Activated protein C resistance in cancer-associated venous thromboembolism

Abstract number: P0838

Goldenberg^* N., Kahn† S. R., Solymoss† S.

†McGill University, Canada ^*The Children's Hospital, USA;

While activated protein C resistance (APCR) is present in up to 5% of healthy subjects, prior studies suggest that this defect may be more common in cancer patients. Evidence from a single published study suggests that APCR may be a risk factor for venous thromboembolism (VTE) in patients with malignancy. We investigated whether the rate of APCR is increased in cancer-patients with acute VTE and whether APCR correlates with other abnormalities of coagulation and fibrinolysis in cancer patients. Plasma activated protein C (APC) sensitivity ratios were performed on peripheral venous blood obtained prior to anticoagulant therapy in adult cancer patients with symptomatic acute deep venous thrombosis (DVT + cancer group, n = 32), cancer patients without history of DVT (cancer group, n = 33), and patients with acute DVT but no cancer (DVT group, n = 58). Clinical data were obtained by chart review. No patients had received chemotherapy within the prior 2 weeks or undergone surgery within 4 weeks, in order to minimize the potential confounding effects of these interventions on hemostasis. The rate of APCR in the DVT + cancer group (9%) was similar to that of the cancer group (3%; P = 0.36) but lower than that in the DVT group (24%; P = 0.16). Median APC sensitivity ratios were not significantly different among the three groups (2.62 in the DVT + cancer group vs. 2.55 in the cancer group and 2.59 in the DVT group; P = 0.29 and P = 0.89, respectively). The APCR rate in cancer patients with metastases (5%) did not differ significantly from that of patients with localized disease (8%; P = 0.55). APCR had a strong positive correlation with elevated fibrinogen levels (R² = 0.98) and a strong negative correlation with increased thrombin–antithrombin complex levels (R² = 0.87) in the DVT + cancer group, and a strong negative correlation with elevated tissue factor levels (R² = 0.93) in the DVT group; no correlations between APCR and other sensitive markers of coagulation and fibrinolysis, including prothrombin fragments 1 + 2, protein C activity, tissue-type plasminogen activator, and plasminogen activator inhibitor-1, were evident. We found APCR rates of 9% in cancer-associated VTE and 3% in cancer patients without VTE, in disagreement with prior findings of an increased frequency of APCR in patients with malignancy. Further, among patients with thrombosis, we found APCR to be less common in those with, as compared to without, malignancy. Our results suggest that APCR may not be a relevant risk factor for VTE in cancer patients, many of whom have other acquired risk factors for thrombosis. Large prospective studies of hemostatic abnormalities in cancer patients, including the Factor V Leiden mutation, are needed to establish whether APCR is an independent predictor of cancer-associated VTE.