Clin Chem Lab Med 2014; 52(9): 1273–1276
Mini Review Massimo Franchini*, Silvia Crestani, Francesco Frattini, Cinzia Sissa and Carlo Bonfanti
ABO blood group and von Willebrand factor: biological implications Abstract: ABO blood group antigens are complex carbohydrate molecules expressed on the surface of red blood cells and a variety of human cells and tissues. It is well known that ABO blood type exerts a profound influence on hemostasis, being a major determinant of von Willebrand factor (VWF), and consequently factor VIII, plasma levels. In this review, we will focus on the molecular mechanisms underlying the interaction between ABO blood group and VWF in normal and pathological conditions. Keywords: ABO; ADAMTS13; desmopressin; LRP1; von Willebrand disease; von Willebrand factor. DOI 10.1515/cclm-2014-0564 Received May 27, 2014; accepted June 3, 2014; previously published online June 19, 2014
Introduction The antigens of the ABO blood group system (A, B and H determinants) are complex carbohydrate molecules expressed on the surface of the red blood cell (RBC) and a variety of human cells and tissues, including the epithelium, sensory neurons, platelets and the vascular endothelium [1, 2]. Thus, it is reasonable that the influence of ABO blood group extends beyond transfusion medicine being involved in several other clinical conditions, mainly infectious, malignant and cardiovascular disorders [3–5]. In particular, a number of clinical studies, systematic reviews and meta-analyses have consistently documented a positive association between ABO blood group and arterial and venous thrombosis, especially *Corresponding author: Massimo Franchini, MD, Director, Dipartimento di Medicina, Trasfusionale ed Ematologia, Azienda Ospedaliera Carlo Poma, Mantova, Italy, Phone: +39 0376 201234, Fax: +39 0376 220144, E-mail: [email protected]
Silvia Crestani, Francesco Frattini, Cinzia Sissa and Carlo Bonfanti: Dipartimento di Medicina Trasfusionale ed Ematologia, Azienda Ospedaliera Carlo Poma, Mantova, Italy
venous thromboembolism (VTE), in which non-O blood type is responsible alone for an approximately two-fold increased risk [4, 6–9]. The profound influence of ABH antigens on hemostasis is supported by their close relationship with von Willebrand factor (VWF) plasma levels, which are approximately 25% lower in blood group O individuals than those with non-O blood group [10–13]. In this review, we discuss the current knowledge on the close link between ABO blood group and VWF, focusing mainly on the biological mechanisms underlying this association. The clinical consequences of such interaction will be not specifically treated in this paper, as they have been already analyzed extensively elsewhere [6, 7, 9].
Biological mechanisms The ABH blood group antigens are synthesized by the sequential action of the ABO glycosyltransferases, which catalyze the addition of specific monosaccharides to a common core precursor antigen (H) to form distinct A and B antigens, while blood group O expresses only the basic, unmodified, H antigen with a fucose moiety attached to precursor oligosaccharide chains [1, 2]. As previously mentioned, VWF plasma levels vary greatly among different individuals according to their ABO blood type, having AB individuals the highest levels, followed by group B and then group A . The presence of ABO blood group determinants on VWF N-glicans provides the molecular basis of the connection between ABO blood type and VWF levels. Among the various mechanisms proposed, that involving the capacity of VWFrelated ABH antigens to influence VWF plasma levels by affecting its clearance rate seems the most plausible [14–16]. This hypothesis is supported by the finding that the VWF propeptide to VWF antigen (VWF:Ag) ratio (a predictor of clearance rate) is significantly increased (1.6 vs. 1.2, p