fibrin and Blood-Coagulation-Disorders

The COVID-19 pandemic has become an urgent issue in every country. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)-like massive intravascular clot formation is frequently seen in this cohort. Therefore, coagulation tests may be considered useful to discriminate severe cases of COVID-19. The clinical presentation of COVID-19-associated coagulopathy is organ dysfunction primarily, whereas hemorrhagic events are less frequent. Changes in hemostatic biomarkers represented by increase in D-dimer and fibrin/fibrinogen degradation products indicate the essence of coagulopathy is massive fibrin formation. In comparison with bacterial-sepsis-associated coagulopathy/DIC, prolongation of prothrombin time, and activated partial thromboplastin time, and decrease in antithrombin activity is less frequent and thrombocytopenia is relatively uncommon in COVID-19. The mechanisms of the coagulopathy are not fully elucidated, however. It is speculated that the dysregulated immune responses orchestrated by inflammatory cytokines, lymphocyte cell death, hypoxia, and endothelial damage are involved. Bleeding tendency is uncommon, but the incidence of thrombosis in COVID-19 and the adequacy of current recommendations regarding standard venous thromboembolic dosing are uncertain.

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; COVID-19; Cytokines; Disseminated Intravascular Coagulation; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Hemorrhage; Hemostasis; Humans; Inflammation; Lung; Lymphocytes; Partial Thromboplastin Time; Protease Inhibitors; Prothrombin Time; Sepsis; Thrombosis

The number of people infected with human immunodeficiency virus (HIV) is rapidly increasing and the majority of those infected are living in sub-Saharan Africa. Some hallmarks of HIV are inflammation and upregulation of inflammatory markers. A pathological coagulation system may accompany these inflammatory changes and potentially result in venous thromboembolism such as a deep vein thrombosis (DVT). In this review, the authors describe the inflammatory profile in HIV, the treatment regimens currently in place in South Africa, and in particular how HIV affects the hematological system, with specific focus on platelets, red blood cells (RBCs; erythrocytes), and fibrin(ogen). They also discuss the presence of DVT in HIV, focus on screening tests, and suggest a more proactive approach to track the inflammatory profile of HIV patients, by specifically using parameters that might point to pathological coagulation; these should involve platelet, RBC, and fibrin(ogen) analysis. They conclude by suggesting that including coagulation function tests to study the effect of treatment interventions would improve outcomes in these individuals, as it could help in the diagnosis of thromboembolic disease. Furthermore, this approach could streamline treatment strategies due to improved monitoring. A better understanding of hypercoagulability of HIV-infected patients is therefore urgently needed. In conclusion, the authors suggest a panel of pathology tests that should be considered as standard procedures when HIV is present.

Topics: Africa, Southern; Anti-HIV Agents; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Fibrin; HIV Infections; Humans; Venous Thromboembolism; Venous Thrombosis

Research on all stages of fibrin polymerization, using a variety of approaches including naturally occurring and recombinant variants of fibrinogen, x-ray crystallography, electron and light microscopy, and other biophysical approaches, has revealed aspects of the molecular mechanisms involved. The ordered sequence of fibrinopeptide release is essential for the knob-hole interactions that initiate oligomer formation and the subsequent formation of 2-stranded protofibrils. Calcium ions bound both strongly and weakly to fibrin(ogen) have been localized, and some aspects of their roles are beginning to be discovered. Much less is known about the mechanisms of the lateral aggregation of protofibrils and the subsequent branching to yield a 3-dimensional network, although the αC region and B:b knob-hole binding seem to enhance lateral aggregation. Much information now exists about variations in clot structure and properties because of genetic and acquired molecular variants, environmental factors, effects of various intravascular and extravascular cells, hydrodynamic flow, and some functional consequences. The mechanical and chemical stability of clots and thrombi are affected by both the structure of the fibrin network and cross-linking by plasma transglutaminase. There are important clinical consequences to all of these new findings that are relevant for the pathogenesis of diseases, prophylaxis, diagnosis, and treatment.

Topics: Animals; Biopolymers; Blood Coagulation Disorders; Fibrin; Humans; Polymerization

Acquired factor XIII (FXIII) deficiency, arising from an autoantibody against factor XIII, is a rare bleeding disorder. This autoimmune disorder most commonly occurs in the elderly. Patients who develop such acquired FXIII inhibitors may present with catastrophic bleeding events and are hard to be diagnosed with the normal general coagulation tests. Though the disease is relatively rare, it is known to cause significant mortality. In this article we briefly describe a patient who presented with extensive bleeding and a normal activated partial thromboplastin time and prothrombin time (PT), but had an acquired inhibitor to FXIII; her primary disease was systemic lupus erythematosus (SLE). Also, we will focus on the clinical features, treatment modalities, fibrin structure and epitope identification for acquired factor XIII inhibitor with a review of the literature.

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Factor Inhibitors; Epitopes; Factor VIII; Factor XIII Deficiency; Female; Fibrin; Hemorrhage; Hemorrhagic Disorders; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic

In the pathogenesis of sepsis, inflammation and coagulation play a pivotal role. Increasing evidence points to an extensive cross-talk between these two systems, whereby inflammation leads to activation of coagulation, and coagulation also considerably affects inflammatory activity. Molecular pathways that contribute to inflammation-induced activation of coagulation have been precisely identified. Pro-inflammatory cytokines and other mediators are capable of activating the coagulation system and down-regulating important physiologic anticoagulant pathways. Activation of the coagulation system and ensuing thrombin generation is dependent on expression of tissue factor and the simultaneous down-regulation of endothelial-bound anticoagulant mechanisms and endogenous fibrinolysis. Conversely, activated coagulation proteases may affect specific cellular receptors on inflammatory cells and endothelial cells and thereby modulate the inflammatory response.

Topics: Antithrombins; Blood Coagulation; Blood Coagulation Disorders; Blood Platelets; Down-Regulation; Fibrin; Fibrinolysin; Fibrinolysis; Humans; Inflammation; Lipoproteins; Plasminogen; Protein C; Receptors, Proteinase-Activated; Thrombin

Understanding mechanisms that underlie lung disorders is crucial to achieving optimum care and improved outcomes in pulmonary medicine. Extensive investigations have revealed that inflammation displays an active role in the pathogenesis of these diseases. The byproduct of these inflammatory reactions has been shown to propagate pulmonary disease in consonance with alteration in haemostatic balance. It is now apparent that the two phenomena constitute an interwoven relationship with protective but damaging effects, when dysregulated. However, the precise role of coagulation abnormalities in pulmonary pathology is still evolving. A large body of evidence suggests that an imbalance in intra-alveolar procoagulant and fibrinolytic activities occurs in a variety of lung conditions. This imbalance may even herald a number of pulmonary diseases. Its sequelae have been observed in lung parenchyma of humans and in animal models of lung inflammation. As the pathogenesis of coagulation-related lung diseases continues to be unraveled, therapeutic measures to mitigate pulmonary disease-specific coagulopathy are emerging. Current efforts are directed at depicting multifaceted molecules capable of selective but simultaneous interference with relevant aspects of the dual coagulation-fibrinolytic pathway.

Topics: Animals; Blood Coagulation; Blood Coagulation Disorders; Fibrin; Humans; Models, Biological; Pneumonia

Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Autoantigens; Autoimmune Diseases; Biopolymers; Blood Coagulation Disorders; Blood Coagulation Factors; Female; Fibrin; Hemorrhagic Disorders; Humans; Lymphoproliferative Disorders; Male; Middle Aged; Paraproteins; Thrombophilia

The thrombin-catalyzed conversion of plasma fibrinogen into fibrin and the development of an insoluble fibrin clot are the final steps in the coagulation cascade during hemostasis. The delicate balance between clot formation and fibrinolysis, which determines clot stability, is controlled by a complex interplay between fibrin and other molecular and cellular components of the hemostatic system, including thrombin activatable fibrinolysis inhibitor (TAFI). TAFI is activated by thrombin and has an important role in the stability of the fibrin clot, which is reviewed here. In particular, the role of TAFI in fibrinolysis and those characteristics of the protein that affect clot stability are described. In addition, the importance of TAFI in the coagulation process and how changes in its availability may contribute to bleeding or thrombotic disorders are discussed.

Topics: Animals; Antibodies; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Carboxypeptidase B2; Disease Models, Animal; Fibrin; Fibrinolysis; Humans; Mice; Mice, Knockout; Plant Proteins; Protease Inhibitors; Protein Structure, Tertiary; Rabbits; Thrombosis

The adhesion receptor P-selectin has long been known to support leukocyte rolling and emigration at sites of inflammation. Recently, P-selectin was also revealed to be a key molecule in hemostasis and thrombosis, mediating platelet rolling, generating procoagulant microparticles containing active tissue factor and enhancing fibrin deposition. Elevated levels of plasma P-selectin are indicative of thrombotic disorders and predictive of future cardiovascular events. Because the interaction between P-selectin and its receptor P-selectin glycoprotein ligand-1 (PSGL-1) represents an important mechanism by which P-selectin induces the formation of procoagulant microparticles and recruits the microparticles to thrombi, anti-thrombotic strategies are currently aimed at inhibiting this interaction. Recent developments also suggest that the procoagulant potential of P-selectin could be used to treat coagulation disorders such as hemophilia A.

Topics: Animals; Blood Coagulation Disorders; Cardiovascular Diseases; Cell Adhesion; Fibrin; Humans; Inflammation; Leukocytes; Membrane Glycoproteins; Mice; Models, Biological; P-Selectin; Phenotype; Protein Binding; Protein Structure, Tertiary; Thromboplastin; Thrombosis

The transmembrane glycoprotein tissue factor (TF) is the initiator of the coagulation cascade in vivo. When TF is exposed to blood, it forms a high-affinity complex with the coagulation factors factor VII/activated factor VIIa (FVII/VIIa), activating factor IX and factor X, and ultimately leading to the formation of an insoluble fibrin clot. TF plays an essential role in hemostasis by restraining hemorrhage after vessel wall injury. An overview of biological and physiological aspects of TF, covering aspects consequential for thrombosis and hemostasis such as TF cell biology and biochemistry, blood-borne (circulating) TF, TF associated with microparticles, TF encryption-decryption, and regulation of TF activity and expression is presented. However, the emerging role of TF in the pathogenesis of diseases such as sepsis, atherosclerosis, certain cancers and diseases characterized by pathological fibrin deposition such as disseminated intravascular coagulation and thrombosis, has directed attention to the development of novel inhibitors of tissue factor for use as antithrombotic drugs. The main advantage of inhibitors of the TF*FVIIa pathway is that such inhibitors have the potential of inhibiting the coagulation cascade at its earliest stage. Thus, such therapeutics exert minimal disturbance of systemic hemostasis since they act locally at the site of vascular injury.

Topics: Animals; Arteriosclerosis; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Vessels; Disseminated Intravascular Coagulation; Fibrin; Gene Expression Regulation; Humans; Neoplasms; Sepsis; Thromboplastin; Thrombosis

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Fibrin; Fibrinolysis; Humans; Reference Values; Serum Globulins; Thrombin

Intracavitary fibrin clots may initiate pannus formation and the immunopathology of RA. Two critical steps, probably host dependent, may determine the development of RA: an altered regulation of extravascular haemostasis or an aberrant reactivity of synovial fibroblasts to the adhered fibrin clots. Current treatments for RA target events downstream of fibrin deposition, perhaps agents acting at an earlier stage should be tried.

Topics: Arthritis, Rheumatoid; Blood Coagulation Disorders; Fibrin; Fibrinolysis; Humans; Synovitis

Topics: Animals; Blood Coagulation; Blood Coagulation Disorders; Factor XIII; Fibrin; Hemorheology; Humans; Solubility; Thrombolytic Therapy; Urea

Prof. Tage Astrup first elaborated the notion that blood fluidity involved a balance between the tendency of blood to clot and for such clots to lyse. It would seem that, at that time, this haemostatic balance involved the notion that forming fibrin orchestrated its own destruction by stimulating fibrinolytic activity. In this review, we have clarified the detail of this balance and developed the thesis that Astrup's far-sighted balance notions involve a variety of control mechanisms. These involve the notion that thrombin, being at first sight a procoagulant, can also, in conjunction with thrombomodulin, act as a stimulus of anticoagulant activity by the generation of activated protein C. The thrombin-activatable fibrinolytic inhibitor (TAFI) is also involved in this balance since the generation of thrombin provokes the neutralisation of fibrinolysis by the TAFI pathway. The kallikrein/factor XII/urokinase pathway is discussed indicating yet another aspect of balance between the generation of coagulation and fibrinolysis. The overall theme of this review, apart from an insight into various aspects of the haemostatic balance, is that blood has a strong tendency to clot when tissue is damaged, and the intact vasculature requires major anticoagulant systems to prevent clots adhering to and stabilising in the vasculature.

Topics: Animals; Blood Coagulation; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Factor XII; Fibrin; Fibrinolysis; Hemostasis; Humans; Models, Biological; Platelet Aggregation; Protein C; Thrombin; Thrombophilia

Topics: Animals; Blood Coagulation Disorders; Fibrin; Fibrinolysis; Humans; Phenotype; Plasminogen; Plasminogen Activators; Plasminogen Inactivators; Thrombolytic Therapy

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Cysteine Endopeptidases; Fibrin; Fibrinogen; Humans; Microcirculation; Neoplasm Metastasis; Neoplasm Proteins; Neoplasms; Thrombin

In balance, available studies employing sophisticated coagulation assays demonstrate enhanced thrombin generation in women with preeclampsia. The etiology is unknown but likely stems from the damage of vascular endothelium. Although activation of the clotting cascade does not cause preeclampsia, it likely contributes to the manifestations by obstruction and trauma of the microvasculature. Markers of clotting cascade activation such as AT III may be useful in the hypertensive preterm patient in whom the diagnosis is unclear.

Topics: Antithrombin III; Blood Coagulation Disorders; Blood Platelets; Factor VIII; Female; Fetal Blood; Fibrin; Glycoproteins; Humans; Pre-Eclampsia; Pregnancy; Protein C; Protein S

Physiologic thrombolysis is efficient, while pathologic aberrations in the fibrinolytic system may result in either thrombotic or hemorrhagic disease. This review considers the molecular interactions involved in fibrinolysis, discusses the normal control mechanisms that provide for localized activation without systemic effects, and describes the molecular mechanism of plasmic degradation of fibrinogen and of cross-linked fibrin. The consequences of excessive or deficient fibrinolysis are discussed and specific examples cited of pathologic hemostasis directly related to abnormalities in the fibrinolytic system.

Topics: alpha-2-Antiplasmin; Animals; Blood Coagulation; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Dogs; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Hemorrhage; Homeostasis; Humans; Iatrogenic Disease; Plasminogen; Plasminogen Activators; Rabbits; Streptokinase; Thrombosis; Urokinase-Type Plasminogen Activator

A modern data review on the importance of fibrinolysis system is given. A considerable success has been scored during the study of molecular parameters of fibrinolysis system: the plasminogen, plasmin, its inhibitors, plasminogen activators and the mechanism of activation system have been characterized. The entrance of A, K, C, P and PP vitamins has been established to be necessary for the normal functioning of the fibrinolysis system; the dependence of the blood fibrinolytic activity upon the initial plasminogen content and concentration of its activators in blood has been revealed. The plasminogen activator depletion in tissues has been shown to be one of the reasons of some pathological states development, especially at cardiovascular diseases. The increase of fibrinolysis level by the active fibrinolytic ferment injection in blood has a medical effect at thrombosis. The ferment fibrinolysin received in the laboratory is successfully used in clinical practice. Some other activators of fibrinolytic system: tricholysine and longolytin from the culture of saprophyte fungi, plasminogen activator from the pig heart and the cells culture of the calf kidney have been received and are being studied.

Topics: Adult; Animals; Antithrombin III; Blood Coagulation Disorders; Cardiovascular Diseases; Cattle; Dogs; Enzymes, Immobilized; Female; Fibrin; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Heart; Humans; Male; Plasminogen; Plasminogen Activators; Rats; Research; Swine; Thrombosis; Tissue Plasminogen Activator; Vitamins

Topics: Antithrombin III; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Fibrin; Fibrinogen; Fibrinolysis; Humans; Nephrotic Syndrome; Renal Veins; Thromboembolism; Thrombophlebitis; Thrombosis

Topics: Abortion, Habitual; Animals; Autoantibodies; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Factor IX; Factor V; Factor VIII; Female; Fibrin; Humans; Immunoglobulins; Isoantibodies; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Pregnancy; Prothrombin; Thrombosis; von Willebrand Factor

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Platelets; Disseminated Intravascular Coagulation; Factor X; Fibrin; Fibrinolysis; Humans; Neoplasms; Neovascularization, Pathologic; Thrombophlebitis; Thromboplastin

Topics: Adult; Blood Coagulation Disorders; Fibrin; Fibrinogen; Humans; Infant, Newborn; Infant, Newborn, Diseases; Liver Diseases; Protein Conformation; Sialic Acids

The authors describe the pathophysiology of disseminated intravascular coagulation and the coagulopathy of utilization. The clinical and laboratory data on different types of shock are described. The efficacy of different antithrombotic agents in shock with disseminated intravascular coagulation is shown.

Topics: Blood Coagulation Disorders; Blood Platelets; Cyclic AMP; Disseminated Intravascular Coagulation; Fibrin; Fibrinolysis; Hemostasis; Humans; Microcirculation; Respiratory Distress Syndrome; Shock; Thrombocytopenia; Thrombosis

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Blood Vessels; Cardiopulmonary Bypass; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Humans; Infant, Newborn; Kidney Diseases; Myocardial Infarction; Neoplasms; Pregnancy; Pulmonary Embolism; Syndrome; Thrombin; Thrombophlebitis; Thrombosis

Disturbances of haemostasis caused immunologically and non-immunologically were observed after transfusion of blood and blood derivatives. Transfusion of heparin blood increased the bleeding susceptibility only in case of pre-existing high-degree defects of haemostasis or if they were performed as massive or exchange transfusions. Massive transfusions with blood stored for a long time will induce complex defects. Under intensive substitution therapy of haemophilia A the so-called paradoxical bleeding will occur in spite of a high factor VIII level. These bleedings are supposed to be disturbances of the thrombocyte function and are caused by fibrin(ogen) derivatives. Post-transfusional thrombocytopenias may be brought to remission by repeated plasmapheresis. Factor specific inhibitory bodies will appear after substitution in a small percentage of haemophilic patients. 5 to 7 days after the onset of therapy an anamnestic reaction can be observed as a titre increase by leaps. Usually, the inhibitory titre will decrease to a mostly low basal value in the course of three to five months. The therapy with cyclophosphamide simultaneously started with the substitution will more frequently prevent the anamnestic reaction or reduce it. Titres with more than 5 units cannot be overcome at the beginning even by higher concentrations of preparations. The substitution therapy should be preceded by exchange transfusions or plasmapheresis of up to 25 units. With still higher titres only procedures of inhibitor-bypassing are possible with factor VIII preparations of animal origin or better with activated prothrombin complex preparations, such as FEIBA. Recent reports give evidence that permanent substitution with factor VIII concentrates at a highest dosage can eliminate the production of inhibitors completely.

Topics: Blood Coagulation Disorders; Blood Transfusion; Cyclophosphamide; Factor IX; Factor IXa; Factor XIII; Fibrin; Fibrinogen; Hemophilia A; Hemostasis; Heparin; Humans; Platelet Aggregation; Thrombocytopenia; von Willebrand Diseases

Topics: Animals; beta-Thromboglobulin; Bleeding Time; Blood Coagulation; Blood Coagulation Disorders; Blood Platelets; Blood Vessels; Epoprostenol; Factor VIII; Fibrin; Fibrinolysis; Humans; Platelet Aggregation; Platelet Count; Prospective Studies; Thrombosis

Topics: Animals; Blood Coagulation; Blood Coagulation Disorders; Blood Physiological Phenomena; Disseminated Intravascular Coagulation; Drug Interactions; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Heparin; Humans; Molecular Biology

Topics: Anticoagulants; Antifibrinolytic Agents; Arterial Occlusive Diseases; Blood Coagulation; Blood Coagulation Disorders; Blood Platelets; Coagulants; Contraceptives, Oral; Estrogens; Female; Fibrin; Humans; Pregnancy; Pregnancy Complications, Hematologic; Thrombin; Thromboembolism; Thrombophlebitis; Thrombosis

Topics: Adolescent; Adult; Antithrombin III; Blood Coagulation; Blood Coagulation Disorders; Child; Factor IX; Factor V; Factor VIII; Fibrin; Fibrinogen; Humans; Pulmonary Embolism; Thrombophlebitis

Topics: alpha 1-Antitrypsin; alpha-Macroglobulins; Antithrombins; Blood Coagulation; Blood Coagulation Disorders; Factor IX; Factor V; Factor VII; Factor VIII; Factor X; Factor XI; Factor XII; Fibrin; Fibrinogen; Humans; Kininogens; Kinins; Molecular Weight; Prothrombin; Thrombin; Tissue Extracts

Topics: Afibrinogenemia; Blood Coagulation Disorders; Fibrin; Fibrinogen; Humans

Topics: Adult; Afibrinogenemia; Aged; Blood Coagulation Disorders; Blood Coagulation Tests; Chemical Phenomena; Chemistry; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Humans; Infant, Newborn; Kidney Diseases; Liver Diseases; Male; Models, Biological; Pregnancy

Coagulation factor XIII (fibrin stabilizing factor, FSF) is detectable in plasma, platelets, placenta and various tissues. In the activated form FSF has the enzymatic properties of a transglutaminase and is capable of stabilizing fibrin by inducing covalent bondings between fibrin monomers. In patients with congenital factor XIII deficiency or acquired immune inhibitors of fibrin stabilization a severe bleeding tendency is evident. There is not yet enough information available concerning the significance of reduced FSF-activity as cofactor in hemorrhagic diathesis and wound healing disturbances in various disease states. There are some indications from experimental studies that there might be an influence of FSF on tumor growth and metastasis as well as arteriosclerosis. The quantitation of the enzyme by radiological and immunological techniques yield reproducible results. Fibrin in its stabilized or non stabilized form can be discriminated in polyacrylamide gel electrophoresis after reduction of fibrin clots.

Topics: Adult; Blood Coagulation Disorders; Electrophoresis, Polyacrylamide Gel; Factor XIII; Factor XIII Deficiency; Female; Fibrin; Hemorrhagic Disorders; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Hematologic

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Hemostasis; Heparin; Humans; Plasminogen; Platelet Adhesiveness; Platelet Aggregation; Thrombin; Urokinase-Type Plasminogen Activator

Topics: Acute Disease; Animals; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Embolism, Amniotic Fluid; Female; Fetal Death; Fibrin; Fibrinogen; Fibrinolysis; Hemoglobinometry; Humans; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications, Hematologic; Puerperal Disorders; Shock, Septic; Thrombin

Topics: Afibrinogenemia; Animals; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Protein Electrophoresis; Fibrin; Fibrinogen; Fibrinolysin; Glycoproteins; Humans; Hydrolysis; Microscopy, Electron; Molecular Conformation; Molecular Weight; Peptide Hydrolases; Snakes; Thrombin; Venoms

Topics: Afibrinogenemia; Anti-Infective Agents; Antigens; Blood Coagulation Disorders; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Factor V; Factor VIII; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Hemagglutination Inhibition Tests; Heparin; Humans; Prothrombin Time; Radioimmunoassay; Thrombin; Thrombocytopenia; Thromboplastin

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Fibrin; Heparin; Humans; Indicator Dilution Techniques

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Calcium; Factor IX; Factor V; Factor VIII; Factor X; Factor XII; Fibrin; Fibrinogen; Humans; Liver Diseases; Phospholipids; Prothrombin; Prothrombin Time; Thromboplastin; Vitamin K Deficiency

Topics: Blood Coagulation Disorders; Electrophoresis, Polyacrylamide Gel; Fibrin; Fibrinogen; Fibrinolysis; Humans; Immunologic Techniques; Peptide Chain Termination, Translational; Peptides; Thrombin

Topics: Abruptio Placentae; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelet Disorders; Blood Transfusion; Disseminated Intravascular Coagulation; Embolism, Amniotic Fluid; Factor XIII Deficiency; Female; Fetal Death; Fetal Diseases; Fibrin; Fibrinogen; Fibrinolysis; Hemophilia A; Humans; Liver Diseases; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Sepsis; Uterine Hemorrhage; Vitamin K

Topics: Amino Acids; Animals; Binding Sites; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Cattle; Crystallization; Factor V; Factor VII; Factor VIII; Factor X; Factor XI; Factor XII; Fibrin; Fibrinogen; Hemophilia A; Humans; Isoelectric Focusing; Isoflurophate; Macromolecular Substances; Molecular Weight; Protein Binding; Protein Conformation; Prothrombin; Species Specificity; Thrombin; Tosyl Compounds

Topics: Acute Kidney Injury; Angiotensin II; Animals; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Catecholamines; Disseminated Intravascular Coagulation; Female; Fibrin; Heparin; Humans; Hypertension, Renal; Kidney Diseases; Kidney Glomerulus; Pre-Eclampsia; Pregnancy; Renin; Thrombosis; Uremia

Topics: Acute Disease; Blood Coagulation Disorders; Blood Coagulation Tests; Chronic Disease; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Fibrinolysis; Graft Rejection; Humans; Kidney; Kidney Transplantation; Male; Pregnancy; Time Factors; Transplantation, Homologous

Topics: Antithrombins; Blood Coagulation; Blood Coagulation Disorders; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Humans; Immunochemistry; Peptide Hydrolases; Prothrombin; Solubility

The experimental and clinical observations analyzed in this review suggest that the deposition of fibrin within glomeruli is an important pathogenic mechanism in the series of events leading to progressive destruction of glomerular capillaries. Neither the causal factors nor the consequences of this type of reaction are peculiar to the glomerulus. Fibrin deposits can occur in any injured blood vessel and, if not rapidly dealt with by fibrinolysis, will lead to endothelial changes and the development of organizing thrombi. It seems that glomerular capillaries are especially vulnerable; there are several reasons for this. First, some immunologic reactions are triggered within the glomeruli and thus produce a local inflammatory response, leading to fibrin deposition. Secondly, the glomerular filtration function allows a progressive local accumulation of potentially damaging particles, such as circulating fibrinogen derivatives (formed during generalized intravascular clotting), or phlogistic immune complexes (as a result of systemic antigen-antibody interaction); these too cause local injury and fibrin deposition. Finally, the glomerular obliteration resulting from the organization of such fibrin deposits leads to irreversible damage and so has more serious implications for the patient than if the lesions occurred elsewhere, where the formation of functionally useful new capillaries is often possible. It seems reasonable to propose, therefore, that the use of anticoagulant may be natural therapy in cases with the risk of rapid, massive, and continuous fibrin accumulation in glomeruli, where glomerular sclerosis and irreversible renal failure are likely.

