title: Impact of chemotherapy on thrombin generation and on the protein C pathway in breast cancer patients.
abstract: Although thromboembolism is a problematic complication of chemotherapy, the pathogenic mechanisms by which chemotherapeutic agents exert prothrombotic effects in vivo are unclear.The objective of this study was to examine the effects of adjuvant chemotherapy on thrombin generation, the protein C anticoagulant pathway, and microparticle tissue factor (MP TF) activity in 26 breast cancer patients (stages I to III). The patients received cyclophosphamide, 5-fluorouracil, and methotrexate, epirubicin, or doxorubicin. Plasma samples were collected on day 1 (baseline), day 2, and day 8 for the first 2 cycles of chemotherapy. Levels of thrombin-antithrombin (TAT) complexes, MP TF activity, and components of the protein C anticoagulant pathway, including protein C, activated protein C (APC), soluble thrombomodulin (sTM), and soluble endothelial protein C receptor (sEPCR), were measured. Compared to prechemotherapy baseline levels, plasma TAT, protein C, and APC were significantly different following the administration of chemotherapy (p < 0.01 for each). Plasma TAT was higher in cycle 1, day 2, and cycle 2, day 8, compared to baseline. Plasma protein C levels were lower in cycle 2, day 8, whereas plasma APC levels were lower in cycle 2, day 1, and cycle 2, day 8. No significant changes were found in plasma sEPCR, sTM, or MP TF activity. This study suggests that adjuvant chemotherapy in women with breast cancer increases thrombin generation and impairs the endothelium-based protein C anticoagulant pathway.
authors: Department of Oncology, McMaster University, Hamilton, Ont., Canada.
authors: Som D
authors: SD
authors: Mukherjee
authors: Laura L
authors: LL
authors: Swystun
authors: Nigel
authors: N
authors: Mackman
authors: Jian-Guo
authors: JG
authors: Wang
authors: Gregory
authors: G
authors: Pond
authors: Mark N
authors: MN
authors: Levine
authors: Patricia C
authors: PC
authors: Liaw
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000990:Antithrombin III; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D000074283:Endothelial Protein C Receptor; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010447:Peptide Hydrolases / Q000097:blood; D011486:Protein C / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000097:blood; D013917:Thrombin / Q000378:metabolism*; D018180:Thrombomodulin / Q000097:blood; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D011486:Protein C; D011956:Receptors, Cell Surface; D018180:Thrombomodulin; C046193:antithrombin III-protease complex; D015251:Epirubicin; D004317:Doxorubicin; D003520:Cyclophosphamide; D000990:Antithrombin III; D013925:Thromboplastin; D010447:Peptide Hydrolases; D013917:Thrombin; D005472:Fluorouracil