thromboplastin and Embolism

Thrombus formation on a disrupted atherosclerotic plaque is a threatening event that leads to vessel occlusion and acute ischemia. In this current perspective, we present evidence for apoptosis as a major determinant of the thrombogenicity of the plaque lipid core and a potential contributor to plaque erosion and associated thrombosis. Moreover, apoptosis may directly affect blood thrombogenicity through the release of apoptotic cells and microparticles into the bloodstream.

Topics: Angina, Unstable; Animals; Apoptosis; Arteriosclerosis; Blood Coagulation; Embolism; Humans; Inflammation; Myocardial Infarction; Phosphatidylserines; Stroke; Thromboplastin; Thrombosis

Topics: Animals; Aorta; Autoradiography; Basement Membrane; Blood Vessels; Embolism; Endothelium; Fibrin; Fibrinolysis; HeLa Cells; Humans; Microscopy, Electron; Mitosis; Neoplasm Metastasis; Neoplasms; Neoplasms, Experimental; Neoplastic Cells, Circulating; Plasminogen; Platelet Adhesiveness; Saphenous Vein; Thromboplastin; Thymidine; Tritium

Topics: Abruptio Placentae; Disseminated Intravascular Coagulation; Embolism; Female; Fibrinogen; Fibrinolysis; Humans; Pregnancy; Thromboplastin; Thrombosis

Topics: Abortion, Induced; Abruptio Placentae; Afibrinogenemia; Amniotic Fluid; Anticoagulants; Blood Coagulation Disorders; Embolism; Embolism, Amniotic Fluid; Female; Fetal Death; Fibrinolysis; History; Humans; Obstetrics; Postpartum Hemorrhage; Postpartum Period; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Thromboplastin

We induced thrombosis of blood vessels in solid tumors in mice by a fusion protein consisting of the extracellular domain of tissue factor (truncated tissue factor, tTF) and the peptide GNGRAHA, targeting aminopeptidase N (CD13) and the integrin alpha(v)beta(3) (CD51/CD61) on tumor vascular endothelium. The designed fusion protein tTF-NGR retained its thrombogenic activity as demonstrated by coagulation assays. In vivo studies in mice bearing established human adenocarcinoma (A549), melanoma (M21), and fibrosarcoma (HT1080) revealed that systemic administration of tTF-NGR induced partial or complete thrombotic occlusion of tumor vessels as shown by histologic analysis. tTF-NGR, but not untargeted tTF, induced significant tumor growth retardation or regression in all 3 types of solid tumors. Thrombosis induction in tumor vessels by tTF-NGR was also shown by contrast enhanced magnetic resonance imaging (MRI). In the human fibrosarcoma xenograft model, MRI revealed a significant reduction of tumor perfusion by administration of tTF-NGR. Clinical first-in-man application of low dosages of this targeted coagulation factor revealed good tolerability and decreased tumor perfusion as measured by MRI. Targeted thrombosis in the tumor vasculature induced by tTF-NGR may be a promising strategy for the treatment of cancer.

Topics: Adult; Angiogenesis Inhibitors; Animals; Cells, Cultured; Drug Delivery Systems; Embolism; Female; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Neoplasms; Neovascularization, Pathologic; Oligopeptides; Salvage Therapy; Thromboplastin; Xenograft Model Antitumor Assays

At sites of vascular injury, thrombin is an important mediator in thrombus growth and stability. Using microfluidic flow devices as well as patterned surfaces of collagen and tissue factor (TF), we sought to determine the role that fibrin plays in clot stability without interfering with the production of thrombin.. We deployed an 8-channel microfluidic device to study coagulation during corn trypsin inhibitor-treated (XIIa-inhibited) whole blood perfusion over lipidated TF linked to a fibrillar collagen type 1 surface. Clot growth and embolization were measured at initial inlet venous (200 s(-1)) or arterial (1000 s(-1)) wall shear rates under constant flow rate or pressure relief mode in the presence or absence of Gly-Pro-Arg-Pro (GPRP) to block fibrin polymerization. Numerical calculations for each mode defined hemodynamic forces on the growing thrombi. In either mode at inlet venous flow, increasing amounts of TF on the surface led to a modest dose-dependent increase (up to 2-fold) in platelet deposition, but resulted in massive fibrin accumulation (>50-fold) only when exceeding a critical TF threshold. At a venous inlet flow, GPRP led to a slight 20% increase in platelet accumulation (P<0.01) in pressure relief mode with thrombi resisting ≈1500 s(-1) before full channel occlusion. GPRP-treated thrombi were unstable under constant flow rate, where shear forces caused embolization at a maximum shear rate of ≈2300 s(-1) (69 dynes/cm2). In constant flow rate mode, the nonocclusive platelet-fibrin deposits (no GPRP) withstood maximum shear rates of ≈29 000 s(-1) (870 dyne/cm2) at ≈95% of full channel occlusion. For arterial inlet shear rate, embolization was marked for either mode with GPRP present when shear forces reached 87 dynes/cm2 (≈2900 s(-1)). Under constant flow rate, platelet-fibrin deposits (no GPRP) withstood maximums of 2400 dynes/cm2 (80,000 s(-1)) at ≈90% of full channel occlusion prior to embolization.. Fibrin increased clot strength by 12- to 28-fold. Under pressure relief mode, ≈2-fold more fibrin was produced under venous flow (P<0.001). These studies define embolization criteria for clots formed with surface TF-triggered thrombin production (±fibrin) under venous and arterial flows.

