thromboplastin and Lymphoma

Hypercoagulability is a common paraneoplastic complication in dogs with various malignant tumors. Importantly, tissue factor procoagulant activity (TF-PCA) induced by TF-bearing microparticles (TF-MPs) is associated with hypercoagulability in human patients with cancer. However, TF-PCA in tumor cells and the association between circulating TF-MPs and hypercoagulability in dogs with malignant tumors remain poorly understood. Therefore, the present study was conducted to evaluate the TF-PCA in various types of canine tumor cell lines and plasma in dogs with malignant tumors. Mammary gland tumor, hemangiosarcoma, and malignant melanoma cell lines, but not lymphoma cell lines, expressed TF on their surfaces and showed cellular surface and MP-associated TF-PCA. The plasma TF-PCA was elevated in some dogs that naturally developed such tumors. No significant difference was observed in plasma TF-PCA between the disseminated intravascular coagulation (DIC) group (median: 43.40; range: 3.47-85.19; n=5) and non-DIC group (median: 7.73; range: 1.70-16.13; n=12). However, plasma TF-PCA was remarkably elevated in three of five dogs with DIC. To the best of our knowledge, this is the first study to evaluate plasma TF-PCA in dogs with malignant tumors. Further studies must be conducted to determine the cellular origin of TF-MPs and the efficacy of plasma TF-PCA as a biomarker of DIC in dogs with malignant tumors.

Topics: Animals; Cell Line, Tumor; Cell-Derived Microparticles; Dog Diseases; Dogs; Female; Flow Cytometry; Hemangiosarcoma; Lymphoma; Mammary Neoplasms, Animal; Melanoma; Neoplasms; Thromboplastin

This study was purposed to investigate the relationship between tissue factor associated platelet microparticles and thrombosis of patients with lymphoma by detecting the density of platelet microparticles and the tissue factor coagulative activity, and to evaluate the possibility of tissue factor coagulative activity for predication of thrombosis in lymphoma patients. This study was divided into 3 groups: A group including 50 healthy persons who did not take any drugs and had no hypercoagulation diseases; B group including 50 cases of lymphoma without thrombosis, and C group including 8 cases of lymphoma with thrombosis. The plasma was isolated from venous blood by centrifugation. The density of platelet microparticles was detected by flow cytometry; the tissue factor coagulative activity of plasma was measured by chromogenic substrate. The results indicated that compared with group A, the density of platelet microparticles increased in group B. Compared with group B, group C had significantly higher density of platelet microparticles and tissue factor coagulative activity (P < 0.01). It is concluded that the density of tissue factor associated platelet microparticle has predictive value for lymphoma with thrombosis, which can be used as target of clinical test.

Topics: Blood Platelets; Case-Control Studies; Cell-Derived Microparticles; Flow Cytometry; Humans; Lymphoma; Thromboplastin; Thrombosis

Hemostatic parameters were examined before and during 102 courses of chemotherapy in 42 patients with malignant lymphoma with high risk for infection. The white blood cell count was significantly reduced in all patients at days 1 and 3, but significantly increased at days 7 and 9, compared to before chemotherapy. At day 7 of chemotherapy, tissue factor (TF) mRNA levels in leukocytes were significantly increased in all patients, especially those with infection. Plasma concentrations of granulocyte elastase derived-XDP (GE-XDP) levels correlated with D-dimer levels during chemotherapy in patients with malignant lymphoma, suggesting that the elevated D-dimer is fibrin products degraded by granulocyte elastase. GE-XDP, C-reactive protein (CRP), GE-XDP and D-dimer were significantly higher in patients with infection, disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS) than those without. In patients with DIC or ARDS, 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 in patients with malignant lymphoma during chemotherapy. Activated leukocytes and granulocyte elastase may elicit a hypercoagulable state and ARDS in patients with malignant lymphoma during chemotherapy.

