Hypercoagulable state in patients with advanced gastrointestinal cancer: evidence for an acquired resistance to activated protein C.
OBJECTIVE
Thromboembolic complications are common in patients with cancer and represent the second cause of death in patients with overt malignant disease. The aim of this study was to investigate the activated protein C pathway in cancer.


METHODS
We studied the coagulation cascade, natural clotting inhibitors, fibrinolytic proteins and resistance to activated protein C in 20 patients with advanced gastrointestinal cancer and 84 volunteers by measuring PT, APTT, fibrinogen, AT III, PC, PS, APC resistance, fibrinolytic system (PLG, ANPL, PAI-1, and t-PA) and activation peptides (D-Dimers, prothrombin 0 fragment 1 + 2/F1 + 2).


RESULTS
Laboratory tests confirmed coagulation abnormalities in cancer patients. Fibrinogen, D-Dimers and F1 + 2 were increased, while t-PA activity was significantly lower than that of controls. APC resistance was higher in cancer patients compared to the control group (55% vs 2%; P < 0.0001). Excess thrombin generation was manifested by increased F1 + 2 plasma levels in APC-resistant cancer patients. Genetic analyses showed that only one patient with a poor response to APC carried a factor V R506Q mutation in exon 10.


CONCLUSIONS
Our findings show a high prevalence of APC resistance in cancer, compatible with an acquired defect in the APC pathway.
De Lucia
D
D
Institute of General Pathology and Oncology, II University of Naples, Italy.
De Vita
F
F
Orditura
M
M
Renis
V
V
Belli
A
A
Conte
M
M
di Grazia
M
M
Iacoviello
L
L
Donati
M B
MB
Catalano
G
G
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D001779:Blood Coagulation Factors / Q000187:drug effects; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects*; D005770:Gastrointestinal Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000378:metabolism*; D013923:Thromboembolism / Q000209:etiology* / Q000378:metabolism*
D000964:Antimetabolites, Antineoplastic; D001779:Blood Coagulation Factors; D011486:Protein C; D005472:Fluorouracil