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factor (VWF) plays a crucial role in both physiological haemostasis and pathological arterial thrombosis. 1 At the high shear rates, VWF mediates the initial tethering of platelets to the injured vessel surface by bridging platelet receptor glycoprotein (GP) Ib and subendothelial collagen. 1 This initial platelet adhesion on the subendothelial surface leads to platelet activation and conformational

von Willebrand factor levels don't always reflect the severity of von Willebrand disease (VWD). Relationship between new flow system (T‐TAS®) and bleeding score (BS) in type 1 VWD was studied. Patients with PL‐T10 > 10 min had higher BS and particularly, PL‐T10 > 8 min correlated best. T‐TAS could be a useful tool for discriminating and predicting the BS in VWD type 1 patients. Summary BackgroundThe 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®]) for assessing physiologic hemostasis in VWD. AimTo evaluate the relationship between T‐TAS, bleeding score (BS) and laboratory test results in type 1 VWD patients. MethodsMicrochips 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 (T10 and T30) from baseline were calculated from flow pressure curves. BS was determined by the use of a standardized questionnaire. ResultsPL‐T10 values correlated with BS (R2 ~ 0.45) better than VWF:RCo (R2 ~ 0.36), irrespective of the flow rate, whereas AR‐T10 showed only a weak correlation with BS (R2 ~ 0.18). Patients with PL‐T10 > 10 min or AR‐T10 > 30 min had lower VWF levels and higher BS than those with PL‐T10 ≤ 10 min or AR‐T10 ≤ 30 min, and the greatest differences were observed with PL‐T10. Clinical severity appeared to correlate best with PL‐T10 > 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‐T10 > 8 min than in those with PL‐T10 ≤ 8 min. ConclusionT‐TAS could be a useful technique for discriminating and predicting BS in VWD type 1 patients.

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Background Emicizumab is a bispecific antibody to factor (F) IXa and FX that mimics the FVIIIa cofactor function. Emicizumab prophylaxis markedly decreases bleeding episodes in patients with hemophilia A (PwHAs), irrespective of the presence of FVIII inhibitors. However, thrombotic microangiopathy (TMA) was reported when repeated high doses of activated prothrombin complex concentrates (aPCC) were concomitantly used with emicizumab. Although bypassing agents (BPAs) are vital in the hemostatic treatment for PwHAs with inhibitors, the mechanism of emicizumab-related TMA remains unclear. Aim To assess the risk of excessive thrombus formation associated with BPAs and emicizumab under high shear conditions. Methods Perfusion flow-chamber experiments under high shear conditions were performed using whole blood from PwHAs in the presence of emicizumab without or together with FVIII or BPAs ex vivo. Results Emicizumab (100 μg/mL) added ex vivo to whole blood from PwHAs improved defective thrombus formation in a similar manner to that observed with the addition of recombinant FVIII at the early phase, while FVIII continued to be important at the later stages. aPCC (1.2 U/mL equivalent to 100 U/kg) or recombinant FVIIa (1.1 µg/mL; equivalent to 90 µg/kg) together with emicizumab further promoted platelet interactions and fibrin formation ex vivo but did not induce excessive thrombus formation. Conclusion Emicizumab enhanced thrombin generation at local sites and improved defective hemostasis in whole blood from PwHAs under high shear conditions. Simple concomitant use of BPAs with emicizumab did not mediate excessive thrombus formation and remains an option for hemostatic management of emicizumab-treated PwHAs with inhibitors.