Topics: Anticoagulants; Antigen-Antibody Complex; Antigen-Antibody Reactions; Basement Membrane; Blood Coagulation; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Endocarditis, Bacterial; Fibrin; Glomerulonephritis; Humans; Hyalin; Kidney Diseases; Kidney Glomerulus; Lupus Erythematosus, Systemic; Phagocytosis; Purpura

Topics: Animals; Anticoagulants; Autoimmune Diseases; Blood Coagulation Disorders; Disease Models, Animal; Fibrin; Heparin; Humans; Kidney; Kidney Cortex Necrosis; Kidney Diseases; Kidney Glomerulus; Mice; Nephritis; Rabbits; Shwartzman Phenomenon; Thrombosis

Topics: Adenosine Diphosphate; Animals; Antigen-Antibody Complex; Arteriosclerosis; Blood Coagulation; Blood Coagulation Disorders; Blood Flow Velocity; Blood Platelets; Cell Membrane; Collagen; Coronary Disease; Cytoplasmic Granules; Factor VII; Factor XII; Fibrin; Fibrinolysis; Humans; Microscopy, Electron; Microtubules; Platelet Adhesiveness; Rabbits; Serotonin; Thrombosis

Topics: Animals; Autopsy; Birth Weight; Blood Coagulation Disorders; Bradykinin; Cardiovascular Diseases; Female; Fibrin; Gestational Age; Humans; Hyaline Membrane Disease; Immune System Diseases; Infant, Newborn; Nervous System Diseases; Neurotransmitter Agents; Oxygen; Pregnancy; Respiratory Tract Diseases; Steroids; Water-Electrolyte Balance

Topics: Acetylcholine; Antimetabolites; Aspirin; Autonomic Nervous System; Blood Circulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Calcium; Cell Aggregation; Clot Retraction; Dicumarol; Epinephrine; Factor IX; Factor V; Factor VII; Factor VIII; Factor X; Fibrin; Fibrinogen; Hemorrhage; Hemostasis; Humans; Prothrombin; Prothrombin Time; Surgical Procedures, Operative; Thrombin; Vasoconstrictor Agents; Vasodilator Agents; Vitamin K

Topics: Amino Acid Sequence; Animals; Blood Coagulation Disorders; Bromides; Chemical Phenomena; Chemistry; Chemistry, Physical; Chromatography; Cyanides; Electrophoresis; Fibrin; Fibrinogen; Fibrinolysin; Humans; Nitrogen; Peptides; Thrombin

Topics: Abruptio Placentae; Adrenal Glands; Aminocaproates; Animals; Basement Membrane; Biopsy; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Brain; Female; Fibrin; Fibrinogen; Fibrinolysis; Fluorescent Antibody Technique; Hemorrhage; Hemorrhagic Disorders; Heparin; Humans; Hypertension, Malignant; Kidney Cortex Necrosis; Kidney Failure, Chronic; Kidney Glomerulus; Liver; Maternal Mortality; Microscopy, Electron; Myocardium; Placental Extracts; Pre-Eclampsia; Pregnancy; Rabbits; Shwartzman Phenomenon; Thromboplastin; Thrombosis

Topics: Adolescent; Adrenal Glands; Adult; Aged; Blood Coagulation Disorders; Child; Female; Fibrin; Hemorrhagic Disorders; Heparin; Humans; Kidney; Male; Meningitis; Middle Aged; Pneumococcal Infections; Sepsis; Splenectomy; Splenic Diseases; Thrombosis; Waterhouse-Friderichsen Syndrome

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Blood Vessels; Capillary Permeability; Fibrin; Fibrinogen; Hemorrhage; Hemostasis; Humans

Topics: Autoimmune Diseases; Biopsy; Blood Coagulation Disorders; Blood Protein Electrophoresis; Diagnosis, Differential; Female; Fibrin; Fibrinogen; Fluorescent Antibody Technique; gamma-Globulins; Glomerulonephritis; Humans; Immunoelectrophoresis; Kidney; Kidney Diseases; Kidney Glomerulus; Pre-Eclampsia; Pregnancy

Topics: Antithrombins; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Factor IX; Factor V; Factor VIII; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Humans; Plasma; Prothrombin Time; Streptokinase

Topics: Animals; Aorta; Arteriosclerosis; Blood Coagulation; Blood Coagulation Disorders; Blood Vessels; Endocrine Glands; Fibrin; Fibrinogen; Fibrinolysis; Hemorrhage; Heparin; Heparin Antagonists; Hepatitis; Humans; Lipid Metabolism; Lipoprotein Lipase; Liver; Liver Cirrhosis; Stress, Physiological; Thrombin; Thrombosis; Triglycerides

Fibrinogen is the first coagulation protein to reach critical levels during traumatic haemorrhage. This laboratory study compares paired plasma samples pre- and post-fibrinogen replacement from the Fibrinogen Early In Severe Trauma studY (FEISTY; NCT02745041). FEISTY is the first randomised controlled trial to compare the time to administration of cryoprecipitate (cryo) and fibrinogen concentrate (Fg-C; Riastap) in trauma patients. This study will determine differences in clot strength and fibrinolytic stability within individuals and between treatment arms.. Clot lysis, plasmin generation, atomic force microscopy and confocal microscopy were utilised to investigate clot strength and structure in FEISTY patient plasma.. Fibrinogen concentration was significantly increased post-transfusion in both groups. The rate of plasmin generation was reduced 1.5-fold post-transfusion of cryo but remained unchanged with Fg-C transfusion. Plasminogen activator inhibitor 1 activity and antigen levels and Factor XIII antigen were increased post-treatment with cryo, but not Fg-C. Confocal microscopy analysis of fibrin clots revealed that cryo transfusion restored fibrin structure similar to those observed in control clots. In contrast, clots remained porous with stunted fibres after infusion with Fg-C. Cryo but not Fg-C treatment increased individual fibre toughness and stiffness.. In summary, our data indicate that cryo transfusion restores key fibrinolytic regulators and limits plasmin generation to form stronger clots in an ex vivo laboratory study. This is the first study to investigate differences in clot stability and structure between cryo and Fg-C and demonstrates that the additional factors in cryo allow formation of a stronger and more stable clot.

Topics: Blood Coagulation Disorders; Factor XIII; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Hemostatics; Humans; Plasminogen Activator Inhibitor 1; Thrombosis

  Treatment of dilutional coagulopathy by transfusing fresh frozen plasma (FFP) remains sub-optimal. We hypothesized that partial replacement of transfused FFP by fibrinogen concentrate results in improved coagulant activity and haemostasis. This was tested in a controlled clinical intervention trial with patients experiencing massive bleeding during major surgery..   Patients undergoing major elective surgery were treated according to current protocols. When transfusion with FFP was required, patients were randomized as follows: group A received 4 units FFP and group B received 2 units FFP plus 2 g fibrinogen concentrate. Blood samples were taken before and after the intervention. Analysts were blinded to the treatment type..   Group A (B) consisted of 21 (22) patients, in 16 (17) of whom bleeding stopped after intervention. Plasma fibrinogen increased significantly more in group B (0·57 g/l) than in group A (0·05 g/l). However, levels of prothrombin and factors VIII, IX and X increased more in group A than in group B. Rotational thromboelastometry (ROTEM) of whole blood and plasma revealed improved fibrin clot formation in group B but not in group A. Thrombin generation [calibrated automated thrombogram (CAT)] in plasma increased more in group A. Principal parameters determining whole-blood thromboelastometry were the fibrinogen level and platelet count. In vitro addition of fibrinogen and prothrombin complex concentrate to pre-intervention samples restored both ROTEM and CAT parameters..   Partial replacement of transfused FFP by fibrinogen increases fibrin clot formation at the expense of less improved thrombin generation. Coagulation factors other than fibrinogen alone are required for full restoration of haemostasis.

Topics: Aged; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Component Transfusion; Blood Loss, Surgical; Female; Fibrin; Fibrinogen; Hemostasis; Humans; Male; Middle Aged; Plasma; Platelet Count; Postoperative Hemorrhage; Prospective Studies; Surgical Procedures, Operative; Thrombelastography

Patients with a recent myocardial infarction have an increased risk of recurrent ischaemic events. In the ESTEEM trial, the oral direct thrombin inhibitor ximelagatran reduced the risk of new ischaemic events when compared with placebo in aspirin treated post myocardial infarction patients. Ximelagatran persistently reduced markers of coagulation activity, i.e. prothrombin fragment 1 + 2 (F1 + 2) and D-dimer levels. The aim of this substudy was to evaluate the levels of these markers and activated thromboplastin time (APTT) in relation to new ischaemic events or bleeding.. In the substudy, 518 out of 1883 patients were included and within 14 days after a myocardial infarction randomized to ximelagatran or placebo for 6 months. The clinical endpoints death, myocardial infarction, severe recurrent ischaemia, ischaemic stroke, and bleeding were evaluated. The levels of F1 + 2, D-dimer, and APTT were analysed at randomization and in serial samples during the study. Ximelagatran treatment appeared to have a larger treatment effect in patients with F1 + 2 and D-dimer levels above the median at randomization with a reduction of ischaemic events from 18 to 9% (P = 0.03) for F1 + 2 and from 20 to 9% for D-dimer (P = 0.009). A reduction of D-dimer levels was found in 60% of the patients 1 week after randomization and these patients had less ischaemic events when compared with patients with unchanged or increased levels (P = 0.03) regardless of treatment. F1 + 2 and D-dimer levels were unrelated to bleeding risk. In the ximelagatran group, increased APTT was not related to ischaemic events but associated with a raised risk of bleeding.. A reduction of initially high coagulation activity, as measured by the D-dimer level, in patients with recent myocardial infarction identifies patients with a decreased risk of new ischaemic events, regardless whether the reduction occurs spontaneously or is induced by pharmacological means. Patients with higher initial coagulation activity seemed to benefit most from long-term treatment with ximelagatran.

Topics: Aged; Anticoagulants; Azetidines; Benzylamines; Blood Coagulation Disorders; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Male; Myocardial Infarction; Myocardial Ischemia; Partial Thromboplastin Time; Peptide Fragments; Protein Precursors; Prothrombin; Risk Factors; Thrombin

The changes in biomarkers of coagulation or fibrinolysis, anticoagulation, inflammation, and endothelial damage occur in patients with systemic inflammatory response syndrome (SIRS). The purpose of this study is to assess the prognostic value of these markers in patients with SIRS-associated hypercoagulopathy.. Sixty-six SIRS patients with a platelet count less than 15.0 x 10(4)/mm3 in three university hospital intensive care units were enrolled in this prospective, comparative study. Blood samples were obtained on day 0 and day 2. Twelve hemostatic, inflammatory, and vascular endothelial indices were measured and the data were compared between the severe group (patients with a total maximum Sequential Organ Failure Assessment score of 10 or more and nonsurvivors; n = 25) and the less-severe group (Sequential Organ Failure Assessment score <10; n = 41).. Significant changes between the groups were observed in platelet count, fibrin or fibrinogen degradation products, interleukin-6, soluble thrombomodulin, antithrombin (AT) activity, and protein C activity, both on day 0 and on day 2. In contrast, the d-dimer, soluble fibrin, plasmin-[alpha]2-antiplasmin complex, and E-selectin levels were higher in the severe group only on day 2. No significant difference was seen regarding the thrombin-AT complex and total plasminogen activator inhibitor on both days. A comparison of the areas under the receiver operating characteristic curve revealed the AT activity to be the best predictor of a progression of organ dysfunction.. The changes in some hemostatic molecular markers and vascular endothelial markers were conspicuous in patients with organ dysfunction. The AT activity is considered to be the most useful predictor of organ dysfunction.

Topics: alpha-2-Antiplasmin; Antithrombin III; Area Under Curve; Biomarkers; Blood Coagulation Disorders; E-Selectin; Endothelium, Vascular; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysin; Hemostasis; Humans; Interleukin-6; Male; Middle Aged; Peptide Hydrolases; Platelet Count; Predictive Value of Tests; Prognosis; Prospective Studies; Systemic Inflammatory Response Syndrome; Thrombomodulin

PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) was a phase III, randomized, double blind, placebo controlled, multicenter trial conducted in patients with severe sepsis from 164 medical centers. Here we report data collected at study entry for 1690 patients and over the following 7 days for the 840 patients who received placebo (in addition to usual standard of care).. Nineteen biomarkers of coagulation activation, anticoagulation, fibrinolysis, endothelial injury, and inflammation were analyzed to determine the relationships between baseline values and their change over time, with 28-day survival, and type of infecting causative micro-organism.. Levels of 13 of the 19 biomarkers at baseline correlated with Acute Physiology and Chronic Health Evaluation II scores, and nearly all patients exhibited coagulopathy, endothelial injury, and inflammation at baseline. At study entry, elevated D-dimer, thrombin-antithrombin complexes, IL-6, and prolonged prothrombin time were present in 99.7%, 95.5%, 98.5%, and 93.4% of patients, respectively. Markers of endothelial injury (soluble thrombomodulin) and deficient protein C, protein S, and antithrombin were apparent in 72%, 87.6%, 77.8%, and 81.7%, respectively. Impaired fibrinolysis (elevated plasminogen activator inhibitor-1) was observed in 44% of patients. During the first 7 days, increased prothrombin time (which is readily measurable in most clinical settings) was highly evident among patients who were not alive at 28 days.. Abnormalities in biomarkers of inflammation and coagulation were related to disease severity and mortality outcome in patients with severe sepsis. Coagulopathy and inflammation were universal host responses to infection in patients with severe sepsis, which were similar across causative micro-organism groups.

Topics: APACHE; Biomarkers; Blood Coagulation Disorders; C-Reactive Protein; Disseminated Intravascular Coagulation; Endothelium; Fibrin; Fibrinolysis; Humans; Inflammation; Partial Thromboplastin Time; Placebos; Prognosis; Protein C; Recombinant Proteins; Sensitivity and Specificity; Sepsis; Severity of Illness Index; Surgical Procedures, Operative; Surgical Wound Infection

The aim of this study was to design a simple laboratory method that can screen the overall haemostatic potential in plasma (OHPP) when a hyper- or hypocoagulable state is present. A fibrin time curve was made via spectrophotometric registration of fibrin generation and lysis in plasma, to which exogenous thrombin and tissue type plasminogen activator was added. The area under the curve, calculated by the sum of absorbance (ABS-sum), varied in correlation to the concentrations of platelets or purified pro-/anticoagulants: tissue factor, von Willebrand factor, fibrinogen, antithrombin, plasminogen, or plasminogen activator inhibitor type 1. The ABS-sums also changed in positive relation to the haemostatic function investigated in 16 menopausal women and 14 young healthy nonpregnant women (controls). The findings imply that the ABS-sums not only offer a general information about fibrin generation and lysis in vitro, but also reflect the OHPP (i.e., final combined effects of platelet activity, coagulation, and fibrinolysis in vivo). Preliminary results were satisfactory; the levels of OHPP, expressed as the ABS-sums, were higher in normal pregnant women than in the controls, and even higher in preeclamptic patients than in pregnant women with no complications, which corresponds to the different grades of hypercoagulability in the three groups. Moreover, the level of OHPP was considerably lower in an untreated infant with von Willebrand's disease type 3 and in factor VIII- or factor IX-deficient plasma samples.

Topics: Adult; Aged; Anticoagulants; Blood Coagulation Disorders; Clinical Laboratory Techniques; Female; Fibrin; Hemostasis; Humans; Infant, Newborn; Mass Screening; Middle Aged; Platelet Count; Pregnancy; Pregnancy Complications, Hematologic; Reference Values; Research Design; Time Factors

To examine whole blood coagulation in uremic patients presenting for surgery with the thromboelastogram and the Sonoclot analyzer.. Prospective, observational study.. Operating rooms of a university-affiliated hospital.. 30 ASA physical status II and III patients with chronic renal failure, and 30 age-matched and gender-matched patients with normal renal function, presenting for elective surgery.. Blood sampling for thromboelastograph and Sonoclot analysis immediately after anesthetic induction, prior to surgical incision.. Thromboelastographic indices of coagulation, reflecting coagulation factor function (R time), fibrinogen-platelet interaction (K time and alpha angle), and qualitative platelet function (maximum amplitude) were hypercoagulable in the uremic group compared with the control group (p < 0.05). Fibrinolysis (%) was decreased in the uremic group (p < 0.05). Fibrin formation (initial slope) and platelet function (time to peak) of the Sonoclot trace also were hypercoagulable in the uremic group (p < 0.05).. The high incidence of arteriovenous graft and fistulae thromboses in uremic patients belies in vitro laboratory evidence of platelet dysfunction. We have demonstrated perioperative hypercoagulability in uremic patients with viscoelastic measures of whole blood coagulation. These data suggest that traditional concern for coagulopathy and platelet dysfunction in uremic patients may require re-assessment in light of this "pro-thrombotic" state.

Topics: Adult; Blood Coagulation Disorders; Blood Viscosity; Elective Surgical Procedures; Female; Fibrin; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Thrombelastography; Uremia

Sex dimorphisms in coagulation are well established, with female-specific hypercoagulability conferring a survival benefit in the setting of trauma-induced coagulopathy (TIC). The mechanism behind these phenomena remains to be elucidated. We hypothesize that estradiol provokes a hypercoagulable profile and alters clot proteomics and fibrin crosslinking.. Whole blood was collected from healthy adult volunteers (n = 30). A battery of thrombelastography (TEG) assays (native, kaolin, platelet-mapping, functional fibrinogen), whole blood thrombin generation, proteomics, and clot structure architecture (via analysis of fibrin crosslinks and fluorescent fibrinogen-visualized clots) were performed after pre-treatment of the blood with physiologic concentrations of beta-estradiol. In addition, a prospective study of coagulation through the menstrual cycle was conducted by collecting blood from women on peak and nadir estrogen days in the standard 28-day menstrual cycle.. On TEG, in females, estradiol provoked a hypercoagulable phenotype, specifically a shorter time to clot formation and greater thrombin generation, greater rate of clot propagation and functional fibrinogen, higher clot strength, and diminished clot fibrinolysis. In both males and females, estradiol increased platelet hyperactivity. Similar changes were seen in time to clot formation and clot strength in vivo during peak estrus of the menstrual cycle. On proteomic analysis, in both males and females, estradiol was associated with increases in abundance of several procoagulant and antifibrinolytic proteins. Crosslinking mass spectrometry analysis showed addition of estradiol increased the abundance of several FXIII crosslinks within the FIBA alpha chain in both sexes. Fluorescent fibrinogen analysis revealed a trend toward increased fiber resolvability index after addition of estradiol.. Estradiol provokes a hypercoagulable phenotype, affecting time to clot formation, clot propagation, clot strength, clot fibrinolysis, and clot structure. In sum, these data highlight the role of estradiol is driving female-specific hypercoagulability and highlights its potential role as a therapeutic adjunct in resuscitation of TIC.

Topics: Blood Coagulation Disorders; Estradiol; Female; Fibrin; Fibrinogen; Humans; Male; Prospective Studies; Proteomics; Sex Characteristics; Thrombelastography; Thrombin; Thrombophilia; Thrombosis

Patients with acetaminophen (APAP)-induced acute liver failure (ALF) display both hyper- and hypocoagulable changes not necessarily recapitulated by standard hepatotoxic doses of APAP used in mice (eg, 300 mg/kg).. We sought to examine coagulation activation in vivo and plasma coagulation potential ex vivo in experimental settings of APAP-induced hepatotoxicity and repair (300-450 mg/kg) and APAP-induced ALF (600 mg/kg) in mice.. APAP-induced ALF was associated with increased plasma thrombin-antithrombin complexes, decreased plasma prothrombin, and a dramatic reduction in plasma fibrinogen compared with lower APAP doses. Hepatic fibrin(ogen) deposits increased independent of APAP dose, whereas plasma fibrin(ogen) degradation products markedly increased in mice with experimental ALF. Early pharmacologic anticoagulation (+2 hours after 600 mg/kg APAP) limited coagulation activation and reduced hepatic necrosis. The marked coagulation activation evident in mice with APAP-induced ALF was associated with a coagulopathy detectable ex vivo in plasma. Specifically, prolongation of the prothrombin time and inhibition of tissue factor-initiated clot formation were evident even after restoration of physiological fibrinogen concentrations. Plasma endogenous thrombin potential was similarly reduced at all APAP doses. Interestingly, in the presence of ample fibrinogen, ∼10 times more thrombin was required to clot plasma from mice with APAP-induced ALF compared with plasma from mice with simple hepatotoxicity.. The results indicate that robust pathologic coagulation cascade activation in vivo and suppressed coagulation ex vivo are evident in mice with APAP-induced ALF. This unique experimental setting may fill an unmet need as a model to uncover mechanistic aspects of the complex coagulopathy of ALF.

Topics: Acetaminophen; Animals; Blood Coagulation Disorders; Chemical and Drug Induced Liver Injury; Fibrin; Fibrinogen; Liver; Liver Failure; Mice; Mice, Inbred C57BL; Thrombin

Topics: Blood Coagulation Disorders; COVID-19; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; SARS-CoV-2

Trauma patients with abnormal fibrinolysis have increased morbidity and mortality. Knowledge of mechanisms differentiating fibrinolytic phenotypes is important to optimize treatment. We hypothesized that subjects with abnormal fibrinolysis identified by whole blood viscoelastometry can also be distinguished by plasma thrombin generation, clot structure, fibrin formation, and plasmin generation measurements.. Platelet-poor plasma (PPP) from an observational cross-sectional trauma cohort with fibrinolysis shutdown (% lysis at 30 minutes [LY30] < 0.9, n = 11) or hyperfibrinolysis (LY30 > 3%, n = 9) defined by whole blood thromboelastography were studied. Noninjured control subjects provided comparative samples. Thrombin generation, fibrin structure and formation, and plasmin generation were measured by fluorescence, confocal microscopy, turbidity, and a fluorescence-calibrated plasmin assay, respectively, in the absence/presence of tissue factor or tissue plasminogen activator (tPA).. Whereas spontaneous thrombin generation was not detected in PPP from control subjects, PPP from hyperfibrinolysis or shutdown patients demonstrated spontaneous thrombin generation, and the lag time was shorter in hyperfibrinolysis versus shutdown. Addition of tissue factor masked this difference but revealed increased thrombin generation in hyperfibrinolysis samples. Compared with shutdown, hyperfibrinolysis PPP formed denser fibrin networks. In the absence of tPA, the fibrin formation rate was faster in shutdown than hyperfibrinolysis, but hyperfibrinolysis clots lysed spontaneously; these differences were masked by addition of tPA. Tissue plasminogen activator-stimulated plasmin generation was similar in hyperfibrinolysis and shutdown samples. Differences in LY30, fibrin structure, and lysis correlated with pH.. This exploratory study using PPP-based assays identified differences in thrombin generation, fibrin formation and structure, and lysis in hyperfibrinolysis and shutdown subgroups. These groups did not differ in their ability to promote tPA-triggered plasmin generation. The ability to characterize these activities in PPP facilitates studies to identify mechanisms that promote adverse outcomes in trauma.. Prognostic/Epidemiological; Level III.

