction of anti‐αIIbβ3 Abs. ConclusionWe demonstrated a unique aGT phenotype due to marked reduction of surface αIIbβ3. Internalization induced by anti‐αIIbβ3 Abs may be responsible in part for the phenotype.

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“…ii) Anti-CD20 (rituximab), has been successfully used in many autoimmune and alloimmune disorders. This may be an useful drug in acquired GT patients [46,47]. iii) Cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody can be used for tolerance induction to prevent alloimmunization in GT [48].…”

Section: Expert Opinionmentioning

confidence: 99%