Tumor-derived tissue factor-bearing microparticles are associated with venous thromboembolic events in malignancy.
OBJECTIVE
Despite the strong association between malignant disease and thromboembolic disorders, the molecular and cellular basis of this relationship remains uncertain. We evaluated the hypothesis that tumor-derived tissue factor-bearing microparticles in plasma contribute to cancer-associated thrombosis.


METHODS
We developed impedance-based flow cytometry to detect, quantitate, and size microparticles in platelet-poor plasma. We evaluated the number of tissue factor-bearing microparticles in a cohort of cancer patients of different histologies (N = 96) and conducted a case-control study of 30 cancer patients diagnosed with an acute venous thromboembolic event (VTE) compared with 60 cancer patients of similar age, stage, sex, and diagnosis without known VTE, as well as 22 patients with an idiopathic VTE.


RESULTS
Tissue factor-bearing microparticles were detected in patients with advanced malignancy, including two thirds of patients with pancreatic carcinoma. Elevated levels of tissue factor-bearing microparticles were associated VTE in cancer patients (adjusted odds ratio, 3.72; 95% confidence interval, 1.18-11.76; P = 0.01). In cancer patients without VTE, a retrospective analysis revealed a 1-year cumulative incidence of VTE of 34.8% in patients with tissue factor-bearing microparticles versus 0% in those without detectable tissue factor-bearing microparticles (Gray test P = 0.002).The median number of tissue factor-bearing microparticles in the cancer VTE cohort (7.1 x 10(4) microparticles/microL) was significantly greater than both the idiopathic VTE and cancer-no VTE groups (P = 0.002 and P = 0.03, respectively). Pancreatectomy in three patients eliminated or nearly eliminated these microparticles which coexpressed the epithelial tumor antigen, MUC-1.


CONCLUSIONS
We conclude that tumor-derived tissue factor-bearing microparticles are associated with VTE in cancer patients and may be central to the pathogenesis of cancer-associated thrombosis.
Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. jzwicker@bidmc.harvard.edu
Jeffrey I
JI
Zwicker
Howard A
HA
Liebman
Donna
D
Neuberg
Romaric
R
Lacroix
Kenneth A
KA
Bauer
Barbara C
BC
Furie
Bruce
B
Furie
D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D016022:Case-Control Studies; D018929:Cell Culture Techniques / Q000379:methods; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000473:pathology* / Q000601:surgery; D012307:Risk Factors; D013925:Thromboplastin / Q000378:metabolism*; D013927:Thrombosis; D054556:Venous Thromboembolism / Q000150:complications* / Q000473:pathology* / Q000601:surgery
D014408:Biomarkers, Tumor; D013925:Thromboplastin