Topics: Blood Coagulation Disorders; Cross-Sectional Studies; Fibrin; Fibrinolysin; Fibrinolysis; Humans; Thrombin; Thromboplastin; Tissue Plasminogen Activator

Although a number of studies have demonstrated increased release of extracellular vesicles (EVs) and changes in their origin differentials after trauma, the biologic significance of EVs is not well understood. We hypothesized that EVs released after trauma/hemorrhagic shock (HS) contribute to endotheliopathy and coagulopathy. To test this hypothesis, adoptive transfer experiments were performed to determine whether EVs derived from severely injured patients in shock were sufficient to induce endothelial dysfunction and coagulopathy. Methods: Total EVs were enriched from plasma of severely injured trauma/HS patients or minimally injured patients by ultracentrifugation and characterized for size and numbers. Under isoflurane anesthesia, noninjured naive C57BL/6J mice were administered EVs at varying concentrations and compared with mice receiving equal volume vehicle (phosphate-buffered saline (PBS)) or to mice receiving EVs from minimally injured patients. Thirty minutes after injection, mice were sacrificed, and blood was collected for thrombin generation (thrombin-antithrombin, thrombin-antithrombin complex [TAT] assay) and syndecan-1 by enzyme-linked immunoabsorbent assay (ELISA). Lungs were harvested for examination of histopathologic injury and costained with von Willebrand factor and fibrin to identify intravascular coagulation. Bronchial alveolar lavage fluid was aspirated from lungs for protein measurement as an indicator of the endothelial permeability. Data are presented as mean ± SD, P < 0.05 was considered significant, and t test was used. Results: An initial proof-of-concept experiment was performed in naive mice receiving EVs purified from severely injured trauma/HS patients (Injury Severity Score [ISS], 34 ± 7) at different concentrations (5 × 106 to 3.1 × 109/100 μL/mouse) and compared with PBS (control) mice. Neither TAT nor syndecan-1 levels were significantly different between groups at 30 minutes after EV infusion. However, lung vascular permeability and histopathologic injury were significantly higher in the EV group, and lung tissues demonstrated intravascular fibrin deposition. Based on these data, EVs from severely injured trauma/HS patients (ISS, 32 ± 6) or EVs from minimally injured patients (ISS, 8 ± 3) were administered to naive mice at higher concentrations (1 × 109 to 1 × 1010 EV/100 μL/mouse). Compared with mice receiving EVs from minimally injured patients, plasma TAT and syndecan-1 levels were significantly higher in the tr

Topics: Animals; Blood Coagulation Disorders; Extracellular Vesicles; Fibrin; Lung Injury; Mice; Mice, Inbred C57BL; Shock, Hemorrhagic; Syndecan-1; Thrombin

Severe coronavirus disease-19 (COVID-19) has been associated with fibrin-mediated hypercoagulability and thromboembolic complications. To evaluate potential biomarkers of coagulopathy and disease severity in COVID-19, we measured plasma levels of eight biomarkers potentially associated with coagulation, fibrinolysis, and platelet function in 43 controls and 63 COVID-19 patients, including 47 patients admitted to the intensive care unit (ICU) and 16 non-ICU patients. COVID-19 patients showed significantly elevated levels of fibrinogen, tissue plasminogen activator (t-PA), and its inhibitor plasminogen activation inhibitor 1 (PAI-1), as well as ST2 (the receptor for interleukin-33) and von Willebrand factor (vWF) compared to the control group. We found that higher levels of t-PA, ST2, and vWF at the time of admission were associated with lower survival rates, and that thrombotic events were more frequent in patients with initial higher levels of vWF. These results support a predictive role of specific biomarkers such as t-PA and vWF in the pathophysiology of COVID-19. The data provide support for the case that hypercoagulability in COVID-19 is fibrin-mediated, but also highlights the important role that vWF may play in the genesis of thromboses in the pathophysiology of COVID-19. Interventions designed to enhance fibrinolysis might prove to be useful adjuncts in the treatment of coagulopathy in a subset of COVID-19 patients.

Topics: Biomarkers; Blood Coagulation Disorders; COVID-19; Fibrin; Fibrinolysis; Humans; Interleukin-1 Receptor-Like 1 Protein; Thrombophilia; Thrombosis; Tissue Plasminogen Activator; von Willebrand Factor

Trauma induced coagulopathy (TIC) is common after severe trauma, increasing transfusion requirements and mortality among patients. TIC has several phenotypes, with primary hyperfibrinolysis being among the most lethal. We aimed to investigate the contribution of hypercoagulation, hemodilution, and fibrinolytic activation to the hyperfibrinolytic phenotype of TIC, by examining fibrin formation in a plasma-based model of TIC. We hypothesized that instabilities arising from TIC will be due primarily to increased fibrinolytic activation rather than hemodilution or tissue factor (TF) induced hypercoagulation.. The influence of TF, hemodilution, fibrinogen consumption, tissue plasminogen activator (tPA), and the antifibrinolytic tranexamic acid (TXA) on plasma clot formation and structure were examined using rheometry, optical properties, and confocal microscopy. These were then compared to plasma samples from trauma patients at risk of developing TIC.. Combining TF-induced clot formation, 15 % hemodilution, fibrinogen consumption, and tPA-induced fibrinolysis, the clot characteristics and hyperfibrinolysis were consistent with primary hyperfibrinolysis. TF primarily increased fibrin polymerization rates and reduced fiber length. Hemodilution decreased clot optical density but had no significant effect on mechanical clot stiffness. TPA addition induced primary clot lysis as observed mechanically and optically. TXA restored mechanical clot formation but did not restore clot structure to control levels. Patients at risk of TIC showed increased clot formation, and lysis like that of our simulated model.. This simulated TIC plasma model demonstrated that fibrinolytic activation is a primary driver of instability during TIC and that clot mechanics can be restored, but clot structure remains altered with TXA treatment.

Topics: Blood Coagulation Disorders; Fibrin; Fibrinogen; Hemodilution; Hemostatics; Humans; Thrombophilia; Thromboplastin; Tissue Plasminogen Activator; Tranexamic Acid

Liver injury has been reported in patients with COVID-19. This condition is characterized by severe outcome and could be related with the ability of SARS-CoV-2 to activate cytotoxic T cells. The purpose of this study is to show the histological and scanning electron microscopy features of liver involvement in COVID-19 to characterize the liver changes caused by the activation of multiple molecular pathways following this infection.. Liver biopsies from 4 patients (3 post-mortems and 1 in vivo) with COVID-19 were analyzed with histology and by scanning electron microscopy.. The liver changes showed significant heterogeneity. The first case showed ground glass hepatocytes and scattered fibrin aggregates in the sinusoidal lumen. The second evidenced intra-sinusoidal thrombi. The third was characterized by sinusoidal dilatation, atrophy of hepatocytes, Disse's spaces dilatation and intra-sinusoidal aggregates of fibrin and red blood cells. The fourth case exhibited diffuse fibrin aggregates in the dilated Disse spaces and microthrombi in the sinusoidal lumen.. In COVID-19-related liver injury, a large spectrum of pathological changes was observed. The most peculiar features were very mild inflammation, intra-sinusoidal changes, including sinusoidal dilatation, thrombotic sinusoiditis and diffuse intra-sinusoidal fibrin deposition. These findings suggested that a thrombotic sinusoiditis followed by a local diffuse intra-vascular (intra-sinusoidal) coagulation could be the typical features of the SARS-CoV-2-related liver injury.

Topics: Aged; Autopsy; Biopsy; Blood Coagulation Disorders; COVID-19; Erythrocytes; Fibrin; Hepatocytes; Humans; Liver; Liver Diseases; Male; Microscopy, Electron, Scanning; Middle Aged; Thrombosis; Young Adult

Topics: Adult; Aged; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; COVID-19; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Homeostasis; Humans; Male; Middle Aged; Partial Thromboplastin Time; Prognosis; Protein C; Prothrombin Time; SARS-CoV-2

Both hyperfibrinolysis and fibrinolysis shutdown can occur after severe trauma. The subgroup of trauma patients with fibrinolysis shutdown resistant to tissue plasminogen activator (t-PA)-mediated fibrinolysis have increased mortality. Fibrin polymerization and structure may influence fibrinolysis subgroups in trauma, but fibrin architecture has not been characterized in acutely injured subjects. We hypothesized that fibrin polymerization measured in situ will correlate with fibrinolysis subgroups.. Blood samples were collected from trauma patients and noninjured controls. We selected samples across a range of fibrinolysis phenotypes (shutdown, physiologic, hyperfibrinolysis) and t-PA sensitivities (sensitive, physiologic, resistant) determined by thrombelastography. Plasma clots were created in situ with fluorescent fibrinogen and imaged using confocal microscopy for analysis of clot architecture in three dimensions. For each clot, we quantified the fiber resolvability, a metric of fiber distinctness or clarity, by mapping the variance of fluorescence intensity relative to background fluorescence. We also determined clot porosity by measuring the size and distribution of the gaps between fibrin fibers in three-dimensional space. We compared these measures across fibrinolysis subgroups.. Fiber resolvability was significantly lower in all trauma subgroups compared with controls (n = 35 and 5, respectively; p < 0.05). We observed markedly different patterns of fibrin architecture among trauma patients stratified by fibrinolysis subgroup. Subjects with t-PA-resistant fibrinolysis shutdown exhibited abnormal, densely packed fibrin clots nearly devoid of pores. Individuals with t-PA-hypersensitive fibrinolysis shutdown had highly irregular clots with pores as large as 2500 μm to 20,000 μm, versus 78 μm to 1250 μm in noninjured controls.. Fiber resolvability was significantly lower in trauma patients than controls, and subgroups of fibrinolysis differ in the porosity of the fibrin clot structure. The dense fibrin network in the t-PA-resistant group may prevent access to plasmin, suggesting a mechanism for thrombotic morbidity after injury.

Topics: Adult; Biomarkers; Blood Coagulation Disorders; Female; Fibrin; Fibrinolysis; Humans; Injury Severity Score; Male; Middle Aged; Polymerization; Retrospective Studies; Thrombelastography; Tissue Plasminogen Activator; Wounds and Injuries; Young Adult

Understanding the coagulation process is critical to developing treatments for trauma and coagulopathies. Clinical studies on tranexamic acid (TXA) have resulted in mixed reports on its efficacy in improving outcomes in trauma patients. The largest study, CRASH-2, reported that TXA improved outcomes in patients who received treatment prior to 3 hours after the injury, but worsened outcomes in patients who received treatment after 3 hours. No consensus has been reached about the mechanism behind the duality of these results. In this paper we use a computational model for coagulation and fibrinolysis to propose that deficiencies or depletions of key anti-fibrinolytic proteins, specifically antiplasmin, a1-antitrypsin and a2-macroglobulin, can lead to worsened outcomes through urokinase-mediated hyperfibrinolysis.

Topics: alpha 1-Antitrypsin; Antifibrinolytic Agents; Blood Coagulation; Blood Coagulation Disorders; Computer Simulation; Fibrin; Fibrin Clot Lysis Time; Fibrinolysin; Fibrinolysis; Hemorrhage; Humans; Membrane Proteins; Mortality; Pregnancy-Associated alpha 2-Macroglobulins; Thrombin; Tranexamic Acid; Urokinase-Type Plasminogen Activator; Wounds and Injuries

Topics: Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Fibrin; Humans; Prothrombin Time; Sepsis

Topics: Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Fibrin; Humans; Prothrombin Time; Sepsis

Type 2 diabetes (T2D) has many cardiovascular complications, including a thrombotic propensity. Many such chronic, inflammatory diseases are accompanied (and may be exacerbated, and possibly even largely caused) by amyloid fibril formation. Recognising that there are few strong genetic associations underpinning T2D, but that amyloidogenesis of amylin is closely involved, we have been seeking to understand what might trigger the disease. Serum levels of bacterial lipopolysaccharide are raised in T2D, and we recently showed that fibrin(ogen) polymerisation during blood clotting can be affected strongly by LPS. The selectivity was indicated by the regularisation of clotting by lipopolysaccharide-binding protein (LBP). Since coagulopathies are a hallmark of T2D, we wondered whether they might too be caused by LPS (and reversed by LBP). We show here, using SEM and confocal microscopy, that platelet-poor-plasma from subjects with T2D had a much greater propensity for hypercoagulability and for amyloidogenesis, and that these could both be reversed by LBP. These data imply that coagulopathies are an important feature of T2D, and may be driven by 'hidden' LPS. Given the prevalence of amyloid formation in the sequelae of diabetes, this opens up novel strategies for both the prevention and treatment of T2D.

Topics: Acute-Phase Proteins; Adult; Aged; Aged, 80 and over; Amyloid; Blood Coagulation Disorders; Carrier Proteins; Diabetes Mellitus, Type 2; Female; Fibrin; Humans; Male; Membrane Glycoproteins; Microscopy, Confocal; Microscopy, Electron, Scanning; Middle Aged; Plasma

Essentials Collagen and thrombin when used simultaneously generate highly activated platelets. The effect of thrombin stimulation on subsequent glycoprotein VI (GPVI) function was observed. Soluble fibrin, but not protease activated receptor (PAR) activation, prevented GPVI activation. Circulating soluble fibrin in coagulopathic blood may cause an acquired GPVI signaling defect.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adenosine Diphosphate; Blood Coagulation Disorders; Blood Platelets; Calcium Signaling; Collagen; Crotalid Venoms; Fibrin; Humans; In Vitro Techniques; Lectins, C-Type; Oligopeptides; Platelet Activation; Platelet Membrane Glycoproteins; Signal Transduction; Solubility; Thrombin

Platelet- and fibrin-dependent thrombus formation is regulated by blood flow and exposure of collagen and tissue factor. However, interactions between these blood-borne and vascular components are not well understood.. Here, we developed a method to assess whole-blood thrombus formation on microspots with defined amounts of collagen and tissue factor, allowing determination of the mechanical properties and intrathrombus composition. Confining the collagen content resulted in diminished platelet deposition and fibrin formation at high shear flow conditions, but this effect was compensated by a larger thrombus size and increased accumulation of fibrin in the luminal regions of the thrombi at the expense of the base regions. These thrombi were more dependent on tissue factor-triggered thrombin generation. Microforce nanoindentation analysis revealed a significantly increased microelasticity of thrombi with luminal-oriented fibrin. At a low shear rate, fibrin fibers tended to luminally cover the thrombi, again resulting in a higher microelasticity. Studies with blood from patients with distinct hemostatic insufficiencies indicated an impairment in the formation of a platelet-fibrin thrombus in the cases of dilutional coagulopathy, thrombocytopenia, Scott syndrome, and hemophilia B.. Taken together, our data indicate that (1) thrombin increases the platelet thrombus volume; (2) tissue factor drives the formation of fibrin outside of the platelet thrombus; (3) limitation of platelet adhesion redirects fibrin from bottom to top of the thrombus; (4) a lower shear rate promotes thrombus coverage with fibrin; (5) the fibrin distribution pattern determines thrombus microelasticity; and (6) the thrombus-forming process is reduced in patients with diverse hemostatic defects.

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Flow Velocity; Blood Platelets; Case-Control Studies; Collagen; Elasticity; Fibrin; Hemophilia B; Humans; Regional Blood Flow; Thrombocytopenia; Thromboplastin; Thrombosis; Time Factors

Essentials Acidosis, an outcome of traumatic injury, has been linked to impaired procoagulant efficiency. In vitro model systems were used to assess coagulation dynamics at pH 7.4 and 7.0. Clot formation dynamics are slightly enhanced at pH 7.0 in blood ex vivo. Acidosis induced decreases in antithrombin efficacy offset impairments in procoagulant activity.. Background Disruption of hydrogen ion homeostasis is a consequence of traumatic injury often associated with clinical coagulopathy. Mechanisms by which acidification of the blood leads to aberrant coagulation require further elucidation. Objective To examine the effects of acidified conditions on coagulation dynamics using in vitro models of increasing complexity. Methods Coagulation dynamics were assessed at pH 7.4 and 7.0 as follows: (i) tissue factor (TF)-initiated coagulation proteome mixtures (±factor [F]XI, ±fibrinogen/FXIII), with reaction progress monitored as thrombin generation or fibrin formation; (ii) enzyme/inhibitor reactions; and (iii) TF-dependent or independent clot dynamics in contact pathway-inhibited blood via viscoelastometry. Results Rate constants for antithrombin inhibition of FXa and thrombin were reduced by ~ 25-30% at pH 7.0. At pH 7.0 (+FXI), TF-initiated thrombin generation showed a 20% increase in maximum thrombin levels and diminished thrombin clearance rates. Viscoelastic analyses showed a 25% increase in clot time and a 25% reduction in maximum clot firmness (MCF). A similar MCF reduction was observed at pH 7.0 when fibrinogen/FXIII were reacted with thrombin. In contrast, in contact pathway-inhibited blood (n = 6) at pH 7.0, MCF values were elevated 6% (95% confidence interval [CI]: 1%-11%) in TF-initiated blood and 15% (95% CI: 1%- 29%) in the absence of TF. Clot times at pH 7.0 decreased 32% (95% CI: 15%-49%) in TF-initiated blood and 51% (95% CI: 35%-68%) in the absence of TF. Conclusions Despite reported decreased procoagulant catalysis at pH 7.0, clot formation dynamics are slightly enhanced in blood ex vivo and suppression of thrombin generation is not observed. A decrease in antithrombin reactivity is one potential mechanism contributing to these outcomes.

Topics: Acidosis; Antithrombin III; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Elasticity; Fibrin; Fibrinogen; Healthy Volunteers; Humans; Hydrogen-Ion Concentration; Ions; Proteome; Thrombin; Thromboplastin; Time Factors; Viscosity

We present a case of acquired dysfibrinogenemia caused by an autoantibody that inhibited fibrin polymerization in a patient previously diagnosed with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes). The patient showed prolonged PT, aPTT, and thrombin time. There was no factor deficiency but fibrinogen antigen and activity were decreased. ELISA for detection of fibrinogen antibodies were performed and IgG purified from the patient's plasma bound to fibrinogen more strongly than did control IgG, indicating the presence of a fibrinogen-specific antibody. Thrombin-mediated fibrin polymerization was severely impaired in the patient, although thrombin-induced fibrinopeptide A release was normal. Scanning electron microscopy was used to investigate the structure of fibrin clots and revealed many pores on the surface of patient's fibrin clots. Since MELAS is often associated with autoimmune disorders, a work-up for the presence of anti-fibrinogen antibody is necessary when bleeding tendency occurs in MELAS patients along with prolonged thrombin time.

Topics: Afibrinogenemia; Autoantibodies; Blood Coagulation Disorders; Disease Progression; Female; Fibrin; Fibrinogen; Humans; Immunoglobulin G; MELAS Syndrome; Middle Aged; Plasma; Polymerization

Carboxypeptidase B2 (CPB2) is a basic carboxypeptidase with fibrin and complement C3a and C5a as physiological substrates. We hypothesized that in polymicrobial sepsis, CPB2-deficient mice would have sustained C5a activity, leading to disease exacerbation.. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP).. Contrary to our hypothesis, Cpb2(-/-) mice had significantly improved survival, with reduced lung edema, less liver and kidney damage, and less disseminated intravascular coagulation. Hepatic pro-CPB2 was induced by CLP, leading to increased pro-CPB2 levels. Thrombomodulin present on mesothelium supported thrombin activation of pro-CPB2. Both wild-type and Cpb2(-/-) animals treated with a C5a receptor antagonist had improved survival, demonstrating that C5a was detrimental in this model. Treatment with a fibrinolysis inhibitor, tranexamic acid, caused a decrease in survival in both genotypes; however, the Cpb2(-/-) animals retained their survival advantage. Administration of a C3a receptor antagonist exacerbated the disease in both wild-type and Cpb2(-/-) mice and eliminated the survival advantage of Cpb2(-/-) mice. C5a receptor is expressed in both peritoneal macrophages and neutrophils; in contrast, C3a receptor expression is restricted to peritoneal macrophages, and C3a induced signaling in macrophages but not neutrophils.. While C5a exacerbates the peritonitis, resulting in a deleterious generalized inflammatory state, C3a activation of peritoneal macrophages may limit the initial infection following CLP, thereby playing a diametrically opposing protective role in this polymicrobial sepsis model.

Topics: Animals; Antifibrinolytic Agents; Blood Coagulation Disorders; Carboxypeptidase B2; Cecum; Cells, Cultured; Complement C3a; Complement C5a; Disease Models, Animal; Enzyme Activation; Fibrin; Inflammation Mediators; Leukopenia; Ligation; Liver; Macrophage Activation; Macrophages, Peritoneal; Male; Mice, Inbred C57BL; Mice, Knockout; Peritonitis; Protective Factors; Punctures; Risk Factors; Sepsis; Thrombin; Thrombomodulin; Time Factors

Epidemiological studies relate influenza infection with vascular diseases like myocardial infarction. The hypothesis that influenza infection has procoagulant effects on humans has been investigated by experimental animal models. However, these studies often made use of animal models only susceptible to adapted influenza viruses (mouse adapted influenza strains) or remained inconclusive. Therefore, we decided to study the influence of infection with human influenza virus isolates on coagulation in the well-established ferret influenza model.. After infection with either a seasonal-, pandemic- or highly pathogenic avian influenza (HPAI-H5N1) virus strain infected animals showed alterations in hemostasis compared to the control animals. Specifically on day 4 post infection, a four second rise in both PT and aPTT was observed. D-dimer concentrations increased in all 3 influenza groups with the highest concentrations in the pandemic influenza group. Von Willebrand factor activity levels increased early in infection suggesting endothelial cell activation. Mean thrombin-antithrombin complex levels increased in both pandemic and HPAI-H5N1 virus infected ferrets. At tissue level, fibrin staining showed intracapillary fibrin deposition especially in HPAI-H5N1 virus infected ferrets.. This study showed hemostatic alterations both at the circulatory and at the tissue level upon infection with different influenza viruses in an animal model closely mimicking human influenza virus infection. Alterations largely correlated with the severity of the respective influenza virus infections.

Topics: Animals; Blood Coagulation; Blood Coagulation Disorders; Disease Models, Animal; Ferrets; Fibrin; Fibrin Fibrinogen Degradation Products; Histocytochemistry; Lung; Male; Orthomyxoviridae Infections; Partial Thromboplastin Time; Thrombin Time; von Willebrand Factor

Acute traumatic coagulopathy (ATC) has been linked to an increase in activated protein C (aPC) from 40 pM in healthy individuals to 175 pM. aPC exerts its activity primarily through cleavage of active coagulation factor Va (fVa). Platelets reportedly possess fVa which is more resistant to aPC cleavage than plasma fVa; this work examines the hypothesis that normal platelets are sufficient to maintain coagulation in the presence of elevated aPC.. Coagulation responses of normal plasma, fV deficient plasma (fVdp), and isolated normal platelets in fVdp were conducted: prothrombin (PT) tests, turbidimetry, and thromboelastography (TEG), including the dose response of aPC on the samples.. PT and turbidimetric assays demonstrate that normal plasma is resistant to aPC at doses much higher than those found in ATC. Additionally, an average physiological number of washed normal platelets (200,000 platelets/mm3) was sufficient to eliminate the anti-coagulant effects of aPC up to 10 nM, nearly two orders of magnitude above the ATC concentration and even the steady-state pharmacological concentration of human recombinant aPC, as measured by TEG. aPC also demonstrated no significant effect on clot lysis in normal plasma samples with or without platelets.. Although platelet fVa shows slightly superior resistance to aPC's effects compared to plasma fVa in static models, neither fVa is sufficiently cleaved in simulations of ATC or pharmacologically-delivered aPC to diminish coagulation parameters. aPC is likely a correlative indicator of ATC or may play a cooperative role with other activity altering products generated in ATC.

Topics: Acute Disease; Anticoagulants; Antigens, CD; Blood Coagulation Disorders; Blood Platelets; Endothelial Protein C Receptor; Factor V; Factor Va; Factor VIII; Fibrin; Fibrinolysis; Humans; International Normalized Ratio; Models, Biological; Nephelometry and Turbidimetry; Phospholipids; Protein C; Proteolysis; Prothrombin Time; Receptors, Cell Surface; Solubility; Thrombelastography; Tissue Plasminogen Activator

Sepsis has a profound impact on the inflammatory and hemostatic systems. In addition to systemic inflammation, it can produce disseminated intravascular coagulation, microvascular thrombosis, consumptive coagulopathy, and multiple organ failure. We have shown that treatment with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDACI), improves survival in a lethal model of cecal ligation and puncture (CLP) in mice, but its effect on coagulation remains unknown. The goal of this study was to quantify the impact of SAHA treatment on coagulopathy in sepsis.. C57BL/6J mice were subjected to CLP, and 1 hour later given intraperitoneally either SAHA dissolved in dimethyl sulfoxide (DMSO) or DMSO only. Sham-operated animals were handled in similar manner without CLP. Blood samples were collected by cardiac puncture and evaluated using the TEG 5000 Thrombelastograph Hemostasis Analyzer System.. Compared with the sham group, all animals in DMSO vehicle group died within 72 hours, and developed coagulopathy that manifested as prolonged initial fibrin formation and fibrin cross-linkage time, and decreased clot formation speed, platelet function, and clot rigidity. SAHA treatment significantly improved survival and was associated with improvement in fibrin cross-linkage and clot formation, as well as platelet function and clot rigidity, without a significant impact on the clot initiation parameters.. SAHA treatment enhances survival and attenuates sepsis-associated coagulopathy by improving fibrin cross-linkage, rate of clot formation, platelet function, and clot strength. HDACI may represent a novel therapeutic strategy for correcting sepsis-associated coagulopathy.

