Increased coagulation factor VIII, IX, XI and XII activities in non-alcoholic fatty liver disease.
OBJECTIVE
Obesity and the metabolic syndrome are established risk factors of venous thromboembolism. As most coagulation factors are produced exclusively by the liver and non-alcoholic fatty liver disease (NAFLD) is tightly related to metabolic disorders, we aimed at studying the association of liver fat with various coagulation factor activities.


METHODS
Plasma prothrombin (PT) and activated partial thromboplastin time, activities of vWF:RCo, FVII, FVIII, FIX, FXI, FXII, FXIII, fibrinogen and D-dimer concentrations were measured in 54 subjects with and 44 without NAFLD diagnosed by proton magnetic resonance spectroscopy. Subjects were recruited retrospectively for metabolic studies in our laboratory. The body composition and features of insulin resistance were measured in all subjects.


RESULTS
FVIII (107±30 vs. 84±22%, P<0.001), FIX (110±14 vs. 94±16%, P<0.001), FXI (109±16 vs. 96±19%, P=0.001) and FXII (113±21 vs. 99±32%, P=0.002) activities were consistently elevated in subjects with as compared with those without NAFLD. Liver fat percentage was positively related to FVIII (r=0.28, P=0.005), FIX (r=0.36, P=0.0003), FXI (r=0.29, P=0.004) and FXII (r=0.30, P=0.003) activities, again independent of age, gender and body mass index (BMI). PT%, vWF:RCo activity and fibrinogen were higher in subjects with as compared with those without NAFLD, but this difference disappeared after adjusting for age, gender and BMI.


CONCLUSIONS
FVIII, FIX, FXI and FXII activities are increased in human NAFLD and correlate with the features of insulin resistance. The relationships between NAFLD and these coagulation factors are independent of age, gender and BMI, suggesting that the fatty liver can contribute to the risk of thrombosis.
Department of Medicine, Division of Diabetes, University of Helsinki, Helsinki, Finland. anna.kotronen@helsinki.fi
Anna
A
Kotronen
Lotta
L
Joutsi-Korhonen
Ksenia
K
Sevastianova
Robert
R
Bergholm
Antti
A
Hakkarainen
Kirsi H
KH
Pietiläinen
Nina
N
Lundbom
Aila
A
Rissanen
Riitta
R
Lassila
Hannele
H
Yki-Järvinen
D000328:Adult; D000367:Age Factors; D000368:Aged; D015992:Body Mass Index; D005164:Factor IX / Q000378:metabolism*; D005169:Factor VIII / Q000378:metabolism*; D005172:Factor XI / Q000378:metabolism*; D005174:Factor XII / Q000378:metabolism*; D005234:Fatty Liver / Q000097:blood / Q000378:metabolism; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005387:Finland; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D010314:Partial Thromboplastin Time; D011516:Prothrombin / Q000378:metabolism; D012737:Sex Factors; D014841:von Willebrand Factor / Q000378:metabolism
D014841:von Willebrand Factor; D011516:Prothrombin; D005169:Factor VIII; D005164:Factor IX; D005174:Factor XII; D005340:Fibrinogen; D005172:Factor XI