thromboplastin and Anemia--Hemolytic

Topics: Adrenergic beta-Antagonists; Anemia, Hemolytic; Animals; Antihypertensive Agents; Cyclic AMP; Factor XII; Humans; Hydralazine; Hypertension, Malignant; Labetalol; Platelet Aggregation; Prostaglandins F; Rabbits; Rats; Renin-Angiotensin System; Thromboplastin; Vasopressins; Water-Electrolyte Imbalance

Topics: Anemia, Hemolytic; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Factor XII; Fibrinogen; Fibrinolysis; Heparin; Humans; Liver Diseases; Meningitis, Meningococcal; Phospholipids; Thrombin; Thromboplastin

Topics: Adenocarcinoma; Anemia, Hemolytic; Animals; Blood Coagulation; Disseminated Intravascular Coagulation; Erythrocyte Aging; Erythrocytes, Abnormal; Fibrinogen; Hemolytic-Uremic Syndrome; Heparin; Humans; Hypertension, Malignant; Iodine Radioisotopes; Kidney Transplantation; Liver Transplantation; Purpura, Thrombotic Thrombocytopenic; Rabbits; Thromboplastin; Transplantation, Homologous; Venoms

Topics: Adenine Nucleotides; Aging; Anemia, Hemolytic; Animals; Blood Coagulation; Endotoxins; Erythrocytes, Abnormal; Fibrinogen; Hemolysis; Humans; Models, Biological; Platelet Adhesiveness; Purpura, Thrombotic Thrombocytopenic; Rabbits; Thrombin; Thrombocytopenia; Thromboplastin; Venoms

Dogs suffering from canine idiopathic immune mediated hemolytic anemia (cIIMHA) are at great risk of dying particularly in the first two weeks after the diagnosis is made. This high mortality risk may be associated with the development of thromboembolism (TE) and/or disseminated intravascular coagulation (DIC) resulting in organ failure. The exact mechanism of the development of TE and/or DIC in cIIMHA is still undetermined. Therefore, this study investigates the presence of tissue factor (TF) in thrombocytes of dogs suffering from cIIMHA, using OptiPrep™ for the isolation of blood cells and immunocytochemistry (ICC) to visualize TF on thrombocytes. The normalised TF quantity, acquired with 'colour deconvolution' (ImageJ plug in), revealed that in cIIMHA dogs the fraction TF positive thrombocytes was statistically significant higher (P < 0.001; mean 0.79; n = 7) compared to the fraction TF positive thrombocytes of the healthy dogs (mean 0.43; n = 9). We further have indications that the fraction of TF positive thrombocytes decreases with time and therapy, but that the progression rate differs individually. Since cIIMHA dogs have more thrombocytes that are TF-positive compared to healthy dogs, this may explain the increased risk to develop TE and DIC. Furthermore, it seems that the number of TF-positive thrombocytes in cIIMHA dogs remains high during the first two weeks of the disease, the time when the animals are at greatest health risk.

Topics: Anemia, Hemolytic; Animals; Blood Platelets; Case-Control Studies; Dog Diseases; Dogs; Neutrophils; Thromboplastin

An excess of free heme is present in the blood during many types of hemolytic anemia. This has been linked to organ damage caused by heme-mediated oxidative stress and vascular inflammation. We investigated the mechanism of heme-induced coagulation activation in vivo. Heme caused coagulation activation in wild-type mice that was attenuated by an anti-tissue factor antibody and in mice expressing low levels of tissue factor. In contrast, neither factor XI deletion nor inhibition of factor XIIa-mediated factor XI activation reduced heme-induced coagulation activation, suggesting that the intrinsic coagulation pathway is not involved. We investigated the source of tissue factor in heme-induced coagulation activation. Heme increased the procoagulant activity of mouse macrophages and human PBMCs. Tissue factor-positive staining was observed on leukocytes isolated from the blood of heme-treated mice but not on endothelial cells in the lungs. Furthermore, heme increased vascular permeability in the mouse lungs, kidney and heart. Deletion of tissue factor from either myeloid cells, hematopoietic or endothelial cells, or inhibition of tissue factor expressed by non-hematopoietic cells did not reduce heme-induced coagulation activation. However, heme-induced activation of coagulation was abolished when both non-hematopoietic and hematopoietic cell tissue factor was inhibited. Finally, we demonstrated that coagulation activation was partially attenuated in sickle cell mice treated with recombinant hemopexin to neutralize free heme. Our results indicate that heme promotes tissue factor-dependent coagulation activation and induces tissue factor expression on leukocytes in vivo. We also demonstrated that free heme may contribute to thrombin generation in a mouse model of sickle cell disease.