Topics: Animals; Blood Coagulation; Blood Coagulation Disorders; Blood Platelets; Disease Models, Animal; Disseminated Intravascular Coagulation; Fibrin; Histone Deacetylase Inhibitors; Hydroxamic Acids; Male; Mice; Mice, Inbred C57BL; Sepsis; Thrombelastography; Vorinostat

Highly sensitive methods for the assessment of clot structure can aid in our understanding of coagulation disorders and their risk factors. Rapid and simple clot diagnostic systems are also needed for directing treatment in a broad spectrum of cardiovascular diseases. Here we demonstrate a method for micro-elastometry, named resonant acoustic spectroscopy with optical vibrometry (RASOV), which measures the clot elastic modulus (CEM) from the intrinsic resonant frequency of a clot inside a microwell. We observed a high correlation between the CEM of human blood measured by RASOV and a commercial thromboelastograph (TEG), (R = 0.966). Unlike TEG, RASOV requires only 150 μL of sample and offers improved repeatability. Since CEM is known to primarily depend upon fibrin content and network structure, we investigated the CEM of purified clots formed with varying amounts of fibrinogen and thrombin. We found that RASOV was sensitive to changes of fibrinogen content (0.5-6 mg/mL), as well as to the amount of fibrinogen converted to fibrin during clot formation. We then simulated plasma hypercoagulability via hyperfibrinogenemia by spiking whole blood to 150 and 200% of normal fibrinogen levels, and subsequently found that RASOV could detect hyperfibrinogenemia-induced changes in CEM and distinguish these conditions from normal blood.

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Elastic Modulus; Fibrin; Fibrinogen; Humans; Sensitivity and Specificity

The automated laboratory analyzer COAGTRON-350 (Trinity Biotech) is used for routine and specific coagulation testing for the detection of fibrin formation utilizing either mechanical principles (ball method) or photo-optical principles, chromogenic kinetic enzyme analysis, and immune-turbidimetric detection systems in one benchtop unit. In this study, we demonstrated and established a parameter for the measurement of factor XIII (FXIII) activity using Berichrom FXIII reagent and the COAGTRON-350 analyzer. The usual protocol used for this reagent, based on the handling method, was slightly modified for this device. The analysis showed that fundamental study for the measurement of FXIII activity under our condition setting was favorable in terms of reproducibility, linearity, and correlation with another assays. Since FXIII is the key enzyme that plays important roles in hemostasis by stabilizing fibrin formation, the measurement of FXIII is essential for the diagnosis of bleeding disorders. Therefore, FXIII activity assessment as well as a routine coagulation testing can be conducted simultaneously with one instrument, which is useful in coagulopathy assessment.

Topics: Automation, Laboratory; Biomarkers; Blood Coagulation Disorders; Blood Coagulation Tests; Factor XIII; Fibrin; Humans; Indicators and Reagents; Nephelometry and Turbidimetry; Sensitivity and Specificity

Impaired fibrin clot lysis is a key abnormality in diabetes and complement C3 is one protein identified in blood clots. This work investigates the mechanistic pathways linking C3 and hypofibrinolysis in diabetes using ex vivo/in vitro studies.. Fibrinolysis and C3 plasma levels were determined in type 1 diabetic patients and healthy controls, and the effects of glycaemia investigated. C3 incorporation into fibrin clots and modulation of fibrinolysis were analysed by ELISA, immunoblotting, turbidimetric assays and electron and confocal microscopy.. Clot lysis time was longer in diabetic children than in controls (599 ± 18 and 516 ± 12 s respectively; p < 0.01), C3 levels were higher in diabetic children (0.55 ± 0.02 and 0.43 ± 0.02 g/l respectively; p < 0.01) and both were affected by improving glycaemia. An interaction between C3 and fibrin was confirmed by the presence of lower protein levels in sera compared with corresponding plasma and C3 detection in plasma clots by immunoblot. In a purified system, C3 was associated with thinner fibrin fibres and more prolongation of lysis time of clots made from fibrinogen from diabetic participants compared with controls (244 ± 64 and 92 ± 23 s respectively; p < 0.05). Confocal microscopy showed higher C3 incorporation into diabetic clots compared with controls, and fully formed clot lysis was prolonged by 764 ± 76 and 428 ± 105 s respectively (p < 0.05). Differences in lysis, comparing diabetes and controls, were not related to altered plasmin generation or C3-fibrinogen binding assessed by plasmon resonance.. C3 incorporation into clots from diabetic fibrinogen is enhanced and adversely affects fibrinolysis. This may be one novel mechanism for compromised clot lysis in diabetes, potentially offering a new therapeutic target.

Topics: Adolescent; Adult; Blood Coagulation Disorders; Blood Coagulation Tests; Case-Control Studies; Complement C3; Diabetes Mellitus, Type 1; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Male

Sepsis induces hypercoagulability, hypofibrinolysis, microthrombosis, and endothelial dysfunction leading to multiple organ failure. However, not all studies reported benefit from anticoagulation for patients with severe sepsis, and time courses of coagulation abnormalities in septic shock are poorly documented. Therefore, the aim of this prospective observational cohort study was to describe the coagulation profile of patients with septic shock and to determine whether alterations of the profile are associated with hospital mortality.. Thirty-nine patients with septic shock on ICU admission were prospectively included in the study. From admission to day 7, analytical coagulation tests, thrombin generation (TG) assays, and thromboelastometric analyses were performed and tested for association with survival.. Patients with septic shock presented on admission prolongation of prothrombin time, activated partial thromboplastin time (aPTT), increased consumption of most procoagulant factors as well as both delay and deficit in TG, all compatible with a hypocoagulable state compared with reference values (P < 0.001). Time courses revealed a persistent hypocoagulability profile in non-survivors as compared with survivors. From multiple logistic regression, prolonged aPTT (P = 0.007) and persistence of TG deficit (P = 0.024) on day 3 were strong predictors of mortality, independently from disease severity scores, disseminated intravascular coagulation score, and standard coagulation tests on admission.. Patients with septic shock present with hypocoagulability at the time of ICU admission. Persistence of hypocoagulability assessed by prolonged aPTT and unresolving deficit in TG on day 3 after onset of septic shock is associated with greater hospital mortality.

Topics: Aged; Anticoagulants; Antithrombin III; Blood Coagulation Disorders; Blood Coagulation Factors; Female; Fibrin; Hospital Mortality; Humans; Intensive Care Units; Logistic Models; Longitudinal Studies; Male; Middle Aged; Partial Thromboplastin Time; Prospective Studies; Protein C; Prothrombin Time; Shock, Septic; Thrombin

To determine whether dogs with ascites secondary to right-sided congestive heart failure (CHF) have bleeding disorders associated with hypofibrinogenemia and discordant plasma fibrin-fibrinogen degradation products (FDPs) and D-dimer assay results (ie, a circulating concentration of FDPs higher than the reference range and a circulating concentration of D-dimer within the reference range).. Retrospective case-control study.. 80 client-owned dogs.. Dogs with ascites secondary to right-sided CHF (group 1; n = 20), unhealthy dogs without cardiac disease (group 2; 40), and dogs with left-sided CHF (group 3; 20) were included in the study. Urine bile acids-to-creatinine concentration ratios were calculated as a marker of liver function. Differences among groups regarding coagulation profile analysis results and prevalence of discordant FDPs and D-dimer assay results were determined.. No significant differences were detected among the 3 groups regarding urine bile acids-to-creatinine concentration ratios. Plasma fibrinogen concentration was significantly lower for group 1 versus groups 2 or 3. Prevalence of discordant FDPs and D-dimer assay results was significantly higher for group 1 versus groups 2 or 3. Eighteen group 1 dogs had discordant FDPs and D-dimer assay results. Ten of these dogs had concurrent hypofibrinogenemia, 2 of which had clinical signs of bleeding. Only 10 dogs in groups 2 or 3 had discordant FDPs and D-dimer assay results; none of these dogs had hypofibrinogenemia or clinical signs of bleeding.. Dogs with right-sided CHF and ascites may be at increased risk for primary hyperfibrinogenolysis (ie, hypofibrinogenemia and discordant FDPs and D-dimer assay results).

Topics: Animals; Ascites; Biomarkers; Blood Coagulation Disorders; Cardiovascular Agents; Case-Control Studies; Dog Diseases; Dogs; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Heart Failure; Male; Partial Thromboplastin Time; Prothrombin Time; Retrospective Studies

The goal of research is learning the change dynamic of "mature" fibrin in ridneys parenchyma in treatment of experimental bilious peritonitis with sodium hypochlorite. The work was made on 31 mongrel dogs, which were divided into two groups: control and experimental. It was revealed on with 24-hours experimental bilious peritonitis the presence of hyaline cylinders in the lumen of glomerular capillaries, which give a positive reaction to the "mature" fibrin. On the 3rd day of treatment with sodium hypochlorite in kidneys was revealed "mature" fibrin mostly extravascular localization with the significant decrease both the average size of "mature" fibrin and its volume fraction, which completely disappeared. what was the evidence of the arresting of hemocoagulation disorders under the influence of sodium hypochlorite.

Topics: Animals; Blood Coagulation Disorders; Disease Models, Animal; Dogs; Fibrin; Kidney Glomerulus; Male; Oxidants; Peritonitis; Sodium Hypochlorite

Patients subjected to haemodilution during surgery are at increased risk of bleeding. We hypothesised that, in the acquired dilutional coagulopathy, insufficient haemostasis is due to either insufficient thrombin generation or insufficient fibrin clot formation. In tissue factor-activated plasmas from patients with coagulation deficiency, we measured time curves of thrombin generation and fibrin clot formation (thromboelastography). Investigated were in study A: 10 patients treated with vitamin K antagonist and five healthy subjects; in study B: 30 patients undergoing cardiopulmonary bypass (CPB) surgery and infused with on average 2,000 ml crystalloids and colloids (no major bleeding); in study C: 58 patients undergoing major general surgery, and transfused with >5,000 ml crystalloids, colloids and red cell concentrates, who experienced major bleeding and were post-transfused with fresh frozen plasma. The treatment with vitamin K antagonist led to a progressive reduction in thrombin generation but not fibrin clot formation. In CPB patients, plasma factor levels post-surgery were 53-60% of normal. This was accompanied by moderate reduction in both haemostatic processes. In plasmas from patients undergoing major surgery, factor levels were 38-41% of normal, and these levels increased after plasma transfusion. Taking preset thresholds for normal thrombin generation and fibrin clot formation, at least one of these processes was low in 88-93% of the patients with (persistent) bleeding, but only in 40-53% of the patients without bleeding. In conclusion, the ability of thrombin generation and fibrin clot formation is independently reduced in acquired dilutional coagulopathy, while minimal levels of both are required for adequate haemostasis.

Topics: Aged; Blood Coagulation; Blood Coagulation Disorders; Blood Loss, Surgical; Blood Transfusion; Crystalloid Solutions; Female; Fibrin; Hemodilution; Hemorrhage; Hemostasis; Humans; Isotonic Solutions; Kinetics; Male; Middle Aged; Perioperative Care; Postoperative Hemorrhage; Thrombin; Vitamin K

Ethanol intoxication is a common contributor to traumatic injury. It is unknown whether ethanol consumption contributes to the coagulation differences seen between men and women after trauma. Our aim was to examine the combined effect of ethanol intoxication and gender on coagulation.. Fifty-eight healthy subjects participated and chose to enter into a control group (CG; n = 20; 10 men and 10 women) or drinking group (DG; n = 38; 20 men and 18 women). Venous blood samples for thrombelastography, plasminogen activator inhibitor, thrombin-antithrombin complex, and tissue plasminogen activator were drawn at the beginning of the study. Subjects then interacted in a social atmosphere for at least 2 hours, eating and consuming alcoholic (DG) or nonalcoholic (CG) beverages. After 2 hours, blood alcohol level was determined and blood was drawn for a second set of coagulation studies.. Demographics were similar between groups except for age (36.7 years CG vs. 29.9 years DG; p = 0.009). All baseline thrombelastography measurements were similar between the CG and DG. Blood alcohol levels in the DG were similar between genders at the end of study. At the end of study, a decreased rate of fibrin formation, decreased clot strength, and a decreased rate of fibrin cross-linking was seen in men but not in women. Fibrinolysis was inhibited in drinkers compared with controls.. Consumption of commonly ingested quantities of alcohol correlated with the development of a hypocoagulable state in men but had no effect on coagulation status in women. This phenomenon may contribute to differences in post-trauma coagulation status previously noted between genders.

Topics: Adult; Alcoholic Intoxication; Antithrombin III; Blood Coagulation Disorders; Case-Control Studies; Ethanol; Female; Fibrin; Fibrinolysis; Humans; Male; Oregon; Peptide Hydrolases; Plasminogen Inactivators; Prospective Studies; Sex Characteristics; Statistics, Nonparametric; Thrombelastography; Tissue Plasminogen Activator; Wounds and Injuries

Recombinant factor VIIa (rFVIIa) has been successfully used in various clinical conditions to treat severe coagulopathy, but its efficacy may be affected by the underlying conditions. We therefore investigated the efficacy of rFVIIa treatment under conditions of hypofibrinogenaemia in a pig model of blunt liver injury.. Severe haemodilution was instigated in four groups of seven anaesthetized pigs. Before inflicting liver injury, animals were assigned to receive either 70 mg kg(-1) fibrinogen (fibrinogen group) or placebo (control group). Thirty seconds after injury, rFVIIa (180 µg kg(-1)) (rFVIIa and fibrinogen+rFVIIa groups) or vehicle (control and fibrinogen groups) was administered. Haemodynamic variables, coagulation parameters, and blood loss were monitored for 2 h. Histology was examined to evaluate the presence of thrombi and the consistency of liver injury.. At the end of the observation period, total blood loss [median (range)] decreased in all intervention groups [fibrinogen: 1275 (1221-1439) ml, P=0.036; rFVIIa: 966 (923-1136) ml, P=0.008; fibrinogen+rFVIIa: 678 (475-756) ml, P=0.008] when compared with control animals [blood loss: 1752 (1735-2221) ml]. The mortality rate in the control group was 100%, whereas only 42% of fibrinogen-substituted animals died (P=0.023). All animals treated with rFVIIa or fibrinogen+rFVIIa (P<0.001) survived and no signs of thromboembolism were observed.. rFVIIa under conditions of hypofibrinogenaemia exhibited a positive impact on coagulation parameters and a reduction in blood loss. These effects were significantly improved after prior substitution with fibrinogen.

Topics: Animals; Blood Coagulation Disorders; Disease Models, Animal; Drug Evaluation, Preclinical; Factor VIIa; Fibrin; Fibrinogen; Hemodilution; Hemodynamics; Hemorrhage; Hemostatics; Liver; Male; Pilot Projects; Prothrombin Time; Recombinant Proteins; Sus scrofa; Thrombelastography; Wounds, Nonpenetrating

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

Although coagulopathy is known to be the major contributor to a poor outcome of traumatic brain injury (TBI), the mechanisms that trigger coagulation abnormalities have not been studied in detail. We undertook a prospective observational study at a neurosurgical ICU (NICU) in a university hospital. We examined 11 patients with severe isolated TBI, at admittance to the hospital and during the next 3 days. We collected cerebrovenous blood samples from a jugular bulb catheter, arterial blood, and cerebrospinal fluid (CSF) samples. We measured concentrations of thrombin-antithrombin complex (TAT), fibrin D-dimer (DD), prothrombin fragment 1 + 2 (F1 + 2), interleukin-6 (IL-6), and complement complex (C5b-9). All patients had some degree of consumption coagulopathy at the study start and a tendency to thrombocytopenia during the next few days. Levels of DD (3.6 +/- 2.7 mg/L), TAT (86 +/- 72 microg/L) and F1 + 2 (5.9 +/- 6.8 nmol/L) were significantly increased shortly after the trauma compared to reference values, with considerable transcranial gradients for TAT (49 microg/L) and F1 + 2 (3.2 nmol/L). Compared to controls, IL-6 levels were increased more than a hundredfold in both blood (283 +/- 192 ng/L) and CSF (424 +/- 355 ng/L) samples, with a transcranial gradient at the study start (107 ng/L). C5b-9 levels were moderately increased in blood samples, 270 +/- 114 microg/L, versus controls, 184 +/- 39 (p < 0.05). We conclude that activation of the coagulation system takes place during the passage of blood through the damaged brain, and is already evident hours after the trauma. IL-6 and activation of the complement system (C5b-9) co-vary with hemostatic parameters in TBI patients.

Topics: Accidents; Adult; Antithrombins; Biomarkers; Blood Coagulation Disorders; Blood Coagulation Tests; Brain Injuries; Complement Membrane Attack Complex; Female; Fibrin; Glasgow Coma Scale; Humans; Inflammation; Interleukin-6; International Normalized Ratio; Male; Middle Aged; Peptide Fragments; Prospective Studies; Prothrombin; Thrombin

Topics: Acyclovir; Antiviral Agents; Blood Coagulation Disorders; Female; Fibrin; Herpes Zoster; Humans; Hyperlipidemias; Infarction, Middle Cerebral Artery; Lymphangiectasis, Intestinal; Middle Aged; Paraproteinemias; Protein S; Protein-Losing Enteropathies; Urinary Tract Infections

Coagulopathy and thrombocytopenia often occur in critically ill patients, and disseminated intravascular coagulation (DIC) can lead to multiple organ dysfunction and a poor outcome. However, the relation between coagulopathy and systemic inflammatory response has not been thoroughly clarified. Thus, we evaluated coagulative activity, organ dysfunction, and systemic inflammatory response syndrome (SIRS) in critically ill patients with thrombocytopenia and examined the balance between coagulopathy and systemic inflammation.. Two hundred seventy-three patients, who were admitted to 13 critical care centers in Japan and fulfilled the criteria of platelet count of less than 150*10(9)/L, were included. Coagulative variables (platelet count, fibrin/fibrinogen degradation products, and DIC scores), organ dysfunction index (Sequential Organ Failure Assessment [SOFA] score), and SIRS score in each patient were evaluated for 4 consecutive days after fulfilling the above entry criteria. The effect of SIRS on coagulopathy and organ dysfunction was evaluated in these patients.. Both the maximum SIRS score and entry SIRS score had significant relation to the maximum SOFA score during the observation period. Coagulation disorders indicated by the minimum platelet count, maximum DIC scores, and positivity for DIC worsened gradually with increases in SIRS scores. Both the minimum platelet count and maximum DIC scores were significantly correlated with the maximum SOFA score, indicating that a relation exists between coagulopathy and organ dysfunction.. In critically ill patients with thrombocytopenia, coagulopathy and organ dysfunction progress with significant mutual correlation, depending on the increase in SIRS scores. The SIRS-associated coagulopathy may play a critical role in inducing organ dysfunction after severe insult.

Topics: Adult; Aged; Analysis of Variance; Blood Coagulation Disorders; Critical Illness; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Multiple Organ Failure; Platelet Count; Sepsis; Systemic Inflammatory Response Syndrome; Thrombocytopenia

The prothrombin gene mutation G20210A is a common risk factor for thrombosis and has been reported to cause APC resistance. However, the inhibition of thrombin formation by APC not only limits fibrin formation but also stimulates fibrinolysis by reducing TAFI activation. We evaluated the influence of prothrombin G20210A mutation on the anticoagulant and fibrinolytic activities of APC (1 microg/ml). Thirty-two heterozygous carriers and 32 non carriers were studied. APC anticoagulant activity was assessed by aPTT prolongation whereas APC fibrinolytic activity was determined by a microplate clot lysis assay. APC-induced aPTT prolongation was markedly less pronounced in carriers than in non carriers. On the contrary, fibrinolysis time was shortened by APC to a comparable extent in both groups. Accordingly, prothrombin levels were strongly correlated with APC-induced aPTT prolongation but not with APC-induced shortening of lysis time. The addition of purified prothrombin to normal plasma (final concentration 150%) caused APC resistance in the clotting assay over the whole range of tested APC concentrations (0.125-1.5 microg/ml). In the fibrinolytic assay, instead, prothrombin supplementation made the sample resistant to low but not to high concentrations of APC (>0.5 microg/ml). Thrombin and TAFIa determination in the presence of 1 microg/ml APC revealed that hyperprothrombinemia, although capable of enhancing thrombin generation, was unable to induce detectable TAFIa formation. It is suggested that APC resistance caused by hyperprothrombinaemia does not translate in impaired fibrinolysis, at least in the presence of high APC levels, because the increase in thrombin formation is insufficient to activate the amount of TAFI required to inhibit plasminogen conversion. These data might help to better understand the relationship between thrombin formation and fibrinolysis down-regulation.

Topics: Activated Protein C Resistance; Anticoagulants; Blood Coagulation Disorders; Carboxypeptidase B2; Down-Regulation; Fibrin; Fibrinolysis; Genetic Predisposition to Disease; Heterozygote; Humans; Mutation; Prothrombin; Prothrombin Time; Thrombin

Two siblings with hypofibrinogenemia have lifelong trauma-related bleeding. Recently, the brother experienced recurrent thrombosis after cryoprecipitate infusions following surgery. The sister had 6 miscarriages. Plasma clots in each were resistant to compression and fibrinolysis and were soluble in 5 M urea. Examination by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed only the presence of crosslinked gamma-gamma fibrin chain dimers without high polymers of alpha n. Fibrin clots contained an abnormal 35-kDa constituent recognized by an antibody to the mature fibrinogen Aalpha-chain residues 241-476 but not by antibodies to Aalpha219-348 or Aalpha349-406. DNA analysis revealed a heterozygous CAA-->TAA mutation at the codon for amino acid 328 of the Aalpha gene in these siblings and 2 asymptomatic family members. The Gln328stop mutation (fibrinogen Keokuk) predicted a 46% truncation and the production of a 35-kDa Aalpha chain. Analysis of purified fibrinogen revealed expression of the abnormal Aalpha chain in 4 family members but found no normal fibrinogen in the 2 hypofibrinogenemic patients. This paradox was resolved when they and their asymptomatic mother were found to be heterozygous for a second Aalpha mutation, a GT-->TT splice site mutation in intron 4 (IVS4 + 1 G> T). However, compound heterozygosity for both mutations was required for the expression of severe hypodysfibrinogenemia and for clinical symptoms.

Topics: Blood Coagulation Disorders; Dimerization; Europe; Family; Female; Fibrin; Fibrinogen; Fibrinogens, Abnormal; Genetic Carrier Screening; Hemostasis; Humans; Male; Mutation; Pedigree; Point Mutation; Sequence Deletion; United States

This study investigates intravascular coagulation and thrombotic obstruction in the splanchnic vasculature after intestinal ischemia in relation to epithelial integrity and function.. Intestinal ischemia was induced in rats by superior mesenteric artery occlusion for 20 or 40 minutes. Intestinal injury was assessed by histologic analysis, biochemical markers, and functional studies. During reperfusion, portal and systemic blood samples were collected to analyze activation of coagulation and fibrinolysis.. Superior mesenteric artery occlusion resulted in mild to moderate intestinal injury. Twenty and 40 minutes of ischemia and 3 hours of reperfusion resulted in local intestinal thrombin generation and conversion of fibrinogen to fibrin, reflected by 3- and 4-fold increases in thrombin-antithrombin complex levels and a 3-fold elevation of fibrin degradation products (D-dimer), respectively. During reperfusion, after a short-lasting initial activation of local fibrinolysis, plasminogen activator activity was suppressed, as indicated by an approximately 4-fold increase in portal plasma levels of the plasminogen activator inhibitor. D-dimer levels showed that activation of coagulation and depression of fibrinolysis resulted in fibrin formation, which was confirmed to be intravascular fibrin deposition by histologic examination.. Intestinal ischemia-reperfusion results in local intravascular coagulation and fibrin deposition.

Topics: Animals; Blood Coagulation; Blood Coagulation Disorders; Fibrin; Fibrinolysis; Glucose; Intestinal Absorption; Intestines; Male; Microcirculation; Rats; Rats, Wistar; Reperfusion Injury; Splanchnic Circulation; Thrombosis; Water

To investigate whether there are any basic abnormalities of coagulation and fibrinolysis in muscular dystrophy, we measured serum levels of the MM isozyme of creatine kinase (CK-MM), fibrin and fibrinogen degradation products (FDP), plasma levels of fibrinogen, antithrombin (AT), and D-dimer in 36 patients with Duchenne muscular dystrophy (DMD), 11 with Becker muscular dystrophy (BMD), 5 with Fukuyama congenital muscular dystrophy (FCMD), 5 with myotonic dystrophy (MyD), and 5 with spinal muscular atrophy (SMA) type 2. FDP levels were elevated in the patients with DMD, BMD, and FCMD (1.0 to 84.9 microg/ml), but not in the patients with MyD and SMA type 2. In DMD, BMD, and FCMD, FDP levels significantly correlated with CK-MM, but not with age, fibrinogen, AT, D-dimer, and type of dystrophy (multiple regression analysis; r(2) = 0.814, P < 0.0001). These findings suggested that enhanced coagulation and fibrinolysis are associated with muscle degeneration in patients with DMD, BMD, and FCMD.

