thromboplastin and Lymphoma--Non-Hodgkin

The incidence of severe complications, such as disseminated intravascular coagulation (DIC) in malignant lymphoma, differs between clinical stages and histological types of the disease, but they occur frequently in stage IV or natural killer (NK) cell lymphoma. Patients with stage IV or NK cell lymphoma exhibit abnormal thrombotic and hemostatic states. One of the mechanisms in DIC might involve elevated cytokine expression by lymphoma cells stimulating the expression of tissue factor (TF) in blood cells or surrounding tissue. During chemotherapy for lymphoma, the white blood cell count was significantly reduced at days 1 and 3, but significantly increased at days 7 and 9. At day 7 of chemotherapy, leukocyte TF mRNA levels were significantly increased. Plasma concentrations of granulocyte elastase derived-XDP (GEXDP) levels correlated with D-dimer levels, suggesting that almost all elevated D-dimer is GE-XDP. C-reactive protein (CRP), GE-XDP and D-dimer were significantly elevated in patients with infection, DIC or acute respiratory distress syndrome (ARDS). Analysis of patients with DIC or ARDS revealed that TF mRNA correlated with D-dimer, and GE-XDP correlated with leukocyte count, CRP and D-dimer, suggesting that inflammatory changes due to thrombosis may cause the activation of leukocytes during chemotherapy.

Topics: C-Reactive Protein; Cytokines; Disseminated Intravascular Coagulation; Humans; Infections; Leukocyte Elastase; Lymphoma, Non-Hodgkin; RNA, Messenger; Thromboplastin

Blood clotting activation and fibrin deposition are common findings in lymphoma patients. We evaluated the capacity of peripheral blood mononuclear cells to produce procoagulant activity (PCA) and plasminogen activator inhibitor (PAI) in 12 children with newly diagnosed lymphoma (8 non-Hodgkin's, 4 Hodgkin's) and in 12 matched healthy donors. In the same subjects we also measured plasma antigen levels of tissue-type PA (t-PA), urokinase-type PA (u-PA), PAI-1, PAI-2, and D-dimer. PCA generated by mononuclear cells after incubation for 20 h at 37 degrees C was significantly higher in patients than in controls (p = 0.027). In all samples it was identified as tissue factor by functional criteria (dependence on factor VII). Moreover, culture medium obtained from patients' mononuclear cells after incubation for 20 h at 37 degrees C contained significantly higher amounts of PAI activity and PAI-2 antigen than control samples (p < 0.001). Plasma PAI-1 and t-PA antigens were significantly augmented in patients (p < 0.005), the mean increase of PAI-I being about 5 times higher than that of t-PA. Plasma levels of D-dimer were markedly increased in the patient's group (p < 0.001), whereas u-PA and PAI-2 antigens did not differ from controls. It is suggested that monocytes from lymphoma patients are endowed with functional abnormalities leading to the simultaneous expression of tissue factor and antifibrinolytic activity. These abnormalities, coupled with a reduced plasma fibrinolytic potential, could play an important pathogenetic role in blood clotting activation and fibrin deposition associated with lymphoma.

Topics: Adolescent; Child; Child, Preschool; Female; Fibrinolysis; Humans; Leukocytes, Mononuclear; Lymphoma, Non-Hodgkin; Male; Plasminogen Activator Inhibitor 2; Thromboplastin

To explore the values of tissue factor (TF) and vascular endothelial growth factor (VEGF) expressions on peripheral CD14+ monocytes in disease assessment, prognosis, and short-term efficacy evaluation of non-Hodgkin lymphoma (NHL) patients.. TF and VEGF expressions on CD14+monocytes in 47 NHL patients (disease group) before chemotherapy and after 4 chemotherapy cycles and in 30 healthy subjects (control group) were detected by flow cytometry, and the potential relationship among TF, VEGF, International Prognostic Index (IPI), and short-term efficacy were analyzed.. TF and VEGF expressions on CD14 + monocytes in disease group were significantly higher than those in control group ( all P <0. 01) and positive correlation was showed between them (r = 0. 708, P = 0.00). TF and VEGF expressions in Ann Arbor stage III and IV (n = 22 and 19) , symptomatic (n = 22) , lactate dehydrogenase (LDH) increased (n = 21) , Eastern Cooperative Oncology Group (ECOG) score 2-4 (n = 12) and extranodal lesions >1 (n = 16) groups were significantly higher than those in Ann Arbor stage II (an = 6) , asymptomatic (an =25) , LDH normal (n = 26) , ECOG score 0-1 ( n = 35) and extranodal lesions ~1 ( na = 31) groups, respectively (all P <0.05). The expressions of TF and VEGF on CD14 + monocytes in high-risk (n = 7) or high-middle-risk (n = 11) groups were significantly increased compared with low-risk (n = 15) or low-middle-risk(n = 14) groups, respectively (all P <0. 01). TF and VEGF expressions in non-remission group before chemotherapy (n = 11) were both obviously higher than those in remission group (an = 36, all P <0. 01) , and after chemotherapy their expressions in remission group were significantly lower than those before chemotherapy (all P <0. 01) , while such significant changes were not observed in the non-remission group ( all P > 0. 05).. The high expressions of TF and VEGF on peripheral CD14 + monocytes can be useful markers in dis-ease assessment, prognosis evaluation and short-term efficacy observation of NHL patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Case-Control Studies; Child; Female; Humans; Lipopolysaccharide Receptors; Lymphoma, Non-Hodgkin; Male; Middle Aged; Monocytes; Prognosis; Thromboplastin; Vascular Endothelial Growth Factor A; Young Adult

