thromboplastin and Syndrome

Clinically relevant clotting abnormalities in cancer patients are referred to as Trousseau's syndrome. While thrombotic complications such as venous thromboembolism are most frequent in every day's practice, cancer patients may also experience severe bleeding symptoms due to complex systemic coagulopathies, including disseminated intravascular coagulation, haemolytic thrombotic microangiopathy, and hyperfibrinolysis. The pathophysiology of Trousseau's syndrome involves all aspects of Virchow's triad, but previous basic research has mainly focused on the cellular and molecular mechanisms underlying blood hypercoagulability in solid cancers and haematological malignancies. In this regard, over-expression of tissue factor (TF), the principal initiator of the extrinsic coagulation pathway, by primary tumour cells and increased shedding of TF-bearing plasma microparticles are critical to both thrombus formation and cancer progression. However, novel findings on intrinsic contact activation in vivo, such as the release of polyphosphates or DNA by activated platelets and neutrophils, respectively, have pointed to additional pathways in the complex pathophysiology of Trousseau's syndrome.

Topics: Animals; Blood Coagulation Factors; Cell-Derived Microparticles; Factor VIII; Hemostasis; Humans; Models, Cardiovascular; Models, Immunological; Neoplasms; Syndrome; Thromboplastin

Rupture of an atherosclerotic plaque with subsequent thrombosis and myocardial ischemia is the patho-physiological mechanism in acute coronary syndromes. Tissue factor (TF) as the main initiator of the extrinsic coagulation cascade plays a central role in the pathogenesis of acute coronary syndromes. The extent of the thrombotic process is modulated by local vascular TF of the ruptured plaque as well as by circulating TF. In addition, TF alters signaling pathways and, thereby, contributes to inflammatory reactions and vascular remodeling. This review addresses current concepts of the role of TF in acute coronary syndromes and discusses potential consequences and therapeutic approaches.

Topics: Acute Disease; Arteriosclerosis; Coronary Disease; Humans; Myocardial Ischemia; Syndrome; Thromboplastin

Topics: Angina Pectoris; Coronary Thrombosis; Humans; Myocardial Infarction; Syndrome; Thromboplastin

The acute coronary syndromes arise from procoagulant changes in complex plaques, which trigger both platelet activation and coagulation pathways. These 2 pathways intersect at a number of points that form positive-feedback loops to sustain and accelerate thrombus formation. In normal hemostasis and with a healthy endothelium, intravascular thrombosis is prevented, and vascular patency is protected by the fibrinolytic system and a number of antithrombotic factors, such as antithrombin, thrombomodulin, and tissue factor pathway inhibitor. However, atherosclerosis is characterized by a hypercoagulable state, and the fibrinolytic balance is skewed toward occlusive thrombus formation at critical sites on vulnerable plaques. This review focuses on cellular and humoral mechanisms and the antithrombotic strategies that are important during the acute phase of an ischemic coronary syndrome, both in patients managed conservatively and in patients scheduled for an interventional procedure. These strategies include fibrinolytic therapy, antiplatelet therapies (aspirin, clopidogrel, glycoprotein IIb/IIIa receptor inhibitors), and low-molecular-weight heparin.

Topics: Acute Disease; Angiotensin-Converting Enzyme Inhibitors; Blood Coagulation; Coronary Disease; Heparin, Low-Molecular-Weight; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Platelet Activation; Platelet Aggregation Inhibitors; Syndrome; Thrombin; Thromboplastin; Thrombosis

Tissue factor (TF) is a transmembrane glycoprotein, currently considered as being the major regulator of the coagulation cascade and the initiator of thrombogenesis in vivo. When TF comes in contact with blood, it forms a high-affinity complex with factors VII/VIIa, activating factors IX and X and thus leading to the formation of an insoluble fibrin clot. The regulation of TF-VIIa activity plays a key role in blood-vessel wall interactions. Selective patterns of cellular expression of TF are observed in tissues. TF is constitutively localized only on the surface of cells anatomically separated from the blood, where it plays an essential role in hemostasis by limiting hemorrhage after vessel wall injury. A number of pathophysiologic stimuli are capable of inducing TF transcription and activity in endothelial cells and monocytes. An aberrant TF expression in contact with blood is implicated in thrombotic complications of atherosclerosis, including acute myocardial infarction. Recent findings have demonstrated cell-derived microparticles containing TF in the circulating blood of patients with acute coronary syndromes, capable of triggering and propagating thrombus growth. This observation suggests a new view of thrombosis that does not necessarily require the exposure of vessel wall-derived TF at the site of vascular injury to initiate and propagate thrombosis.