Topics: Adolescent; Adult; Blood Coagulation Disorders; Child; Creatine Kinase; Creatine Kinase, MM Form; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Heart Failure; Humans; Isoenzymes; Male; Muscular Dystrophy, Duchenne; Regression Analysis; Spinal Muscular Atrophies of Childhood

A 35-year-old woman experienced symptomatic calf pain while taking a combination of fenfluramine and phentermine. All symptoms resolved when the medications were stopped, but pain returned when fenfluramine was restarted. Laboratory evaluation revealed mild elevations of aspartate aminotransferase and lactate dehydrogenase and a remarkably shortened prothrombin time (6.3 seconds). Additional studies revealed that the clots were composed of very thin fibrin fibers. All laboratory abnormalities, including the abnormal fibrin structure, completely resolved when fenfluramin was stopped. Direct addition of fenfluramine or phentermine to normal plasma did not alter either coagulation kinetics or fibrin structure, supporting the concept that the induced changes may have originated at the hepatic level. Clots composed of thin fibers are much more resistant to fibrinolysis, and could potentially put such patients at risk for thrombotic complications. This is the first report of clotting abnormalities associated with fenfluramine use. Subsequent to its use in this patient, fenfluramine was removed from clinical use due to reports of acquired valvular heart disease.

Topics: Adult; Blood Coagulation Disorders; Female; Fenfluramine; Fibrin; Humans; Prothrombin Time; Time Factors

Topics: Blood Coagulation Disorders; Breast Neoplasms; Cell Hypoxia; Female; Fibrin; Fibrinogen; Humans; Middle Aged; Neoplasm Metastasis

Topics: Acute Disease; Animals; Antithrombin III; Blood Coagulation Disorders; Complement Activation; Cytokines; Disseminated Intravascular Coagulation; Endotoxemia; Fibrin; Gene Expression Regulation; Hemorrhage; Humans; Lipoproteins; Lung Injury; Primates; Protein C; Reactive Oxygen Species; Respiratory Distress Syndrome; Sepsis; Thromboplastin; Transcription, Genetic; Tumor Necrosis Factor-alpha

Hemorrhagic shock due to major trauma predisposes to the development of acute respiratory distress syndrome. Because lung fibrin deposition is one of the hallmarks of this syndrome, we hypothesized that resuscitated shock might predispose to the development of a net procoagulant state in the lung. A rodent model of shock/resuscitation followed by low-dose intratracheal lipopolysaccharide (LPS), a clinically relevant "two-hit" model, was used to test this hypothesis. Resuscitated shock primed the lungs for an increased tissue factor and plasminogen activator (PA) inhibitor-1 gene expression in response to LPS, while the fibrinolytic PA was reduced. These alterations were recapitulated in isolated alveolar macrophages, suggesting their role in the process. LPS-induced tumor necrosis factor (TNF) was also augmented in animals after antecedent shock/resuscitation, and studies using anti-TNF antibodies revealed that TNF expression was critical to the induction of the procoagulant molecules and the reduction in PA. By contrast, TNF did not appear to play an important role in neutrophil sequestration in this model, inasmuch as anti-TNF had no effect on lung neutrophil accumulation or chemokine expression. However, treatment prevented albumin leak by preventing alveolar neutrophil activation. The inclusion of the antioxidant N-acetyl-cysteine in the resuscitation fluid resulted in prevention of both the development of the net procoagulant state and lung neutrophil sequestration, suggesting a role for upstream oxidant effects in the priming process. These studies provide a cellular and molecular basis for lung fibrin deposition after resuscitated shock and demonstrate a divergence of pathways responsible for fibrin generation and neutrophil accumulation.

Topics: Acetylcysteine; Animals; Antioxidants; Blood Coagulation Disorders; Bronchoalveolar Lavage Fluid; Capillary Leak Syndrome; Disseminated Intravascular Coagulation; Fibrin; Fibrinolysis; Gene Expression Regulation; Lipopolysaccharides; Lipoproteins; Macrophage Activation; Macrophages, Alveolar; Male; Models, Biological; Neutrophils; NF-kappa B; Oxidative Stress; Plasminogen Activator Inhibitor 1; Pulmonary Alveoli; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Respiratory Distress Syndrome; Shock, Hemorrhagic; Shock, Septic; Thromboplastin; Transcription, Genetic; Tumor Necrosis Factor-alpha

Congenital homozygous dysfibrinogenemia was diagnosed in a man with a history of 2 thrombotic strokes before age 30. His hemostatic profile was characterized by a dramatically prolonged plasma thrombin clotting time, and no clotting was observed with reptilase. Complete clotting of the abnormal fibrinogen occurred after a prolonged incubation of plasma with thrombin. The release of fibrinopeptides A and B by thrombin and of fibrinopeptide A by reptilase were both normal. Thrombin-induced fibrin polymerization was impaired, and no polymerization occurred with reptilase. The polymerization defect was characterized by a defective site "a," resulting in an absence of interaction between sites A and a, indicated by the lack of fragment D(1) (or fibrinogen) binding to normal fibrin monomers depleted in fibrinopeptide A only (Des-AA fm). By SDS-PAGE, the defect was detected on the gamma-chain and in its fragment D(1). The molecular defect determined by analysis of genomic DNA showed a single base change (A-->T) in exon VIII of the gamma-chain. The resulting change in the amino acid structure is gamma 330 aspartic acid (GAT) --> valine (GTT). It is concluded that the residue gamma-Asp(330) is essential for the normal functioning of the polymerization site a on the fibrinogen gamma-chain.

Topics: Adult; Afibrinogenemia; Amino Acid Substitution; Binding Sites; Blood Coagulation Disorders; Coagulation Protein Disorders; Electrophoresis, Polyacrylamide Gel; Fibrin; Fibrinogens, Abnormal; Fibrinolysin; Fibrinolytic Agents; Hemostatics; Homozygote; Humans; Male; Mutation; Protein Binding; Protein Subunits; Stroke; Thrombin; Thrombin Time; Thrombophilia; Thrombosis

In eleven of 15 investigated dogs suffering from autoimmune haemolytic anaemia an increased concentration of soluble fibrin (p < 0.001) and in all of these 15 dogs an increased concentration of fibrin(ogen) degradation products was observed. The increased turnover indicated by these markers of intravascular coagulation and hyperfibrinolysis was decompensated in approximately the half of the patients which was shown by a decrease of platelet count, activity of different coagulation factors as well as of the inhibitor antithrombin III. The consumption induced decrease of activity was especially related to prekallikrein and high molecular weight kininogen reflecting an activation mainly of the initial intrinsic system by the haemolytic anaemia and was also indicated by the activated partial thromboplastin time which was distinctly prolonged in some cases. The results of this study demonstrate the necessity of an anticoagulant therapy in dogs suffering from autoimmune haemolytic anaemia.

Topics: Anemia, Hemolytic, Autoimmune; Animals; Anticoagulants; Antithrombin III; Blood Coagulation Disorders; Blood Coagulation Factors; Dog Diseases; Dogs; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Kininogens; Male; Partial Thromboplastin Time; Prekallikrein

A template was devised for rapid analysis of the intervals, slopes and peak amplitude of the Sonoclot Signature.

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Platelets; Blood Viscosity; Cardiopulmonary Bypass; Elasticity; Equipment Design; Fibrin; Fibrinogen; Humans; Intraoperative Complications; Liver Transplantation; Monitoring, Intraoperative; Platelet Count; Postoperative Complications; Signal Processing, Computer-Assisted; Time Factors; Ultrasonics

Using urea-solubilized human fibrin monomer as an immunogen, we raised in mice a battery of monoclonal antibodies that reacted with the immunogen but not with urea-treated or native fibrinogen. Although they all failed to react with acid-solubilized fibrin monomer (acid-FM) alone, an antibody designated as IF-43 was found to recognize acid-FM, which was bound with fibrinogen or its derivatives to form a 1:2 complex of soluble fibrin. The epitope for this antibody, thus, appears to be exposed most probably by conformation changes induced in the acid-FM molecule upon formation of the complex. Because IF-43 was able to recognize fibrin-derived plasmic fragment E treated with urea but not the thrombin- and urea-treated amino-terminal disulfide knot of fibrinogen, the presence of the A alpha (52-78) residue segment seems to be prerequiste for the epitope expression. The antibody was found to react with soluble fibrin monomer spiked to normal plasma dose-dependently up to 200 micrograms/mL. By an aggregation assay using latex beads coated with IF-43, we found that concentrations of soluble fibrin monomer in plasma derived from patients with thrombotic diseases were mostly elevated, but not necessarily correlated with those of the D-dimer, reflecting another aspects of the disease. Furthermore, the soluble fibrin monomer in plasma derived from patients with thrombotic diseases was found to be depleted solely of the A peptides, but not the B peptides, based on its subunit polypeptide compositions lacking the beta-chain on immunoblotting.

Topics: Animals; Antibodies, Monoclonal; Antibody Specificity; Blood Coagulation Disorders; Blotting, Western; Epitopes; Fibrin; Fibrinogen; Humans; Latex Fixation Tests; Macromolecular Substances; Mice; Molecular Weight; Oxidation-Reduction; Protein Conformation; Solubility

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Endothelium, Vascular; Fibrin; Fibrinogen; Humans; Monitoring, Intraoperative; Monitoring, Physiologic; Thrombelastography

After the formation of a platelet-plug, generation of fibrin is necessary for its stabilization. Both congenital and acquired deficiencies of clotting factors occur, leading to retarded formation of fibrin. In congenital disorders, preoperative correction is possible and necessary. In acquired deficiencies, the type and feasibility of correction depends on the cause of the deficiency.

Topics: Blood Coagulation Disorders; Fibrin; Hemophilia A; Hemophilia B; Hemostasis, Surgical; Humans; Vitamin K Deficiency; von Willebrand Diseases

Experimentally induced infection with high doses of Mycoplasma pulmonis results in acute pneumonia characterized by severe pulmonary hemorrhage, edema, and, often, death in C3H/HeN mice. To determine whether specific disease manifestations were associated with coagulopathy, we measured serum fibrin, fibrinogen degradation products, and plasma fibrinogen concentrations in C3H/HeN mice infected with high doses of a virulent strain of M. pulmonis. We also examined the lungs and other tissues from infected mice for the presence of intravascular fibrin clots and other lesions. Increased concentrations of fibrinogen degradation products indicated that coagulopathy occurs in acute M. pulmonis infection; however, intravascular fibrin clots were not present. Rather than decreasing, as might be expected during a consumptive coagulopathy, fibrinogen concentrations increased. The hyperfibrinogenemia probably is associated with an acute phase response to M. pulmonis infection.

Topics: Animals; Blood Coagulation Disorders; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Lung; Mice; Mice, Inbred C3H; Mycoplasma Infections; Rodent Diseases

Fibrinogen, fibrin monomer, and D dimer were analyzed in 41 cases of chronic subdural hematoma (SDH) to characterize local rebleeding, coagulation, and fibrinolysis using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. Chronic SDH's were divided into five groups according to their appearance on computerized tomography: high-density, isodensity, low-density, mixed-density, and layering types. The concentration of fibrinogen, which indicates rebleeding, was higher in the mixed-density (15.7 +/- 3.4 mg/dl (mean +/- standard error of the mean)) and layering (15.7 +/- 2.6 mg/dl) types of hematoma, and lower in the low-density hematomas (1.4 +/- 0.6 mg/dl) compared with the isodense hematomas (6.9 +/- 1.1 mg/dl). Fibrin monomer, which indicates coagulative activity, had a distribution similar to that of fibrinogen: 87 +/- 22, 18 +/- 8, 175 +/- 40, and 177 +/- 23 micrograms/ml in isodense, low and mixed-density, and layering types of hematomas, respectively. The D dimer, which indicates fibrinolytic activity, was higher in the layering hematoma type (2032 +/- 384 micrograms/ml), and lower in low-density hematomas (301 +/- 164 micrograms/ml) compared to isodense (1310 +/- 256 micrograms/ml) and mixed-density (1039 +/- 207 micrograms/ml) types of hematomas. These observations suggest the following characterization of each type of chronic SDH. The layering type is active, with a high tendency to rebleed and for hyperfibrinolytic activity. The mixed-density type has a high tendency to rebleed with lower hyperfibrinolytic activity than the layering type. The low-density hematoma is stable with a low tendency to rebleed and to fibrinolytic activity.

Topics: Adult; Aged; Aged, 80 and over; Blood Coagulation Disorders; Chronic Disease; Electrophoresis, Polyacrylamide Gel; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Hematoma, Subdural; Humans; Immunoblotting; Male; Middle Aged; Recurrence; Sodium Dodecyl Sulfate

To test the hypothesis that hypercoagulability after brain trauma was related to the severity of injury and also to outcome, new coagulation markers were used in 20 patients with isolated brain trauma. In addition to routine coagulation tests, soluble fibrin (SF), D-dimer, and antithrombin (AT) levels were assessed. Thirteen of 20 patients had a Glasgow coma score (GCS) of < or = 7 on admission and severe disability (SD) or worse on the Glasgow outcome scale (GOS). Eight patients had a very bad outcome [GOS = dead (D) or vegetative (V)]. All patients had increased SF levels (ref. < 15 nmol/L) at admission. Six patients with SF < 50 nmol/L had a good outcome with moderate disability (MD) or better. Patients with increasingly higher SF levels had a worse outcome: Three of five patients with SF 50 to 150 nmol/L were severely disabled (SD) or worse; four of six patients with SF > 150 nmol/L remained vegetative (V) or died (D). Four of the six patients with the highest D-dimer levels at admission remained vegetative (V) or died (D). Six of 13 patients with a significant drop in AT levels had a bad outcome (D or V) whereas only two of seven patients without AT consumption did poorly. Routine coagulation studies were often pathologic, i.e., reduced platelet count, but there was no relation to outcome. Increased SF and D-dimer levels at admission followed by a secondary decrease in AT concentration and platelets seem to be good markers of the posttraumatic hypercoagulation often seen after brain injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Biomarkers; Blood Coagulation Disorders; Brain Injuries; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Partial Thromboplastin Time; Prognosis; Prothrombin Time; Severity of Illness Index; Solubility

In order to investigate the coagulation and fibrinolysis state in arterial peripheral thrombosis and thrombolysis, we studied 33 consecutive patients (mean age = 65, range: 28-88), 25 males and 8 females diagnosed of acute or subacute lower limb arterial thrombosis, treated with an intrathrombus infusion of rt-PA (0.1 mg/Kg/h) for three hours. Plasma levels of antithrombin III (AT-III), protein C (PC), plasminogen (Pg) and alpha 2-antiplasmin (AP), total and free protein S (PS), thrombin-antithrombin III complex (TAT), F1.2 fragment of prothrombin (F1.2), fibrinogen (Fg), soluble fibrin monomers (FM), tissue-plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), total fibrinogen/fibrin degradation products (TDP) and D dimer (DD) were determined prior to the therapeutic regime, at the end of the treatment, and 24 hours later. Levels of AT-III and protein C were somewhat low during the complete study. There was an increase in t-PA, TDP and D Dimer and a decrease of fibrinogen, alpha 2-antiplasmin and plasminogen at 3 hours. An elevation of TAT, fibrin monomers and F1.2 levels was found at three hours. A positive correlation between TAT and F1.2 was observed (r = 0.57, p < 0.05). There was also a positive correlation between soluble fibrin and TAT (r = 0.59, p < 0.05) and with F1.2 (r = 0.56. p < 0.05). These latter facts reflect an hypercoagulable situation induced during loco-regional thrombolytic therapy.

Topics: Adult; Aged; Aged, 80 and over; Antithrombin III; Blood Coagulation Disorders; Blood Proteins; Female; Fibrin; Fibrinolysis; Humans; Injections, Intra-Arterial; Male; Middle Aged; Peptide Fragments; Peptide Hydrolases; Plasminogen Activators; Prothrombin; Recombinant Proteins; Thrombolytic Therapy; Thrombosis

Snake bites in Hong Kong are most commonly due to Tr. albolabris (White-lipped pit viper, bamboo snake). We studied 21 cases of envenoming by Tr. albolabris prospectively in order to document the incidence and severity of associated coagulation abnormalities. Eighteen patients (86%) had increased blood concentrations of fibrin degradation products (FDP) ranging from 10-40 micrograms/l to greater than 200 micrograms/l (normal: less than 10 micrograms/l), the majority of whom also had detectable soluble fibrin monomers. Among these 21 patients, 10 had decreased blood concentrations of fibrinogen ranging from 0.3 kg/l to 1.9 g/l (normal: 2-4 gl/l). In 11 cases (52%), the euglobulin clot lysis time was shortened (less than 150 minutes) in association with elevated blood concentrations of FDP (n = 10) and decreased circulating fibrinogen levels (n = 8). Thrombocytopenia and/or prolongation of prothrombin time (PT), activated partial thromboplastin time (APTT) and/or thrombin time (TT) were present in 10 patients (28%). Increased blood concentrations of FDP and decreased circulating fibrinogen levels were present in most of these cases. Envenoming by Tr. albolabris is therefore frequently associated with a coagulopathy compatible with increased fibrin/fibrinogenolysis. Measurement of blood concentrations of FDP is the most sensitive test for detecting the coagulopathy. There is, however, little correlation between the patterns of clinical manifestations and coagulation abnormalities although more severe clinical features were usually associated with high circulating FDP levels. Only one patient developed systemic bleeding but no fatality was observed. The coagulation abnormalities are usually correctable by replacement therapy. Further studies are required to study the mechanisms of this coagulopathy and its relationship with venom antigenaemia.

Topics: Adult; Aged; Animals; Blood Coagulation Disorders; Blood Coagulation Tests; Crotalid Venoms; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Hong Kong; Humans; Male; Middle Aged; Prospective Studies; Serum Globulins; Snake Bites; Thrombocytopenia; Viperidae

The molecular defect in the abnormal fibrinogen Dusart (Paris V) that is associated with thrombophilia was determined by sequence analysis of genomic DNA that had been amplified using the polymerase chain reaction. The propositus was heterozygous for a single base change (C-->T) in the A alpha-chain gene, resulting in the amino acid substitution A alpha 554 Arg-->Cys. Restriction analysis of the amplified DNA derived from the family members showed that his father and his two sons were also heterozygous. Electron microscopic studies on fibrin formed from purified fibrinogen Dusart demonstrated fibers that were much thinner than in normal fibrin. In contrast to the previously observed defective binding of plasminogen, the binding of thrombospondin to immobilized fibrinogen Dusart was similar to that of normal fibrinogen. Immunoblot analysis of plasma fibrinogen demonstrated that a substantial part of the fibrinogen Dusart molecules were disulfide-linked to albumin. The plasma of the affected family members also contained fibrinogen-albumin complexes. Furthermore, small amounts of high molecular weight complexes containing fibrinogen were detected in all the heterozygous individuals. These data indicate that the molecular abnormality in fibrinogen Dusart (A alpha 554 Arg-->Cys) results in defective lateral association of the fibrin fibers and disulfide-linked complex formation with albumin, and is associated with a family history of recurrent thrombosis in the affected individuals.

Topics: Adult; Base Sequence; Blood Coagulation Disorders; Fibrin; Fibrinogen; Fibrinogens, Abnormal; Gene Amplification; Humans; Immunoblotting; Male; Microscopy, Electron; Molecular Sequence Data; Mutation; Platelet Membrane Glycoproteins; Protein Binding; Sequence Analysis, DNA; Structure-Activity Relationship; Sulfhydryl Compounds; Thrombosis; Thrombospondins

A 58-year-old man with multiple myeloma and paraproteinemia (IgG kappa) acquired cryoglobulinemia 2 years after the initial diagnosis of the disease. This cryoglobulin interfered specifically with fibrin aggregation. The patient's fibrinogen was functionally normal; however, clotting times (thrombin clotting time, reptilase clotting time) were prolonged in the untreated plasma and in the supernatant after removal of the cryoglobulins. Untreated patient's serum, and even more pronounced, the cryoprecipitate inhibited the association of fibrin monomers obtained from healthy controls. The inhibitory activity on fibrin aggregation diminished upon treatment-induced reduction of plasma protein levels.

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Cryoglobulinemia; Fibrin; Fibrinogen; Humans; Immunoglobulin kappa-Chains; Male; Middle Aged; Multiple Myeloma; Myeloma Proteins; Plasmapheresis; Polymers; Temperature

In 14 patients undergoing chronic hemodialysis, we investigated the safety and efficacy of the low molecular fragment (CY-216) in comparison to unfractionated heparin (UFH) in the prevention of clotting in the extracorporeal circuit (ECC). In this study, 168 hemodialysis sessions were undertaken with UFH in 2 bolus doses (5,437 +/- 1,477 SD IU) and 231 with CY-216 in a single bolus dose [initial dose 150 anti-Xa U Institut Choay (IC)/kg]. There were no clots in the bubble trap in any UFH sessions, and 14.8% had coagulated fibers in the dialyzer. Clotting in the bubble trap was observed in 2 CY-216 sessions (0.8%) and coagulated fibers in 22.6% of the sessions. At the end of the study, the mean dose of CY-216 was 250 anti-Xa UIC/kg but a dose of 350 anti-Xa UIC/kg was needed in the 2 patients treated by recombinant human erythropoietin. Anti-Xa levels at the end of the runs were higher (0.47 +/- 0.1 U/ml) in the CY-216 group than in the UFH group (0.28 +/- 0.1 U/ml). There was a correlation between anti-Xa levels and efficacy in the CY-216 group. An anti-Xa activity above 0.4 U/ml was needed in order to minimize thrombus formation. Antithrombin III-protease complexes (ATM) and D dimer fibrin derivatives (D dimer) were used as thrombotic markers but they were of little value for the detection of fibrin formation in the ECC. Our findings suggest that CY-216 administered as a single bolus dose seems to be of similar effectiveness to UFH.

Topics: Aged; Antithrombin III; Blood Coagulation; Blood Coagulation Disorders; Extracorporeal Circulation; Female; Fibrin; Heparin; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Renal Dialysis

An 81-year-old woman, who presented with sudden episodes of spontaneous bleeding, was found to have a specific inhibitor of factor XIII. Her fibrin clots had approximately 70% gamma-gamma and no alpha polymer formation, under conditions where normal fibrin was fully cross-linked; the patient's clots were soluble in urea or monochloroacetic acid. Factor XIII activity in her plasma was 24%, measured by the dansylcadaverine incorporation assay. When mixed with normal plasma, the patient's plasma inhibited fibrin cross-linking; however, in mixtures of patient and normal plasma, there was no inhibition of factor XIII activity when assayed by the incorporation of dansylcadaverine into casein. Thus, this inhibitor was active against fibrin cross-linking but not against ligation of small molecules to casein. Consequently, gel electrophoresis of reduced, sodium dodecyl sulfate-solubilized fibrin clots was a simple, quantitative method that was used to measure inhibitor activity. This inhibitor is unique and has been designated inhibitor New Haven. It was neutralized by anti-IgG and anti-kappa. It did not inhibit the activation of factor XIII but did inhibit fibrin cross-linking. There was complex formation between the inhibitor and activated factor XIII (A', A*) but not between A2 or fibrinogen. Only A', A* and the 56-Kd fragment bound to affinity columns made with this IgG. The inhibitor significantly decreased the binding of A', A* to fibrin clots. These data indicate that the epitope for this inhibitor is in a fibrin binding site. It is hidden in the zymogen and expressed on A' and A*, indicating that the conformational change occurring with the cleavage of the activation peptide is sufficient to expose the fibrin binding site.

Topics: Aged; Aged, 80 and over; Autoantibodies; Binding Sites; Blood Coagulation Disorders; Cadaverine; Epitopes; Factor XIII; Female; Fibrin; Humans; Immunoglobulin G; Transglutaminases

We describe a 50-year-old man with a severe acquired haemorrhagic syndrome. He had slightly prolonged clotting times using bovine thrombin, human thrombin and reptilase. His plasma contained a polyclonal IgG which interfered with the generation of fibrin monomers without inhibiting the aggregation of preformed monomers. The inhibitor delayed thrombin-induced fibrinopeptide A release. The IgG bound to insolubilized synthetic fibrinopeptide A (one binding site per molecule) and, with higher affinity, to fibrinogen (two binding sites per molecule). It did not bind to insolubilized fibrin monomers. The IgG did not impair the catalytic activity of thrombin toward a small synthetic substrate but inhibited the binding of thrombin to fibrinogen without binding to thrombin. The binding of the anti-fibrinopeptide A autoantibody to fibrinogen might have impaired thrombin-induced fibrinogen to fibrin conversion in vivo. This may have favoured the reported haemorrhagic syndrome which was associated with severe chronic renal insufficiency.

Topics: Autoantibodies; Binding Sites; Blood Coagulation Disorders; Fibrin; Fibrinogen; Fibrinopeptide A; Hemorrhage; Humans; Immunoglobulin G; Kidney Failure, Chronic; Male; Middle Aged; Thrombin

Immunohistochemical techniques were applied to rheumatoid synovium in order to detect components of coagulation and fibrinolysis pathways within these tissues. These techniques revealed an intact coagulation pathway and plasminogen activator inhibitor-2 associated with macrophage-like cells that were present throughout these tissues, especially in subsurface areas. Cell-associated thrombin generation appeared to account for conversion of abundant fibrinogen to fibrin. Occasional macrophage-like cells also stained for urokinase but tissue-type plasminogen activator and plasminogen activator inhibitor-1 were restricted to vascular endothelium. Intense synovial fibrin deposition (with the limited evidence for associated fibrinolysis) may contribute to local inflammation and explain certain clinical features of rheumatoid arthritis. These findings suggest novel treatment hypotheses for this disease.

