ADAMTS13, VWF, and Endotoxin Are Interrelated and Associated with the Severity of Liver Cirrhosis via Hypercoagulability

Figures

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  Figure 1. Study design. A total of 99 patients with CLD were included in this study. None of the included patients had any history of coagulopathy, sepsis, or platelet disorders. We investigated the relationship(s) among ADAMTS13:AC, VWF:Ag, and parameters related to Et in patients with CLD to determine the cause of the imbalance between ADAMTS13:AC and VWF:Ag in these patients. CLD, chronic liver diseases; ADAMTS13, a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13; ADAMTS13:AC, ADAMTS13 activity; VWF, von Willebrand factor; VWF:Ag, VWF antigen; Et, endotoxins.

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  Figure 2. Relationship between ADAMTS13:AC and participant characteristics. (a–c) ADAMTS13:AC directly correlated with Alb (r = 0.405, p < 0.05), PT (r = 0.423, p < 0.05), and Plt (r = 0.302, p < 0.05). (d,e) ADAMTS13:AC inversely correlated with T-Bil (r = −0.441, p < 0.05) and Cre (r = −0.289, p < 0.05). ADAMTS13, a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13. ADAMTS13:AC, ADAMTS13 activity; Alb, albumin; PT, prothrombin time; Plt, platelet count; T-Bil, total bilirubin; Cre, creatinine.

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  Figure 3. Relationship between endotoxin levels and liver cirrhosis. Endotoxin levels increased as LC progressed and were highest in patients with Child–Pugh class C cirrhosis (p < 0.001 for between Child–Pugh classes C and A or chronic hepatitis, and p < 0.05 for between Child–Pugh classes C and B). Box plots represent, from top to bottom, sample maximum, upper-quartile range, median and lower-quartile range, and sample minimum. LC, liver cirrhosis.

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  Figure 4. Relationship between endotoxin levels and ADAMTS13:AC, endotoxin levels and VWF:Ag, and endotoxin levels and VWF:Ag/ADAMTS13:AC. (a) Patients with endotoxin levels of >5 pg/mL had lower ADAMTS13:AC than those with endotoxin levels of ≤5 pg/mL (p < 0.05). (b) Patients with endotoxin levels of >5 pg/mL had higher VWF:Ag than those with endotoxin levels of ≤5 pg/mL (p < 0.05). (c) Patients with endotoxin levels of >5 pg/mL had higher VWF:Ag/ADAMTS13:AC than those with endotoxin levels of ≤5 pg/mL (p < 0.05). Box plots represent, from top to bottom, sample maximum, upper-quartile range, median and lower-quartile range, and sample minimum. ADAMTS13, a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13; ADAMTS13:AC, ADAMTS13 activity; VWF, von Willebrand factor; VWF:Ag, VWF antigen; VWF:Ag/ADAMTS13:AC, ratio of VWF:Ag to ADAMTS13:AC.

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  Figure 5. Relationship between endotoxin levels and patient characteristics. (a,b) Endotoxin levels were inversely correlated with Alb (r = −0.307, p < 0.05) and PT (r = −0.308, p < 0.05). (c,d) Endotoxin levels were directly correlated with T-Bil (r = 0.295, p < 0.05) and Cre (r = 0.246, p < 0.05). Alb, albumin; PT, prothrombin time; T-Bil, total bilirubin; Cre, creatinine.

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  Figure 6. Relationship between endotoxin levels and ADAMTS13:INH and between endotoxin levels and VWFM patterns. (a) Patients with detectable ADAMTS13:INH had higher endotoxin levels than those with undetectable ADAMTS13:INH (p < 0.05). (b) Patients with normal and UL VWFM patterns had higher endotoxin levels than those with degraded VWFM (p < 0.05). Box plots represent, from top to bottom, sample maximum, upper-quartile range, median and lower-quartile range, and sample minimum. ADAMTS13, a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13; ADAMTS13:INH, ADAMTS13 inhibitor; VWF, von Willebrand factor; VWFM, VWF multimer; UL, unusually large.