PB0291 - VWD2M-C: A fugitive diagnosis. About a case.

Sunday, June 23, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Co-Author(s)

AW

Adriana I. Woods, PhD

Departamento de Hemostasia y Trombosis. Academia Nacional de Medicina.
Ciudad Autonoma de Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina

Co-Author(s)

MA

María F. Alberto

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

Santiago Castera, Sr.

Biochemist, Ms.
Departamento de Hemostasia y Trombosis. Academia Nacional de Medicina
CABA, Ciudad Autonoma de Buenos Aires, Argentina
CB

Claudio of Berger, Sr.

Biochemist
Central Laboratory, Biochemistry, Instituto Universitario del Hospital Italiano de Buenos Aires,
CABA, Ciudad Autonoma de Buenos Aires, Argentina
ML

Marina S. Lopez

Biochemist
Central Laboratory, Biochemistry, Instituto Universitario del Hospital Italiano de Buenos Aires
CABA, Ciudad Autonoma de Buenos Aires, Argentina
MM

Marta E. Martinuzzo

Biochemist, PhD
Central Laboratory, Biochemistry, Instituto Universitario del Hospital Italiano de Buenos Aires
CABA, Ciudad Autonoma de Buenos Aires, Argentina
AB

Alicia N. Blanco

PhD
Departamento de Hemostasia y Trombosis. Academia Nacional de Medicina.
CABA, Ciudad Autonoma de Buenos Aires, Argentina

Presenting Author(s)

Analia Sánchez-Luceros, MD, PHD

MD, PhD
Departamento de Hemostasia y Trombosis. Academia Nacional de Medicina.
CABA, Ciudad Autonoma de Buenos Aires, Argentina

Background: VWD2M-C is characterized by decreased VWF:CB but normal VWF and VWF:RCo levels. This defect is caused by disease-causing variants (DCVs) at the A3 domain affecting VWF-collagen binding.

Aims: We describe a 60-year-old male who was referred from another center with laboratory results suggestive of VWD2. The patient's ISTH-BAT was 5, without family bleeding history. He had a diagnosis of metabolic syndrome.

Methods: Hemostatic assessment was performed: PT, APTT, FVIII, VWF:Ag, VWF:RCo, VWF:CB1, VWF:CB3, VWF multimers, platelet count (PC) and platelet functional studies (lumi-aggregometry, mepacrine uptake), PFA-200 closure time (CT), VWF:GPIbR/VWF:Ag ratio. The patient was studied twice, to confirm the abnormal findings. VWFA1-A3-domains were sequenced (Sanger methodology).

Results: The patient presented normal VWF:Ag, VWF:RCo and VWF multimers, but low VWF:CB1 and VWF:CB3 levels (Table 1). PFA-200 CT was extremely prolonged with Col/Epi cartridge and slightly prolonged Col/ADP one, and abnormal VWF:GPIbR/VWF:Ag ratio
Lumi-aggregometry: normal RIPA (high and low doses), arachidonic acid and collagen; absence of the second wave and ATP release under ADP and epinephrine stimulation. Normal content of platelets’dense granules was confirmed by mepacrine uptake.
The missense change c.5191T>A→p.(Ser1731Thr) in exon 30 (A3-domain) was identified in heterozygous state.
The remaining studies did not reveal any other abnormality (Table 1).

Conclusion(s): The p.Ser1731Thr was previously described to be associated with VWD2M-C in individuals with no/mild bleeding symptoms. In our patient, it seemed to be responsible for the abnormal PFA-200CT. However, it cannot be ruled out that the platelet function alteration with ADP/adrenaline contributes to the abnormality of this test, particularly more prolonged CT with PFA-COL/EPI cartridge which is a pattern more frequent in thrombocytopathies, as well as to the patient's bleeding phenotype.
Since the VWF:RCo measures the VWF-platelet interaction, and the VWF:CB, the VWF-collagen interaction, it is of utmost importance to perform both assays to overcome the potential lack patients' VWD2M-C diagnosis.