Topics: Arthritis, Rheumatoid; Blood Coagulation Disorders; Factor V; Factor VII; Factor X; Factor XIII; Fibrin; Fibrinogen; Humans; Immunohistochemistry; Macrophages; Plasminogen Inactivators; Synovial Membrane; Thromboplastin

Desmopressin acetate (DDAVP) is known to stimulate the release of tissue-type plasminogen activator (t-PA) from endothelial cells, but it is unclear whether the increased t-PA actually elicits the plasmin generation and fibrin(ogen)olysis in the circulating blood. We measured plasma levels of plasmin-alpha 2-plasmin inhibitor complex, fibrinogen degradation products (FgDP) and fibrin degradation products (FbDP) following desmopressin infusion in 19 patients with bleeding disorders or thrombophilia. Administration of desmopressin (0.3-0.4 microgram/kg) produced a 4.0-fold increase in plasmin-alpha 2-plasmin inhibitor complex at 30 min, whereas neither FgDP nor FbDP was elevated significantly. These findings indicate that desmopressin infusion provokes the generation of plasmin in vivo, but most of the plasmin generated is complexed to alpha 2-plasmin inhibitor and does not degradate fibrin or fibrinogen.

Topics: alpha-2-Antiplasmin; Antifibrinolytic Agents; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysin; Fibrinolysis; Humans; Infusions, Intravenous; Tissue Plasminogen Activator

A relationship between blood coagulation system and tumor growth is discussed. The role of hemocoagulation disorders in the pathogenesis, dissemination and advancement of disease at molecular, cellular, body and population level is discussed on the basis of the authors' results and literature data. Rastr electron microscopy and immunofluorescent method revealed fibrin on the surface of tumor cells both in vivo and in vitro which is thought to play a masking and protective role. Studies of clotting and anticlotting factors in various subgroups of healthy subjects and patients with precancer and cancer revealed a steady-state increase in blood coagulability in cancer patients of old age. On these grounds, blood fibrinogen level was used for screening. Increased fibrinogen level was associated with higher tumor occurrence. The authors' concept of the pathogenetic role of the coagulation system in tumor growth provided a rationale for the use of direct and indirect anticoagulants in addition to cytotoxic drugs for breast, ovarian and gastric cancer. As a result, cytotoxic treatment was more effective and better tolerated.

Topics: Adult; Anticoagulants; Antineoplastic Agents; Blood Coagulation Disorders; Breast Neoplasms; Cell Line; Cells, Cultured; Drug Therapy, Combination; Female; Fibrin; Fibrinogen; Humans; Lung Neoplasms; Male; Middle Aged; Stomach Neoplasms; Surface Properties; Tumor Cells, Cultured

Cardiopulmonary By-Pass (CPB) Surgery may at times induce a haemostatic defect, at present not too well understood, causing severe bleeding from the operative site and chest tube drain. We present here some data on antigen increase in tissue Plasminogen Activator (tPA) and D 2 Dimer (D2D) detected during CPB and apparently not compensated by enhanced Plasminogen Activator Inhibitor type 1 (PAI 1) activity. tPA concentration (antigenic) ranged around 6.15 ng/ml (SD 5.6) before thoracotomy and 5.8 g/ml (SD 4.74) 5-10 minutes after a heparin 250 IU/Kg bolus injection. During CPB, tPA increased to 20.34 ng/ml (SD 9.17) before protamine infusion, and 16.93 ng/ml (SD 8.13) after heparin neutralization. As the D2D went up to 2000-4000 ng/ml (before/after protamine) and it was not correlated by fibrinogen consumption or FDP production, we find these observations suggestive of fibrin-dependent fibrinolytic activity, as an acquired haemostatic defect developed during CPB.

Topics: Adult; Aged; Bleeding Time; Blood Coagulation Disorders; Cardiopulmonary Bypass; Extracorporeal Circulation; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Humans; Middle Aged; Plasminogen Inactivators; Tissue Plasminogen Activator

The coagulation abnormalities in 20 cases of acute promyelocytic leukemia (APL) treated at a single institution were reviewed. A remarkably uniform picture of defibrination and increased FDPs with well-preserved levels of other coagulation factors including AT-III was seen. Our data, together with those available in the literature, do not support DIC as the underlying mechanism of bleeding but seem rather to point to increased proteolysis as the cause.

Topics: Adult; Blood Coagulation Disorders; Female; Fibrin; Fibrinolysis; Hemorrhage; Humans; Leukemia, Promyelocytic, Acute; Male; Retrospective Studies

A new case of heterozygous dysfibrinogenemia characterized by the replacement of NH2-terminal amino acid of fibrin beta-chain was found in a 50-year-old man. Despite a prolonged thrombin time, the propositus' fibrinogen had a normal reptilase time with the normal release of fibrinopeptide A. Release of fibrinopeptide B by thrombin was strongly affected, but a very high concentration of thrombin almost completely released fibrinopeptide B with a normal elution pattern on reversed-phase high performance liquid chromatography (HPLC). Lysylendopeptidase-cleavage of purified B beta-chains analyzed on HPLC showed the decrease of one peptide compared with the normal and the appearance of an abnormal peptide peak. These peptides were treated with thrombin and further separated on HPLC. Amino acid sequence analysis of the abnormal peptide demonstrated that B beta glycine-15, NH2-terminus of the fibrin beta-chain, was replaced by cysteine. These findings will be of particular importance because they strongly support the hypothesis that the NH2-terminal portion of the fibrin beta-chain is involved in the polymerization reaction by thrombin. The propositus' daughter and two sisters had the same abnormal fibrinogen. This unique inherited abnormal fibrinogen was designated as fibrinogen Ise. During these studies, we found that a very high concentration of thrombin cleaves not only the A alpha Arg19-Val20 bond but also the COOH-terminal region of alpha-chains, which results in the generation of further degraded alpha-chains with apparent molecular weights of 44,000 or less.

Topics: Amino Acid Sequence; Batroxobin; Blood Coagulation Disorders; Blood Coagulation Tests; Chromatography, High Pressure Liquid; Cysteine; Fibrin; Fibrinogens, Abnormal; Fibrinopeptide A; Fibrinopeptide B; Glycine; Humans; Male; Middle Aged; Molecular Sequence Data; Thrombin

Orbitometry (Hartert) is a rheological ex-vivo method to follow up physical assembly of a coagulum in layers during natural intensity of flow by orbital movement. Fibrin elasticity in the Orbitometers mode of Resonance Thrombography is differentiated from platelet activity as well as e.g. from the effects of disseminated coagulation-minimal in liver disease and maximal during disturbances of delivery. Transition into the mode of dynamic Tendography (Hartert) will e.g. register all fast going tests lasting minutes or seconds. It is comparable to an accelerated form of Thrombelastography (Hartert), the intercourse of which with coagulum yet is an exclusively static operation. Another category is measurement of blood and plasma viscosity. In concentrated blood it seizes plasticity of blood cells as well as their intensity of aggregation in orbital flow. The latest methodical development of Orbitometry is control of platelet activity in its function of adhesion. This is realized by measurement of specific physical effects released in platelet containing coagulum. They generate a structural degradation of fibrin elasticity modul as well as a tendency for coagulum adhesion. The practical use of Adhesiography is control of anticoagulants and platelet protecting substances in their quantitative influence on coagulum structure and on the mentioned platelet activities. A special disturbance of these platelet depending mechnisms obviously is getting evidence in case of v. Willebrand's syndrome.

Topics: Blood Coagulation Disorders; Blood Platelets; Blood Viscosity; Fibrin; Humans; In Vitro Techniques; Oscillometry; Rheology; Thrombelastography; Thrombosis

Fibrin(ogen) degradation product (FDP) and D-dimer levels were evaluated in 168 liver cirrhosis (LC) patients without evidence of bleeding. Eighty-two (48%) had FDP higher than 10 micrograms/ml; only 43 of them had a concomitant increase of D-dimer. These alterations were more frequent in older and decompensated patients and correlated to the Child-Turcotte score. In the patients with elevated FDP and/or D-dimer levels the mean values of platelets, prothrombin activity and fibrinogen were not significantly different from those of the other patients and remained fairly stable over the period of the study. Finally, an increase of FDP is frequent in LC and this may suggest a diagnosis of disseminated intravascular coagulation (DIC), but a concomitant increase of D-dimer is rarely detectable, thus excluding this diagnosis. Moreover, even in the cases with increased levels of D-dimer the presence of clinical or laboratory evidence of a consumption coagulopathy, expression of a manifest DIC, seems to be unusual.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Liver Cirrhosis; Male; Middle Aged; Platelet Count; Prothrombin

The mean levels of fibrinopeptide A (FPA), thrombin-antithrombin complex (TAT), and soluble fibrin (tPA method) in cancer patients (n = 32) were intermediate between those of patients with cerebral infarction and pancreatitis who had the most abnormal results and patients with myocardial infarction and pneumonia who had the least abnormal results. Patients with disseminated malignancies (n = 16) had significantly higher mean levels of FPA (10.6 vs. 5.3 nmol/l) and TAT (11.0 vs. 4.4 pmol/l) than patients with limited malignancies (n = 16). The difference in soluble fibrin (fibrin monomer, FM; 22.1 vs. 18.0 nmol/l) was not significant. The values of FPA, FM, and TAT in the patient population correlated significantly. There was a negative correlation between the level of antithrombin and test results for FPA (-0.69), FM (-0.48), and TAT (-0.38) in the cancer patients. Even cancer patients with locally limited disease may have elevated FPA, FM, and TAT test results, indicating a state of definite hypercoagulation.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Antithrombin III; Blood Coagulation Disorders; Blood Coagulation Tests; Cerebral Infarction; Female; Fibrin; Fibrinopeptide A; Humans; Male; Middle Aged; Myocardial Infarction; Neoplasms; Pancreatitis; Peptide Hydrolases; Pneumonia; Predictive Value of Tests; Reference Values

Fibrin glue (FG), made with highly concentrated human fibrinogen and clotting factors, was used to achieve parenchymal organ hemostasis in patients with disordered coagulation secondary to massive transfusion, chronic disease, and disseminated intravascular coagulation; it was effective in controlling liver hemorrhage in seven patients and in the performance of a splenorrhaphy in one other patient. The coagulation profile was grossly abnormal in all patients, and the mean +/- SD intraoperative blood loss was 5.1 +/- 4.2 L; patients received 14 +/- 10 U of blood perioperatively. The amount of FG required to achieve hemostasis varied directly with the extent of injury and intraoperative blood loss (r = .84), and all patients with a blood loss greater than 4 L required at least 25 mL of FG to stop bleeding. Two patients died postoperatively secondary to cardiac arrest and adult respiratory distress syndrome. Because FG does not depend on adequate platelet or clotting factor levels to be effective, it is especially useful in patients with parenchymal organ hemorrhage and disordered coagulation.

Topics: Adult; Aged; Aprotinin; Blood Coagulation Disorders; Chronic Disease; Disseminated Intravascular Coagulation; Drug Combinations; Factor XIII; Female; Fibrin; Fibrin Tissue Adhesive; Fibrinogen; Hemostasis, Surgical; Humans; Liver; Male; Spleen; Thrombin; Tissue Adhesives; Transfusion Reaction

A scheme of physicochemical determination of fibrinogen and the major molecular derivatives in a single sample of plasma is suggested, available for the majority of clinical laboratories. Such determination gives valuable information for a clinician. Among other things, the level of rapidly thrombin clotted fibrinogen portion is determined, as is the content of high-molecular fibrin monomer complexes, not clotted with thrombin, and the level of fibrinogen and fibrin proteolytic degradation products. Clinical (in 42 patients with various conditions) and experimental (coagulopathy in amniotic fluid embolism) application of this scheme has confirmed its clinico-diagnostic value.

Topics: Blood Coagulation Disorders; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Molecular Conformation

In an abnormal fibrinogen with impaired fibrin monomer polymerization designed as fibrinogen Osaka II, we have identified substitution of Arg by Cys at position 275 of the gamma chain. This Cys is linked to a free cysteine molecule by a disulfide link as evidenced by fast atom bombardment mass spectrometry. This finding was supported by identification of a single cysteine released from isolated abnormal fragment D1 upon reduction. This unique cystine structure at the mutation site has not been reported heretofore in any abnormal protein including fibrinogen. The substitution may well perturb the structure required for fibrin monomer polymerization, specifically that assigned to the carboxyl-terminal D domain of fibrinogen. Indeed, isolated fragment D1 with the Cys substitution failed to inhibit thrombin-mediated clotting of normal fibrinogen and normal fibrin monomer polymerization, while normal fragment D1 inhibited them markedly. Our data seem to provide supporting evidence that the putative polymerization site(s) assigned to the D domain of fibrinogen may be structure-dependent, including the carboxyl-terminal segment of the gamma chain as well as a contiguous region that contains the gamma 275 residue.

Topics: Adolescent; Aged; Amino Acid Sequence; Amino Acids; Arginine; Blood Coagulation Disorders; Calcium; Chromatography, High Pressure Liquid; Cysteine; Cystine; Egtazic Acid; Electrophoresis, Polyacrylamide Gel; Female; Fibrin; Fibrinogen; Fibrinogens, Abnormal; Fibrinolysin; Humans; Male; Molecular Sequence Data; Mutation; Peptide Fragments; Serine Endopeptidases; Thrombin Time

Plasma fibrinolytic activity was measured in 34 patients with systemic lupus erythematosus (SLE) and 12 normal subjects. Patients with SLE showed a significantly reduced resting level of plasma tissue plasminogen activator (t-PA) compared to normal. The reduction in t-PA was demonstrated both by a functional assay (fibrin-plate lysis, FP) and an immunochemical assay (ELISA). Measurement of the fibrinolytic response following venous occlusion allowed division of the patients into two groups. In the first (24 patients), there was a normal increase in t-PA response, demonstrated both by the functional and immunochemical assays. In the second (10 patients), there was a significantly reduced plasma t-PA response measured by FP. Seven of the patients in this second group, which included four patients with histological evidence of vasculitis, showed a similar failure of t-PA response (ELISA) after venous occlusion. These results suggest that their impaired fibrinolytic response may be related to defective t-PA release secondary to endothelial cell damage. The remaining three patients in the latter group had a normal t-PA (ELISA) response despite a reduced FP response, suggesting the presence of an inhibitor.

Topics: Adult; Aged; Blood Coagulation Disorders; Enzyme-Linked Immunosorbent Assay; Female; Fibrin; Fibrinolysis; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Partial Thromboplastin Time; Prothrombin Time; Thrombin Time; Tissue Plasminogen Activator

Four cases of lung cancer were analysed for aspects relating to optical light microscopy and ultrastructure of coagulation disorders. Criteria of intravasal coagulopathy were positively verified from all four cases and were found to have grown manifest in the form of prethrombi in veins, arterioles, and venules, masses of fibrin monomer in capillaries, and the sludge phenomenon. Extravasation of fibrin was also observed around highly differentiated cancer cells as well as in tumour stroma and in necrotic foci. Most of the fibrin was identified in the forms of monomers and their ultrastructural variants. Morphological criteria of locally delimited coagulation disorders in the microcirculation of tumours are discussed together with the role played by fibrin in growth and dissemination of neoplasms.

Topics: Arteries; Blood Coagulation Disorders; Fibrin; Humans; Lung Neoplasms; Male; Microcirculation; Middle Aged; Thrombosis; Veins

Fibrinogen was isolated from the plasma of a 25-year-old female with a history of mild bleeding and several recent moderate to severe hemorrhagic episodes. Coagulability with thrombin approached 100% and varied directly with the time of incubation with the enzyme. High-performance liquid chromatography analysis of thrombin-induced fibrinopeptide release demonstrated retarded fibrinopeptide A (FPA) and fibrinopeptide B (FPB) release and the presence of an abnormal A peptide (FPA) amounting to 50% of the total. The same biochemical abnormalities were found in her asymptomatic father. Amino acid analysis and carboxypeptidase digestion of FPA demonstrated the substitution of His for Arg at A alpha 16. In contrast to the thrombin- and reptilase-sensitive Arg-Gly bond in the normal A alpha chain, the abnormal A alpha chain (A alpha) sequence is resistant to reptilase attack but is slowly cleaved by thrombin. To evaluate whether Birmingham A alpha and A alpha chains had been assembled nonselectively into heterodimeric (ie, 50% A alpha, A alpha) and homodimeric (ie, 25% A alpha, A alpha; 25% A alpha, A alpha) species, the clot and the clot liquor resulting from reptilase treatment of normal or Birmingham fibrinogen were separated, and each was then further incubated with thrombin to release remaining fibrinopeptides. Assuming that fibrinogen Birmingham contained heterodimeric molecules and that these and the normal molecules were completely incorporated into a reptilase clot, the expected coagulability would be 75%. In addition, subsequent thrombin treatment of the reptilase clot would release 50% of the total FPA and 75% of the total FPB present in the original sample. On the other hand, if only homodimeric fibrinogen species (50% A alpha, A alpha; 50% A alpha, A alpha) existed, the maximum reptilase coagulability would be 50%, and after thrombin treatment, 50% of the total FPB and no FPA would be recovered from the reptilase clot. We found the propositus's fibrinogen to be 68% coagulable, and we recovered 45% of the FPA and 70% of the FPB from the reptilase clot. Essentially the same coagulability and distribution of fibrinopeptides was found in the reptilase clot from her father's fibrinogen. We therefore conclude that fibrinogen Birmingham contains heterodimeric species (A alpha, A alpha) amounting to approximately 50% of the circulating fibrinogen molecules. The existence of heterodimers is consistent with a nonselective intracellular process of constituent

Topics: Adult; Amino Acids; Blood Coagulation Disorders; Female; Fibrin; Fibrinogen; Fibrinogens, Abnormal; Fibrinopeptide A; Heterozygote; Humans

An inherited association of dysfibrinogenaemia and protein C deficiency was found in three members of the same family. The propositus was a 48-year-old man who suffered from severe and rapidly complicated atherosclerosis of the aorta and lower limbs arteries, which perhaps suggests that the association of these two molecular abnormalities may have enhanced the thrombotic process. The abnormal fibrinogen had a reduced ability to bind thrombin which may be thrombogenic. We found the same inherited association of dysfibrinogenaemia and protein C deficiency in a patient with venous thrombosis. The functional abnormality of the fibrinogen, which could have been responsible for thrombosis, was delayed proteolysis by plasmin. Not only fibrinogen, but also fibrin clots were resistant to plasmic degradation. These observations raise two questions: (1) Is the association of a protein C deficiency with a dysfibrinogenaemia fortuitous or the result of a common mechanism? (2) Is there a link between an increased thrombotic tendency and either both of the defects of haemostasis that we have found, or only one of them?

Topics: Adult; Blood Coagulation Disorders; Female; Fibrin; Fibrinogen; Fibrinopeptide A; Humans; Infant; Male; Middle Aged; Pedigree; Protein C Deficiency

Thrombin preferentially cleaves fibrinopeptides A (FPA) from fibrinogen resulting in the formation of desAA-fibrin from which most of the fibrinopeptides B (FPB) are then released with an enhanced rate. Kinetics of fibrinopeptide release from normal and dysfunctional fibrinogens were investigated in order to further characterize the mechanism of accelerated FPB release during desAA-fibrin polymerization. Dysfunctional fibrinogens London I and Ashford, exhibiting primary polymerization abnormalities (i.e., an abnormality present when all fibrinopeptides have been cleaved), which in the case of fibrinogen London I is believed to be caused by a defect in the D-domain, were shown to exhibit a decreased rate of FPB release compared with normal fibrinogen. While Gly-Pro-Arg-Pro, an inhibitor of fibrin polymerization, was shown to decrease the rate of FPB release from normal fibrinogen by a factor of 5, normal fragment D1, although inhibiting clot formation of normal fibrinogen, did not influence the acceleration of FPB release. On the other hand, the presence of fragment D1 did not enhance FPB release from fibrinogen London I, suggesting that interaction of D-domains in functional isolation with desAA-fibrin E-domains is not sufficient to enhance FPB release. Although clot formation was inhibited by the concentrations of fragment D1 used, the formation of small desAA-fibrin oligomers was hardly affected. Thus, small fibrin polymers, but not desAA-fibrin monomers, act as optimal substrates for the release of FPB by thrombin.

Topics: Blood Coagulation Disorders; Fibrin; Fibrinogen; Fibrinogens, Abnormal; Fibrinopeptide B; Humans; Kinetics; Nephelometry and Turbidimetry; Polymers; Thrombin

Blood coagulation function was serially studied in 84 children with nephrotic syndrome. Fifty-eight had minimal change disease, six had focal glomerulosclerosis and 20 had other forms of renal disease associated with the nephrotic syndrome. Qualitatively similar abnormalities in fibrinogen metabolism were present in all groups with clinically overt nephrotic syndrome; plasma fibrinogen concentration and high molecular weight fibrin(ogen) complexes (HMWFC) were grossly elevated (P less than 0.001 in most groups). With disease remission fibrinogen and HMWFC concentrations decreased to the normal range, usually with concomitant transient increase in plasma fibrinolytic activity (P less than 0.02). Alterations in concentrations of other proteins involved in coagulation and fibrinolysis differed depending on the underlying cause for the nephrotic syndrome. Antithrombin III concentration was normal except in the focal glomerulosclerosis group. The results demonstrate that a coagulopathy characterized by pathological degree of thrombin action on fibrinogen complicates the nephrotic state and may be initiated by different mechanisms. It is suggested that this coagulopathy, which remits with clinical improvement, is consequent upon local intrarenal activation of the blood coagulation system.

Topics: Adolescent; alpha 1-Antitrypsin; alpha-Macroglobulins; Antithrombin III; Blood Coagulation Disorders; Child; Child, Preschool; Factor XIII; Fibrin; Fibrinogen; Fibrinolysis; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Humans; Molecular Weight; Nephrosis, Lipoid; Nephrotic Syndrome

The occurrence of a consumption coagulopathy as well as prethrombotic and thrombotic states are connected with the formation of thrombin. The proteinase acts upon physiological substrates leading to activation products, e.g. fibrinopeptides, platelet factors or thrombin-antithrombin III-complex. For the determination of such products we have developed immunochemical assays, which detect parameters of a direct or indirect action of thrombin in a specific and sensitive manner: 1. ELISA for determination of platelet factor 4; 2. Latex-test for determination of D-Dimer; 3. ELISA for determination of thrombin-antithrombin III complex. Preliminary results from clinical investigations indicate that the determination of these parameters can be valuable for the diagnosis of activation processes of the clotting system.

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Enzyme Activation; Enzyme-Linked Immunosorbent Assay; Fibrin; Fibrinolysin; Humans; Platelet Factor 4; Thrombin; Thrombosis

We report on three unrelated individuals with the same uncommon type of dysfibrinogenemia, originating from Bergamo, Essen and Perugia. None of them showed bleeding symptoms while the Bergamo patient and members of her family presented with a thrombotic tendency. The presence of a defective fibrinogen was suggested by prolonged thrombin and reptilase times. Furthermore, fibrinogen concentrations of less than 0.28 g/L were determined by the functional assay whereas values of 1.5-2.4 g/L were measured by heat precipitation or electroimmunoassay. Fibrinogen was isolated by affinity chromatography on insoluble fibrin monomer. The rate of fibrinopeptide release by thrombin was normal while the fibrin polymerization reaction was strongly delayed. An abnormal peptide (gamma 265-310) was isolated by high-performance liquid chromatography after cyanogen bromide cleavage of the purified gamma-chain of fibrinogen Bergamo II and Essen. The same peptide was also isolated following cyanogen bromide treatment of the intact fibrinogen Perugia. Sequence analyses of these peptides demonstrated the same amino acid exchange in all three fibrinogens: gamma 275 arginine----histidine. The described fibrinogen variants appear to possess a molecular defect which has thus far only been observed in fibrinogen Haifa.

Topics: Amino Acid Sequence; Arginine; Blood Coagulation Disorders; Child, Preschool; Female; Fibrin; Fibrinogen; Fibrinogens, Abnormal; Genetic Variation; Histidine; Humans; Middle Aged; Protein Conformation

A congenitally abnormal fibrinogen was isolated from blood of a young man with deep-vein thrombosis. Two other affected members of his family had three episodes of severe arterial thrombosis. The fibrinogen showed a delayed clotting by thrombin, but a normal clotting by Arvin, Reptilase, and prothrombin-staphylocoagulase complex. Analysis of the fibrinopeptides A and B by High Performance Liquid Chromatography did not reveal an abnormal peptide structure. The rate of release of A and B peptides by thrombin was strongly delayed, whereas the rate of release of fibrinopeptide A by Arvin appeared to be normal. The fibrin polymerization rate was normal. Interactions between the abnormal fibrinogen, platelets and the fibrinolytic system were also normal. Evidence is presented that the defective interaction between fibrinogen Milano II and thrombin is associated with a defective binding of thrombin to the fibrin moiety of the abnormal fibrinogen.

