Hyperhomocysteinemia and hypercoagulability in primary biliary cirrhosis.
OBJECTIVE
To assess the hypercoagulability in PBC and its relationship with homocysteine (HCY) and various components of the haemostatic system.


METHODS
We investigated 51 PBC patients (43F/8M; mean age: 63+/-13.9 yr) and 102 healthy subjects (86 women/16 men; 63+/-13 yr), and evaluated the haemostatic process in whole blood by the Sonoclot analysis and the platelet function by PFA-100 device. We then measured HCY (fasting and after methionine loading), tissue factor (TF), thrombin-antithrombin complexes (TAT), D-dimer (D-D), thrombomodulin (TM), folic acid, vitamin B6 and B12 plasma levels. C677T 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism was analyzed.


RESULTS
Sonoclot RATE values of patients were significantly (P<0.001) higher than those of controls. Sonoclot time to peak values and PFA-100 closure times were comparable in patients and controls. TAT, TF and HCY levels, both in the fasting and post-methionine loading, were significantly (P<0.001) higher in patients than in controls. Vitamin deficiencies were detected in 45/51 patients (88.2%). The prevalence of the homozygous TT677 MTHFR genotype was significantly higher in patients (31.4%) than in controls (17.5%) (P<0.05). Sonoclot RATE values correlated significantly with HCY levels and TF.


CONCLUSIONS
In PBC, hyper-HCY is related to hypovitaminosis and genetic predisposing factors. Increased TF and HCY levels and signs of endothelial activation are associated with hypercoagulability and may have an important role in blood clotting activation.
Gastroenterology Unit, Department of Clinical Pathophysiology, University of Florence, Viale Morgagni 85 50134, Firenze, Italy.
Maria Rosa
MR
Biagini
Alessandro
A
Tozzi
Rossella
R
Marcucci
Rita
R
Paniccia
Sandra
S
Fedi
Stefano
S
Milani
Andrea
A
Galli
Elisabetta
E
Ceni
Marco
M
Capanni
Raffaele
R
Manta
Rosanna
R
Abbate
Calogero
C
Surrenti
D000328:Adult; D000368:Aged; D000990:Antithrombin III; D005260:Female; D005492:Folic Acid / Q000097:blood; D006487:Hemostasis; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications*; D008105:Liver Cirrhosis, Biliary / Q000097:blood* / Q000150:complications*; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000097:blood; D010979:Platelet Function Tests; D018180:Thrombomodulin / Q000097:blood; D019851:Thrombophilia / Q000097:blood / Q000150:complications*; D013925:Thromboplastin / Q000378:metabolism; D014805:Vitamin B 12 / Q000097:blood; D025101:Vitamin B 6 / Q000097:blood
D018180:Thrombomodulin; C046193:antithrombin III-protease complex; D006710:Homocysteine; D025101:Vitamin B 6; D000990:Antithrombin III; D013925:Thromboplastin; D005492:Folic Acid; D010447:Peptide Hydrolases; D014805:Vitamin B 12