Defective ADAMTS13 synthesis as a possible consequence of NASH in an obese patient with recurrent thrombotic thrombocytopenic purpura.
OBJECTIVE
Thrombotic thrombocytopenic purpura (TTP) is a rare and devastating hematologic disorder frequently associated with multiple organ failure and sometimes death. This syndrome is mainly associated with severe deficiency of ADAMTS13, a disintegrin and metalloprotease with thrombospondin (TSP)-1 repeats, cleaving high molecular weight von Willebrand Factor (ULVWF) multimers. Decreased plasma ADAMTS13 activity results in the accumulation of ULVWF multimers with consequent platelet activation. Recently, obesity has been considered as a potential independent risk factor for TTP, but the reason of this association is still unknown.


RESULTS
We describe an unusual case of fatal recurrent TTP in a morbid obese female with non-alcoholic steatohepatitis (NASH) and severe ADAMTS13 activity deficiency due neither to an inhibitory autoantibody nor to a gene mutation.


CONCLUSIONS
Visceral obesity is associated with non-alcoholic fatty liver disease (NAFLD) and NASH: we hypothesized that these conditions can influence ADAMTS13 antigen and activity. In fact, hepatic stellate cells (HSC) are the main producers of ADAMTS13, and a decrease in ADAMTS13 activity has been reported in liver disease.
Internal Medicine, Department of Medicine, University of Padova, Padova, Italy.
Anna Maria
AM
Lombardi
Roberto
R
Fabris
Giulia
G
Berti de Marinis
Piero
P
Marson
Filippo
F
Navaglia
Mario
M
Plebani
Roberto
R
Vettor
Fabrizio
F
Fabris
D051722:ADAM Proteins / Q000172:deficiency* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000071120:ADAMTS13 Protein; D000328:Adult; D004789:Enzyme Activation; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis / Q000209:etiology*; D009765:Obesity / Q000150:complications*; D010976:Platelet Count; D011697:Purpura, Thrombotic Thrombocytopenic / Q000150:complications* / Q000175:diagnosis
D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
ADAMTS13; non-alcoholic steatohepatitis; obesity; thrombotic thrombocytopenic purpura