thromboplastin and Purpura--Thrombotic-Thrombocytopenic

Thrombocytopenia-associated multiple organ failure (TAMOF) is a clinical phenotype that encompasses a spectrum of syndromes associated with disseminated microvascular thromboses, such as the thrombotic microangiopathies thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) and disseminated intravascular coagulation (DIC). Autopsies findings in TTP, HUS, or DIC reveal specific findings that can differentiate these 3 entities. Von Willebrand factor and ADAMTS-13 play a central role in TTP. Shiga toxins and the complement pathway are vital in the development of HUS. Tissue factor is the major protease that drives the pathology of DIC. Acute kidney injury (AKI) is a common feature in patients with TAMOF.

Topics: Acute Kidney Injury; ADAM Proteins; ADAMTS13 Protein; Antibodies, Monoclonal, Humanized; Complement Inactivating Agents; Complement System Proteins; Disseminated Intravascular Coagulation; Hemolytic-Uremic Syndrome; Humans; Multiple Organ Failure; Purpura, Thrombotic Thrombocytopenic; Shiga Toxins; Thromboplastin; von Willebrand Factor

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

Severe deficiency of ADAMTS13 activity was recently found in patients with thrombotic thrombocytopenic purpura (TTP). The great advance associated with these basic and clinical studies on ADAMTS13 is the possible elucidation of the pathogenesis of TMA (thrombotic microangiopathy). However, the exact pathogenetic mechanism in TMA without severe deficiency of ADAMTS13 activity remains unknown due to heterogeneity of the disease. In this study, there were 7 patients with TTP, 7 with HUS, 3 with drug-induced HUS, 1 with VOD, and 1 with IVL out of 19 TMA patients with a moderate deficiency (6-70%) of ADAMTS13 activity. Five of the 7 TTP patients had a poor outcome. Plasma thrombomodulin and t-PA-PAI-1 complex levels in TMA patients with a moderate deficiency of ADAMTS13 activity were significantly higher than those in patients with a severe deficiency of ADAMTS13 activity. These data suggest that the etiology in these patients may be systemic vascular endothelial cell damage.

Topics: ADAM Proteins; ADAMTS13 Protein; Adolescent; Adult; Aged; Biomarkers; Female; Fibrin; Hemolytic-Uremic Syndrome; Humans; Lipoproteins; Male; Metalloendopeptidases; Middle Aged; Peptide Fragments; Protein Precursors; Prothrombin; Purpura, Thrombotic Thrombocytopenic; Thromboplastin

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

To investigate the clinical significance of determination of plasma tissue factor (TF) antigen, we have developed a highly sensitive enzyme-linked immunosorbent assay (ELISA) for plasma TF, using two different monoclonal antibodies against TF apoprotein, 6B4 (catching antibody) and 5G9 (detecting antibody), and tetramethyl benzidine/H2O2 as substrates. Titration curves of recombinant human TF in buffer containing Triton X-100 were linear within the range from 50 to 2000 pg/ml. The total assay time was 3 h. Ultracentrifugation and immunoblot analysis indicated that human plasma and urine contained 50,000 g sedimentable and non-sedimentable forms of TF, both of which were detected by our ELISA method. Plasma and urine concentrations of TF in healthy subjects and patients with various diseases were measured by the ELISA method. In healthy subjects, plasma and urinary TF levels were found to be 149 +/- 72 pg/ml (n = 30) and 175 +/- 60 pg TF/urine creatinine mg (n = 95), respectively. TF was increased in plasma of patients with disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura, vasculitis associated with collagen diseases, diabetic microangiopathy and chronic renal failure receiving haemodialysis, but not in the plasma of endotoxaemic patients without DIC. The plasma TF/serum creatinine ratio did not show a positive correlation. Measurement of TF antigen in plasma may be useful for evaluating the endothelial damage and cell destruction in TF-containing tissues.

Topics: Adult; Aged; Blood Coagulation Disorders; Diabetes Mellitus; Disseminated Intravascular Coagulation; Enzyme-Linked Immunosorbent Assay; Female; Hematologic Diseases; Humans; Immunoblotting; Male; Middle Aged; Purpura, Thrombotic Thrombocytopenic; Reference Standards; Thromboplastin; Ultracentrifugation; Vasculitis

Topics: Blood Cell Count; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelet Disorders; Blood Platelets; Diagnosis, Differential; Disseminated Intravascular Coagulation; Female; Hemoglobinometry; Hemophilia A; Hemophilia B; Hemorrhage; Humans; Male; Prothrombin Time; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombotic Thrombocytopenic; Rheumatic Diseases; Telangiectasia, Hereditary Hemorrhagic; Thromboplastin; von Willebrand Diseases