Topics: Aged; Antineoplastic Agents; C-Reactive Protein; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Hemostasis; Humans; Infections; Leukocyte Count; Leukocyte Elastase; Leukocytes; Lymphoma; Male; Middle Aged; Prospective Studies; Respiratory Distress Syndrome; RNA, Messenger; Thromboplastin; Time Factors

This paper presents an analysis of 24 cases in which recombinant factor VIIa (rFVIIa) was used in the management of hemorrhage in patients with thrombocytopenia associated with hematologic malignancies. This is the largest case aggregation to date and focuses on preliminary experience in the off-label use of this hemostatic agent. Data were extracted from the international, Internet-based registry, www.haemostasis.com, accessed in September 2003. The search results were manually cross-checked against monthly summary reports. The physicians providing the cases were contacted individually to approve the use of their cases, supply any information missing from the database, and validate the data already held. Patients with acute myeloid leukemia, acute lymphoblastic leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, Burkitt's lymphoma, B-cell or T-cell lymphoma, or aplastic anemia received rFVIIa at total doses of between 18 and 1040 mug/kg body weight. Bleeding stopped in 11 of 24 (46%) patients, markedly decreased in 8 of 24 (33%) patients, and decreased in 4 of 24 (17%) patients. In most patients, the response was achieved within 2.5 hours of administration of rFVIIa. The use of rFVIIa was generally well tolerated -- 1 case of ischemic stroke was considered to be possibly related to rFVIIa administration, but this has yet to be confirmed. A review of these 24 cases submitted to the www.haemostasis.com database suggests that rFVIIa is beneficial in the management of hemorrhage in patients with thrombocytopenia and hematologic malignancies. This warrants further investigation in rigorously controlled clinical trials.

Topics: Adolescent; Adult; Anticoagulants; Child; Child, Preschool; Factor VIIa; Female; Hemorrhage; Humans; Internet; Leukemia; Lymphoma; Male; Medical Audit; Middle Aged; Prothrombin; Thrombocytopenia; Thromboplastin

The clinical and laboratory findings in seven female patients with primary autoimmune diseases, one female patient with lymphoplasmacytoid (LP) immunocytoma and IgM paraproteinemia, and two male patients with multiple myeloma are described. The common denominator in all patients was a lupus anticoagulant or a closely related coagulation disorder. Recurrent thrombosis was observed in six patients with autoimmune diseases and in two patients with malignant monoclonal gammopathies. Other clinical manifestations included cerebral disorders (four patients with autoimmune disease/two patients with monoclonal gammopathy), repeated obstetric complications (6/1), asymptomatic valvular heart disease (6/1), renal dysfunction (6/2), hepatic involvement (2/2), and arthropathy (2/0). Laboratory investigations revealed a biologic false-positive serological test for syphilis in six patients with autoimmune disease and one with monoclonal gammopathy, antinuclear antibodies (4/0), antibodies against DNA (4/1), and a positive direct Coombs test (3/1) which was accompanied by hemolytic anemia in two patients (1/1). Additionally slight leukocytopenia (2/1) and thrombocytopenia (6/2) were observed; abnormal bleeding was only seen in one patient with severe thrombocytopenia. Other complications characteristic of LP immunocytoma or multiple myeloma were missing. The obvious similarities between the patients with autoimmune diseases and the patients with malignant monoclonal gammopathies suggest analogous pathogenetic mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Abortion, Spontaneous; Autoantibodies; Autoimmune Diseases; Blood Coagulation Factors; Blood Coagulation Tests; Brain Diseases; Female; Humans; Immunoglobulins; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Lymphoma; Multiple Myeloma; Paraproteinemias; Pregnancy; Thromboplastin; Thrombosis

Analysis of fresh surgical specimens of normal tissue and tumor tissue show a cellular antithrombin activity to be present in certain organs. In normal tissues it was noted chiefly in normal colon, testes, breast, and uterus. In malignant tissues it was prominent in adenocarcinomas of the colon, breast, and lung. No epidermoid tumors showed evidence of thrombin binding. The thrombin- binding activity required the presence of intact cells and was distinct from the soluble antithrombins normally present in plasma and serum. There is growing evidence to suggest an interrelationship between clotting and the growth and dissemination of cancer. The implications of cellular antithrombins are reviewed in this context.

Topics: Adenocarcinoma; Antithrombins; Blood Coagulation Tests; Carcinoma, Squamous Cell; Female; Humans; Lymphoma; Male; Neoplasms; Thrombin Time; Thromboplastin