PB0856 - Time course of thrombocytopenia during DDAVP test in a boy with a de novo c.4121G>A (p.Arg1374His) variant of the VWF gene.

Monday, June 26, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Juan P. Frontroth, Biochemist (he/him/his)

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
CP

Carolina M. Pepe

Biochemist
Hospital de Pediatria Prof Dr Juan P Garrahan
CABA, Ciudad Autonoma de Buenos Aires, Argentina
AC

Alejandro Chaves

molecular biologyst
Hospital de Pediatria Prof Dr Juan P Garrahan
CABA, Ciudad Autonoma de Buenos Aires, Argentina
SA

Silvina Annetta

Biochemist
Hospital de Pediatria Prof Dr Juan P Garrahan
CABA, Ciudad Autonoma de Buenos Aires, Argentina
RS

Rodolfo E. Sueldo, PhD

Biochemist
Laboratorio de Hematología y Hemostasia. Hospital César Milstein Laboratorio de Hemostasia. Servicio de Hematología y Oncología Hospital de Pediatría Prof. Dr. Juan P. Garrahan
Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina
Carolina Cervio, MD (she/her/hers)

staff Pediatric Hematologist
Hospital de Pediatría "Prof. Dr. Juan P. Garrahan"
Buenos Aires, Buenos Aires, Argentina
BB

Belén B. Bianco

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

Gabriela B. Sciuccati, MD (she/her/hers)

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

Background: Thrombocytopenia following DDAVP is reported in patients with von Willebrand disease (VWD) type 2B. Noteworthy, in other VWD subtypes, thrombocytopenia could also be observed during DDAVP test.

Aims: To report a patient with type 2M VWD phenotype with a VWF gene c.4121G>A (p.Arg1374His) variant who developed thrombocytopenia during DDAVP test.

Methods: DDAVP test was performed following local protocol. Platelet count (PC) and morphology, PT, aPTT, FVIII:C,VWF:Ag, VWF:RCo were evaluated at 0 and 30,60,120 and 240min post-DDAVP infusion. His parents were also studied. Exon 28 of VWF gene was analyzed by Sanger-sequencing in the proband and his parents.

Results: A 13.2-year-old boy with a VWD type 2M phenotype with mucocutaneous bleeding (ISTH-BAT=7) underwent a DDAVP test. No history of thrombocytopenia or hyper-responsiveness to low dose ristocetin (LDR) was reported. Values at diagnosis of proband, father and mother are depicted in Table 1. It could not be determined if the two VWF variants in the proband were in cis or trans. Values of DDAVP test showed in table 2. After 30min DDAVP infusion, proband showed a PC decrease from 244x109L-1 to 87x109L-1, with recovery at 60min. Giant platelet clumps(>100 platelets) in blood smears were observed. Increase of VWF:RCo (40%) and enhanced response to LDR in platelet aggregation mixing-studies were observed at 30 and 60 minutes.

Conclusion(s): These findings confirm that some VWF gene variants, formerly not considered as VWD 2B, behaves like VWD 2B. DDAVP test improves diagnosis of VWD, releasing stored molecules of VWF with higher affinity for platelet GPIb, explaining the transient thrombocytopenia. Due to the absence of the p.Arg1374His variant in his parents, the proband seems to express a de novo variant. Whether the p.Arg1374His variant should be included in the type 2B VWD group remains to be discussed.