Topics: Anemia, Hemolytic; Anemia, Sickle Cell; Animals; Antibodies; Blood Coagulation; Capillary Permeability; Cells, Cultured; Factor XI; Factor XIIa; Female; Gene Deletion; Gene Expression; Heme; Hemopexin; Humans; Injections, Intravenous; Leukocytes, Mononuclear; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; RNA, Small Interfering; Swine; Thromboplastin

We explored the possibility that heme, an inflammatory mediator and a product of intravascular hemolysis in patients with hemolytic anemia including sickle cell disease, could modulate hemostasis by an effect on endothelial tissue factor (TF) expression.. Levels of TF mRNA, protein and procoagulant activity were measured in heme-treated endothelial cells.. Heme induces TF expression on the surface of both macrovascular and microvascular endothelial cells in a concentration-dependent manner, with 12-fold to 50-fold induction being noted (enzyme-linked immunosorbent assay) between 1 and 100 microm heme (P < 0.05). Complementary flow cytometry studies showed that the heme-mediated endothelial TF expression was quantitatively similar to that of tumor necrosis factor-alpha (TNF-alpha). Heme also upregulated the expression of TF mRNA (8-fold to 26-fold), protein (20-fold to 39-fold) and procoagulant activity (5-fold to 13-fold) in endothelial cells in a time-dependent manner. The time-course of heme-mediated TF antigen expression paralleled the induction of procoagulant activity, with antibody blocking studies demonstrating specificity for TF protein. Interleukin (IL)-1alpha, and TNF-alpha are not involved in mediating the heme effect, as antibodies against these cytokines and IL-1-receptor antagonist failed to block heme-induced TF expression. Inhibition of heme-induced TF mRNA expression by sulfasalazine and curcumin suggested that the transcription factor nuclear factor kappaB is involved in mediating heme-induced TF expression in endothelial cells.. Our results demonstrate that heme induces TF expression by directly activating endothelial cells, and that heme-induced endothelial TF expression may provide a pathophysiologic link between the intravascular hemolytic milieu and the hemostatic perturbations previously noted in patients with hemolytic anemia including sickle cell disease.

Topics: Anemia, Hemolytic; Anemia, Sickle Cell; Cells, Cultured; Endothelium, Vascular; Heme; Hemostasis; Humans; NF-kappa B; RNA, Messenger; Thromboplastin; Transcriptional Activation; Tumor Necrosis Factor-alpha; Up-Regulation

We measured plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular coagulation (DIC) to examine the relationship between TFPI and vascular endothelial cell injury. TF antigen was detected in the plasma of healthy volunteers, and the levels were significantly increased in the patients with DIC, but decreased slightly in those with TTP. Plasma TFPI levels were significantly decreased in patients with TTP compared with those in healthy volunteers. The concentration of plasma thrombomodulin (TM) antigen was significantly higher in those with TTP than in normal volunteers. One month after treatment, TTP patients showed a significant decrease in plasma TM levels, and a significant increase in plasma TFPI levels, but plasma levels of TF antigen were not significantly increased. As plasma TFPI/TF ratio was significantly increased after treatment, the hypercoagulable state was therefore improved after treatment. There was no significant difference in plasma TF and TFPI levels between those who achieved complete remission (CR) and those who died. However, plasma TM levels were significantly higher in those who died than in those who achieved CR. Plasma TFPI levels might reflect injury of vascular endothelial cells as do plasma TM levels, and decreased plasma TFPI/TF ratio and vascular endothelial cell injuries might play causative roles in TTP.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Hemolytic; Combined Modality Therapy; Disseminated Intravascular Coagulation; Endothelium, Vascular; Female; Humans; Lipoproteins; Male; Middle Aged; Mitomycin; Plasma Exchange; Platelet Aggregation Inhibitors; Purpura, Thrombotic Thrombocytopenic; Remission Induction; Thrombomodulin; Thromboplastin; Treatment Outcome

A case of an acquired circulating anticoagulant occurring in a patient suffering from chronic lymphocytic leukaemia with haemolytic anaemia and autoimmune disorders has been reported. The anticoagulant was found to belong to the IgM class. Coagulation studies show that this anticoagulant inhibits the reaction between human prothrombinase andfactor II.

Topics: Anemia, Hemolytic; Autoantibodies; Autoimmune Diseases; Blood Coagulation Tests; Female; Humans; Immunoglobulin M; Leukemia, Lymphoid; Prothrombin; Thromboplastin

Topics: Acute Kidney Injury; Anemia, Hemolytic; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Transfusion; Coronary Disease; Female; Heart Arrest; Hemorrhagic Disorders; Humans; Hyaline Membrane Disease; Infant, Newborn; Ischemia; Kidney Transplantation; Male; Obstetric Labor Complications; Pregnancy; Shock, Septic; Shwartzman Phenomenon; Thrombocytopenia; Thromboembolism; Thromboplastin; Toxemia; Wounds and Injuries

Topics: Anemia, Hemolytic; Blood Coagulation; Erythrocytes; Humans; Thrombelastography; Thromboplastin

Topics: Anemia; Anemia, Hemolytic; Anemia, Hypochromic; Anemia, Pernicious; Blood Coagulation; Blood Proteins; Chloramphenicol; Epidemiology; Epoetin Alfa; Erythropoietin; Haptoglobins; Hematologic Diseases; Hematology; Hemochromatosis; Humans; Iron-Dextran Complex; Leukemia; Polycythemia; Thromboplastin; Vitamin B 12