title: Phenotypic identification of platelet-type von Willebrand disease and its discrimination from type 2B von Willebrand disease: a question of 2B or not 2B? A story of nonidentical twins? Or two sides of a multidenominational or multifaceted primary-hemostasis coin?
abstract: Platelet-type von Willebrand disease (PT-VWD) and type 2B von Willebrand disease (2B-VWD) have different etiologies although both present with a similar clinical bleeding and basic laboratory phenotype. Both PT-VWD and 2B-VWD represent gain-of-function mutations that lead to enhanced binding between plasma von Willebrand factor (VWF) and its platelet ligand, glycoprotein Ib alpha (GP1BA). However, 2B-VWD results from a functionally abnormal VWF molecule arising from mutations in the VWF gene, whereas PT-VWD is caused by hyperresponsive platelets resulting from mutations in the platelet GP1BA gene. A definitive diagnosis of PT-VWD versus 2B-VWD is critical for treatment decisions (as differential therapies might be respectively required) and also for family counseling. However, laboratory discrimination of PT-VWD versus 2B-VWD is problematic because simple phenotypic testing will not permit their differentiation, and the more complex testing approaches that might permit their differentiation are rarely applied, or are perhaps poorly applied. Although differential identification of PT-VWD versus 2B-VWD can most definitively be achieved by identifying the gene defect at either the VWF or GP1BA loci, such tests are not commonly available, not always successful, and even if available and successful might not be readily available to serve time-critical treatment decisions. Accordingly, simple laboratory tools to enable discrimination of the two disorders would be a valuable addition to the test repertoire of the hemostasis laboratory. This article provides a review of PT-VWD-related literature and an overview of a phenotypic laboratory test process that should enable the effective identification of PT-VWD and its discrimination from 2B-VWD.
authors.affiliation: Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Westmead, Australia. favaloro@swahs.health.nsw.gov.au
authors.forename: Emmanuel J
authors.initials: EJ
authors.lastname: Favaloro
mesh_terms: D001792:Blood Platelets / Q000502:physiology; D003937:Diagnosis, Differential; D006487:Hemostasis; D006801:Humans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000097:blood / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D010979:Platelet Function Tests / Q000379:methods; D019038:Platelet Glycoprotein GPIb-IX Complex; D011485:Protein Binding; D009626:Terminology as Topic; D014842:von Willebrand Diseases / Q000097:blood* / Q000145:classification* / Q000175:diagnosis / Q000235:genetics; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019038:Platelet Glycoprotein GPIb-IX Complex; C094990:adhesion receptor; D014841:von Willebrand Factor