PB1369 - Relevance of the Absence of Integrin αIIb expression by Flow Cytometry in Acquired Glanzmann’s Thrombasthenia

Tuesday, June 27, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Nuria Revilla, MD, PhD

Hospital Universitario Fundación Jiménez Díaz, Instituto Investigación Sanitaria FJD (IIS-FJD) Madrid, Spain.
Madrid, Madrid, Spain

Co-Author(s)

EC

Esther Chica-Gullón

Hematologist
Servicio de Hematología y Hemoterapia, Hospital de Getafe, Madrid, Spain.
Madrid, Madrid, Spain
JG

José A. García-Vela

Hematologist
Servicio de Hematología y Hemoterapia, Hospital de Getafe, Madrid, Spain
Madrid, Madrid, Spain
Ana Zamora-Cánovas

Biotechnology
Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Pascual Parrilla, Murcia, Spain.
Murcia, Murcia, Spain
NS

Nieves Somolinos De Marcos

Hematologist
Servicio de Hematología y Hemoterapia, Hospital de Getafe, Madrid, Spain
Madrid, Madrid, Spain
IL

Irene Lucea

Hematologist
Centro de Transfusiones de la Comunidad de Madrid, Spain
Madrid, Madrid, Spain
MA

Macarena Asensio

Biochemist
Academia Nacional de Medicina, Buenos Aires, Argentina
Buenos Aires, Buenos Aires, Argentina
ER

Ernesto Roldán

Immunologist
Servicio de Inmunología, Hospital Universitario Ramón y Cajal, Madrid, Spain
Madrid, Madrid, Spain
JB

José María Bastida

MD
Hematology Department, Complejo Asistencial Universitario de Salamanca (CAUSA), Instituto de Investigación Biomédica de Salamanca (IBSAL), Universidad de Salamanca (USAL), Spain
Salamanca, Castilla y Leon, Spain
LB

Laurentino Benito-Parra

Hematologist
Servicio de Hematología y Hemoterapia, Hospital de Getafe, Madrid, Spain
Madrid, Madrid, Spain
PL

Pilar Llamas-Sillero

Hematologist
Department of Hematology, Hospital Universitario Fundación Jiménez Díaz, Instituto Investigación Sanitaria FJD (IIS-FJD), Madrid, Spain
Madrid, Madrid, Spain
José RIVERA Rivera, PhD

PhD
Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Pascual Parrilla, Murcia, Spain
Murcia, Murcia, Spain

Background: Acquired Glanzmann thrombasthenia (aGT) is a bleeding disorder generally caused by function-blocking anti-αIIbβ3 autoantibodies. Its diagnosis is usually associated with thrombocytopenia and normal expression of platelet glycoproteins by flow cytometry (FC), unlike the hereditary GT disorder.

Aims: To characterize an unusual case of aGT showing absence of αIIb expression at diagnosis and during treatment.

Methods: A 69-year-old woman presenting with chronic immune thrombocytopenia (ITP) and undergoing anticoagulant therapy (atrial fibrillation and history of thrombosis), showed exacerbated bleeding symptoms (ISTH-BAT=12) despite anticoagulation discontinuation and a recovery of normal platelet count with eltrombopag. Clinical assessment, platelet phenotyping and DNA analysis were performed.

Results: Blood coagulation tests were normal. Anti-αIIbβ3 antibodies were detected by Luminex bead-based platelet assay in patient plasma. PFA-100 closure times (col-adp & col-epi) were prolonged (>299 and >277s). Platelet aggregation was absent with all agonists but ristocetin. FC showed normal expression of β3 but absence of αIIb (CD41a) expression (Fig1A). Binding of fibrinogen to agonist-activated platelets was almost absent. Patient plasma mildly inhibited platelet aggregation (Fig1B) and CD41a expression (Fig1C), while sharply reduced fibrinogen binding (Fig1D). Molecular alterations in ITGA2B and ITGB3 genes were ruled out by Next Generation Sequencing.
Eltrombopag was discontinued and rituximab therapy was initiated (375 mg/m2/week) with resolution of bleeding symptoms, but a decreased in platelet count < 20x10e9/L. Absence of CD41a expression and thrombocytopenia remained up to two months after starting a second immunosuppressant therapy (Fig2). Anti-αIIbβ3 antibodies became negative 3 months after a CD41a weak expression was recovered in 65% of platelets. Eltrombopag was restarted and the patient was safely treated with anticoagulant therapy. After 6 months follow-up, the patient showed no further bleeding symptoms.

Conclusion(s): Treatment of aGT associated with ITP must be individualized. FC monitoring may be useful to guide treatments in these patients.

Funding: ISCIII&Feder PI22/00926 and SETH