WB SYK inhibition prevents from VITT Ab–mediated multicellular thrombus formation ex vivo. (A-B) Whole blood from healthy individuals was incubated with IgG from HCs or patients with VITT in the presence of exogenous PF4 (10 μg/mL) and SYK inhibitors R406 or lanraplenib (both 5 μM) or vehicle control before recalcification and perfusion through microfluidic channels at a venous shear rate of 250 sec–1 (10 dyne/cm2) for 25 minutes. (A) After perfusion, images were acquired at magnification ×40. Scale bar, 20 μm. (B) Violin plots showing the percentage of total surface area coverage (% SAC) by DiOC6 (nonprocoagulant PLTs), annexin-V (procoagulant PS), fibrin, count of Hoechst-positive–labeled cells (leukocytes); and cumulative total % SAC with DiOC6, PS, and fibrin–labeled thrombus captured in the microfluidic channel. The number of patients tested is reported in each graph. Unpaired or paired t test is shown. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001. N, number of patients tested; ns, nonsignificant.
