Increased D-dimer levels correlate with binding of activated protein C, but not tissue factor expression, on peripheral blood monocytes in cancer patients

Nijziel, Marten R.; Oerle, René van; Pampus, E.C.M. van; Vet, Henrica C.W. de; Hillen, H.F.P.; Hamulyák, Karly

doi:10.1002/1096-8652(200008)64:4<282::aid-ajh8>3.0.co;2-2

Cited by 6 publications

(5 citation statements)

References 22 publications

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“…In the current study we did observe a wide variation in monocyte TF expression between subjects. Our results of TF expression are, however, in keeping with previous studies (8,9) and thus, we propose that in vivo individuals may express varying levels of TF antigen, possibly contributing to the high and low responder phenomenon reported previously in studies of LPS induced TF activity (30). There was a significant effect of time on monocyte TF expression in both pregnant women and non-pregnant control subjects.…”

Section: Discussionsupporting

confidence: 90%

“…Early studies reported that cells in contact with blood did not, under normal conditions, express TF (5). However, recent findings suggest that TF antigen is expressed in vivo (6)(7)(8)(9). In addition, monocytes and endothelial cells can be stimulated to express TF by the inflammatory cytokines, tumour necrosis factor-alpha (TNF-␣), interferon-gamma (IFN-␥), interleukin (IL)-1␤, IL-6, IL-8, and by bacterial lipopolysaccharide (LPS), homocysteine, P-selectin and C-reactive protein (10)(11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

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Tissue Factor Expression on Monocyte Subpopulations during Normal Pregnancy

Holmes

Wallace²,

Gilmore³

et al. 2002

Thromb Haemost

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SummaryPregnancy is often referred to as a hypercoagulable state due to changes in the haemostatic system. Tissue factor (TF) is the initiator of blood clotting in vivo. The effect of pregnancy on monocyte TF expression was determined in a longitudinal case control study (89 pregnant, 39 non-pregnant). Using whole blood flow cytometry and CD14 as a monocyte marker, TF expression was measured on all CD14 positive, CD14Bright and CD14Dim cells. TF expression was significantly lower in pregnant women than in non-pregnant control subjects, on all CD14 positive cells at 20 and 35 weeks, on CD14Bright cells at 12 and 35 weeks and on CD14Dim cells at 20 weeks. Additionally, we report that a higher percentage of CD14Dim than CD14Bright cells express TF. These results suggest that, in order to maintain homeostasis in haemostasis in an otherwise hypercoagulable state, monocyte TF expression is reduced during normal pregnancy.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Tissue Factor Expression on Monocyte Subpopulations during Normal Pregnancy

Holmes

Wallace²,

Gilmore³

et al. 2002

Thromb Haemost

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“…The CD16+ monocyte subset was reported to be significantly elevated in patients with malignant disease [36]. In particular, a recent study on breast cancer showed that CD16+ monocytes were 1.7-fold increased in patients as compared to healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Intermediate Monocytes but Not TIE2-Expressing Monocytes Are a Sensitive Diagnostic Indicator for Colorectal Cancer

et al. 2012

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We have conducted the first study to determine the diagnostic potential of the CD14++CD16+ intermediate monocytes as compared to the pro-angiogenic subset of CD14++CD16+TIE2+ TIE2-expressing monocytes (TEMs) in cancer. These monocyte populations were investigated by flow cytometry in healthy volunteers (N = 32) and in colorectal carcinoma patients with localized (N = 24) or metastatic (N = 37) disease. We further determined blood levels of cytokines associated with monocyte regulation. The results revealed the intermediate monocyte subset to be significantly elevated in colorectal cancer patients and to show the highest frequencies in localized disease. Multivariate regression analysis identified intermediate monocytes as a significant independent variable in cancer prediction. With a cut-off value at 0.37% (intermediate monocytes of total leukocytes) the diagnostic sensitivity and specificity ranged at 69% and 81%, respectively. In contrast, TEM levels were elevated in localized cancer but did not differ significantly between groups and none of the cytokines correlated with monocyte subpopulations. Of interest, in vitro analyses supported the observation that intermediate monocytes were more potently induced by primary as opposed to metastatic cancer cells which may relate to the immunosuppressive milieu established in the advanced stage of metastatic disease. In conclusion, intermediate monocytes as compared to TIE2-expressing monocytes are a more sensitive diagnostic indicator of colorectal cancer.

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“…141 Interestingly, in cancer patients, the increase of D-dimer concentration was significantly correlated with the monocyte APC content but not with monocyte TF levels or TAT complexes, which reflects a local, rather than systemic, thrombin and fibrin formation. 142 It is suggested that the APC formed locally enters the circulation and binds to peripheral blood monocytes. APC bound to monocyte is known to inhibit cytokine production by these cells and therefore may be involved in regulatory responses of monocytes in cancer patients.…”

Section: Antithrombinmentioning

confidence: 99%

“…APC bound to monocyte is known to inhibit cytokine production by these cells and therefore may be involved in regulatory responses of monocytes in cancer patients. 142 The presence of PC system components in various types of tumor tissue suggests its role in tumor biology. Interestingly, it was revealed that these proteins may exert a stimulatory effect on cancer progression (e.g., angiogenesis).…”

Section: Antithrombinmentioning

confidence: 99%

The Role of Hemostatic System Inhibitors in Malignancy

Wojtukiewicz

Sierko

Kisiel

2007

Semin Thromb Hemost

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Malignancy is associated with alterations in the hemostatic system that present as thromboembolic or bleeding complications. Antineoplastic treatment further escalates blood coagulation and fibrinolytic abnormalities. Moreover, hemostatic system inhibitors play a role in tissue maintenance or, contrarily, contribute to cancer progression. The inhibitors regulate migration, proliferation, apoptosis, angiogenesis, and distant metastases formation, as well as interfere with host defense system mechanisms. They exhibit different functions depending on tumor type, histologic grade, and clinical stage of the disease. The activity of coagulation inhibitors underlies the pathomechanisms of some complications resulting from therapeutic procedures, such as radiation injury to normal tissues. Because coagulation activation is widely recognized to influence cancer growth and distant dissemination, numerous attempts were made to introduce various forms of coagulation inhibitors to antineoplastic treatment. This review summarizes up-to-date information on preclinical and clinical benefits and pitfalls of hemostatic system inhibitors administration in cancer, with special emphasis on tumor biology and prophylaxis and treatment of various complications observed in the course of malignant disease.

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Increased D-dimer levels correlate with binding of activated protein C, but not tissue factor expression, on peripheral blood monocytes in cancer patients

Cited by 6 publications

References 22 publications

Tissue Factor Expression on Monocyte Subpopulations during Normal Pregnancy

Tissue Factor Expression on Monocyte Subpopulations during Normal Pregnancy

Intermediate Monocytes but Not TIE2-Expressing Monocytes Are a Sensitive Diagnostic Indicator for Colorectal Cancer

The Role of Hemostatic System Inhibitors in Malignancy

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