Blocking the VWF-GPIb interaction prevents and treats acquired TTP in baboons. All baboons in the control (left panel), prevention (middle panel), and treatment (right panel) group received repeated injections of the inhibitory anti-ADAMTS13 mAb 3H9 (black arrow heads). Severe thrombocytopenia was observed in the control group (29 ± 5 × 109/L starting at day 3; A) together with hemolytic anemia evident from the severe decrease in Hp levels (1.8 ± 0.2 g/L at day 0 and 0 ± 0g/L at day 10, n = 3, P < .001; D). As baboons in the control group did not receive any GBR600, VWF activity (VWF:RCo/VWF:Ag) was not inhibited (G). Baboons in the prevention group were treated with GBR600 for 5 days (white arrow heads, middle panel). Platelet counts did not change (476 ± 39 × 109/L at day 0 and 408 ± 43 × 109/L at day 10, n = 3, B) and the decrease in Hp levels was moderate (1.5 ± 0.2 g/L at day 0 and 0.4 ± 0.2 g/L at day 10, P = .02, n = 3; E). Inhibition of VWF:RCo activity was observed when GBR600 was administered (H). Baboons in the treatment group (n = 3) received daily injections of GBR600 (right panel, white arrow heads) from day 4 onward. Severe thrombocytopenia was observed at day 3 and 4 but quickly normalized when GBR600 was injected (434 ± 25 × 109/L at day 7 versus 463 ± 48 × 109/L at day 0, P = NS, n = 3, C). Hemolytic anemia was evident from the severe decrease in Hp levels (1.6 ± 0.4 g/L at day 0 to 0 g/L at day 4, P = .01, n = 3; F). Injection of GBR600 from day 4 onward resulted in subsequent inhibition of VWF activity (I). Data are mean ± SEM, n = 3 in each group.
