Markers of Hypercoagulability in Breast Cancer: What Is Their Clinical Relevance?

Cancer is generally combined with an increased risk of venous thromboembolism. This risk is linked to a hypercoagulable state whose precise mechanism remains unclear. It depends on the histological type, the stage of cancer and the anti-neoplasic treatment. This study aims to identify a hypercoagulability in patients with breast cancer and to define the most relevant procoagulant markers.

A prospective study was carried out at the day hospital in the cancer department of the University Hospital H. Bourguiba in Sfax-Tunisia, from January to June 2012, including only patients with breast cancer. The thrombin generation was carried out on a venous citrated sampling (3. 2%) according to the technique of Calibrated Automated Thrombogram assay (CAT®, Diagnostica Stago, Asnières, France). The parameters of the thrombogram were analyzed: endogenous thrombin potential (ETP), peak of thrombin (peak) and mean rate index (MRI). The rates of platelet-derived microparticles expressing phosphatidyl-serine (MPP-PS+) were determined by flow cytometry using monoclonal antibodies anti-CD41 and anti-annexin V marked respectively by phycoerythrin (PE) and fluorescein isothiocyanate (FITC). D-dimers were measured by the STA-Liatest D-DI (Diagnostica-Stago) technique. The procoagulant activity of phospholipids (PPL) was measured by STA®-Procoag-PPL (Diagnostica-Stago). The plasma levels of tissue factor (TFa) were measured in a one-stage kinetic chromogenic method. This home-assay measures the ability of TF-FVIIa to activate factor X.

Sixty one patients were included. Their mean age was 51. 8 ± 10. 9 years old. The study of the thrombogram parameters showed a significant increase of the peak of thrombin (343. 8±79. 2 nM) and of the velocity or MRI (153±56 nM/min) in patients compared to control subjects (288±48 nM, p=0. 001 and 109±33 nM/min, p<0. 001 respectively). Only 36% of patients had a significant increase of thrombin generation. D-dimers levels reached in average 1230±1760 ng/ml and 61% of patients presented relevant high values (>500 ng/ml). MPP-PS+ in cancer patients were significantly higher (9684±7865/μl) than in controls (695±361/μl, p<0. 001) but nearly 94% of patients present particularly high levels of this parameter (≥1614/μl). PPL levels were significantly higher in patients with a shorter time compared to controls (43. 4±10. 4sec versus 72 sec ± 5. 6 sec) with 97% of cancer patients below the inferior limit (60. 8sec). Besides, TFa levels were significantly increased in patients (1. 6±1. 2 pM) compared to controls (0. 22pM ± 0. 12) with 87% of cancer patients presenting particularly high values (≥0. 46pM).

Breast cancer, considered more like a tumor with a low vascular risk, is combined with a state of cell activation and hypercoagulation, almost constant, reflected by an increase of procoagulant microparticles, TF and PPL levels. Besides, thrombin generation showed a less pronounced increase in this clinical context and could contribute to discriminate patients with high or low high risk of thrombosis in breast cancer patients. This has to be confirmed by prospective studies with a clinical follow-up of cancer patients.

No relevant conflicts of interest to declare.