Chaari Mourad, Ayadi Ines, Rousseau Aurelie, Lefkou Eleftheria, Van Dreden Patrick, Sidibe Fatoumata, Ketatni Hela, Galea Vassiliki, Khaterchi Amir, Bouzguenda Racem, Frikha Mounir, Ghorbal Lilia, Daoud Jamel, Kallel Choumous, Quinn Martin, Gligorov Joseph, Lotz Jean Pierre, Hatmi Mohamed, Elalamy Ismail, Gerotziafas Grigoris T
Service d'Hématologie Biologique Hôpital Tenon, Hôpitaux Universitaires de l'Est Parisien, Assistance Publique Hôpitaux de Paris, Paris, France.
BMC Cancer. 2014 Dec 22;14:991. doi: 10.1186/1471-2407-14-991.
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.
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.
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.
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.
对于乳腺癌患者，不建议进行常规血栓预防，但鼓励进行个体化风险评估。纳入高凝生物标志物可提高风险评估模型（RAM）识别静脉血栓栓塞（VTE）风险患者的敏感性。为此，我们研究了癌症相关特征对高凝生物标志物的影响。
使用血栓图-凝血酶监测仪评估凝血酶生成（TG），采用流式细胞术评估血小板衍生微粒（Pd-MP）水平，通过凝血试验测量促凝磷脂依赖性凝血时间（PPL-ct），并对62例乳腺癌女性患者和30例年龄匹配的健康女性进行D-二聚体评估。
与对照组相比，患者的TG、Pd-MP、D-二聚体水平显著升高，PPL-ct缩短。PPL-ct与Pd-MP水平呈负相关，97%的患者Pd-MP水平升高。76%的患者TG升高，59%的患者D-二聚体升高。在疾病的任何阶段，与对照组相比，TG均显著升高。局部、区域或转移阶段患者的TG无显著差异。癌症局部或区域阶段患者亚组之间的Pd-MP或Pd-MP/PS+无显著差异。与区域阶段患者相比，转移疾病患者的Pd-MP和Pd-MP/PS+水平显著更高。转移阶段患者的D-二聚体升高。诊断后化疗时间少于6个月的患者与化疗时间间隔>6个月的患者相比，TG显著更高。与非转移疾病患者相比，转移疾病患者的Pd-MP和D-二聚体水平显著更高。
在乳腺癌患者中，疾病分期、诊断后经过的时间以及化疗的应用是细胞和血浆高凝性的决定因素。Pd-MP的水平和促凝活性与癌症的生物学活性和总体负担相互关联。TG反映了癌症诊断初期乳腺癌和化疗的促凝特性。因此，在VTE的RAM中加权纳入细胞和血浆高凝性生物标志物可能会提高其预测价值。
