Resistance to activated protein C and low levels of free protein S in Greek patients with inflammatory bowel disease.
OBJECTIVE
Patients with inflammatory bowel disease (IBD) frequently suffer from thromboembolic events. A recently identified mechanism for thrombophilia, the poor anticoagulant response to activated protein C, has been suggested as one of the leading risk factors for thrombosis. The aim of this study was to evaluate the frequency of thrombophilic abnormalities, including activated protein C-resistance (APCR), in Greek patients with ulcerative colitis (UC) and Crohn's disease (CD).


METHODS
Forty-eight patients with UC, 36 with CD, and 61 matched healthy controls (HC) were studied. Cases with presence of lupus anticoagulant, use of anticoagulants or heparin, and pregnancy were excluded. Disease activity in CD was evaluated by use of the Crohns Disease Activity Index (CDAI) score and in UC by the Truelove-Witts grading system. Plasma levels of protein C, free protein S, antithrombin III (AT-III), activated protein C resistance (APCR), and fibrinogen were determined in IBD patients, as well as in HC. All the cases and controls with abnormal APCR were further studied by genetic testing for the factor V Leiden mutation.


RESULTS
Mean fibrinogen levels in UC and CD patients were significantly elevated (p<0.0001), compared with HC. The mean values of free protein S, as well as mean APCR, were significantly lower in UC and CD patients than in the HC (p<0.0001). Seven (five UC and two CD) of 84 IBD patients (8.3%) and three of the HC (4.9%) had the factor V Leiden mutation. No significant difference was observed for the other thrombophilic parameters. Fibrinogen levels and profound free protein S deficiency were found related to disease activity.


CONCLUSIONS
Thrombophilic defects are common in Greek patients with IBD and they could interfere either in the disease manifestation or in the thrombotic complications.
Koutroubakis
I E
IE
Department of Gastroenterology, University Hospital of Heraklion, Crete, Greece.
Sfiridaki
A
A
Mouzas
I A
IA
Maladaki
A
A
Kapsoritakis
A
A
Roussomoustakaki
M
M
Kouroumalis
E A
EA
Manousos
O N
ON
D020016:Activated Protein C Resistance / Q000150:complications*; D000328:Adult; D000990:Antithrombin III / Q000032:analysis; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000032:analysis; D017293:Protein S / Q000032:analysis*; D019851:Thrombophilia / Q000097:blood / Q000150:complications
D011486:Protein C; D017293:Protein S; D000990:Antithrombin III; D005340:Fibrinogen