Topics: Adult; Blood Coagulation Disorders; Fibrin; Fibrinogen; Fibrinogens, Abnormal; Fibrinopeptide A; Fibrinopeptide B; Humans; Male; Pedigree; Platelet Aggregation; Thrombin; Thrombophlebitis; Thrombosis

In this short review I have tried to report the literature findings and describe some of our observations on fibrinolysis and atherosclerosis. Although at this time it is difficult to state that diminished FA plays a pathogenic role in atherosclerosis, it certainly seems to represent a risk factor.

Topics: alpha-2-Antiplasmin; Animals; Arteriosclerosis; Blood Coagulation Disorders; Fibrin; Fibrinolysis; Fibrinolytic Agents; Humans; Plasminogen Activators; Thromboembolism; Thrombosis

A gamma-chain variant with a lower molecular weight than the normal gamma chain was detected in a new congenital abnormal fibrinogen with impaired polymerization of the fibrin monomer and with normal release of fibrinopeptides A and B in a 45-year-old male. Purified fibrinogen analyzed on SDS-polyacrylamide gel electrophoresis under the reduced condition contained an abnormal protein band with an apparent molecular weight of 48,000 compared with the gamma chain with a molecular weight of 50,000. This abnormal protein band was found to be a gamma-chain variant from the molar ratio of A alpha chain:B beta chain:gamma chain:abnormal protein (about 2:2:1:1), with positive staining for carbohydrate and crosslinking ability. Crosslinked fibrin contained three types of gamma-gamma dimers with apparent molecular weights of 94,000 (the same as normal major gamma-gamma dimer), 92,000 and 90,000, and the plasmic digests of crosslinked fibrin in the presence of calcium retained three types of gamma-gamma dimer remnants. This suggests that the abnormal gamma-chain variant has a shorter polypeptide chain not in the NH2-terminal but in the COOH-terminal portion, probably at or near the polymerization site. This patient's two daughters had the same abnormal fibrinogen. This unique inherited abnormal fibrinogen was designated as fibrinogen Kyoto, and the gamma-chain variant as gamma Kyoto.

Topics: Blood Coagulation Disorders; Female; Fibrin; Fibrinogen; Humans; Macromolecular Substances; Male; Molecular Weight; Pedigree

To explore the pathophysiology of the necrotizing enterocolitis caused by polycythemia in the newborn dog, the effect of acute polycythemia on fibrinogen disappearance rate was studied in 38 puppies (3-14 days). All pups received an exchange transfusion removing 65 ml/kg of blood and transfusing 85 ml/kg of either whole blood (control, resulting hematocrit = 37), or packed red blood cells (polycythemia, resulting hematocrit = 68). Necrotizing enterocolitis was found in 15 of 19 polycythemic and four of 19 control pups (p less than 0.01). 125I fibrinogen and Evan's blue (an albumin marker) were injected 2 h after transfusion and the concentration of clottable labeled fibrinogen and albumin tracer were measured at 1/2 and 2 h after injection. The fraction of the tracer that disappeared over the 1 1/2-h period was calculated. In the polycythemic group 45 +/- 18 SD% of the clottable fibrinogen disappeared versus only 28 +/- 15% in the control group (p less than 0.01). In the polycythemic group 36 +/- 21% of the albumin tracer disappeared versus 31 +/- 12% in the control group (NS). Thus polycythemia in the newborn dog is associated with an increased disappearance rate of clottable fibrinogen not associated with a general increase in protein disappearance rate. Thus an intravascular coagulopathy is evident in the polycythemic animals. Whether this coagulopathy is the cause of the necrotizing enterocolitis or is secondary to the necrotizing enterocolitis seen in this animal model cannot be determined from this experiment.

Topics: Animals; Animals, Newborn; Blood Coagulation Disorders; Blood Viscosity; Disease Models, Animal; Dogs; Enterocolitis, Pseudomembranous; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Iodine Radioisotopes; Lactates; Male; Polycythemia; Time Factors

Inherited qualitative abnormalities of fibrinogen have been documented in more than 100 families. These dysfibrinogenemias usually are clinically silent, but in some cases are associated with bleeding, thrombosis, or defective wound healing. Abnormalities of the fibrinogen molecule may impair any of the major steps involved in the conversion of fibrinogen into stabilized fibrin; i.e., cleavage of the fibrinopeptides by thrombin, polymerization, and cross-linking of fibrin. Biochemical studies of several abnormal fibrinogens have demonstrated that the functional defects are the result of single amino acid substitutions. The hereditary dysfibrinogenemias are the first coagulation disorder in which the pathophysiology has been elucidated on a molecular level. Studies of these "experiments of nature" have important implications in such diverse processes as wound healing and thrombosis.

Topics: Biopolymers; Blood Coagulation Disorders; Chemical Phenomena; Chemistry; Fibrin; Fibrinogen; Heterozygote; Humans; Protein Binding; Thrombin; Thrombosis; Wound Healing

A functionally abnormal fibrinogen was detected in a 27-year-old woman with no prior history of bleeding. Investigation of the defect revealed abnormal release of fibrinopeptide A and incomplete polymerization of fibrin monomers. Crosslinking of polymerized fibrin by Factor XIII was normal. To further characterize the dysfibrinogen, the increase in mechanical impedance during clot development was measured. Fibrinogen Seattle II showed several differences from normal fibrinogen: delayed onset of clotting, decreased rate of clot formation, and lower final clot impedance. Taken cumulatively, these data are consistent with an amino acid substitution at or near residue 16 in one of the A alpha chains, the point at which thrombin cleaves.

Topics: Adult; Blood Coagulation; Blood Coagulation Disorders; Factor XIII; Female; Fibrin; Fibrinogen; Fibrinogens, Abnormal; Fibrinopeptide A; Humans

A congenital dysfibrinogenemia was found in a 32-year-old asymptomatic female and her immediate family. The propositus, apparently a heterozygote for the abnormality, characteristically showed defective release of fibrinopeptide A from half of her fibrinogen molecules. No fibrinopeptide A was cleaved off from the isolated abnormal molecule by thrombin or snake venoms (Reptilase and Ancrod) as evidenced by radioimmunoassay, high performance liquid chromatography and determination of the NH2-terminal amino acids. The abnormal fibrinogen formed a solid gel solely by the release of fibrinopeptide B upon incubation with thrombin. We provisionally designate this abnormal fibrinogen as "Fibrinogen Kawaguchi", although possible identity with other abnormal fibrinogens is not excluded.

Topics: Adult; Amino Acid Sequence; Blood Coagulation Disorders; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinogens, Abnormal; Fibrinopeptide A; Hemostasis; Humans; Pedigree; Thrombin Time

A congenital dysfibrinogenemia, fibrinogen Baltimore IV, has been found in a 56-year-old Caucasian man. Clinical laboratory studies disclosed a slightly prolonged prothrombin time, but were otherwise unremarkable. Release of fibrinopeptides by thrombin occurs normally, as does ligation of the fibrin polymer by Factor XIII. Approximately half of the isolated fibrin monomers polymerize normally, but the remainder polymerize at about 2% of the initial rate. The functional defect is thus limited to a decrease in the rate of fibrin monomer polymerization.

Topics: Afibrinogenemia; Blood Coagulation Disorders; Fibrin; Humans; Male; Middle Aged; Pedigree; Polymers

Topics: Blood Coagulation Disorders; Fibrin; Fibrinogen; Fibrinopeptide A; Fibrinopeptide B; Humans; Polymers; Prothrombin Time; United States; Wound Healing

A patient with an acquired inhibitor to factor XIII is reported. The patient's plasma produced a profound inhibition of factor XIII activity in normal plasma measured by a dansylcadaverine casein assay and stimulated a very abnormal pattern of fibrin cross-linking, not normally seen with factor XIII. Partial characterisation of the inhibitor suggests that it is heat stable and not an immunoglobulin.

Topics: Acetates; Blood Coagulation Disorders; Blood Coagulation Tests; Electrophoresis, Polyacrylamide Gel; Factor XIII; Female; Fibrin; Hemorrhagic Disorders; Humans; Urea

We examined normal and abnormal fibrinogen (fibrinogen "Grenoble") by two-dimensional gel electrophoresis to obtain data on possible defects at the molecular level. Fibrinogen Grenoble is characterized by an abnormal rate of fibrin monomer aggregation. The electrophoretic analysis revealed the presence of abnormal gamma chains. Two kinds of gamma chains can be detected in fibrinogen Grenoble: (a) normal gamma chains and (b) gamma chains Grenoble (gamma G) with a greater molecular mass but no modification in isoelectric point. The latter chain can be detected in whole plasma by two-dimensional gel electrophoresis. Metrological analysis was performed in an attempt to quantify observed differences between normal fibrinogen and fibrinogen Grenoble. On use of gels stained either with Coomassie Brilliant Blue or with silver, the partly qualified evaluation gives about 60% normal gamma chain and 40% gamma chain Grenoble.

Topics: Blood Coagulation Disorders; Electrophoresis; Electrophoresis, Polyacrylamide Gel; Female; Fibrin; Fibrinogen; Fibrinogens, Abnormal; Humans; Isoelectric Focusing; Isoelectric Point; Macromolecular Substances; Middle Aged; Molecular Weight

A patient with functionally defective fibrinogen has been studied. Fibrinogen Almeria I was found to have a prolonged of latency time (LT) and a decrease in rate of gelation (RG) when plasma or isolated fibrinogen were activated by thrombin or reptilase. This fibrinogen also has the unusual formation of cross-linked fibrin; the existence of unpolymerized alpha chains was confirmed.

Topics: Adult; Batroxobin; Blood Coagulation Disorders; Female; Fibrin; Fibrinogen; Fibrinogens, Abnormal; Humans; Polymers; Thrombin Time

The fibrin-mediated enhancement of the activation of plasminogen by tissue-type plasminogen activator observed with normal fibrin, is strongly decreased with fibrin Dusard, although the binding of tissue-type plasminogen activator to this fibrin is normal. This impaired fibrin-mediated plasminogen activation is most likely related to the history of recurrent thrombosis and pulmonary embolism observed in this family.

Topics: Blood Coagulation Disorders; Fibrin; Fibrinogen; Fibrinogens, Abnormal; Fibrinolysis; Humans; Plasminogen; Plasminogen Activators

The distinction between venomous, potentially dangerous snakes and snakes considered to be harmless to humans is not always clear. A man was bitten by an assumed harmless pet snake, Rhabdophis subminatus (the red neck keelback), that had been obtained from a pet store. The patient experienced a severe coagulopathy with life-threatening hemorrhage unresponsive to transfusion. Since this snake frequently is sold legally in the United States, we wish to alert the medical community to its potential danger and to discuss the pathophysiological mechanism by which the coagulopathy was produced.

Topics: Adult; Animals; Animals, Domestic; Blood Coagulation Disorders; Blood Coagulation Tests; Fibrin; Gastrointestinal Hemorrhage; Hematuria; Humans; Male; Snake Bites

Fibrin deposition and platelet thrombus dimensions on subendothelium were studied in four groups of patients with coagulation factor deficiencies. Five patients with factor VIII deficiency (APTT 120 +/- 8 sec) and three patients with factor IX deficiency (APTT 125 +/- 11 sec) were severe bleeders, whereas four patients with factor XII deficiency and seven with factor XI deficiency were either asymptomatic or only mild bleeders despite APTT values of 439 +/- 49 and 153 +/- 13 sec, respectively. Everted segments of deendothelialized rabbit aorta were exposed at a shear rate of 650 sec(-1) for 5 and 10 min to directly sampled venous blood in an annular chamber. Blood coagulation was evaluated by measuring fibrin deposition (percent surface coverage) on the subendothelium and post-chamber fibrinopeptide A levels; platelet thrombus dimensions on the subendothelium were evaluated by determining the total thrombus volume per surface area (using an optical scanning technique) and the average height of the three tallest thrombi. Consistent differences were observed among the patient groups for both the 5-min and 10-min exposure times. The larger of the 5- and 10-min exposure-time values was used to calculate group averages. Fibrin deposition in normal subjects was 81% +/- 5% surface coverage, and post-chamber fibrinopeptide A values were 712 +/- 64 ng/ml. Markedly decreased fibrin deposition and fibrinopeptide A levels were observed in factor VIII deficiency (2% +/- 1% and 102 +/- 19 ng/ml) and factor IX deficiency (11% +/- 7% and 69 +/- 11 ng/ml). In contrast, significantly higher values were obtained in patients deficient in factor XI (33% +/- 5% and 201 +/- 57 ng/ml) and factor XII (66% +/- 12% and 306 +/- 72 ng/ml). Differences in thrombus dimensions were also observed. In normal subjects, the value for thrombus volume and average height of the tallest thrombi were 8.3 +/- 1.3 cu micron/sq micron and 145 +/- 11 micron, respectively, and in patients were as follows: FVIII, 2.7 +/- 0.6 and 71 +/- 7; FIX, 4.5 +/- 1.8 and 88 +/- 14; FXI, 11.8 +/- 1.9 and 125 +/- 10; and FXII, 7.9 +/- 3.1 and 130 +/- 25. Platelet thrombus dimensions were normal in a patient with fibrinogen deficiency, indicating that the smaller thrombi in factor VIII and factor IX deficiencies were probably due to impaired evolution of thrombin rather than diminished fibrin formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adolescent; Adult; Aged; Blood Coagulation Disorders; Blood Platelets; Endothelium; Factor XI Deficiency; Factor XII Deficiency; Female; Fibrin; Fibrinogen; Fibrinopeptide A; Hemophilia A; Hemophilia B; Humans; In Vitro Techniques; Male; Middle Aged; Partial Thromboplastin Time; Platelet Adhesiveness; Prothrombin Time; Thromboplastin

Topics: Blood Coagulation Disorders; Edetic Acid; Electrophoresis, Polyacrylamide Gel; Fibrin; Fibrinogen; Humans

Fibrinogen Manchester is an abnormal fibrinogen with an impaired release of fibrinopeptide A (FPA) and a polymerization abnormality. In the accompanying article we have identified the amino acid substitution in fibrinogen Manchester as A alpha 16 Arg leads to His. When fibrinogen Manchester was digested with low thrombin concentrations approximately 40-50% of the total FPA content was release at a rate similar to FPA release from normal fibrinogen. The fibrin so formed exhibited an impaired polymerization of monomers. Digestion of fibrinogen Manchester with high concentrations of thrombin for prolonged times released the remaining FPA which had an abnormal retention time when studied by high performance liquid chromatography (HPLC). This fibrinopeptide has been shown previously to contain the A alpha 16 Arg leads to His substitution. fibrin resulting from this exhaustive digestion had normal polymerization of monomers. The normal and substituted FPAs were isolated by HPLC and compared in a double antibody competitive-binding assay for normal FPA. The immunological cross-reactivity of the abnormal peptide was reduced, so that approximately 5 times more abnormal peptide was required on a molar basis to displace labelled normal FPA. Normal intact fibrinogen was 10-fold less reactive (on a half molar basis) than free normal FPA and the crossreactivity of fibrinogen Manchester was measurably less than that of normal fibrinogen. It is concluded that immunological measurement alone of FPA released from abnormal fibrinogens may not give a complete description of the kinetics of peptide release if the amino acid substitution lies within the FPA sequence. The combination of radioimmunoassay and HPLC, however, provides a powerful analytical approach that should be useful in classifying and characterizing abnormal fibrinogens.

Topics: Blood Coagulation Disorders; Chromatography, High Pressure Liquid; Cross Reactions; Female; Fibrin; Fibrinogen; Fibrinogens, Abnormal; Fibrinopeptide A; Fibrinopeptide B; Humans; Male; Thrombin

Congenital dysfibrinogenaemia is described in three members of a family presenting with recurrent thrombosis and in two other young members not yet affected. An abnormality in the polymerization of fibrin monomers was noted. In addition, the pathological fibrin clots were found to be less sensitive to degradation by a post venous occlusion euglobulin solution than normal fibrin. After fibrin clot incubation with lys-plasminogen at different concentrations, the biological activity of plasminogen in patient fibrin clot on S 2251 after SK-addition, was less than that observed with normal fibrin. It is speculated that defective in vivo thrombolysis might explain the recurrent thrombosis observed in this family. This finding represents a new concept in understanding thromboembolic diseases.

Topics: Adolescent; Adult; Aged; Blood Coagulation; Blood Coagulation Disorders; Fibrin; Fibrinogen; Humans; Male; Pedigree; Syndrome; Thromboembolism

A 73-year-old female was found to have prolonged thrombin and reptilase times in the immediate post-operative period. These abnormalities were not corrected by the addition of normal plasma. They were subsequently shown to be due to an IgG immunoglobulin which inhibited fibrin monomer polymerization. The IgG immunoglobulin activity could be neutralized completely by prior incubation with either patient or normal fibrinogen, uncrosslinked fibrin monomers or IgG antisera. No inhibitory effect on thrombin activity, fibrinopeptide A release or on the fibrin cross-linking reaction of factor XIIIa could be detected. Purified patient fibrinogen was functionally normal as demonstrated by normal fibrinogen-fibrin polymerization and fibrinopeptide A release. No underlying cause for this phenomenon was found. The presence of the inhibitor was associated with excessive blood loss during the post-operative period.

Topics: Aged; Autoantibodies; Biopolymers; Blood Coagulation Disorders; Female; Fibrin; Fibrinogen; Hip Prosthesis; Humans; Immunoglobulin G; Postoperative Complications; Thrombin Time

We prospectively studied the hemostatic system of ten persons bitten by the Eastern diamondback rattlesnake (Crotalus adamanteus) during 1978-1980. Blood was drawn when the patients arrived in the emergency room and every 6 hr thereafter. All envenomated victims developed incoagulable blood (defined by a thrombin time greater than or equal to 120 sec, normal less than 20 sec). Platelet counts and plasma levels of antithrombin III and factors II and VIII were not drastically altered, which distinguished this disorder from classic disseminated intravascular coagulation. Fibrinogen levels were markedly decreased (mean coagulable level of 0 mg/dl and antigenic levels of 99 mg/dl). Plasminogen levels were 20% of normal, alpha-2-plasminogen inhibitor was 17% of normal, and plasminogen activator was 20 times normal. Levels of fibrin degradation products peaked at a mean of 7,680 micrograms/ml. The magnitude and duration of the coagulopathy were proportional to the clinical severity of envenomation. Treatment with antivenin blunted the coagulopathy. Because venom from the Eastern diamondback rattlesnake does not directly activate plasminogen, we conclude that coagulopathy following envenomation by that reptile appears to be due to partial proteolysis of fibrinogen with secondary activation of plasminogen by released plasminogen activator, probably of endothelial origin.

Topics: Antivenins; Blood Coagulation Disorders; Enzyme Inhibitors; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Plasminogen; Snake Venoms; Thrombin Time

A prospective study of coagulation disturbances and endotoxemia in 42 patients having major pancreatic or biliary surgery was performed. Endotoxin, soluble fibrin, and fibrin degradation products were measured before and after operation in 28 patients with obstructive jaundice and in 14 nonjaundiced controls. In the control group there was one death and no unexplained fever or postoperative hemorrhage. The jaundiced group had more complications: seven deaths, nine episodes of fever, and six episodes of hemorrhage. Soluble fibrin was detected only in patients with obstructive jaundice, in whom it occurred in 38 percent before operation. Positive endotoxin assay was as common in control patients as in the jaundiced group, but in the latter endotoxin was associated (p less than 0.05) with increased FDP and soluble fibrin. Patients with endotoxin or increased FDP levels before operation for jaundice carry a poor prognosis (7 of 11 died). Preoperative bowel preparation in 16 of the jaundiced patients did not affect the outcome.

Topics: Adult; Blood Coagulation Disorders; Cholestasis; Endotoxins; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Male; Platelet Count; Preoperative Care

Topics: Adult; Blood Coagulation Disorders; Fetal Blood; Fibrin; Fibrinogen; Humans; Infant, Newborn; Liver; Liver Cirrhosis

A new autosomally inherited dysfibrinogenaemia was recognized in 3 members of an Italian family. No bleeding tendency or thrombotic disease in any of the affected members were demonstrated. Coagulation tests revealed prolonged prothrombin, thrombin and Reptilase times. Plasma fibrinogen levels were normal with immunologic method and slightly reduced with chronometric assay: the other blood coagulation factors were normal. In addition, cross-immunoelectrophoresis performed on patients' plasma was indistinguishable from the normal. Dysfibrinogenaemia was confirmed by studying the purified fibrinogen. The fibrin polymerization curve, measured spectrophotometrically, showed a lower slope than the normal. A delay in fibrin monomer aggregation was revealed when compared to the normal at an equal concentration. The release of fibrinopeptides was normal. SDS polyacrylamide gel electrophoresis, isoelectric focusing and cross-immunoelectrophoresis of purified fibrinogen were not able to demonstrate any structural abnormality. The fibrinogen was named fibrinogen Genova.

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Child; Female; Fibrin; Fibrinogen; Humans; Macromolecular Substances; Male; Pedigree; Thrombin; Thrombin Time

Topics: Aged; Batroxobin; Blood Coagulation Disorders; Cross-Linking Reagents; Factor VIII; Female; Fibrin; Fibrinolysin; Fibrinopeptide A; Humans; Hydrolysis; Male; Michigan; Pedigree; Polymers; Radioimmunoassay; Thrombin

A 13-year-old girl with chronic aggressive hepatitis, postnecrotic cirrhosis, ulcerative colitis, and a coagulation defect acquired an antibody that specifically interfered with fibrin formation. We sought to characterize the antibody and determine the mechanism of its inhibitory activity. The patient's purified fibrinogen was functionally normal; however, the antibody inhibited the self-assembly of fibrin and prolonged the clotting times of the patient's plasma. This antibody, which belonged to the IgG class of immunoglobulins, acted early in the polymerization process to inhibit the association of fibrin monomers, as indicated by a prolonged lag time and a decreased slope in the polymerization curves. It did not inhibit fibrinopeptide cleavage or fibrin cross-linking. Affinity chromatography indicated that the antibody bound strongly to both fibrinogen and fibrin monomer.

Topics: Adolescent; Autoantibodies; Blood Coagulation Disorders; Blood Coagulation Tests; Colitis, Ulcerative; Female; Fibrin; Fibrinogen; Humans; Immunoglobulin G; Liver Diseases; Polymers

Topics: Blood Coagulation Disorders; Female; Fibrin; Fibrinogen; Humans; Placenta Previa; Platelet Count; Pregnancy; Pregnancy Complications, Hematologic

Le Veen shunts successfully alleviated ascites in 19 of 24 patients (79 percent). Clinical clotting typical of disseminated intravenous coagulation occurred in nine of these patients (37 percent) and was fatal in seven (78 percent). Laboratory findings suggesting disseminated intravenous clotting were present in five other patients (21 percent) but were not associated with troublesome bleeding. Coagulopathy was reversed in 7 of 14 patients (50 percent), if the shunt was ligated and supportive measures were taken early in the postoperative course. Failure to recognize or take immediate action resulted in progressive disseminated intravenous clotting associated with a mortality of 50 percent (7 of 14 patients).

Topics: Adult; Aged; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Peritoneovenous Shunt; Postoperative Complications; Vascular Surgical Procedures

Congenital and hereditary abnormal fibrinogen is the most common of the inherited disorders of fibrinogen. There is no uniform clinical pattern which characterizes the disease and the diagnosis is evoked on the results of laboratory tests which show an abnormal conversion of fibrinogen to fibrin. This abnormality should be confirmed on the purified defective fibrinogen. Characterization of the abnormality includes physical, immunological, functional and structural analyses. Studies related to fibrinogen behavior upon plasmin digestion and those related to polymerization also provide useful information. Recognition of the specific nature of the molecular defect is dependent on molecular analysis. A single distinctive amino acid substitution is currently recognized for Fibrinogen Detroit, Lille and München.

Topics: Blood Coagulation Disorders; Fibrin; Fibrinogen; Humans

A 38-year-old male patient with a life-long history of easy bruising and mild bleeding had a prolonged activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). Reptilase (Bathrops atrox) clotting time was normal. His undiluted and diluted plasma prolonged the APTT, PT, and TT of normal plasma. Fibrin produced from patient plasma was insoluble in 5 M urea. Plasma fibrinogen level was increased when measured as clottable protein and by Laurell electroimmunoassay. Specific assays of plasma factors II, V, VII, X, VIII, IX, XI, and XII were normal. A circulating antithrombin in patient plasma was excluded by demonstrating normal thrombin-induced platelet aggregation of gel-separated platelets in the presence of patient plasma. Purified patient fibrinogen reproduced the anticoagulant effect of patient plasma. Patient fibrinogen antigen was similar to normal fibrinogen antigen by immunodiffusion, immunoelectrophoresis (pH 5.2 and 8.6), and crossed immunoelectrophoresis. His unreduced purified fibrinogen had normal migration on polyacrylamide slab gels. Also, the migration in gel slabs of A alpha, B beta and gamma-polypeptide chains, produced by mercaptoethanol reduction of purified patient fibrinogen, was similar to reduced normal fibrinogen. Thrombin-induced total fibrinopeptide release was normal. However, fibrin monomers produced from patient fibrinogen by thrombin (devoid of fibrinopeptides A and B) reaggregated abnormally; fibrin monomers produced by reptilase (devoid of only fibrinopeptides A) reaggregated normally. Fibrin generated from patient plasma in the presence of factor XIII and calcium, was defective in the formation of covalently bonded alpha-alpha polymers and demonstrated an increased susceptibility to the lytic effects of plasmin (generated in vitro by the addition of streptokinase).