Patients with haematological malignancies carry increased risk of venous thrombosis (VT). However, the mechanisms that link these malignancies to activated coagulation have not been fully identified. Since anti-haemostatic agents are studied in clinical trials for their potential to prolong survival in cancer patients, a detailed characterisation of haemostatic markers in cancer subtypes is needed. Hence, in this study, we measured the plasma concentrations and mRNA expression in blood mononuclear cells of haemostatic parameters in 93 patients with haematological neoplasias (acute myeloid leukaemia, chronic lymphatic leukaemia, multiple myeloma, and non-Hodgkin's lymphoma) before start and after completion of cancer therapy. At diagnosis we found activation of coagulation and fibrinolysis, especially in patients with acute myeloid leukaemia. This hypercoagulation was not associated with increased levels of tissue factor (TF) or factor VII (fVII) antigen or mRNA, or levels of activated fVII. In conclusion we found a hypercoagulable state in patients with haematological malignancy that did not seem to be initiated by TF.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Coagulation; Case-Control Studies; Factor VII; Female; Fibrin Fibrinogen Degradation Products; Glycoproteins; Hematologic Neoplasms; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid, Acute; Lipoproteins; Longitudinal Studies; Lymphoma, Non-Hodgkin; Male; Middle Aged; Multiple Myeloma; Norway; Peptide Fragments; Prothrombin; RNA, Messenger; Thrombophilia; Thromboplastin; Venous Thrombosis

This study was performed to evaluate the mechanisms leading to tumor vessel occlusion by tissue factor-based drugs, which are used in vascular targeting approaches for the treatment of malignant tumors.. The effects of nontargeted soluble tissue factor were evaluated in vitro and in vivo. Tumor-bearing mice were treated with (1) the extracellular portion of tissue factor (soluble tissue factor), (2) low nontoxic doses of lipopolysaccharides, or (3) a combination thereof. The combination treatment showed the best effects and resulted in selective thrombosis of tumor vessels. On the basis of our data from subsequent in vitro analyses, including surface plasmon resonance measurements and endothelial cell based coagulation assays, we propose a model on how soluble tissue factor, although lacking its membrane anchor, can promote selective tumor vessel occlusion.. To our knowledge, this is the first report to describe the molecular mechanisms of coagulation induction by untargeted soluble tissue factor in vivo. Combination treatments including soluble tissue factor might represent an alternative vascular targeting approach for the treatment of malignant tumors.

Topics: Animals; Blood Coagulation; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Embolization, Therapeutic; Enzyme Activation; Factor Xa; Humans; Lipopolysaccharides; Lymphoma, Non-Hodgkin; Mice; Mice, Inbred BALB C; Mice, SCID; Peptide Fragments; Recombinant Proteins; Solubility; Surface Plasmon Resonance; Teratocarcinoma; Thromboplastin; Tumor Necrosis Factor-alpha; Xenograft Model Antitumor Assays

Experiments were made to evaluate the potential role played by thrombogenic factors on the hematogenous arrest of circulating tumor cells in mice with demonstrable coagulopathies associated with the presence of a primary tumor, by administration of "therapeutic" doses of anticoagulants. The effects of warfarin, aspirin and heparin administration on the early arrest patterns of 125IdUrd-labelled TA3 carcinoma and Gardner lymphosarcoma cells injected intravenously into tumor-bearing mice were examined. Several hematologic parameters of carcinoma- and lymphosarcoma-bearing animals were measured prior to anticoagulation experiments and the results indicated that mice had coagulopathies similar to those found in cancer patients with disseminated intravascular coagulation syndrome, i.e., thrombocytopenia and elevated fibrinogen levels. Despite the presence of coagulation abnormalities and effective anticoagulation in recipient animals, all three agents were without effect on localization patterns of both tumor types. It was concluded that the proposed involvement of thrombogenesis in metastasis was probably not due to any role played by those clotting factors inhibited by aspirin, warfarin and heparin in early intravascular tumor cell arrest.

Topics: Animals; Anticoagulants; Aspirin; Blood Coagulation; Carcinoma; Heparin; Lymphoma, Non-Hodgkin; Mice; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms, Experimental; Neoplastic Cells, Circulating; Thromboplastin; Warfarin

Topics: Adolescent; Adult; Blood Coagulation Disorders; Blood Coagulation Factors; Child; Child, Preschool; Factor VII; Factor VIII; Factor XIII; Female; Humans; Infant; Kaolin; Lymphoma, Non-Hodgkin; Male; Prothrombin Time; Pulmonary Embolism; Thrombocytopenia; Thrombophlebitis; Thromboplastin; Wiskott-Aldrich Syndrome