Article: PDF OnlyThe hypercoagulable state in cancer patients evidence for impaired thrombin inhibitionsFalanga, A.; Ofosu, F. A.; Delaini, F.; Oldani, E.; Dewar, L.; Lui, L.; Barbui, T.Author Information A. Falanga, F. Delaini, E. Oldani and T. Barbui are with the Department of Haematology, Ospedali Riuniti Bergamo, Largo Barozzil, 24100 Bergamo, Italy, F. A. Ofosu, L. Dewar and L. Lui are with the Canadian Red Cross Society, Blood Services and Department of Pathology, McMaster University, Hamilton, Canada. Blood Coagulation & Fibrinolysis: January 1994 - Volume 5 - Issue 1 - p S19-23 Buy Abstract Activation of prothrombin and the subsequent reactions of thrombin with its substrates and its major inhibitors, antithrombin III (AT III) and heparin cofactor II (HC II), likely reflect both intravascular and extravascular coagulation. Several studies have reported increased in vivo coagulation in cancer. Whether the increased thrombin production in malignancy is accompanied by a corresponding increase in thrombin inhibition is unknown. This study quantified prothrombin fragment 1 + 2 (F1 + 2), thrombin-AT III (TAT), thrombin-AT III-vitronectin (TAT.V), and thrombin-HC II-vitronectin (THCII.V) in the plasmas of healthy volunteers (n = 37); patients with localized solid tumours before treatment was initiated (n = 39); and five patients with non-Hodgkin's lymphoma, both before and during weekly chemotherapy. Two of the five non-Hodgkin's lymphoma patients developed deep venous thrombosis (DVT) during chemotherapy. In normal plasma, where the concentrations of the four parameters likely reflect haemostasis, the sum of TAT, TAT.V and THCII.V was 61% that of F1 + 2, compared with 30% in cancer plasmas. In addition, the mean ± SEM of F1 + 2 in the plasmas of cancer patients (1.56 ± 0.09 nM) was significantly elevated (P < 0.001) when compared with healthy volunteers (0.89 ± 0.06 nM). Eight weeks of chemotherapy increased the F1 + 2 and the binary TAT in plasmas of the non-Hodgkin's lymphoma patients by approximately 1.5− and 2.9-fold, respectively. Thus, increased prothrombin activation in cancer patients, without corresponding increases in concentrations of thrombin-inhibitor complexes, raise the possibility that a significant portion of the thrombin generated in vivo escapes inhibition in cancer and contributes to the high risk of DVT in malignancy. © Lippincott-Raven Publishers.