Tissue factor procoagulant activity of plasma microparticles in patients with cancer-associated disseminated intravascular coagulation.
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.
Langer
Florian
F
Onkologisches Zentrum, II. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany. langer@uke.uni-hamburg.de
Spath
Brigitte
B
Haubold
Katja
K
Holstein
Katharina
K
Marx
Guy
G
Wierecky
Jan
J
Brümmendorf
Tim H
TH
Dierlamm
Judith
J
Bokemeyer
Carsten
C
Eifrig
Barbara
B
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
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