Topics: Angina, Unstable; Animals; Arteriosclerosis; Blood Coagulation; Cardiovascular Diseases; Disease Models, Animal; Factor IX; Factor VII; Factor VIIa; Factor X; Fibrinolytic Agents; Helminth Proteins; Hemostasis; Humans; Myocardial Infarction; Syndrome; Thromboplastin; Thrombosis

Recent advances in basic science have linked some systemic risk factors to endothelial dysfunction which gives rise to atherosclerotic disease and triggers the progression of thrombotic complications. Superficial erosion of the stenotic plaque can be observed in one-third of acute coronary syndromes (ACS). In these cases the presence of classic risk factors such as diabetes mellitus, hypercholesterolemia and smoking favor a state of "vulnerable blood" or high risk. Increased thrombogenicity can exacerbate thrombus formation and is able to trigger an ACS. The vessel endothelium regulates contractile, mitogenic and thrombotic activities of the vessel wall. Risk factors impair both homeostasis and hemostasis of the vessel wall and promote inflammatory signals. Platelet and monocyte activation favors the expression of tissue factor (TF), thus triggering the coagulation cascade with thrombin generation and clot formation. Increased blood thrombogenicity linked to classic risk factors may be associated with circulating TF levels which are much higher than those observed in healthy subjects without risk factors. These observations not only emphasize the usefulness of aggressive management of risk factors but open a new avenue for future studies to devise therapeutic strategies to treat ACS by inhibiting TF expression.

Topics: Acute Disease; Coronary Artery Disease; Coronary Thrombosis; Diabetes Complications; Humans; Hypercholesterolemia; Risk Factors; Smoking; Syndrome; Thromboplastin

Tissue factor is a key enzyme in coagulation process. It is primary known as a cofactor for factor VIIa-mediated triggering of blood coagulation, which proceeds in a cascade of extracellular reactions. Tissue factor forms a catalytic complex with VIIa and intitiates coagulation by activating factor IX and X, ultimately resulting in thrombin formation. Being a transmembranic glycoprotein it takes a signalling information to another cell activity after endothelium or other tissue damage. Tissue factor plays a pivotal role in blood clotting physiology and pathology especialy in atherothrombosis. Thrombogenic tissue factor on cell-derived microparticles is present in the circulating blood of patients with acute coronary syndromes. Tissue factor is found in adventitia of blood vessels and the lipid core of atherosclerotic plaques (but not in vascular cells contacting directly with blood). Although the molecular mechanisms responsible for these phenomena remain unclear, it is thought that they are brought about by the action of intracellular signaling, resulting in gene transcription and subsequent protein synthesis. By expressing on monocyte or macrofage cell membrane surface it is involved in proinflammatory action and plaque destabilisation. This shifted the emphasis to investigations of what happened on the cell surface, and later to the cell biology of tissue factor and its inducibility in monocytes/macrophages and endothelial cells. Recent studies have suggested that tissue factor also plays non-hemostatic roles in blood vessel development, tumor angiogenesis and metastasis, inflamation. Tissue factor upregulates a number of genes involved in regulation of growth, transcription, and cellular motility, as well as cytokines, makes it possible to suggest a link between the formation of the tissue factor / VIIa complex and the cellular processes. Regulation of tissue factor activity by natural tissue factor pathway inhibitor (synthesized by vascular endothelial cells) or by special drugs is a new insight in thrombosis and vessel reocclusion preventive therapy. Tissue factor concentration in circulating blood has a higher informativity comparing to troponine and CRB values.

