A prothrombotic state in breast cancer patients treated with adjuvant chemotherapy.

Cancer is often associated with abnormal activation of coagulation leading to a prothrombotic state. Some chemotherapeutic agents used for cancer may induce thrombosis but their biological alterations in the hemostatic system are not yet well understood. This study evaluated alterations of coagulative and fibrinolytic parameters following chemotherapy. In plasma samples of 38 patients (median age: 49 years) receiving CMF (schedule 1-21 or 1-8) for Stage II breast cancer, we evaluated: PT, aPTT, antithrombin III (AT-III), protein C (PC), protein S (PS), thrombin-antithrombin complex (TAT), prothrombin fragment F 1 + 2 (F 1 + 2), fibrinogen (Fbg), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1) and D-dimer (D-D). PT, aPTT, and Fbg were determined with routine methods; AT-III, PC, and PS were measured with coagulative tests; PC and PS were also evaluated with immunoenzymatic methods, t-PA, PAI-1, D-D, TAT, and F 1 + 2 were measured with immunoenzymatic methods. All tests were performed immediately before starting therapy and after each cycle. A PC antigen decrease appeared soon after beginning therapy and lasted throughout chemotherapy. The lowest values were present after the first treatment both in the CMF 1-21 group (mean +/- SD = 72.5 +/- 10.8%) and in the CMF 1-8 group (mean +/- SD = 77.2 +/- 6.9%): PC activity was also decreased. PS antigen decreased after the first administration (mean +/- SD = 73.3 +/- 10% in CMF 1-21 group, and 72.5 +/- 4.9% in CMF 1-8 group): PS activity also decreased. PAI-1 antigen levels increased (mean +/- SD = 43.1 +/- 20.4 ng/ml in the CMF 1-21 group, and 37.5 +/- 12.2 ng/ml in CMF 1-8 group) lasting up to the last cycle. CMF provokes a trend toward hypercoagulability; this effect should be considered when chemotherapy is employed in advanced cancer patients at high risk for thrombosis, or in patients with other risk factors.

Plasma D-dimer measurement as a marker of gynecologic tumors: comparison with Ca 125.

BACKGROUND: Fibrin is formed and degraded intra-abdominally in ovarian cancer, and the cross-linked fibrin degradation product, D-dimer (D-D), has been found in increased concentrations in the plasma of these patients. METHODS: D-dimer and Ca 125 levels were determined simultaneously in 110 patients with gynecologic neoplasms. D-dimer and Ca 125 assays were performed using the Dimertest Stripwell EIA Kit (Ortho) and CA 125-II EIA assay (Roche), respectively. RESULTS: D-dimer plasma and Ca 125 serum levels were significantly higher in patients with ovarian cancer (mean +/- SE = 894.2 +/- 173.7 ng/ml and 760.5 +/- 292.7 U/ml, respectively) than in those with uterine cancer (mean DD +/- SE = 109.7 +/- 23.5 ng/ml and mean Ca 125 +/- SE = 50.0 +/- 23.1 U/ml) or those with benign disease (mean D-D +/- SE = 70.5 +/- 5.5 ng/ml and mean Ca 125 +/- SE = 6.6 +/- 2.8 U/ml). The levels of both markers increased with regard to ovarian cancer disease status. Mean D-D +/- SE was 90.0 +/- 22.8 ng/ml and mean Ca 125 +/- SE was 2.1 +/- 1.2 U/ml in patients with complete remission; mean D-D +/- SE was 143.3 +/- 33.5 ng/ml and mean Ca 125 +/- SE was 26.2 +/- 13.6 U/ml in patients with partial remission. In active disease, both markers had very high levels: D-D mean +/- SE = 1021.6 +/- 173.0 ng/ml and Ca 125 mean +/- SE = 1154.7 +/- 458.1 U/ml. In all groups of ovarian cancer patients, D-dimer sensitivity was better than that of Ca 125. In advanced ovarian cancer patients, the D-dimer concentration in ascites was up to 100 fold that in plasma. CONCLUSIONS: Our results suggest that D-dimer can serve as a sensitive indicator to monitor the extent and course of the disease in ovarian cancer patients. The patient follow-up is ongoing to establish the predictive value of D-dimer measurement with respect to prognosis.