title: Comprehensive evaluation of haemostatic function in von Willebrand disease patients using a microchip-based flow chamber system.
abstract: The diagnosis of von Willebrand disease (VWD) is difficult due to the wide spectrum of clinical phenotypes associated with this disorder. We have analysed and characterized haemostatic function in VWD patients using a microchip-based flow chamber system. Microchips coated with either collagen [platelet (PL)-chip] or collagen/thromboplastin [atherome (AR)-chip] were used to evaluate platelet thrombus formation at 1000 s(-1) and fibrin-rich platelet thrombus formation at 240 s(-1) respectively. Blood samples from an asymptomatic patient with VWD type 1 [von Willebrand factor (VWF): RCo 3.2%; bleeding score (BS 2] displayed normal thrombus formation in both PL- and AR-chips, whereas blood from a symptomatic type 1 patient (VWF: RCo 14%, BS 9) had significantly delayed capillary occlusion. Nearly complete suppression of the flow pressure increase was observed in symptomatic patients with VWD type 2A (BS 13) and 2N (BS 27), whereas no flow pressure was found for the type 3 patient (BS 6). Fibrin-rich platelet thrombus formation was only weakly increased by the in vitro addition of factor VIII (FVIII) to blood samples from the type 3 patient, but was normalized by the addition of VWF/FVIII. The in vivo effects of treatment with desmopressin or VWF/FVIII for the symptomatic patients were analysed using two types of microchips. The PL-chip was highly sensitive for patients' VWF-mediated platelet functions, whereas the AR-chip allowed assessment of overall haemostatic ability, including sensitivity to both VWF and FVIII. The combined analysis with PL- and AR-chips may be potentially useful for the diagnosis of VWD based on clinical phenotypes, and for monitoring drug effects.
authors.affiliation: Department of Pediatrics, Nara Medical University, Kashihara, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ogiwara
authors.forename: K
authors.initials: K
authors.lastname: Nogami
authors.forename: K
authors.initials: K
authors.lastname: Hosokawa
authors.forename: T
authors.initials: T
authors.lastname: Ohnishi
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
authors.forename: M
authors.initials: M
authors.lastname: Shima
mesh_terms: D003894:Deamino Arginine Vasopressin / Q000627:therapeutic use*; D004338:Drug Combinations; D005169:Factor VIII / Q000627:therapeutic use*; D005260:Female; D006487:Hemostasis; D006490:Hemostatics / Q000627:therapeutic use*; D006801:Humans; D014842:von Willebrand Diseases / Q000097:blood*; D014841:von Willebrand Factor / Q000627:therapeutic use*
chemical_list: D004338:Drug Combinations; D006490:Hemostatics; C509423:factor VIII, von Willebrand factor drug combination; D014841:von Willebrand Factor; D005169:Factor VIII; D003894:Deamino Arginine Vasopressin
keywords: clinical phenotype; desmopressin; factor VIII; flow chamber system; von Willebrand disease; von Willebrand factor