Topics: Age Factors; Aged; Arteriosclerosis; Blood Coagulation; C-Reactive Protein; Diabetes Complications; Female; Humans; Hypercholesterolemia; Hypertension; Male; Myocardial Infarction; Risk Factors; Sex Factors; Syndrome; Thromboplastin; Thrombosis; Troponin T

The acute coronary syndromes, that include unstable angina, acute myocardial infarction, and many cases of sudden cardiac death, exact a considerable price on society in terms of mortality, morbidity, and health care costs. The coronary atherosclerotic lesion is often an indolent and progressive entity that can destabilize causing an acute syndrome with or without warning. The majority of acute coronary syndromes result from events such as rupture or disruption of the atherosclerotic plaque with intracoronary thrombosis and ischemia of the distal myocardium as a result. Advances in our understanding of the process underlying the acute coronary syndromes has allowed for the identification of targets and rational therapeutic strategies for the prevention and treatment of these syndromes. Many of these therapeutic strategies involve the reversal of prethrombotic forces that often coexist with coronary atherosclerosis. Even with recent advances in our approach to atherosclerosis, intracoronary thrombosis, and the resulting acute coronary syndromes, an unacceptably high event rate persists after these syndromes. Further advances in the prevention and treatment of coronary atherosclerosis and its thrombotic complications depends on a more thorough understanding of the biology of the atherosclerotic plaque and the factors which influence its stability.

Topics: Angina, Unstable; Blood Coagulation; Coronary Vessels; Disease Progression; Humans; Life Style; Myocardial Infarction; Rupture, Spontaneous; Syndrome; Thrombolytic Therapy; Thromboplastin; Treatment Outcome

Advances in our knowledge of the biochemistry of coagulation have facilitated the development of sensitive and specific assays that are able to detect the generation of coagulation enzymes in vivo. It has been demonstrated that the factor VII-tissue factor pathway functions under normal conditions to generate factor Xa and convert prothrombin to thrombin. Furthermore, the factor VII-tissue factor pathway is also mainly responsible for the activation of factor IX with minimal contribution from the contact phase. However the relatively high levels of factor IXa generated are unable to convert factor X to factor Xa under basal conditions. Prospective studies are required to determine whether "biochemically" hypercoagulable individuals (i.e., those with elevated levels of free factor VIIa, activation peptides of factor IX, factor X, or prothrombin) are more likely to develop arterial or venous thrombosis.

Topics: Basal Metabolism; Blood Coagulation; Dietary Fats; Factor VIIa; Humans; Myocardial Ischemia; Syndrome; Thromboplastin; Triglycerides

Topics: Animals; Blood Coagulation; Blood Coagulation Disorders; Blood Platelets; Capillary Permeability; Factor VII; Factor XII; Factor XII Deficiency; Hemostasis; Humans; Kininogens; Molecular Weight; Plasminogen; Prekallikrein; Syndrome; Thromboplastin

Topics: Afibrinogenemia; Blood Coagulation; Blood Coagulation Tests; Diagnosis, Differential; Disseminated Intravascular Coagulation; Fibrinolysis; Hemostasis; Humans; Models, Biological; Syndrome; Thromboplastin; Toxemia

Topics: Humans; Immunohistochemistry; Male; Middle Aged; Multiple Myeloma; Syndrome; Thrombophlebitis; Thromboplastin

To gain insight into the contribution of platelet-dependent thrombin formation in haemostasis and thrombosis, we investigated under flow conditions the haemostatic functions of platelets from a patient with Scott syndrome. Scott platelets are characterised by a diminished platelet-dependent thrombin generation. Thrombin generation was determined by calibrated automated thrombography and flow-based experiments were performed to reveal collagen-mediated platelet activation and fibrin deposition. Our studies indicate that adherent Scott platelets do not differ from control platelets in the formation of stable platelet aggregates under static and flow conditions. While for adherent control platelets a shape change, e.g. balloon formation, and externalisation of phosphatidylserine (PS) is associated with an increase in intracellular calcium concentration, this is not the case for Scott platelets. The calcium-induced morphological changes in control platelets are accompanied with a diminished recruitment of free flowing platelets. Scott platelets, not showing a calcium-induced shape change, also lost the ability to recruit free flowing platelets. These findings rebut the hypothesis that the mild bleeding tendency of Scott syndrome patients is due to a preserved adhesive activity of patient's platelets. Perfusion of tissue factor (TF)-activated control blood over immobilised collagen results in the formation of fibrin fibers that radiate from platelet aggregates. Although platelet aggregates were also observed after perfusion with TF-activated Scott blood, fibrin deposition was not observed. In conclusion, our findings indicate that platelet adhesion and spreading on a collagen matrix in the absence of fibrin formation is sufficient to sustain haemostasis under non-traumatic conditions.