Topics: Adult; Anticoagulants; Blood Coagulation; Blood Platelets; Collagen Type I; Computer Simulation; Embolism; Factor XIIa; Fibrin; Humans; Liposomes; Male; Microfluidic Analytical Techniques; Microscopy, Confocal; Models, Biological; Numerical Analysis, Computer-Assisted; Oligopeptides; Plant Proteins; Platelet Adhesiveness; Platelet Aggregation; Regional Blood Flow; Stress, Mechanical; Thrombin; Thromboplastin; Thrombosis; Time Factors; Young Adult

The identification of the presence of antiphospholipid in plasma is recognised to be of diagnostic and prognostic importance in subjects with thrombotic disease, recurrent miscarriage or collagen vascular disorders. A number of coagulation assays are currently employed for the detection of lupus anticoagulant (LA), many of which are influenced by reagent dependent and methodological variables. In the present study lyophilised plasma samples from three subjects with "strong", "weak" and "absent" LA were tested in 220 centres. The most commonly used tests for LA were Activated Partial Thromboplastin Time (APTT), Dilute Russell Viper Venom Time (DRVVT) and Kaolin CLotting Time (KCT). Median DRVVT ratios were 1.75, 1.17 and 1.10 for the three samples. The presence of a strong LA was not detected by 4% of laboratories. The correct diagnosis was made by 94% of users of DRVVT and 85% of users of KCT. A weak LA was not detected by over half of centres. Correction was observed on addition of plasma and also in platelet neutralisation. The correct diagnosis was made by 37% of users of DRVVT and 27% of users of KCT. Lupus Anticoagulant was falsely considered to be present in a Factor IX deficient plasma by approximately one quarter of laboratories. Amongst users of DRVVT and KCT absence of LA in this sample was correctly reported by 73% and 69% of centres respectively. The accuracy of testing for LA in the present study is suboptimal and this is likely to have important clinical consequences. There is clearly a need for greater conformity in the selection and performance of LA tests to facilitate accurate diagnosis of this important group of disorders.

Topics: Antiphospholipid Syndrome; Blood Coagulation; Blood Coagulation Tests; Diagnosis, Differential; Embolism; Female; Hemophilia B; Heterozygote; Humans; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Male; Partial Thromboplastin Time; Quality Control; Reproducibility of Results; Retinal Vessels; Thromboplastin; United Kingdom

Tissue factor (TF) is a major activator of the coagulation cascade and may play a role in initiating thrombosis after intravascular injury. To investigate whether medial vascular smooth muscle provides a source of TF following arterial injury, the induction of TF mRNA and protein was studied in balloon-injured rat aorta. After full length aortic injury, aortas were harvested at various times and the media and adventitia separated using collagenase digestion and microscopic dissection. In uninjured aortic media, TF mRNA was undetectable by RNA blot hybridization. 2 h after balloon injury TF mRNA levels increased markedly. Return to near baseline levels occurred at 24 h. In situ hybridization with a 35S-labeled antisense rat TF cRNA probe detected TF mRNA in the adventitia but not in the media or endothelium of uninjured aorta. 2 h after balloon dilatation, a marked induction of TF mRNA was observed in the adventitia and media. Using a functional clotting assay, TF procoagulant activity was detected at low levels in uninjured rat aortic media and rose by approximately 10-fold 2 h after balloon dilatation. Return to baseline occurred within 4 d. These data demonstrate that vascular injury rapidly induces active TF in arterial smooth muscle, providing a procoagulant that may result in thrombus initiation or propagation.

