Evaluation of clinical severity in patients with type 2N von Willebrand disease using microchip-based flow-chamber system

Int J Hematol. 2020 Mar;111(3):369-377. doi: 10.1007/s12185-019-02782-z. Epub 2019 Nov 18.


Type 2N von Willebrand disease (VWD) is characterized by impaired factor VIII (FVIII) binding to von Willebrand factor (VWF). Type 2N VWD patients generally exhibit mild bleeding tendency, but some exhibit a more severe hemorrhagic pattern. An assay for assessing hemostatic potential and predict clinical severity could significantly improve clinical management in these patients. We examined the relationship between bleeding score (BS) and the potential for thrombus formation in whole blood from type 2N VWD patients with various BS using rotational thromboelastometry (ROTEM) and microchip flow-chamber system (T-TAS®). Collagen-coated PL-chips, or thromboplastin- and collagen-coated AR-chips, were utilized in the T-TAS to assess platelet thrombus formation at high shear flow, or fibrin-rich platelet thrombus formation at low shear flow, respectively. Neither ROTEM nor the T-TAS using PL-chips reflected the BS. The AR-chip parameters in the T-TAS, however, were highly sensitive to different BS levels among these patients, despite similar FVIII/VWF-related measurements including FVIII/VWF binding. Additionally, the results with AR-chip assay were restored to normal after infusions of FVIII/VWF concentrates in the most severe patients. The data indicate that T-TAS using AR-chips may be a useful assay for predicting clinical severity and assessing therapeutic efficiency in type 2N VWD patients.

Keywords: Bleeding score; Clinical severity; Microchip flow-chamber system; Type 2N von willebrand disease; Von willebrand factor.

MeSH terms

  • Humans
  • Platelet Function Tests / methods*
  • Severity of Illness Index
  • Thrombelastography / methods
  • von Willebrand Disease, Type 2 / diagnosis*
  • von Willebrand Disease, Type 2 / genetics