Evaluation of clinical severity in patients with type 2N von Willebrand disease using microchip-based flow-chamber system
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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.
KeywordsMicrochip flow-chamber system Type 2N von willebrand disease Von willebrand factor Bleeding score Clinical severity
We greatly thank Prof. Dr. Yoshiaki Tomiyama (Osaka University) and Dr. Hiroyuki Sugawara (Sumitomo Hospital) who was the patients’ home doctor for keeping the patients’ condition stable for a long term.
YN: analyzed the data, made the figure, wrote the paper; KN: ran the clinic, performed the experiments, designed the research, interpreted the data, wrote the paper, edited the manuscript and approved the final version to be published, TK: analyzed VWF gene, KY, KO, SF, NS, MT: ran the clinic and performed the experiments; MS: supervised the research.
This work was partly supported by a Grant-in-Aid for Scientific Research (KAKENHI) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) to KN (Grant No. 18K07885).
Compliance with ethical standards
Conflict of interest
The authors have no conflicts of interest to disclose.
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