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Platelets; Calcium; Female; Fibrin; Hemorrhage; Humans; Middle Aged; Platelet Aggregation; Regional Blood Flow; Syndrome; Thrombin; Thromboplastin

Tissue factor (TF) and its specific inhibitor, tissue factor pathway inhibitor (TFPI), are important contributors to the initiation of the coagulation process.. To compare plasma levels of soluble TF (sTF) and free-TFPI (f-TFPI) between patients with stable angina pectoris (SAP) and acute coronary syndrome (ACS) and to assess the impact of the two variables on long-term prognosis.. Patients with SAPs (n = 1146) and acute coronary syndrome (n = 523) from the AtheroGene study were included and followed for 2.3 years. Because of the strong impact of unfractionated heparin (UFH) on f-TFPI levels, but not on sTF levels, patients having received UFH before blood drawing were excluded from the analyses on f-TFPI (n = 226).. On admission, no significant differences in sTF levels were observed between SAP and ACS patients. By comparison to patients with stable angina, f-TFPI levels significantly increased in patients with acute unstable angina and further increased in patients presenting with non-ST-elevation myocardial infarction and ST-elevation myocardial infarction (P < 10(-4)). Among the 1669 individuals with a coronary artery disease, 56 died from a cardiovascular cause. In prospective analyses, high sTF levels were independently associated with an increased risk of cardiovascular death in individuals with ACS (fully adjusted hazard ratio associated with one quartile increase = 2.06; 95% confidence interval 1.24-3.45; P = 0.006) but not in those with SAP (hazard ratio = 1.07; 95% confidence interval 0.78-1.46; P = 0.67). In SAP and ACS patients, high f-TFPI levels were not independently associated with an increased risk of cardiovascular death.. Plasma sTF levels were predictive of cardiovascular mortality in individuals with ACS, whereas f-TFPI levels were associated with the severity of myocardial damage on admission but were not independently related to outcome.

Topics: Aged; Angina Pectoris; Biomarkers; Cardiovascular Diseases; Cohort Studies; Coronary Stenosis; Female; Follow-Up Studies; Germany; Humans; Lipoproteins; Male; Middle Aged; Myocardial Infarction; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Assessment; Severity of Illness Index; Syndrome; Thromboplastin; Time Factors

Trousseau's syndrome is a prothrombotic state associated with malignancy that is poorly understood pathophysiologically.. Here we report studies on the blood of a 55-year-old man with giant-cell lung carcinoma who developed a severe form of Trousseau's syndrome. His clinical course was dominated by an extremely hypercoagulable state. Despite receiving potent antithrombotic therapy, he suffered eleven major arterial and venous thrombotic events over a 5 month period. We examined the patient's blood for tissue factor (TF), the major initiator of coagulation, and found its concentration in his plasma to be forty-one-fold higher than the mean concentration derived from testing of 16 normal individuals.. Almost all of the TF in the patient's plasma was associated with cell-derived microvesicles, likely shed by the cancer cells.

Topics: Blood Coagulation; Carcinoma, Giant Cell; Cytoplasmic Vesicles; Enzyme-Linked Immunosorbent Assay; Factor VIIa; Humans; Immunohistochemistry; Lipoproteins; Lung Neoplasms; Lymph Nodes; Male; Middle Aged; Reference Values; Syndrome; Thromboplastin; Thrombosis

Lemierre's syndrome presents a classic clinical picture, the pathophysiology of which remains obscure. Attempts have been made to trace genetic predispositions that modify the host detection of pathogen or the resultant systemic reaction.. A 17-year old female, with no previous medical history, was admitted to the intensive care unit for septic shock, acute respiratory distress syndrome and Lemierre's syndrome. Her DNA was assayed for single nucleotide polymorphisms previously incriminated in the detection of the pathogen, the inflammatory response and the coagulation cascade. We observed functional variations in her Toll like 5 receptor (TLR 5) gene and two coagulation variations (Tissue Factor (TF) 603 and Plasminogen-Activator-Inhibitor-1 (PAI-1) 4G-4G homozygosity) associated with thrombotic events.. The innate immune response and the prothrombogenic mutations could explain, at least in part, the symptoms of Lemierre's syndrome. Genomic study of several patients with Lemierre's syndrome may reveal its pathophysiology.

