Anti-glycoprotein antibodies and sequestration pattern of indium-labeled platelets in immune thrombocytopenia

Abstract

Anti-glycoprotein antibodies play an important role in the pathophysiology of immune thrombocytopenia (ITP). The sequestration pattern of platelets in spleen and liver can be studied with Indium-111 labeled autologous platelet scans. No studies have investigated the role of anti-GP antibodies in sequestration pattern in ITP patients. In this study we examined the association between antibodies and 1) platelet sequestration site and 2) clearance rate of platelets. All ITP patients receiving an Indium-111 labeled autologous platelet study between 2014 and 2018 were included. Antibodies were measured using the direct MAIPA method to determine the presence and titer of anti-GPIIb/IIIa, anti-GPIb/IX and anti-GPV antibodies. Multivariate regression models were used to study the association between anti-GP antibodies, sequestration site and clearance rate. Seventy-four patients were included, with a mean age of 36 years. Forty-seven percent of the patients showed a predominantly splenic sequestration pattern, 29% mixed and 25% a hepatic pattern. In 53% of the patients anti-GP antibodies were detected. Regression models showed a significant association between splenic sequestration and GPV autoantibodies.. Furthermore, in patients where antibodies were present the clearance rate was higher in patients with a splenic sequestration. Anti-GPV antibodies are associated with a splenic sequestration pattern in ITP patients. These associations provide insight in the possible pathophysiological mechanisms of ITP, which may lead to better detection and treatment of this partly idiopathic and prevalent disease.

Antiplatelet antibody predicts platelet desialylation and apoptosis in immune thrombocytopenia

“…Interestingly, this result is consistent with the finding by Amini and colleagues, who recently reported the lack of hepatic uptake of Indium-111 labeled platelet in patients with antiGPV antibodies. 49 Of note, serum from one anti-GPV positive patient induced significant loss of platelet ΔΨm, indicating anti-GPV may drive ITP via platelet apoptosis. While APA testing is available in specialized platelet laboratories, routine testing has not been recommended, and ITP remains a disease without any confirmatory investigation or a “gold standard” test.…”

Study of platelet kinetics in immune thrombocytopenia to predict splenectomy response

“…The antibody-mediated desialylation has been suggested as the cause of treatment refractoriness in other studies, even independently of the antibody specificity. 45,48,49 A recent work has studied the correlation of the anti-platelet antibodies with platelet sequestration, 50 showing no clear association with the anti-GPIb/IX or anti-GPIIb/IIIa specificities, but interestingly, they found an association between the anti-GPV antibodies and the splenic clearance, whose significance remains to be elucidated. Unfortunately, we did not measure the anti-platelet antibodies in our study, so we cannot establish conclusions about this aspect, while future lines of investigation should address this variable.…”

The interplay between GPIb/IX antibodies, platelet hepatic sequestration, and TPO levels in patients with chronic ITP

“…In this study, we investigated both the association between (1) GPIb/IX antibodies and the site of platelet sequestration by indium (In)-labeled autologous platelet scintigraphy and (2) GPIb/IX antibodies and TPO levels in a cohort of 53 patients with chronic and nonsplenectomized ITP. 11 The included patients had a clinical indication for a scintigraphy scan as indicated by the treating hematologist (indication for a second/third-line therapy with splenectomy as 1 of the therapeutic options), and had a mean age at diagnosis of 36 ± 18 (standard deviation) years. Importantly, we stratified these patients by the degree of thrombocytopenia: mild (platelet counts > 50 x 10 9 /L) and moderate/severe (<50 x 10 9 /L).…”