Comprehensive analysis of ADAMTS13 in patients with liver cirrhosis

Abstract

Decreased plasma ADAMTS13 activity (ADAMTS13:AC) results in the accumulation of unusually large von Willebrand factor multimer (UL-VWFM) and the formation of platelet thrombi. It remains controversial whether or not plasma ADAMTS13:AC decreases in patients with liver cirrhosis (LC), and its relationship to clinical features has not been fully investigated. We measured ADAMTS13:AC and its related parameters in plasma in 33 patients with chronic hepatitis (CH) and in 109 patients with LC. ADAMTS13:AC decreased with increasing severity of liver disease (controls means 100%, CH 87%, Child A-LC 79%, Child B-LC 63%, and Child C-LC 31%), and showed severe deficiency (<3% of controls) in five end-stage LC. Activities measured by act-ELISA strongly correlated with those determined by the VWFM assay and ADAMTS13 antigen. Multivariate analysis showed Child-Pugh score and spleen volume independent factors contributing to ADAMTS13:AC. VWFM patterns were normal in 53% of cases, degraded in 31%, and unusually large in 16%. Patients with unusually large VWFM had the lowest ADAMTS13:AC as well as the highest Child-Pugh score, serum creatinine and blood ammonia levels. Plasma inhibitor against ADAMTS13 detected in 83% of patients with severe to moderate ADAMTS13:AC deficiency mostly showed marginal zone between 0.5 and 1.0 BU/ml. The IgG-type autoantibodies specific to plasma derived-ADAMTS13 was detected by Western blot in only five end-stage LC with severe ADAMTS13:AC deficiency. In conclusion, both plasma ADAMTS13 activity and antigen levels decreased with increasing severity of cirrhosis. An imbalance between the decreased ADAMTS13:AC and its increased substrate may reflect the predisposing state for platelet thrombi formation in patients with advanced LC.

ADAMTS-13 Antigen and Activity Levels in Thrombocytopenic Disorders Including Thrombotic Thrombocytopenic Purpura in Kuwait

“…None of the hepatitis patients in this study were reported to have cirrhosis, which may suggest that lower levels of this protease may only be seen upon progression of the medical condition. This is confirmed by results of other studies where a decrease of ADAMTS-13 activity was evident with increasing severity of liver disease and liver cirrhosis [13,22,23]. We also found that ADAMTS-13 antigen levels were lower in patients compared to controls; however, the decrease was not statistically significant (p = 0.08).…”

Minimal effects of acute liver injury/acute liver failure on hemostasis as assessed by thromboelastography

“…Plausible explanations include increased factor VIII levels due to increased endothelial cell activation/injury, decreased ADAMTS13 activity, or increased levels of platelets and fibrinogen as “acute phase reactants.” In fact, platelet counts tended to be higher in patients with ALF compared to ALI (200 vs. 150 × 10 9 /L, respectively; P =0.09) and correlated directly with ammonia ( r =0.30; P =0.031). ADAMTS13, a protease synthesized in hepatic stellate cells, degrades highly active, large multimers of von Willebrand factor (vWF) [26], and is decreased in proportion to the severity of chronic liver failure [27]. Conceivably, patients with ALF may be deficient in ADAMTS13, leading to an accumulation of large vWF multimers, and consequently to an increase in TEG parameters which reflect platelet function.…”

What's new in the diagnosis and pathophysiology of thrombotic thrombocytopenic purpura

“…For example, ~10% of patients with severe cirrhosis (Child class C) may have ADAMTS13 activity <10%. 34 However, preexisting cirrhosis does not exclude the possibility of typical acquired TTP with severe ADAMTS13 deficiency that will respond to plasma exchange.…”