Topics: Adolescent; Female; Fusobacterium Infections; Fusobacterium necrophorum; Humans; Pharyngitis; Plasminogen Activator Inhibitor 1; Polymorphism, Single Nucleotide; Respiratory Distress Syndrome; Shock, Septic; Syndrome; Thrombophlebitis; Thromboplastin; Toll-Like Receptor 5

Histamine plays an important role in vascular disease. Tissue factor (TF) expression is induced in vascular inflammation and acute coronary syndromes.. This study examined the effect of histamine on tumor necrosis factor-alpha- (TNF-alpha-) vs. thrombin-induced endothelial TF expression.. Histamine (10(-8)-10(-5) mol L-1), TNF-alpha (5 ng mL-1), and thrombin (1 U mL-1) induced TF expression in human endothelial cells. Although TF expression by TNF-alpha and thrombin was identical, histamine augmented TNF-alpha-induced expression 7.0-fold, but thrombin-induced expression only 2.6-fold. Similar responses occurred with TF activity. The H1-receptor antagonist mepyramine abrogated these effects. Differential augmentation by histamine was also observed at the mRNA level. Histamine-induced p38 activation preceded a weak second activation to both TNF-alpha and thrombin. Histamine-induced c-Jun NH2-terminal kinase (JNK) activation was followed by a strong second activation to TNF-alpha, and less to thrombin. Selective inhibition of this second JNK activation by SP600125 reduced TF induction to histamine plus TNF-alpha by 67%, but to histamine plus thrombin by only 32%. Histamine augmented TNF-alpha- and thrombin-induced vascular cell adhesion molecule 1 (VCAM-1) expression to a similar extent. Consistent with this observation, VCAM-1 induction to TNF-alpha and thrombin was mediated by p38, but not by JNK.. Histamine differentially augments TNF-alpha- vs. thrombin-induced TF expression and activity, which is mediated by the H1-receptor, occurs at the mRNA level, and is related to differential JNK activation.

Topics: Acute Disease; Anthracenes; Cell Adhesion; Cells, Cultured; Coronary Disease; Endothelial Cells; Enzyme Activation; Gene Expression Regulation; Hemostatics; Histamine; Humans; JNK Mitogen-Activated Protein Kinases; Receptors, Histamine H1; Signal Transduction; Syndrome; Thrombin; Thromboplastin; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1; Vasculitis

The case history is presented of a patient with Trousseau's syndrome in which tissue factor originating from lung cancer appeared responsible for recurrent DVT/PE. This is thought to be the first such case to be reported.

Topics: Adenocarcinoma; Adult; Humans; Lung Neoplasms; Male; Pulmonary Embolism; Recurrence; Syndrome; Thromboplastin; Venous Thrombosis

Increased platelet activation is well documented in patients with acute coronary syndromes and can be detected by various methods, including flow cytometry and enzyme-linked immunosorbent assay. However, such techniques require several steps and cannot provide quick results. Platelet activation ultimately results in procoagulant phospholipid exposure and we have previously described a simple activated factor X-activated clotting time (XACT) test that is insensitive to resting platelets but that is significantly shortened by activated platelets, microparticles and procoagulant phospholipids. Our aim was to determine whether the XACT test could be used to distinguish patients with chest pain due to cardiac ischaemia from those having chest pain due to non-cardiac causes. We thus carried out XACT tests on ethylenediamine tetraacetic acid whole blood and plasma samples obtained from 46 patients presenting to the emergency department with chest pain and from 30 controls. Sixteen cases (30%) were subsequently diagnosed as acute coronary syndromes. Blood samples from these patients displayed overall significantly shortened XACT results relative to both healthy controls (P<0.001) and chest pain not due to cardiac ischaemia (P<0.004). This discrimination was much better with whole blood samples than when platelet-poor plasmas were tested (P=0.153), suggesting that free microparticles were not the only factors responsible. Thus, the detection of increased procoagulant phospholipid activity in whole blood by shortened XACT results may be a simple and rapid diagnostic marker of some cardiac ischaemic events.

