Impact of breast cancer stage, time from diagnosis and chemotherapy on plasma and cellular biomarkers of hypercoagulability

Mourad Chaari (1, 2) , Ines Ayadi (2) , Aurelie Rousseau (3) , Eleftheria Lefkou (1) , Patrick van Dreden (4) , Fatoumata Sidibe (1) , Hela Ketatni (1) , Vassiliki Galea (1) , Amir Khaterchi (1) , Racem Bouzguenda (2) , Mounir Frikha (2) , Lilia Ghorbal (2) , Jamel Daoud (2) , Choumous Kallel (2) , Martin Quinn (1) , Joseph Gligorov (1, 2) , Jean-Pierre Lotz (1) , Mohamed Hatmi (5) , Ismail Elalamy (1, 3) , Grigoris T Gerotziafas (1, 3)

1 CHU Tenon [AP-HP]
2 Hopital Habib Bourguiba - Habib Bourguiba Hospital [Sfax]
3 UMRS893 - Centre de Recherche Saint-Antoine
4 Diagnostica Stago
5 IP - Institut Pasteur [Paris]

Background In breast cancer patients routine thromboprophylaxis is not recommended but individualized risk assessment is encouraged. The incorporation of hypercoagulability biomarkers could increase the sensitivity of risk assessment models (RAM) to identify patients at VTE risk. To this aim we investigated the impact of cancer-related characteristics on hypercoagulability biomarkers. Methods Thrombin generation (TG) assessed with the Thrombogramme-Thrombinoscope®, levels of platelet derived microparticles (Pd-MP) assessed with flow cytometry, procoagulant phospholid dependent clotting time (PPL-ct) measured with a clotting assay and D-Dimers (were assessed in a cohort of 62 women with breast cancer and in 30 age matched healthy women. Results Patients showed significantly higher TG, Pd-MP, D-Dimers levels and shortened PPL-ct compared to the controls. The PPL-ct was inversely correlated with the levels of Pd-MP, which were increased in 97% of patients. TG and D-Dimers were increased in 76% and 59% of patients respectively. In any stage of the disease TG was significantly increased as compared to the controls. There was no significant difference of TG in patients with local, regional of metastatic stage. There was no significant difference in Pd-MP or Pd-MP/PS+ between the subgroups of patients with local or regional stage of cancer. Patients with metastatic disease had significantly higher levels of Pd-MP and Pd-MP/PS+ compared to those with regional stage. The D-Dimers increased in patients with metastatic stage. In patients on chemotherapy with less than 6 months since diagnosis TG was significantly higher compared to those on chemotherapy who diagnosed in interval > 6 months. Patients with metastatic disease had significantly higher levels of Pd-MP and D-Dimers compared to those with non-metastatic disease. Conclusion In breast cancer patients the stage, the time elapsed since the diagnosis and the administration of chemotherapy are determinants of cellular and plasma hypercoagulability. The levels and the procoagulant activity of Pd-MP are interconnected with the biological activity and the overall burden of cancer. TG reflects the procoagulant properties of both breast cancer and chemotherapy in the initial period of cancer diagnosis. Thus the weighted incorporation of the biomarkers of cellular and plasma hypercoagulabilty in RAM for VTE might improve their predictive value.

Mots clés: Breast cancer; Venous thromboembolism; Thrombin generation; Microparticles; D-Dimers; Risk assessment model

Domaines: Cancer

Mourad Chaari, Ines Ayadi, Aurelie Rousseau, Eleftheria Lefkou, Patrick van Dreden, et al.. Impact of breast cancer stage, time from diagnosis and chemotherapy on plasma and cellular biomarkers of hypercoagulability. BMC Cancer, 2014, 14, pp.991. ⟨10.1186/1471-2407-14-991⟩. ⟨hal-01310928⟩