Therapeutic efficacy of rhADAMTS13. (A) Platelet counts. All mice were challenged with 2000 VWF:RCoU/kg BW rhVWF at time point zero. Four groups of animals (●; rhVWF) did not receive any further treatment, and platelet count was assessed 15, 30, and 180 minutes and 1 day after challenge. These mice developed a thrombocytopenia (also shown in Figure 3). Three groups of mice received therapeutic treatment with 320 FRETS-U/kg BW of rhADAMTS13 (▴; rhA13), 15, 30, or 180 minutes after challenge with rhVWF. Platelet count of these groups was assessed on day 1. Data derived from the rhVWF-challenged controls (●; rhVWF) indicated that the animals allocated to treatment had already developed a thrombocytopenia at the time point of treatment. At day 1, platelet counts were higher for all rhADAMTS13-treated groups (▴) compared with the untreated group (●; rhVWF 1 day). Deductively, therapeutic administration of rhADAMTS13 caused a stabilization of the platelet counts at the respective time point of treatment (eg, rhVWF +15 minutes vs rhADAMTS13 + 15 minutes). (B) Pathologic changes. The same animals as in panel A were scrutinized on day 1 for pathologic changes in the heart. Incidences and severity of myocardial hemorrhage (○), myocardial necrosis (□), and neutrophil infiltration of the myocardium (♢) were highest in the nontreated control group (n = 6). Therapeutic treatment with 320 FRETS-U/kg BW of rhADAMTS13 (n = 6) had a beneficial treatment interval-dependent effect on the incidence and severity of pathologic changes.