Topics: Acute Disease; Aged; Angina Pectoris; Blood Coagulation Factors; Blood Coagulation Tests; Chest Pain; Coronary Disease; Factor X; Female; Humans; Male; Middle Aged; Phospholipids; Pilot Projects; Platelet Activation; Predictive Value of Tests; Syndrome; Thromboplastin; Time Factors

Scott syndrome is an hereditary bleeding disorder characterized by a deficiency in platelet procoagulant activity. Unlike normal blood cells, Scott platelets, as well as erythrocytes and lymphocytes, are strongly impaired in their ability to scramble their membrane phospholipids when challenged with Ca2+. In normal cells this collapse of membrane asymmetry leads to surface exposure of phosphatidylserine. Here we report that Scott erythrocytes show an apparent defect in tyrosine phosphorylation on treatment with Ca2+-ionophore. Diminished tyrosine phosphorylation was also apparent in activated Scott platelets, but much less pronounced than observed in red blood cells. On the other hand, tyrosine phosphorylation profiles observed in Scott red blood cell ghosts after sealing in the presence of adenosine triphosphate (ATP) were indistinguishable from those obtained from normal ghosts. Several observations argue in favor of a mechanism in which tyrosine phosphorylation in red blood cells is facilitated by, rather than required for scrambling of membrane lipids. Staurosporin blocks tyrosine phosphorylation in normal red blood cells, but does not inhibit the lipid scrambling process. White ghosts from normal erythrocytes, resealed in the absence of ATP, exhibit Ca2+-induced lipid scrambling without tyrosine phosphorylation. A selective inhibitor of Ca2+-induced lipid scrambling also showed an apparent inhibition of tyrosine phosphorylation in ionophore-treated normal red blood cells, similar to that observed in Scott erythrocytes. While this inhibitor also suppressed Ca2+-induced lipid scrambling in ghosts that were sealed in the presence of ATP, it did not inhibit tyrosine kinase activity. We conclude that the apparent deficiency in tyrosine phosphorylation in Scott cells is an epiphenomenon, possibly associated with a defect in phospholipid scrambling, but not causal to this defect.

Topics: Adenosine Triphosphate; Blood Coagulation Disorders; Blood Platelets; Calcium; Carrier Proteins; Cell Membrane; Enzyme Inhibitors; Erythrocyte Membrane; Humans; Ionophores; Membrane Lipids; Membrane Proteins; Methomyl; Phosphatidylserines; Phospholipid Transfer Proteins; Phospholipids; Phosphorylation; Protein Processing, Post-Translational; Protein-Tyrosine Kinases; Staurosporine; Syndrome; Thromboplastin

Topics: Adult; Aged; Aged, 80 and over; Blood Coagulation Disorders; Blood Platelets; Female; Humans; Male; Middle Aged; Syndrome; Thromboplastin

Elevation of cytoplasmic Ca2+ levels in human erythrocytes induces a progressive loss of membrane phospholipid asymmetry, a process that is impaired in erythrocytes from a patient with Scott syndrome. We show here that porcine erythrocytes are similarly incapable of Ca2+-induced redistribution of membrane phospholipids. Because a complex of phosphatidylinositol 4,5-bisphosphate (PIP2) and Ca2+ has been proposed as the mediator of enhanced transbilayer movement of lipids (J Biol Chem 269:6347,1994), these cell systems offer a unique opportunity for testing this mechanism. Analysis of both total PIP2 content and the metabolic-resistant pool of PIP2 that remains after incubation with Ca2+ ionophore showed no appreciable differences between normal and Scott erythrocytes. Moreover, porcine erythrocytes were found to have slightly higher levels of both total and metabolic-resistant PIP2 in comparison with normal human erythrocytes. Although loading of normal erythrocytes with exogenously added PIP2 gave rise to a Ca2+-induced increase in prothrombinase activity and apparent transbilayer movement of nitrobenzoxadiazolyl (NBD)-phospholipids, these PIP2-loaded cells were also found to undergo progressive Ca2+-dependent cell lysis, which seriously hampers interpretation of these data. Moreover, loading Scott cells with PIP2 did not abolish their impaired lipid scrambling, even in the presence of a Ca2+-ionophore. Finally, artificial lipid vesicles containing no PIP2 or 1 mole percent of PIP2 were indistinguishable with respect to transbilayer movement of NBD-phosphatidylcholine in the presence of Ca2+. Our findings suggest that Ca2+-induced redistribution of membrane phospholipids cannot simply be attributed to the steady-state concentration of PIP2, and imply that such lipid movement is regulated by other cellular processes.

