Tissue factor procoagulant activity of plasma microparticles in patients with cancer-associated disseminated intravascular coagulation.

TY - JOUR

T1 - Tissue factor procoagulant activity of plasma microparticles in patients with cancer-associated disseminated intravascular coagulation.

AU - Langer, Florian

AU - Spath, Brigitte

AU - Haubold, Katja

AU - Holstein, Katharina

AU - Marx, Guy

AU - Wierecky, Jan

AU - Brümmendorf, Tim

AU - Dierlamm, Judith

AU - Bokemeyer, Carsten

AU - Eifrig, Barbara

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

M3 - SCORING: Zeitschriftenaufsatz

VL - 87

SP - 451

EP - 457

JO - ANN HEMATOL

JF - ANN HEMATOL

SN - 0939-5555

IS - 6

M1 - 6

ER -