thromboplastin and Leukemia--Lymphocytic--Chronic--B-Cell

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

The aim of study was to evaluate TF activity and TFPI concentration in patients with haematological malignancies and urinary tract tumors. TFPI concentration and activity and TF concentration were measured in 20 patients suffering from acute myeloblastic leukaemia (AML), 21 patients with chronic myelogenous leukaemia (CML), 17 patients with chronic lymphatic leukaemia (CLL), 16 patients with multiple myeloma (MM) and 65 healthy adults. TFPI and TF concentrations were measured also in patients with renal cell carcinoma (n = 12) and bladder cancer (n = 17) and patients with benign prostatic hyperplasia (BPH) (n = 15). Patients with AML, CML, CLL, and cancer revealed elevated TFPI concentrations. Patients with AML, CML, CLL, MM showed decreased TFPI activity. However TFPI concentration correlated inversely with TFPI activity only in the AML group. No significant changes were observed in TF concentrations in all investigated groups.

Topics: Biomarkers, Tumor; Carcinoma, Renal Cell; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Kidney Neoplasms; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Lipoproteins; Male; Multiple Myeloma; Prostatic Hyperplasia; Thromboplastin; Urinary Bladder Neoplasms; Urologic Neoplasms

Tissue factor (TF) antigen and activity were measured in leukemic cell homogenates. In leukemic cell homogenate, especially that of acute promyelocytic leukemia (APL), both TF antigen and activity were significantly higher than these levels in the mononuclear cells obtained from healthy volunteers. Both TF antigen and activity were significantly higher in myelocytic leukemia than in lymphocytic leukemia cells. In leukemic cell homogenates, there was a close correlation between TF antigen and TF activity. The TF activity/TF antigen ratio was significantly higher in myelocytic leukemia than in lymphocytic leukemia cells. As the TF activity was not increased in lymphocytic leukemia cell homogenates to which were added phospholipids, the decrease in TF activity in lymphocytic leukemia might not be due to phospholipid in the leukemic cell membrane. Values for TF activity, TF antigen, and the TF activity/TF antigen ratio in leukemic cell homogenate from patients with disseminated intravascular coagulation (DIC) were significantly higher than those in patients without DIC. Therefore, the measurement of TF antigen and activity in leukemic cells could be useful for the prediction of DIC.

Topics: Antigens, Neoplasm; Disseminated Intravascular Coagulation; Humans; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Monocytic, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myelomonocytic, Acute; Leukemia, Promyelocytic, Acute; Leukemia, T-Cell; Leukocytes, Mononuclear; Neoplasm Proteins; Thromboplastin

Nonmalignant lymphoid tissue and tissue from patients with nodular sclerosis, Hodgkin's disease, and large cell lymphocytic lymphoma was examined by immunohistochemical techniques for the occurrence in situ of components of coagulation and fibrinolysis reaction pathways. Staining for material interpreted as fibrinogen was observed in abundance in both malignant and reactive lymphoid tissue. Fibrin also occurred to a variable extent but focally in all tissues. Components of coagulation pathways, including tissue factor, factor VII, factor X, and factor XIII ("a" subunit), were restricted to tissue macrophages. Double-labeling techniques revealed fibrin in direct apposition to tissue macrophages. We conclude that fibrinogen and fibrin occur in both benign and malignant lymphoid tissue and that the transformation of fibrinogen to fibrin is attributable to macrophage-initiated thrombin formation. We postulate that both systemic and local hypercoagulability associated with these disorders may be attributable to macrophage activation resulting in expression of procoagulant activity.

Topics: Adolescent; Adult; Aged; Factor VII; Factor VIII; Factor X; Female; Fibrin; Fibrinogen; Fibrinolysis; Hodgkin Disease; Humans; Immunohistochemistry; Leukemia, Lymphocytic, Chronic, B-Cell; Lymph Nodes; Lymphoid Tissue; Lymphoma, Large B-Cell, Diffuse; Macromolecular Substances; Macrophages; Male; Middle Aged; Sclerosis; Thromboplastin