ACTIVATED-PROTEIN-C RESISTANCE IN CANCER-PATIENTS

Background: Resistance to activated protein C (aPC) is usually linked to factor V Leiden, but may occur in other disorders associated with h ypercoagulability. In this study, we investigated the frequency of res istance to aPC in patients with advanced cancer and examined the relat ionship of aPC resistance to other markers of coagulation activation. Methods: Patients (n = 39) had an established diagnosis of advanced ca ncer; controls (n = 20) were healthy persons. aPC resistance was measu red as the ratio of activated partial thromboplastin times with and wi thout aPC (aPC-sensitivity ratio, aPC-SR). The factor V Leiden mutatio n was detected by a polymerase-chain-reaetion based technique. Other a ssays were performed by standard laboratory methods. Data were analyze d using t tests and the Pearson correlation. Results: aPC-SR was below 2 SD for 5 of the cancer patients (13%), but none of the controls; on ly 1 of the 5 had the factor V Leiden mutation. aPC-SR was inversely c orrelated (p < 0.01) with factor VIII and fibrinogen in patients and w ith prothrombin activation fragment 1.2 (F1.2) in controls. Patient fa ctor VIII, von Willebrand factor, (vWF), fibrinogen, F1.2 and D dimer were all significantly increased (p < 0.01); antithrombin III, protein C and proteins were similar to controls. Factor VIII correlated with vWF (p < 0.001) and F1.2 with d-dimer (p < 0.001). Other associations (p < 0.05) were observed between factor V and protein C, fibrinogen an d protein C, factor V and antithrombin III and protein C and antithrom bin III. Four cancer patients had a history of thromboembolism; their aPC-SR was similar to that of patients without thrombosis. Of the seve ral coagulation measures examined, only vWF was higher in the patients with thrombosis (p = 0.01). Interpretation: Cancer patients have evid ence of intravascular coagulation and increases in procoagulants and m ay have aPC resistance. The aPC resistance is not due to factor V Leid en, but is rather associated with elevated levels of factor VIII and f ibrinogen, and in itself does not predict thrombosis.