The role of genetics in the pathogenesis and diagnosis of type 1 Von Willebrand disease

Abstract

Purpose of review Von Willebrand disease (VWD) is a common bleeding disorder, but diagnosis of VWD is challenging, particularly with type 1 VWD. Although most clinicians use specific tests of von Willebrand factor (VWF) activity to classify patients with VWD, genetic testing for VWF defects is another potential method of diagnosis. Recent findings Studies of patients with type 1 VWD report consistently that many, but not all, study participants have VWF gene defects. Certain populations, including those with VWF levels less than 30 IU/dl and those with clearance defects, are more likely to have a VWF sequence variant. In addition, a number of loci outside the VWF gene have been shown to affect VWF levels, including ABO, CLEC4M, STXBP5, and STAB2. Summary Genetic defects in VWF are common, but not all defects lead to disease. Type 1 VWD in particular does not always have an associated VWF sequence variant. New data stemming from genome-wide association studies on modifier genes suggest that the etiology of type 1 VWD is multifactorial.

The Vascular Endothelium and Coagulation: Homeostasis, Disease, and Treatment, with a Focus on the Von Willebrand Factor and Factors VIII and V

“…In this regard, three types of vWD have been described [ 235 ]. Type I, which comprises the majority of cases, is characterized by a quantitative deficiency of vWF that usually results in impaired pro-vWF transport (levels < 20 IU/dl) [ 236 ]. Type II involves a mutation-derived functional vWF deficiency.…”

Case Report: An Unusual Case of Nutcracker Syndrome and Literature Review

“…Patients with acquired VWD may experience recurrent hematuria (34). Unlike other coagulation factor deficiencies, VWD, particularly type 1 VWD, is notoriously difficult to diagnose (35). Initial hemostasis laboratory evaluations usually include the following: (i) a platelet count and complete blood cell count; (ii) partial thromboplastin time (PTT); (iii) prothrombin time; and (iv) optionally either fibrinogen level or thrombin time.…”

Diagnóstico de la enfermedad de von Willebrand

“…Una de las desventajas de las pruebas genéticas es que se han encontrado muchas variantes del gen VWF que anteriormente se denominaban patógenas en individuos sanos, particularmente en la población afroamericana. También existe escasa correlación entre las variantes genéticas y la EVW tipo 1, que es la más común [25,51].…”