Topics: Animals; Aorta, Thoracic; Catheterization; Cells, Cultured; DNA Probes; Embolism; Gene Library; In Situ Hybridization; Kinetics; Male; Muscle, Smooth, Vascular; Rats; Rats, Sprague-Dawley; Reference Values; RNA; RNA, Messenger; Thromboplastin; Time Factors

Monozygotic twinning has been associated with a variety of vascular disruptive defects including congenital hydranencephaly/porencephaly. Data involving 24 cases of congenital hydranencephaly/porencephaly associated with twinning are reported. In these cases, the finding of a preponderance of monozygotic twins and the common association of a deceased co-twin support the hypothesis of a vascular disruptive etiology. These defects are presumed to be secondary to embolic phenomena or thromboplastin release from the deceased co-twin to the survivor via the vascular interconnections of a conjoined monochorionic placenta. In all cases of hydranencephaly/porencephaly, a careful examination of the placenta and membranes for evidence of a deceased co-twin is warranted prior to providing recurrence risk counseling.

Topics: Anencephaly; Brain; Diseases in Twins; Disseminated Intravascular Coagulation; Embolism; Female; Fetal Death; Humans; Hydranencephaly; Infant, Newborn; Male; Placenta; Pregnancy; Thromboplastin; Twins; Twins, Monozygotic

Topics: Animals; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Disseminated Intravascular Coagulation; Embolism; Female; Humans; Leukemia; Male; Postoperative Complications; Pregnancy; Pregnancy Complications, Hematologic; Shock; Thromboplastin; Thrombosis; Wounds and Injuries

Topics: Disseminated Intravascular Coagulation; Embolism; Female; Humans; Maternal-Fetal Exchange; Microcirculation; Placenta; Pregnancy; Pregnancy Complications, Hematologic; Thromboplastin

Topics: Animals; Blood Coagulation Disorders; Cricetinae; Embolism; Female; Fibrinogen; Humans; Infant, Newborn; Placenta; Pregnancy; Respiratory Distress Syndrome, Newborn; Thromboplastin

Topics: Adenosine Diphosphate; Animals; Blood Coagulation; Cheek; Cricetinae; Ear, External; Embolism; Female; Fibrin; Fibrinogen; Injections, Intraperitoneal; Injections, Intravenous; Leukocytes; Male; Microcirculation; Microscopy, Phase-Contrast; Platelet Adhesiveness; Rabbits; Sulfonic Acids; Thromboplastin

Topics: Anticoagulants; Blood Coagulation Tests; Cardiovascular Diseases; Embolism; Humans; Myocardial Infarction; Prothrombin; Thromboplastin; Thrombosis

Topics: Afibrinogenemia; Amniotic Fluid; Animals; Embolism; Female; Fibrinolysis; Haplorhini; Meconium; Pregnancy; Pregnancy, Animal; Thromboplastin

Topics: Blood Coagulation Tests; Diagnosis; Drug Therapy; Embolism; Heparin; Oxyphenbutazone; Pharmacology; Phenylbutazone; Preventive Medicine; Prothrombin; Pyrazoles; Thromboembolism; Thromboplastin; Thrombosis

Topics: Animals; Blood Chemical Analysis; Blood Coagulation; Blood Coagulation Factors; Dogs; Electrocardiography; Embolism; Embryo, Mammalian; Embryo, Nonmammalian; Hemorrhage; Heparin; Injections, Intra-Arterial; Injections, Intravenous; Liver; Pathology; Pulmonary Embolism; Research; Spleen; Thromboplastin

Topics: Amniotic Fluid; Blood; Blood Coagulation Disorders; Embolism; Embolism, Amniotic Fluid; Female; Fibrinolysis; Humans; Infant, Newborn; Meconium; Obstetric Labor Complications; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Complications, Hematologic; Prothrombin Time; Thrombelastography; Thromboplastin

Topics: Aminocaproates; Aminocaproic Acid; Drug Therapy; Embolism; Factor V; Factor VIII; Fibrinogen; Fibrinolysis; Geriatrics; Hemorrhage; Humans; Male; Postoperative Complications; Prostatectomy; Prothrombin; Thromboplastin; Thrombosis; Toxicology

Topics: Afibrinogenemia; Amniotic Fluid; Blood Coagulation Disorders; Embolism; Embolism, Amniotic Fluid; Female; Humans; Hyaluronoglucosaminidase; Pregnancy; Thrombocytopenia; Thromboplastin

Topics: Embolism; Humans; Radiography; Thromboplastin; Thrombosis; X-Rays

Topics: Embolism; Hospitals, General; Humans; Massachusetts; Thromboplastin; Thrombosis