Von Willebrand factor propeptide and pathophysiological mechanisms in European and
Iranian patients with type 3 von Willebrand disease enrolled in the 3WINTERS-IPS study
Pagliari, Maria Teresa; Rosendaal, Frits R.; Ahmadinejad, Minoo; Badiee, Zahra; Baghaipour, Mohammad-Reza; Baronciani, Luciano; Hidalgo, Olga Benitez; Bodo, Imre [Bodó, Imre (Belgyógyászat, ha...), szerző] Belgyógyászati és Hematológiai
Klinika (SE / AOK / K); Budde, Ulrich; Castaman, Giancarlo; Eshghi, Peyman; Goudemand, Jenny; Karimi, Mehran; Keikhaei, Bijan; Lassila, Riitta; Leebeek, Frank W. G.; Fernandez, Maria Fernanda Lopez; Mannucci, Pier Mannuccio; Marino, Renato; Oldenburg, Johannes; Peake, Ian; Santoro, Cristina; Schneppenheim, Reinhard; Tiede, Andreas; Toogeh, Gholamreza; Tosetto, Alberto; Trossaert, Marc; Yadegari, Hamideh; Zetterberg, Eva M. K.; Peyvandi, Flora; Federici, Augusto B.; Eikenboom, Jeroen ✉
Angol nyelvű Sokszerzős vagy csoportos szerzőségű szakcikk (Folyóiratcikk) Tudományos
Background Type 3 von Willebrand disease (VWD) is a severe bleeding disorder caused
by the virtually complete absence of von Willebrand factor (VWF). Pathophysiological
mechanisms of VWD like defective synthesis, secretion, and clearance of VWF have previously
been evaluated using ratios of VWF propeptide (VWFpp) over VWF antigen (VWF:Ag) and
factor (F)VIII coagulant activity (FVIII:C) over VWF:Ag. Objective To investigate
whether the VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios may also be applied to understand
the pathophysiological mechanism underlying type 3 VWD and whether VWFpp is associated
with bleeding severity. Methods European and Iranian type 3 patients were enrolled
in the 3WINTERS-IPS study. Plasma samples and buffy coats were collected and a bleeding
assessment tool was administered at enrolment. VWF:Ag, VWFpp, FVIII:C, and genetic
analyses were performed centrally, to confirm patients' diagnoses. VWFpp/VWF:Ag and
FVIII:C/VWF:Ag ratios were compared among different variant classes using the Mann-Whitney
test. Median differences with 95% confidence intervals (CI) were estimated using the
Hodges-Lehmann method. VWFpp association with bleeding symptoms was assessed using
Spearman's rank correlation. Results Homozygosity/compound heterozygosity for missense
variants showed higher VWFpp level and VWFpp/VWF:Ag ratio than homozygosity/compound
heterozygosity for null variants ([VWFpp median difference, 1.4 IU/dl; 95% CI, 0.2-2.7;
P = .016]; [VWFpp/VWF:Ag median difference, 1.4; 95% CI, 0-4.2; P = .054]). FVIII:C/VWF:Ag
ratio was similarly increased in both. VWFpp level did not correlate with the bleeding
symptoms (r = .024; P = .778). Conclusions An increased VWFpp/VWF:Ag ratio is indicative
of missense variants, whereas FVIII:C/VWF:Ag ratio does not discriminate missense
from null alleles. The VWFpp level was not associated with the severity of bleeding
phenotype.
