Association between blood rheology,thrombosis and cancer survival in patients with gynecologic malignancy

Abstract

In cancer patients impaired blood rheology in the presence of coagulation activation may reduce blood flow in the vascular microcirculation that favors thrombosis but may also support tumor progression and metastasis. In 451 patients with gynecological cancer and 177 patients with corresponding benign tumor disease preoperatively, during adjuvant treatment, when venous thrombosis (VT) or cancer progression was diagnosed hematocrit (micro centrifuge), hemoglobin, leukocytes, platelets (Coulter Counter); red blood cell (RBC) aggregation (aggr.) during stasis and low shear conditions (MA 1, Myrenne), plasma viscosity (viscosimeter KSPV 1 Fresenius), and fibrinogen (Multifibren Behring Dade) were investigated. One hundred and twelve healthy women served as controls. Preoperatively, mean plasma viscosity (pv) was significantly higher in cancer patients as compared to patients with the corresponding benign tumor disease (breast cancer: n={} 261; pv {}={} 1.32 vs. 1.27 mPa s; p={} 0.023; ovarian cancer: n={} 68; pv {}={} 1.39 vs. 1.31 mPa s; p<{} 0.001; endometrial cancer: n={} 70; pv {}={} 1.37 vs. 1.25 mPa s; p<{} 0.001; cervical cancer: n={} 52; pv = 1.33 vs. 1.26 mPa s; p={} 0.004). RBC aggr. was significantly lower in controls compared to the preoperative values in cancer patients but mean (median) values (RBC aggr. stasis < 21) were within the normal range in all. Preoperatively, plasma viscosity was a significant risk factor for the overall survival in ovarian cancer patients ( p={} 0.02) and for subsequent thrombosis in ovarian ( p={} 0.02) and cervical cancer patients ( p={} 0.007). In the multivariate analysis plasma viscosity was an independent prognostic marker for the overall survival of breast cancer patients ( r={} 99.45; 95% CI: 7.32–980.2; p<{} 0.0001). An optimized preoperative cut‐off value above 1.40 mPa s (Log‐Rank‐test) was significantly associated with poor outcome in the Kaplan–Mayer survival estimates, even in node‐negative breast cancer.

In gynecologic cancer patients the combination of an increase in RBC aggregation and plasma viscosity impairs blood‐flow‐properties and may induce hypoxia in the microcirculation that favors thrombosis, settlement of tumor‐cells and thus metastasis. Improvement of blood fluidity and thus oxygen transfer in the tumor‐vascular‐microcirculation may increase susceptibility of systemic anti‐cancer therapy.