title: Tissue factor procoagulant activity of plasma microparticles in patients with cancer-associated disseminated intravascular coagulation.
abstract: Tissue factor (TF) expressed on sub-cellular membrane vesicles, so-called plasma microparticles (MPs), has recently emerged as a potential key player in intravascular coagulation activation in various disease states. In this report, we demonstrate significantly increased levels of TF-specific procoagulant activity (PCA) of plasma MPs in five patients presenting with overt disseminated intravascular coagulation (DIC) due to an underlying malignancy, including non-small-cell lung cancer (n = 1), melanoma (n = 1), prostate cancer (n = 2), and acute promyelocytic leukemia (n = 1). Clotting experiments on available tumor cell samples suggested that cancer cells were a potential source of circulating TF-positive MPs at least in three of the five patients. Furthermore, follow-up plasma samples from two surviving patients revealed that response of their malignancies to specific anti-cancer therapy was paralleled by resolution of overt DIC and a significant decline in MP-associated TF PCA. Levels of plasma TF antigen, as assessed by an enzyme-linked immunosorbent assay, were also increased at presentation albeit to a lesser extent compared to MP-associated TF PCA, likely due to insufficient solubilization of the phospholipid-incorporated full-length TF molecule by the detergent. In summary, our findings suggest that MP-associated TF PCA may play an important pathogenic role in the evolution of overt DIC in various types of malignancy.
authors.affiliation: Onkologisches Zentrum, II. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany. langer@uke.uni-hamburg.de
authors.forename: Florian
authors.initials: F
authors.lastname: Langer
authors.forename: Brigitte
authors.initials: B
authors.lastname: Spath
authors.forename: Katja
authors.initials: K
authors.lastname: Haubold
authors.forename: Katharina
authors.initials: K
authors.lastname: Holstein
authors.forename: Guy
authors.initials: G
authors.lastname: Marx
authors.forename: Jan
authors.initials: J
authors.lastname: Wierecky
authors.forename: Tim H
authors.initials: TH
authors.lastname: Brümmendorf
authors.forename: Judith
authors.initials: J
authors.lastname: Dierlamm
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Barbara
authors.initials: B
authors.lastname: Eifrig
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000990:Antithrombin III / Q000378:metabolism; D000991:Antithrombins / Q000378:metabolism; D004211:Disseminated Intravascular Coagulation / Q000097:blood* / Q000209:etiology; D005165:Factor V / Q000378:metabolism; D005176:Factor XIII / Q000378:metabolism; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000150:complications*; D010447:Peptide Hydrolases / Q000378:metabolism; D010976:Platelet Count; D013925:Thromboplastin / Q000378:metabolism*; D014227:Triazines / Q000378:metabolism
chemical_list: D000991:Antithrombins; D005338:Fibrin Fibrinogen Degradation Products; D014227:Triazines; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; C053507:4-azido-7-phenylpyrazolo-(1,5a)-1,3,5-triazine; D000990:Antithrombin III; D005165:Factor V; D005340:Fibrinogen; D005176:Factor XIII; D013925:Thromboplastin; D010447:Peptide Hydrolases