Figure 7
Figure 7. Platelet counts, mortality rates, and histological changes in mice with antibody-mediated inhibition of ADAMTS13 after being challenged with rmVWF. (A) Schematic representation of an animal protocol used to induce acquired deficiency of plasma ADAMTS13 activity and the time points for blood collection and complete blood count analysis in mice. (B) Plasma ADAMTS13 activity in WT after a single bolus infusion of scFv4-20 (5 µg/g body weight). Plasma from TG and KO mice also receiving scFv4-20 was used as a negative control. (C-E) Platelet counts, percentage of mice with thrombocytopenia (defined by greater than 30% reduction in platelet count from their baseline), and mortality rate, respectively, in TG (closed) and WT (open) mice that received an intraperitoneal injection of scFv4-20 (100 µg) before (pre) and 24 hours (d1) after being challenged with rmVWF at the dosage of 5 µg/g body weight. (F-H) Platelet counts, percentage of thrombocytopenia, and the mortality rate, respectively, in TG (closed) and WT (open) mice with scFv4-20 after being challenged with rmVWF at the doses of 10 µg/g body weight. ANOVA determined the statistical significance of the differences among various groups. **P < .01. (I) Occlusive thrombi were commonly found in histology analysis of the major organs including brain, heart, lung, kidneys, and liver in WT mice with scFv4-20 and rmVWF challenge at the dosage of 10 µg/g body weight (a,c,e,g,i). Such occlusive thrombi were rarely seen in TG mice receiving similar treatment (b,d,f,h,j).

Platelet counts, mortality rates, and histological changes in mice with antibody-mediated inhibition of ADAMTS13 after being challenged with rmVWF. (A) Schematic representation of an animal protocol used to induce acquired deficiency of plasma ADAMTS13 activity and the time points for blood collection and complete blood count analysis in mice. (B) Plasma ADAMTS13 activity in WT after a single bolus infusion of scFv4-20 (5 µg/g body weight). Plasma from TG and KO mice also receiving scFv4-20 was used as a negative control. (C-E) Platelet counts, percentage of mice with thrombocytopenia (defined by greater than 30% reduction in platelet count from their baseline), and mortality rate, respectively, in TG (closed) and WT (open) mice that received an intraperitoneal injection of scFv4-20 (100 µg) before (pre) and 24 hours (d1) after being challenged with rmVWF at the dosage of 5 µg/g body weight. (F-H) Platelet counts, percentage of thrombocytopenia, and the mortality rate, respectively, in TG (closed) and WT (open) mice with scFv4-20 after being challenged with rmVWF at the doses of 10 µg/g body weight. ANOVA determined the statistical significance of the differences among various groups. **P < .01. (I) Occlusive thrombi were commonly found in histology analysis of the major organs including brain, heart, lung, kidneys, and liver in WT mice with scFv4-20 and rmVWF challenge at the dosage of 10 µg/g body weight (a,c,e,g,i). Such occlusive thrombi were rarely seen in TG mice receiving similar treatment (b,d,f,h,j).

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