Topics: 4-Chloro-7-nitrobenzofurazan; Calcium; Erythrocyte Membrane; Erythrocytes; Hemophilia A; Humans; In Vitro Techniques; Kinetics; Lipid Bilayers; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositol Phosphates; Phospholipids; Reference Values; Syndrome; Thromboplastin

We report two cases of renal vein thrombosis, unusual because of acute expression, right renal vein localization, absence of the usual renal or perirenal causes, surgical management and a never before reported etiology. In one case the thrombosis was secondary to primary antiphospholipid syndrome, in the other it was secondary to heparin associated thrombocythemia. In this case surgical management was performed during prostacyclin infusion.

Topics: Acute Disease; Autoantibodies; Blood Coagulation Disorders; Combined Modality Therapy; Epoprostenol; Female; Heparin; Humans; Male; Middle Aged; Phospholipids; Renal Veins; Syndrome; Thrombocytopenia; Thromboplastin; Thrombosis

The erythrocytes from a patient with Scott syndrome, a bleeding disorder characterized by an isolated defect in expression of platelet procoagulant activity, have been studied. When incubated with the calcium ionophore A23187, Scott syndrome red blood cells (RBCs) expressed less than 10% of the prothrombinase (enzyme complex of coagulation factors Va and Xa) activity of A23187-treated RBCs obtained from normal controls. Consistent with the results from enzyme assay, the ionophore-treated Scott syndrome erythrocytes exhibited diminished membrane vesiculation and decreased exposure of membrane binding sites for factor Va compared with identically treated controls. When examined by scanning electron microscopy, untreated Scott syndrome RBCs were indistinguishable from normal cells. After incubation with A23187, however, the morphology of Scott syndrome RBCs contrasted markedly from normal erythrocytes. Whereas the Ca2+ ionophore induced marked echinocytosis and spiculation of normal RBCs, Scott syndrome RBCs remained mostly discoid under these conditions, with only an occasional echinocyte-like cell observed. These aberrant responses to intracellular Ca2+ were also observed for resealed ghosts prepared from Scott syndrome erythrocytes, indicating that they are related to a defect in the membrane or membrane-associated cytoskeleton. The finding that the erythrocytes of this patient share many of the membrane abnormalities reported previously for Scott syndrome platelets suggests that this defect is common to both cell lines and involves a membrane component required for vesicle formation and for expression of prothrombinase sites.

Topics: Adult; Blood Coagulation Disorders; Blood Platelets; Calcimycin; Calcium; Erythrocyte Membrane; Erythrocytes; Factor Va; Flow Cytometry; Fluorescent Antibody Technique; Humans; Kinetics; Magnesium; Membrane Proteins; Microscopy, Electron, Scanning; Syndrome; Thromboplastin

Activation of human platelets by complement proteins C5b-9 is accompanied by the release of small plasma membrane vesicles (microparticles) that are highly enriched in binding sites for coagulation factor Va and exhibit prothrombinase activity. We have now examined whether assembly of the prothrombinase enzyme complex (factors VaXa) is directly linked to the process of microparticle formation. Gel-filtered platelets were incubated without stirring with various agonists at 37 degrees C, and the functional expression of cell surface receptors on platelets and on shed microparticles was analyzed using specific monoclonal antibodies and fluorescence-gated flow cytometry. In addition to the C5b-9 proteins, thrombin, collagen, and the calcium ionophore A23187 were each found to induce formation of platelet microparticles that incorporated plasma membrane glycoproteins GP Ib, IIb, and IIIa. These microparticles were enriched in binding sites for factor Va, and their formation paralleled the expression of catalytic surface for the prothrombinase enzyme complex. Little or no microparticle release or prothrombinase activity were observed when platelets were stimulated with epinephrine and ADP, despite exposure of platelet fibrinogen receptors by these agonists. When platelets were exposed to thrombin plus collagen, the shed microparticles contained activated GP IIb-IIIa complexes that bound fibrinogen. By contrast, GP IIb-IIIa incorporated into C5b-9 induced microparticles did not express fibrinogen receptor function. Platelets from a patient with an isolated defect in inducible procoagulant activity (Scott syndrome) were found to be markedly impaired in their capacity to generate microparticles in response to all platelet activators, and this was accompanied by a comparable decrease in the number and function of inducible factor Va receptors. Taken together, these data indicate that the exposure of the platelet factor Va receptor is directly coupled to plasma membrane vesiculation and that this event can be dissociated from other activation-dependent platelet responses. Since a catalytic membrane surface is required for optimal thrombin generation, platelet microparticle formation may play a role in the normal hemostatic response to vascular injury.

