Developments in the diagnostic procedures for von Willebrand disease

Abstract

Summary Von Willebrand disease (VWD) is the most common inherited bleeding disorder but its diagnosis can be challenging due to the heterogeneity of the disease. VWD is mainly associated with mild mucocutaneous bleeding, although there are more severe phenotypes with bleeding from the gastrointestinal tract or even the joints. Also, surgical interventions and trauma may lead to critical bleeding events. These bleeding episodes are all related to quantitative or qualitative defects of von Willebrand factor (VWF), a multimeric glycoprotein produced by endothelial cells and megakaryocytes, which mediates platelet adhesion and aggregation and binds factor VIII (FVIII) in the circulation. This review describes the diagnostic procedures required for correct diagnosis. Accurate diagnosis and classification is required for proper treatment and counseling. Assessment of bleeding starts with the medical history. After a positive bleeding or family history, subsequent laboratory investigations will start with a panel of standard screening tests for hemostatic defects. Patients suspected of having VWD will be tested for plasma VWF antigen levels, the ability of VWF to bind platelets and FVIII activity. When VWD is confirmed, a set of subtyping tests can classify the patients as VWD types 1, 2 (A, B, M or N) or 3. The performance of some additional assays and analyses, such as VWF propeptide measurement or genetic analysis, may help in identifying the pathological mechanism behind certain defects or can guide in the choice of treatment.

Preoperative screening for bleeding disorders: A comprehensive laboratory assessment of clinical practice

“…The laboratory package was extensive but not exhaustive, meaning that some abnormalities might have been missed. These include platelet storage pool diseases,29, 38 and some vWD types 39. We did not perform repeated measures, which is usually performed in the diagnostic work‐up of bleeding disorders, as many variables such as stress and circadian variation influence hemostatic measurements 7, 40, 41.…”

Detection of inherited and acquired hemostatic disorders in surgical patients

“…Cependant, seulement 1 % de ces patients souffriront d'un épisode hémorragique important durant leur vie. 5 Il est néanmoins probable que plusieurs personnes souffrent d'épisodes de saignements liés à une mvW non diagnostiquée. 5 Lorsqu'il s'agit de population chirurgicale, il existe d'autres troubles de saignement acquis souvent non diagnostiqués.…”

“…5 Il est néanmoins probable que plusieurs personnes souffrent d'épisodes de saignements liés à une mvW non diagnostiquée. 5 Lorsqu'il s'agit de population chirurgicale, il existe d'autres troubles de saignement acquis souvent non diagnostiqués. La sténose de la valve aortique (SA), la maladie valvulaire cardiaque la plus répandue, est associée à une tendance de saignement chez environ 20 % de ces patients.…”

“…Nevertheless, only 1% of these patients will develop a significant bleeding episode during their life span. 5 It is likely, however, that many people may experience undiagnosed vWD-related bleeding episodes. 5 In the setting of a surgical population, there are other acquired bleeding disorders that are often underdiagnosed.…”

“…5 It is likely, however, that many people may experience undiagnosed vWD-related bleeding episodes. 5 In the setting of a surgical population, there are other acquired bleeding disorders that are often underdiagnosed. Aortic valve stenosis (AS), the most common heart valve disease, is associated with a bleeding tendency in about 20% of these patients.…”