Assessing the clinical severity of type 1 von Willebrand disease patients with a microchip flow-chamber system

Background The clinical phenotype of von Willebrand disease (VWD) is heterogeneous, and von Willebrand factor ristocetin cofactor activity (VWF:RCo) does not always reflect clinical severity, especially in VWD type 1. We have reported the potential of a microchip flow-chamber system (Total-Thrombus Formation Analysis System [T-TAS((R))]) for assessing physiologic hemostasis in VWD. Aim To evaluate the relationship between T-TAS, bleeding score (BS) and laboratory test results in type 1 VWD patients. Methods Microchips coated with collagen (platelet chip [PL-chip]) or collagen/thromboplastin (AR-chip) were used to assess platelet thrombus formation (PTF) at high shear rates or fibrin-rich PTF at low shear rates, respectively, in whole blood from 50 patients. The times needed for the flow pressure to increase by 10 kPa and 30 kPa (T-10 and T-30) from baseline were calculated from flow pressure curves. BS was determined by the use of a standardized questionnaire. Results PL-T-10 values correlated with BS (R-2 similar to 0.45) better than VWF:RCo (R-2 similar to 0.36), irrespective of the flow rate, whereas AR-T-10 showed only a weak correlation with BS (R-2 similar to 0.18). Patients with PL-T-10 > 10 min or AR-T-10 > 30 min had lower VWF levels and higher BS than those with PL-T-10 10 min or AR-T-10 30 min, and the greatest differences were observed with PL-T-10. Clinical severity appeared to correlate best with PL-T-10 > 8 min. BS was significantly higher in patients with VWF:RCo of < 10 IU dL(-1) than in those with VWF:RCo of 10 IU dL(-1) to < 25 IU dL(-1) and 25-40 IU dL(-1). In patients with VWF:RCo of < 10 IU dL(-1), BS was significantly higher in those with PL-T-10 > 8 min than in those with PL-T-10 8 min. Conclusion T-TAS could be a useful technique for discriminating and predicting BS in VWD type 1 patients.