Topics: Antibodies, Monoclonal; Blood Coagulation Factors; Blood Platelets; Cell Membrane; Collagen; Complement Membrane Attack Complex; Flow Cytometry; Humans; Platelet Activation; Platelet Membrane Glycoproteins; Syndrome; Thrombin; Thromboplastin

Topics: Antibodies; Aspirin; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Cell Adhesion; Cell Communication; Cyclooxygenase Inhibitors; Disseminated Intravascular Coagulation; Epoprostenol; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Humans; Indomethacin; Monocytes; Neoplasm Transplantation; Neoplasms; Syndrome; Thrombocytopenia; Thrombocytosis; Thromboembolism; Thromboplastin

Bernard-Soulier syndrome is a rare constitutional thrombopathy, the main clinical feature is a bleeding tendency which is variable. The long bleeding time, in spite of a normal or little decreased platelet count, has been recently explained: the giant platelets have a defective adhesion to subendothelium. This abnormal adhesion could be related with an abnormal pattern of platelet membrane glycoproteins. Interactions between vessel wall, von Willebrand's factor and platelets are discussed.

Topics: Adenosine Diphosphate; Blood Coagulation Factors; Blood Platelets; Cell Membrane; Cell Survival; Collagen; Factor VIII; Factor XI; Glycoproteins; Humans; Platelet Adhesiveness; Platelet Aggregation; Purpura, Thrombocytopenic; Ristocetin; Serotonin; Sialic Acids; Syndrome; Thromboplastin; von Willebrand Factor

Topics: Blood Cell Count; Blood Coagulation; Blood Platelets; Blood Protein Disorders; Cholestasis; Diagnosis, Differential; Duodenal Neoplasms; Factor VII; Hemorrhage; Heparin; Humans; Liver Neoplasms; Neoplasm Metastasis; Pancreatic Neoplasms; Syndrome; Thromboplastin

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Brain Injuries; Ethanol; Factor V; Fibrinogen; Fibrinolysis; Gels; Humans; Platelet Aggregation; Syndrome; Thromboplastin

Topics: Animals; Antifibrinolytic Agents; Blood Coagulation; Blood Coagulation Tests; Cyclohexanecarboxylic Acids; Drug Combinations; Hemorrhage; Male; Radiation Injuries, Experimental; Rats; Syndrome; Thromboplastin

Topics: Adult; Astigmatism; Deafness; Humans; Lens, Crystalline; Male; Marfan Syndrome; Nystagmus, Pathologic; Osteogenesis Imperfecta; Osteosclerosis; Sclera; Syndrome; Thromboplastin

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Tests; Hemorrhage; Humans; Prothrombin Time; Syndrome; Thromboplastin

Topics: Anticoagulants; Blood; Geriatrics; Hemorrhagic Disorders; Polycythemia; Pulmonary Heart Disease; Syndrome; Thromboplastin

Topics: Diagnosis, Differential; Hemophilia A; Hemorrhagic Disorders; Humans; Medicine; Syndrome; Thromboplastin

Topics: Hemoglobinuria; Hemoglobinuria, Paroxysmal; Humans; Plasma; Syndrome; Thromboplastin

Topics: Hemophilia A; Humans; Syndrome; Thromboplastin; von Willebrand Diseases

Topics: Factor VIII; Hemophilia A; Humans; Syndrome; Thromboplastin

Topics: Factor IX; Factor VIII; Hemorrhagic Disorders; Plasma; Serum; Serum Globulins; Syndrome; Thromboplastin

Topics: Child; Diagnosis, Differential; Hemorrhagic Disorders; Humans; Infant; Syndrome; Thromboplastin