Impaired hemostatic capacity in patients with low von Willebrand factor

Introduction In the most recent guidelines on the diagnosis of von Willebrand disease (VWD),1 not only patients with von Willebrand Factor (VWF) < 30 IU/dL, but also those with a bleeding tendency and VWF levels 30-5IU/dl were defined as having VWD. However, data on the hemostatic capacity are scare in patients with VWD and no data on differences between patients with <30 IU/dL and those with 30-5IU/dL are available. Recently, we could show an impairment of the hemostatic potential in patients with bleeding disorder of unknown cause (BDUC),2 who share a similar phenotype to patients with low VWF.3 Method We analyzed the hemostatic capacity and compared clinical data of 38 patients with low VWF levels (30-50 IU/dL) to 10 patients with very low VWF levels (<30 IU/dL), 383 patients with BDUC and 100 healthy controls (HC). Patients had been consecutively included into the Vienna bleeding biobank (VIBB), a prospective cohort-study (EC No 603/2009).2 The hemostatic capacity was assessed by thrombin generation (TG, Technothrombin, Technoclone, Vienna, Austria) and plasma clot formation and lysis (PCF, method by Wolberg et al, according to SCC recommendations of the ISTH4,5). Results Patients’ characteristics and bleeding phenotype are summarized in Table 1. Blood group O was more common in VWD patients compared to BDUC and HC. Patients with low VWF levels did not differ significantly in bleeding severity (measured by the Vicenza and ISTH bleeding score and the number of bleeding manifestations) in comparison to patients very low VWF levels (<30 IU/dL) or BDUC, albeit a tendency towards increased bleeding severity in patients with very low VWF was seen ([ Tab. 1 ]). Tab. 1 Clinical characteristics and bleeding phenotype in all patient groups and healthy controls. TG and PCF, but not clot lysis, were equally impaired in patients with low- and very low VWF compared to HC (Table 2). Compared to BDUC, TG was also significantly decreased in low VWF patients, whereas there were no relevant differences in PCF. No strong correlations of the hemostatic capacity with the bleeding phenotype (Vicenza and ISTH-BAT scores, number of bleeding manifestations) was seen (data not shown). Age (β=-0.149, p<.001), sex (β=0.206, p<.001) and fibrinogen levels (β=0.330, p<.001) affected TG (AUC) in multivariate analysis (linear regression, R2=0.207) of all patients, whereas there was no significant impact of VWF- or FVIII levels, or blood group O. PCF (R2=0.360) was determined by factor VIII- (β=0.251,p<.001) and fibrinogen levels (β=0.534,p<.001) but also not by VWF or blood type [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ]. Conclusion In our study, we have observed a predominance of female sex and blood group O in patients with low VWF, in line to published data. We found a significantly decreased hemostatic capacity in patients with low VWF levels, which was to the same extend impaired as in patients with very low VWF. Our data support the diagnosis of VWD in bleeding patients with low VWF ([ Tab. 2 ]). Tab. 2 Thrombin generation and plasma clot formation/lysis in patients with low VWF in comparison to very low VWF, BDUC and healthy controls. Publication History Article published online: 20 February 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany