VPB0249 - Persistent autoantibodies against Factor XI in a girl with an inborn error of immunity

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: Virtual

Presenting Author(s)

Eliana S. Annetta, Biochemist

Biochemist staff
Hospital de Pediatría "Prof. Dr. J.P.Garrahan"
CABA, Ciudad Autonoma de Buenos Aires, Argentina

Co-Author(s)

MH

Mirta D. Hepner

biochemist staff
Hospital de Pediatría "Prof. Dr. J.P.Garrahan"
CABA, Ciudad Autonoma de Buenos Aires, Argentina
Juan P. Frontroth, Biochemist

biochemist staff
Hospital de Pediatría "Prof. Dr. J.P.Garrahan"
CABA, Ciudad Autonoma de Buenos Aires, Argentina
Carolina Cervio, MD

Pediatric Hematologist
Hospital de Pediatría "Prof. Dr. Juan P. Garrahan"
Buenos Aires, Buenos Aires, Argentina
Rodolfo E. Sueldo

Biochemist
Laboratorio de Hematología y Hemostasia. Hospital César Milstein
Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina
VG

Veronica Goris

Biochemist
Laboratorio de Biologia Molecular Inmunologia. Hospital de Pediatría Prof Dr JP Garrahan
Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina
MO

Matias Oleastro

M.D
Servicio de Inmunologia y Reumatologia. Hospital de Pediatría Prof Dr JP Garrahan
Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina
GS

Gabriela B. Sciuccati, MD

Pediatric Hematologist
Hospital de Pediatría "Prof. Dr. J.P.Garrahan"
CABA, Ciudad Autonoma de Buenos Aires, Argentina

Background: FXI inhibitor in patients without congenital deficiency is a rare acquired disorder, characterized by the presence of neutralizing autoantibodies, usually IgG, targeting functional epitopes of FXI. They are mainly associated with autoimmune diseases.

Aims: To describe a persistent autoantibody against FXI in a girl with a probable inborn error of immunity (IEI)

Methods: A 6-year-old girl with an IEI under evaluation was referred to the Hematology Department because of an abnormal aPTT detected during pre-operative coagulation screening for an elective tonsillectomy. The patient had history of recurrent infections and non-malignant lymphoproliferation. She is the only-child of healthy unrelated parents, with neither personal nor family history of bleeding.
Laboratory evaluation included complete blood count, coagulation screening tests, lupus anticoagulant (LA), coagulation factors measurement, mixing studies, Bethesda inhibitor assay and plasma IgG adsorption with protein A Sepharose (pAS).

Results: Haemostasis screening showed a markedly prolonged aPTT (ratio:2.53). The index of circulating anticoagulant (29.6%) revealed the presence of an inhibitor. LA was negative, FXI: < 1%, Bethesda titer for FXI inhibitor:12.4BU/ml. Plasma IgG adsorption with pAS fully removed detectable inhibitor ( < 0.6BU/ml) (Table1)
Parental coagulation profiles were normal.
The patient received a single dose of rFVIIa 30µg/kg before tonsillectomy and tranexamic acid before and after this procedure. No bleeding complications were observed.
FXI persisted < 1% during the three years follow-up and a novel CARD11 heterozygous variant was identified (c.746A>C) (functional analyses in progress)

Conclusion(s): We report a child with acquired factor XI deficiency probably related to an IEI. To our knowledge, there are no pediatric reports of long-lasting neutralizing anti-FXI antibodies in patients with an IEI. This scenario may be an expression of the underlying immune dysregulation. Results of adsorption with pAS strongly suggest that these antibodies are IgG isotype. The identification of a neutralizing FXI inhibitor allowed for an accurate management of the surgical procedure.