Antiplatelet Antibodies Do Not Predict the Response to Intravenous Immunoglobulins during Immune Thrombocytopenia

Abstract

Immune thrombocytopenia (ITP) is a rare autoimmune disease due to autoantibodies targeting platelet glycoproteins (GP). The mechanism of platelet destruction could differ depending on the specificity of antiplatelet antibodies: anti-GPIIb/IIIa antibodies lead to phagocytosis by splenic macrophages, in a Fcγ receptor (FcγR)-dependent manner while anti-GPIb/IX antibodies induce platelet desialylation leading to their destruction by hepatocytes after binding to the Ashwell–Morell receptor, in a FcγR-independent manner. Considering the FcγR-dependent mechanism of action of intravenous immunoglobulins (IVIg), we assumed that the response to IVIg could be less efficient in the presence of anti-GPIb/IX antibodies. We conducted a multicentric, retrospective study including all adult ITP patients treated with IVIg who had antiplatelet antibodies detected between January 2013 and October 2017. Among the 609 identified, 69 patients were included: 17 had anti-GPIb/IX antibodies and 33 had anti-GPIIb/IIIa antibodies. The response to IVIg was not different between the patients with or without anti-GPIb/IX (88.2% vs. 73.1%). The response to IVIg was better in the case of newly diagnosed ITP (odds ratio (OR) = 5.4 (1.2–24.7)) and in presence of anti-GPIIb/IIIa (OR = 4.82 (1.08–21.5)), while secondary ITP had a poor response (OR = 0.1 (0.02–0.64)). In clinical practice, the determination of antiplatelet antibodies is therefore of little value to predict the response to IVIg.

Emerging Therapies in Immune Thrombocytopenia

“…Used at 1 g/kg for 1–2 days, they provide a response in up to 90% of the cases [ 20 ]. The unresponsiveness occurring in 10–20% of ITP patients could be due to a destruction of platelets not dependent on FcγR, as proposed for anti-GPIb/IX antibodies [ 21 ], a hypothesis that is controversial in clinical practice [ 22 , 23 ]. Another explanation could be the predominant involvement of cytotoxic T lymphocytes (CTLs) in the destruction of platelets as demonstrated in an original ITP murine model [ 24 ].…”

Platelet variability index: a measure of platelet count fluctuations in patients with immune thrombocytopenia

“…IVIG, IV anti-D Ig [anti-D], or corticosteroids) supports the diagnosis (36). Platelet antibody tests were not used to categorize 'definite' ITP since the sensitivity of platelet antibodies is low (26) and the correlation with IVIG response is inconsistent (37). While a response to treatment is a useful marker to identify patients with ITP, it can only be used retrospectively and thus it is not a useful criterion for the clinician evaluating a new patient with thrombocytopenia.…”

“… 36 Platelet antibody tests were not used to categorize “definite” ITP because the low sensitivity 26 and the poor correlation with IVIG response. 37 Although a response to treatment is a useful marker to identify patients with ITP, it can only be used retrospectively and thus is not a useful criterion for the clinician evaluating a new patient with thrombocytopenia. In this study, we showed that the PVI score can serve as a surrogate for treatment response and help differentiate ITP from non-ITP patients based on historical platelet count values.…”

Detecção de autoanticorpos antiplaquetários na trombocitopenia imune em adultos

“…9 ou a possibilidade de associação entre anticorpos antiglicoproteínas IIb-IIIa com sangramentos mais graves 10 ou uma menor resposta a IgIV 11 e esplenectomia devido a interferência no mecanismo do ácido sialico e destruição plaquetária pelos hepatócitos em pacientes com anticorpos antiglicoproteína Ib-IX. Contudo, estes achados não foram replicados em outros estudos e seguem necessitando de mais evidências para confirmação5,12 .O último guideline da ASH de PTI 2 indica que esses testes podem ser úteis, porém o diagnóstico da doença segue sendo clínico e de exclusão 1 .…”

“…Outro estudo 87 também descreveu que pacientes positivos para anticorpos tinham maior probabilidade de piora clínica do que pacientes negativos para anticorpos.Estudos que avaliam o impacto da positividade destes testes na resposta ao tratamento instituído para PTI ainda são limitados. Há evidência sugestiva de que a presença isolada de antiGPIb-IX poderia predizer resposta a corticóide ou IgIV 11 , porém esse achado não se confirmou em estudos subsequentes5,12 . Em nosso estudo, apenas um paciente apresentou anticorpo apenas contra GPIb-IX.…”