Determinants of acquired activated protein C resistance and D-dimer in breast cancer

作者：Tinholt Mari^*; Sandset Per Morten; Mowinckel Marie Christine; Garred Oystein; Sahlberg Kristine Kleivi; Kristensen Vessela N; Borresen Dale Anne Lise; Jacobsen Anne Flem; Skretting Grethe; Iversen Nina

来源：Thrombosis Research, 2016, 145: 78-83.

DOI：10.1016/j.thromres.2016.08.003

• Breast cancer
• Activated protein C resistance
• D-dimer
• Single nucleotide polymorphisms
• Coagulation factors
• Coagulation inhibitors
• Clinicopathological breast cancer characteristics

Background: We have previously reported acquired activated protein C (APC) resistance and elevated plasma D-dimer levels in breast cancer patients. Here, we aimed to identify phenotypic and genetic determinants that contribute to the acquired APC resistance and increased D-dimer levels in breast cancer. Healthy controls served as reference. We also addressed whether higher APC resistance or D-dimer levels could be potential markers of clinicopalhological breast cancer characteristics.
Materials and methods: 358 breast cancer patients and 273 healthy controls were enrolled and hemostatic plasma parameters were determined; factor (F) V, FVIII, FIX, FX, fibrinogen, von Willebrand factor (VWF), normalized APC sensitivity ratio (n-APC-sr), protein C, protein S, antithrombin, tissue factor pathway inhibitor (TFPI), and D-dimer. Common single nucleotide polymorphisms were genotyped in coagulation-related genes in the breast cancer patients.
Results: The phenotypic hemostatic factors explained 25% and 31% of the variability in acquired APC resistance and D-dimer levels, respectively, in the breast cancer patients. Fibrinogen 0.35, P < 0.001), protein C (beta = 0.28, P< 0.001), and FIX (beta = 022, P = 0.026) were identified as determinants of n-APC-sr (in FV Leiden non-carriers), whereas TFPI (beta = 0.28, P < 0.001), antithrombin (beta = -0.25, P < 0.001), and FX (beta = 0.15, P = 0.040) were the major determinants of D-dimer. Moreover, borderline higher APC resistance (> 75th percentile) was found in patients with triple negative tumors (odds ratio (OR) 1.97, 95%, Cl 0.99-3.90).
Conclusions: This study reports phenotypic hemostatic parameters that determine acquired APC resistance and D-dimer levels in breast cancer patients. The explanatory power was modest, however, our findings are hypothesis generating and may contribute to further understand the background for cancer associated-coagulopathy and thrombosis.

• 出版日期2016-9