PB0982 - MGUS-IgA with anti-thrombin activity in a patient with a severe acquired haemorrhagic syndrome.

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Co-Author(s)

AB

Alicia N. Blanco

Biochemist, PhD
Departamento de Hemostasia y Trombosis, Instituto de Investigaciones Hematologicas, Academia Nacional de Medicina
CABA, Ciudad Autonoma de Buenos Aires, Argentina
MA

Maria F. Alberto

Head of Chemical Division
National Academy of Medicine
Ciudad Autonoma de buenos aires, Ciudad Autonoma de Buenos Aires, Argentina
MR

Maria L. Romero

Head of Thrombosis Division
National Academy of Medicine
Ciudad Autonoma de Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina
MM

Marta E. Martinuzzo

Biochemist Supervisor Hemostasis Central Laboratory
Hospital Italiano de Buenos Aires
CIUDAD AUTONOMA DE BUENOS AIRES, Buenos Aires, Argentina
SG

Silvia Grosso

Biologist Haemostasis Division
National Academy of Medicine
Ciudad Autonoma de Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina
MI

Marcelo Ingratti

Biologist Haemostasis Division
National Academy of Medicine
Ciudad Autonoma de Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina

Presenting Author(s)

Mirta del valle Arias

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

Co-Author(s)

AS

Analia Sánchez-Luceros

MD, Dr.
Laboratorio de Hemostasia y Trombosis IMEX-CONICET-ANM y Departamento de Hemostasia y Trombosis, Instituto de Investigaciones Hematologicas, Academia Nacional de Medicina
CABA, Ciudad Autonoma de Buenos Aires, Argentina

Background: Acquired coagulation disorders are difficult to identify especially in presence of a lupus anticoagulant (LA).

Aims: We describe a 30-year-old man with a severe acquired haemorrhagic syndrome that could not be justified by laboratory findings.

Methods: Initial laboratory tests showed a strong LA, APTT 83s not corrected by NPP (ICA30), not enhanced by incubation at 37°C, positive PNP, positive screen/confirm DRVVT, FVIII 3.5IU/dL and FIX 4.5IU/dL. Solid phase antiphospholipid antibodies (IgG, IgM, IgA: ACA, aBGPI, aPT, aPS), urea solubility and euglobulin lysis time were normal. VWD, thrombocytopathies and acquired haemophilia (FVIII 91%-chromogenic assay) were excluded. During outpatient follow-up for several years the positive LA remained.

Results: The patient was admitted to treat several major bleeding episodes (ISTH criteria) with aFVIIr. As clinical manifestations could not be justified by laboratory the presence of a heparinoid was considered and discarded. Finally, a MGUS-IgA lambda (0.3g/dL) was diagnosed. Complementary studies have shown decreased thrombin-activated FXIII activity (13%) not corrected by NPP, but normal FXIIIA (95%) and FXIIIB (137%). Direct FXIII inhibitory effect was discarded (IgA-FXIII immune-complexes test), so we speculated that an anti-thrombin effect might interfere with the activation of FVIII, FIX, FXIII. Immunocapture of IgA using a polyclonal anti-human IgA was performed, followed by incubation with bovine thrombin (10IU/mL) and addition of thrombin chromogenic substrate. Colour development (405nm) showed catalytic activity only in the presence of patient's IgA (Figure1). Patient’s IgA anti-thrombin activity was confirmed by ELISA (Figure2).

Conclusion(s): These results suggest that a MGUS-IgA fraction interaction with thrombin might be interfering with its binding to natural substrates, explaining the haemorrhagic manifestations. Bypass agents in this case allowed the successful treatment of major bleeding episodes even before the defect was identified. We think that in patients with recurrent severe bleeding, extensive evaluation of haemostasis should be carried out in order to achieve correct diagnosis.