Original articleHigh Plasma d-dimer Level is Associated with Decreased Survival in Patients with Lung Cancer
Introduction
The activation of coagulation and fibrinolysis is frequently associated with malignancy, although the mechanism involved is not completely understood. About 90% of cancer patients with metastatic disease and one-half of patients with cancer have abnormal coagulation parameters [1]. The extent of such activation has been reported to correlate with tumour stage and prognosis in some malignancies, such as lung, breast and colorectal cancer 2, 3, 4, 5, 6, 7, 8.
Tumour cells can produce procoagulant molecules that activate coagulation either directly or indirectly by initiating an inflammatory response. Oncogenic events in cancer cells (e.g. the expression of mutant K-ras, epidermal growth factor receptor (EGFR), phosphatase and tensin homologue (PTEN) or p53) lead to an increase in procoagulant molecule levels and activity, and thereby promote tumour aggressiveness, angiogenesis and hypercoagulability [9]. Several biologically active plasmin and/or thrombin cleavage fragments of fibrinogen and/or cross-linked fibrin elicit pro-angiogenic or anti-angiogenic effects that may contribute to wound healing and tumorigenesis. Fibrinogen or fibrin fragment E, for example, can stimulate angiogenesis in some in vitro and in vivo assay systems 10, 11.
d-dimer is a stable end product of fibrin degradation and levels of d-dimer are elevated by enhanced fibrin formation and fibrinolysis [12]. Elevated plasma d-dimer levels have been reported to be associated with poor prognosis in patients with lung cancer 2, 7, 8. Fibrinogen is recognised by multiple integrin and non-integrin receptors found on tumour cells, stromal cells and inflammatory cells [13]. In one study, the poorer prognosis was noted in 286 lung cancer patients who had elevated fibrinogen, d-dimers and a prolonged prothrombin time [14]. Prothrombin fragment (F1+2) is generated during the conversion of prothrombin to thrombin by activated factor X. The upward trend in plasma levels of F1+2 has been correlated with an increased risk of death [15].
The aim of the present study was to analyse the association between pre-treatment plasma levels of d-dimer, fibrinogen and F1+2 and clinicopathological parameters, the response to chemotherapy and outcome in patients with lung cancer.
Section snippets
Materials and Methods
This study included 78 patients with histologically proven carcinoma of the lung (stage III–IV). The pre-treatment evaluation included a complete history, a physical examination with evaluation of the Karnofsky performance status (PS) score, a complete blood cell count and a serum chemistry analysis. All patients were classified according to the 1997 staging system [16]. All patients gave informed consent before entering this study.
Results
Between September 2004 and September 2005, 128 consecutive patients with lung cancer were admitted to the Trakya University Hospital. Eighty-four patients who had the inclusion criteria were prospectively enrolled into this study. Six of the 84 were not evaluated due to no follow-up. Therefore, 78 were included in the analysis. Patients had a median age of 61 years (range 37–82). The patients' characteristics are shown in Table 1.
The results of comparisons between the haemostatic parameters and
Discussion
The biological significance of the haemostatic abnormalities in cancer is not clear. There is some evidence to suggest that the capacity of neoplastic cells to activate the coagulation system and to express increased fibrinolytic activity facilitates their growth and contributes to their invasive and metastatic behaviour [6]. In lung cancer tissues, fibrin deposits may promote cell proliferation and neovascularisation of the growing tumour; they may protect tumour cells from immune or
References (22)
- et al.
Coagulation disorders in cancer
Hematol Oncol Clin North Am
(1996) - et al.
Evaluating the prethrombotic state in lung cancer using molecular markers
Chest
(1993) - et al.
Prognostic significance of haemostatic parameters in patients with lung cancer
Respir Med
(2004) - et al.
Predictive value of D-dimer plasma levels in response and progressive disease in patients with lung cancer
Lung Cancer
(2006) - et al.
Haemostatic abnormalities in lung cancer: prognostic implications
Eur J Cancer
(1997) Revisions in international system for staging lung cancer
Chest
(1997)- et al.
A randomized clinical trial of combination chemotherapy with and without low-molecular-weight heparin in small cell lung cancer
J Thromb Haemost
(2004) - et al.
Plasma levels of D-dimer in lung cancer
Cancer
(2003) - et al.
Plasma D-dimer levels in operable breast cancer patients correlate with clinical stage and axillary lymph node status
J Clin Oncol
(2000) - et al.
High preoperative plasma D-dimer level is associated with advanced tumour stage and short survival after curative resection in patients with colorectal cancer
Jpn J Clin Oncol
(2001)
Prognostic significance of plasma D-dimer levels in patient with lung cancer
Thorax
Cited by (109)
Factor VIII as a Novel Biomarker for Diagnosis, Prognosis, and Therapy Prediction in Human Cancer and Other Disorders
2024, Avicenna Journal of Medical BiotechnologyPrognostic value of coagulation markers in patients with colorectal caner: A prospective study
2024, Health Science Reports