Blood coagulation during adjuvant epirubicin/cyclophosphamide chemotherapy in patients with primary operable breast cancer.
Influences of adjuvant epirubicin/cyclophosphamide (EC) chemotherapy on blood coagulation were investigated in patients with operable breast cancer and the incidence of thromboembolic events was recorded. In 50 consecutive node-positive breast cancer patients, serial coagulation studies (fibrinogen method of Clauss, antithrombin III, protein C amidolytic methods, D dimer enzyme-linked immunoadsorbent assay [ELISA] techniques, and plasminogen activator inhibitor [PAI] activity u-PA inhibition test) and impedance plethysmography (IPG) for screening of deep vein thrombosis (DVT) were performed preoperatively and postoperatively, before each of six cycles of adjuvant chemotherapy (60 mg/m2 epirubicin and 600 mg/m2 cyclophosphamide) and 3 months thereafter. Seventy-two healthy women served as controls. During chemotherapy, the phlebographically proven DVT incidence was 10% (n = 2 after second cycle; n = 3 after third cycle). Preoperative levels of D-dimer, fibrinogen, and the PAI activity were significantly higher than in healthy women and only mean levels of the D-dimer were significantly higher in patients with DVT compared with patients without DVT. Postoperatively, only D-dimer and fibrinogen levels significantly increased, while in the course of chemotherapy, these levels were significantly decreased. Mean D-dimer levels and PAI increased steadily in patients with DVT. Preoperatively and during chemotherapy, levels of antithrombin III and protein C were within the normal range. Only one patient with DVT had decreased protein C levels throughout chemotherapy. Monitoring with sophisticated coagulation tests during adjuvant EC chemotherapy for breast cancer does not identify patients at higher risk for DVT development. Preoperatively, in patients with later DVT, an imbalance of hemostasis is already present; thus, thrombosis might predominantly be initiated by malignancy-induced hypercoagulability and secondarily by the influence of EC chemotherapy. Prospective randomized trials must determine whether prophylactic anticoagulation during EC chemotherapy reduces the incidence of DVT.