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Tests; Electrophoresis; Epitopes; Fibrin; Fibrinogen; Fibrinolysin; Humans; Immunodiffusion; Immunoelectrophoresis, Two-Dimensional; Male

Routine testing on plasma from a patient due to undergo a coronary artery bypass graft operation revealed a prolonged thrombin clotting time associated with a normal plasma fibrinogen level when this was determined by a method not dependent upon the rate of fibrin formation. Fibrinogen purified from the patient's plasma by precipitation with beta-alanine also gave a prolonged thrombin time and this confirmed the presence of a dysfibrinogenaemia. Increasing calcium chloride concentration, addition of protamine sulphate and decreasing ionic strength all produced a partial correction of the clotting defect. Addition of normal plasma to patient's plasma failed to correct the prolonged thrombin clotting time and a pH dependence of the defect was also observed. Kinetic studies of fibrinopeptide release, using a specific radioimmunoassay, demonstrated no delay in the release of patient fibrinopeptide A. The functional defect was localized as an abnormality in the polymerization of fibrin monomers by studying fibrin monomers prepared and isolated from plasma and from purified fibrinogen solution. An electrophoretic examination of the patient's fibrinogen using both agarose and polyacrylamide gels failed to demonstrate any alteration in mobility or any structural defect associated with the polypeptide chains A alpha, B beta and gamma. All seven of the living siblings of the propositus and also his daughter showed no abnormality in any clotting assay. However, because the propositus did not suffer from liver disease it has been assumed that the abnormality is genetic in origin.

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Tests; Electrophoresis, Polyacrylamide Gel; Fibrin; Fibrinogen; Fibrinopeptide A; Humans; Hydrogen-Ion Concentration; Immunodiffusion; Immunoelectrophoresis; Macromolecular Substances; Male; Pedigree; Thrombin

Topics: Adult; Animals; Blood Coagulation Disorders; Child; Child, Preschool; Crotalid Venoms; Female; Fibrin; Fibrinogen; Humans; Male; Snake Bites; Snakes

Rats infected with Trypanosoma brucei rhodesiense developed anemia, thrombocytopenia, and hypocomplementemia. Anemia, thrombocytopenia, and sharp reductions in parasitemia were associated with elevated titers of cold-active hemagglutinin, antibody to fibrinogen/fibrin-related products, and immunoconglutinin. Depletion of lytic complement, prolonged partial thromboplastin times, and presence of fibrin monomers in the blood occurred at the time anemia and significant elevations in precipitable immune complexes were observed. Terminally, consumption of immunologic factors coincided with accelerated partial thromboplastin times. At death, convulsions and hemoptysis with labored breathing suggested that the animals died of respiratory failure and that disseminated intravascular coagulation may have occurred. It is suggested that microthrombiosis might have resulted from the immunologic interaction of complex-coated blood cells with immunoconglutinin and contributed to the terminal disease signs.

Topics: Agglutinins; Anemia; Animals; Antigen-Antibody Complex; Autoantibodies; Blood Coagulation Disorders; Complement System Proteins; Fibrin; Fibrinogen; Rats; Thrombocytopenia; Trypanosomiasis, African

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Transfusion; Calcium; Disseminated Intravascular Coagulation; Factor XIII; Factor XIII Deficiency; Female; Fibrin; Fibrinogen; Half-Life; Hemorrhage; Humans; Leukemia; Liver Diseases; Male; Plasma; Pregnancy; Thrombin; Time Factors

In 20 patients with acute leukemia the thrombin-mediated fibrin monomer complexes (SFMC) were determined before and after remission induction chemotherapy for several weeks to assess the extent of hypercoagulability. Increased levels of SFMC were observed in patients with high leukocyte cell counts after induction chemotherapy which may reflect the release of thromboplastic material from destructed leukemic cells. Patients with low leukocyte counts showed only a moderate increase in SFMC. A low concentration of antithrombin III (< 20 mg/100 ml) or a drop from a previously normal value was a prognostic unfavorable sign. An elevated level of plasmin-mediated fibrin-split-products could not be related to the course of therapy.

Topics: Acute Disease; Adolescent; Antineoplastic Agents; Antithrombin III; Blood Coagulation Disorders; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Leukemia; Leukocyte Count; Male; Middle Aged

A coagulopathy associated with severe hemolysis was a limiting factor in obtaining long-term survivors among calves with total artificial hearts in 1969. Conversion of design from sac-type hearts to flexible diaphragm hearts, and from Silastic Dacron-fibril intimas to smooth polyurethane intimas, resulted in an abatement of the coagulopathy. In the most recent series of animals studied at this laboratory, platelet counts are normal and platelet survivals are half of normal. Plasma hemoglobins are normal. The coagulation system is still activated at specific loci within the total artificial heart, but is best compensated for in calves treated with antiplatelet drugs, having polyurethane hearts.

Topics: Animals; Anticoagulants; Blood; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Cattle; Fibrin; Heart Valve Prosthesis; Heart, Artificial; Hemoglobins; Platelet Adhesiveness; Polyethylene Terephthalates; Polyurethanes; Prosthesis Design; Silicone Elastomers; Surface Properties; Thrombosis

Topics: Blood Coagulation Disorders; Fibrin; Hemostatic Techniques; Hemostatics; Humans; Oral Hemorrhage; Tooth Extraction

Abnormalities of fibrin formation were studied in 42 young adult patients with benign viral hepatitis. It was observed that there was a constant increase in thrombin time and reptilase time, evoking an abnormality of the second stage of fibrin formation, or the aggregation of fibrin monomers. This abnormality is not associated with the presence of inhibitors in the patients' serums, and is maximum at an alkaline pH. The hypothesis of an abnormality of the fibrinogen molecule, a dysfibrinogenemia, is the most likely cause, and this has to be confirmed by biochemical and immunochemical studies.

Topics: Adolescent; Adult; Blood Coagulation Disorders; Blood Coagulation Tests; Fibrin; Hepatitis, Viral, Human; Humans; Thrombin

Systemic hemostatic agents are reviewed. Among the agents discussed are vitamin K preparations (phytonadione, menadione, menadione sodium bisulfite, menadiol sodium diphosphate); and blood products (whole blood, plasma, cryoprecipitate, factor VIII concentrates, factor IX concentrates and fibrinogen concentrates). Normal and abnormal hemostasis and fibrinolysis are discussed, as is the general management of systemic hemostatic defects. Specific disorders covered are clotting factor deficiencies, hemophilia A, factor VIII inhibitors, von Willebrand disease, hemophilia B (Christmas disease), other congenital coagulation disorders, acquired deficiency of factors II, VII, IX and X, and defibrination syndrome.

Topics: Antibodies; Blood Coagulation Disorders; Factor VIII; Fibrin; Fibrinolysis; Hemophilia A; Hemophilia B; Hemostasis; Hemostatics; Humans; Transfusion Reaction; von Willebrand Diseases

Two new families of congenital dysfibrinogenemia originating from French Canada are reported. The dysfibrinogenemia in the first family is characterized by an abnormal aggregation of the fibrin monomers; the defect in the second family is due to a faulty release of fibrinopeptides during the proteolytic phase of the thrombin-fibrinogen reaction.

Topics: Blood Coagulation Disorders; Female; Fibrin; Fibrinogen; Hemorrhagic Disorders; Humans; Male

Topics: Adult; Blood Coagulation Disorders; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Pregnancy; Pregnancy Complications, Hematologic

Progression of intermittent partial or total impaction of the poppet from a prosthetic mitral valve may be difficult to evaluate in patients with chronic obstructive pulmonary disease and atrial fibrillation. Heart sounds may be distant; opening and closing clicks of the poppet are muffled and irregular. Echocardiography provides a noninvasive method to detect early prosthetic malfunction at a time when the patient is clinically asymptomatic.

Topics: Atrial Fibrillation; Blood Coagulation Disorders; Echocardiography; Fibrin; Heart Valve Prosthesis; Hemodynamics; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Mitral Valve

Circulating anticoagulants are unusual in drug-induced syndromes. We evaluated the prolonged thrombin time of plasma from a patient with a procainamide-induced syndrome. This defect was shown to be due to a circulating anticoagulant that was not of fibrin or fibrinogen origin and that prolonged thrombin and reptilase clotting times of plasma. Subclinical doses of heparin sodium induced hemorrhagic manifestations in this patient. Following cessation of heparin therapy, the circulating anticoagulant persisted but the bleeding tendency abated. All clinical and laboratory manifestations of this syndrome abated gradually following cessation of procainamide therapy.

Topics: Aged; Batroxobin; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Fibrin; Fibrinogen; Humans; Male; Procainamide; Syndrome; Thrombin

The kinetics of the thrombin-catalysed release of fibrino-peptides A and B from human fibrinogen have been investigated and a mechanism correlating the release of fibrinopeptides to fibrin formation is presented. The sequential release of fibrinopeptides results in sequential activation of two sets of polymerisation sites.

Topics: Binding Sites; Blood Coagulation; Blood Coagulation Disorders; Calcium; Fibrin; Fibrinogen; Fibrinopeptide A; Fibrinopeptide B; Humans; Kinetics; Macromolecular Substances; Protein Binding; Thrombin

The question is still open, whether a pathologic formation of fibrinogen or an insufficient stabilized fibrin are causative factors within the complex disorders in hemostasis in patients with liver cirrhosis. Thus, 45 patients with liver cirrhosis, which was proven by liver biopsy, were investigated by means of sodium-dodecyl-sulfate (SDS) polyacrylamidgel-electrophoresis in order to evaluate, whether the liver produces a pathological fibrinogen or whether the formation of fibrin from fibrinogen is defect. The fibrin stabilizing factor (factor XIII) was measured by immunological methods. In order to have a mean of the stage of the disease, 37 patients were subdivided by the extend or their porto-caval collateral circulation and further 8 patients were investigated having bleeding from esophageal varices. By the results evidence accrued that in advanced stages of liver cirrhosis and a marked porto-caval collateral circulation polymerization of fibrinogen was insufficiently, especially, the formation of alpha-chains was altered, whereas the formation of gamma-dimers, the separation of fibrinopeptides from fibrinogen, and the aggregation of fibrinmonomers were normal. This defect in fibrin structure was positive correlated with the stage of liver cirrhosis, which correlated negative with the plasma activity of factor XIII. In vitro, the defect in fibrin formation, from fibrinogen was abolished by adding factor XIII to the assay. Thus, in liver cirrhosis fibrin formation is altered because of factor XIII deficiency, but a normal fibrinogen is synthesized by the liver. In consequence, the administration of factor XIII preparations is suggested as one clinical action among others to benefit the hemostatic disorders, especially in patients with bleeding from esophageal varices.

Topics: Blood Coagulation Disorders; Blood Platelets; Cell Count; Electrophoresis, Polyacrylamide Gel; Factor XIII; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Hemostasis; Humans; Liver Cirrhosis; Sodium Dodecyl Sulfate

Topics: Adult; Atmosphere Exposure Chambers; Atmospheric Pressure; Blood Cells; Blood Coagulation Disorders; Blood Platelets; Diving; Embolism, Air; Erythrocytes; Fibrin; Humans; Male; Microscopy, Electron, Scanning

Soluble fibrinogen--fibrin complex levels were found to be significantly higher in plasma samples from pregnant women with babies suffering from intrauterine growth retardation, when compared with levels found in normal pregnancy. As soluble fibrinogen--fibrin complexes are formed following activation of the coagulation pathway in vitro and in vivo these findings may reflect the increased local intravascular coagulation within the placenta demonstrated histologically in pregnancies complicated by growth retardation. The use of more sensitive methods for detecting alterations in coagulation, fibrinolysis and platelet function may prove useful in the diagnosis of intrauterine growth retardation antenatally.

Topics: Blood Coagulation Disorders; Chromatography, Gel; Female; Fetal Growth Retardation; Fibrin; Fibrinogen; Humans; Placenta; Pregnancy; Pregnancy Complications, Hematologic

Topics: Adolescent; Adult; Blood Coagulation Disorders; Fibrin; Fibrinogen; Hepatitis, Viral, Human; Humans

The objective of oestrogen replacement therapy in the menopause is the prevention of pathology attributable to oestrogen lack. Care should be taken to ensure that such therapy is free from harmful side effects. To date, there have been no long-term longitudinal studies or clinical reports that have positively identified oestrogen usage in "normal" postmenopausal women, with inappropriate thrombosis directly attributable to an oestrogen-induced alteration in the coagulation mechanism. This is surprising since certain coagulation factors change and the peripheral blood flow decreases in the elderly, predisposing them to enhanced clot formation. There is also the well-documented (but controversial) association between oestrogens, oral contraceptives and thrombosis. Whether this paradox can be explained by differences in the type and/or potency of the oestrogens used in ORT, remains to be determined. At present it may be concluded that ORT per se does not place the postmenopausal women at greater risk from developing arterio-venous thrombosis.

Topics: Aging; Antithrombins; Blood Circulation; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Blood Vessels; Estrogens; Factor X; Female; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Humans; Menopause; Platelet Adhesiveness; Platelet Aggregation; Thrombosis

Topics: Animals; Blood Coagulation Disorders; Chromatography, Affinity; Disease Models, Animal; Endotoxins; Fibrin; Fibrinogen; Iodine Radioisotopes; Rabbits; Salmonella enteritidis

The frequent occurrence of abnormal fibrin polymerisation in patients with liver disease has recently been reported. To investigate this further, fibrin polymerisation was studied in 68 patients with cirrhosis or chronic active liver disease. Thirty-three of these patients demonstrated impairment of this phase of blood coagulation. When other tests of liver function were compared in patients demonstrating this abnormality and those in whom fibrin polymerisation was normal, it was found that the former group demonstrated significantly reduced albumin concentrations (p less than 0.0002), raised bilirubin and aspartate aminotransferase levels (p less than 0.0006 and less than 0.003 respectively), and greater prolongation of the one-stage prothrombin time (p less than 0.001) with more marked reduction in factor VII levels (p less than 0.002) compared with the latter patients. It is concluded that defective fibrin polymerisation occurring in patients with liver disease indicates the presence of severely impaired hepatocellular function. This might account for the grave prognosis reported in cirrhotic patients with abnormal fibrin polymerisation who also suffer bleeding from gastro-oesophageal varices.

Topics: Aspartate Aminotransferases; Bilirubin; Blood Coagulation Disorders; Chronic Disease; Factor VII; Fibrin; Fibrinogen; Humans; Liver Cirrhosis; Liver Diseases; Prothrombin Time; Serum Albumin; Serum Globulins

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Tests; Ethanol; Female; Fibrin; Humans; Labor, Obstetric; Obstetric Labor Complications; Postpartum Period; Pregnancy; Solubility

Plasma from patients with both acute and chronic liver disease has been examined for evidence of acquired dysfibrinogenaemia, using electrophoretic methods and coagulation tests. An examination of isolated fibrins upon SDS polyacryamide gel electrophoresis failed to demonstrate any molecular or structural defect associated with the polypeptide chains of the patients' fibrinogen or fibrinogen derivatives produced by thrombin or plasmin. However, purified fibrin monomers isolated from plasma using both Reptilase and thrombin exhibited delayed polymerization rates and the occurrence of acquired dysfibrinogenaemia in liver disease is therefore confirmed.

Topics: Acute Disease; Ancrod; Batroxobin; Blood Coagulation Disorders; Blood Coagulation Tests; Chronic Disease; Fibrin; Fibrinogen; Humans; Liver Diseases; Thrombin

Topics: Acute Kidney Injury; Anemia; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Fibrin; Hemostasis; Humans; Kidney Diseases; Kidney Failure, Chronic; Peritoneal Dialysis; Polycythemia; Renal Dialysis

To test the possibility that a functionally abnormal fibrinogen may exist in some patients with liver disease, we studied the plasma and purified fibrinogens of five patients whose plasma thrombin times were prolonged at least 40% over normal controls. In no patient was there evidence of disseminated intravascular coagulation and/or fibrinolysis. No abnormalities were detected by immunoelectrophoresis of plasmas or purified fibrinogens. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of reduced patient fibrinogens showed normal mobility and amount of Aalpha, Bbeta, and gamma chains. Alkaline polyacrylamide gel electrophoresis and gradient elution, DEAE-cellulose chromatography of admixtures of radio-iodinated patient (125)I-fibrinogen and normal (131)I-fibrinogen showed identical mobility in the gel and simultaneous elution from the column, respectively. Thrombin and Reptilase (Abbott Scientific Products Div., Abbott Laboratories, South Pasadena, Calif.) times of purified patient fibrinogens were prolonged, and calcium ions improved but did not completely correct these defects. Increasing amounts of thrombin progressively shortened the clotting times of patient fibrinogens but not to the level of normal. Addition of equal amounts of patient fibrinogen to normal fibrinogen resulted in a prolongation of the thrombin time of the normal protein. Thrombin-induced fibrinopeptide release was normal. Fibrin monomers prepared from patient plasmas and purified fibrinogens demonstrated impaired aggregation at low (0.12) and high (0.24) ionic strength. These studies demonstrate that some patients with liver disease and prolonged plasma thrombin times have a dysfibrinogenemia functionally characterized by an abnormality of fibrin monomer polymerization.

Topics: Alcoholism; Batroxobin; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Chemical and Drug Induced Liver Injury; Fibrin; Fibrinogen; Humans; Liver Cirrhosis; Liver Diseases; Prothrombin Time; Thrombin

Topics: Anticoagulants; Blood; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Female; Fibrin; Fibrinogen; Humans; Infant, Newborn; Infant, Newborn, Diseases; Pregnancy; Umbilical Cord

Topics: Arginine; Blood Coagulation Disorders; Fibrin; Humans; Neoplasm Metastasis; Neoplasms; Thrombosis

Consumptive coagulopathy and disseminated intravascular coagulation can be observed in rats exposed to 4 ata of oxygen. These events clearly precede the death of the animal and appear to be initiated by an activation of coagulation factor XII (Hageman). The onset and the extent of consumptive coagulapathy are greatly enhanced by a single and low intravenous dose of lead acetate. Mechanisms of activation of the intrinsic coagulation system and its role in oxygen toxicity are being discussed.

Topics: Animals; Blood Coagulation Disorders; Fibrin; Lead; Lead Poisoning; Lung; Male; Microscopy, Electron; Oxygen; Prothrombin Time; Rats; Species Specificity; Thromboplastin

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Disease Progression; Factor V; Factor VII; Fibrin; Fibrin Fibrinogen Degradation Products; France; Humans; Hyaline Membrane Disease; Infant, Newborn; Intensive Care Units, Neonatal; Plasminogen; Prothrombin; Respiratory Distress Syndrome, Newborn; Retrospective Studies; Risk Factors; Severity of Illness Index; Time Factors

An unusual bleeding disorder clinically resembling factor XIII deficiency is presented. The only detectable coagulation abnormality was rapid clot dissolution in 1% monochloroacetic acid. This abnormality was ascribed to the sustained increase of a pepsin-like plasma protease which is activated at low pH. Asystematic search for similar phenomena revealed that massive blood transfusion may also enhance plasma-clot solubility in acid, possibly by release of a red cell protease. We conclude that the acid clot solubility test is not a specific indicator of factor XIII deficiency, but this simple assay is recommended for further studies of acid plasma protease activity. The diagnostic relevance and pathophysiologic importance of increased pepsin-like activity in plasma remain to be elucidated.

Topics: Acetates; Adult; Blood Coagulation Disorders; Factor XIII; Factor XIII Deficiency; Female; Fibrin; Humans; Peptide Hydrolases; Solubility; Wound Healing

Fibrin formation from fibrin monomer (FM) complexes was studied in experimental animals utilizing a previously described technique for quantitating fibrin deposition. A uniform thrombin infusion was used to produce FM, fibrinolysis being inhibited by EACA. In vivo complex formation between FM and 125I-fibrinogen was demonstrated chromatographically. A direct correlation was found between blood fibrinogen concentration and fibrin deposition in organs. By contrast, an inverse correlation between fibrinogen concentration and both enzymatic or non-enzymatic fibrin formation was found in vitro. The mechanism by which fibrinogen potentiates FM precipitation in vivo could not be explained by coprecipitation of fibrinogen in the complex which could not be demonstrated. The inhibitory effect of HN2 on fibrin deposition despite the associated hyperfibrinogemia induced by this drug is believed to underscore the importance of leukocytes in certain types of fibrin deposition. A correlation between the leukocyte count and fibrin formation from FM was also found. It was concluded that the risk of intravascular fibrin deposition is increased by a raised fibrinogen level especially when accompanied by leukocytosis.

Topics: Animals; Blood Coagulation Disorders; Blood Vessels; Endotoxins; Fibrin; Fibrinogen; Leukocyte Count; Mechlorethamine; Rabbits; Thrombin

Intravascular coagulation was induced by two appropriately spaced doses of endotoxin and by infusion of thromboplastin. The resulting fibrin deposition was measured by a previously described quantitative technique. Evidence of thrombin elaboration was obtained indirectly by measurement of fibrin monomer (FM) and by the detection and isolation of a thrombin-induced anticlotting activity. Venous segments were isolated at intervals and examined for thrombus formation following 40 minutes of stasis. Endotoxin triggered thrombin elaboration was not detectable in the circulation for at least one hour and was not accompanied by any thrombosis in isolated venous segments. No thrombin elaboration was found in leukopenic rabbits given endotoxin. In the thromboplastin infused animals, the quantity of fibrin deposited in the organs was comparable to that found after endotoxin. However, thrombin was found in the blood immediately and was associated with thrombosis in the isolatet venous segments. Less thrombin-induced anticoagulant activity was found after thromboplastin than after endotoxin. The findings suggest that endotoxin-induced intravascular coagulation is probably not caused by a mechanism of systemic hypercoagulability due to the release of thromboplastic material into the blood stream. A focal process of thrombin elaboration involving leukocytes is postulated. The study is believed relevant to patients with disseminated intravascular coagulation in whom venous thromboembolism is rarely found despite evidence of extensive microvascular fibrin deposition.

Topics: Animals; Blood Coagulation Disorders; Blood Vessels; Disseminated Intravascular Coagulation; Endotoxins; Fibrin; Fibrinogen; Leukocytes; Leukopenia; Mechlorethamine; Rabbits; Thrombin; Thromboplastin

Sufficient clotting factors to ensure coagulation and replacement of lost volume and oxygen-carrying capacity are necessary to obviate many of the complications that may occur when massive transfusions are used in patients with multiple injuries. A regimen that has been successful includes immediate infusion of plasma protein fraction, packed red cells, fresh-frozen plasma, and nonspecific platelets.

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Blood Proteins; Blood Transfusion; Disseminated Intravascular Coagulation; Fibrin; Humans; Respiratory Insufficiency; Thrombocytopenia; Transfusion Reaction; Wounds and Injuries

A case report of a patient with primary fibrinolysis resulting in hemorrhage after an oral surgical procedure has been presented. A comparison was made between DIC and primary fibrinolysis in patients with carcinoma of the prostate gland; etiology, clinical findings, diagnosis, and treatment were discussed.

Topics: Aged; Alveoloplasty; Aminocaproates; Blood Cell Count; Blood Coagulation Disorders; Blood Platelets; Blood Transfusion; Chlorothiazide; Diethylstilbestrol; Estrogens, Conjugated (USP); Fibrin; Fibrinolysis; Hematocrit; Hemoglobins; Humans; Male; Methyldopa; Oral Hemorrhage; Postoperative Complications; Prothrombin Time; Thromboplastin; Tooth Extraction

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Fibrin; Fibrinolysis; Hemostasis; Humans; Thrombin; Thromboplastin

In 42 children with congenital heart disease coagulation factor levels were studied serially during the first 20 hours following cardiopulmonary bypass surgery. The acyanotic patients, and also cyanotic patients who survived the operation, showed a progressive improvement in their coagulation profile from initial low postoperative levels. In 12 cyanotic patients who died within 72 hours, however, the coagulation factor levels either remained low, or fell further, until death. Fresh frozen plasma was administered to eight of these patients without apparent benefit. The abnormal coagulation profile correlated significantly with low skin temperature and increased blood loss and was considered to represent excess intravascular coagulation secondary to low cardiac output and poor tissue perfusion.

Topics: Blood Coagulation Disorders; Blood Platelets; Blood Transfusion; Cardiopulmonary Bypass; Child; Child, Preschool; Cyanosis; Disseminated Intravascular Coagulation; Extracorporeal Circulation; Factor V; Factor VIII; Fibrin; Fibrinogen; Heart Defects, Congenital; Hematocrit; Heparin; Humans; Infant; Microscopy, Phase-Contrast; Plasminogen; Protamines; Skin Temperature

Topics: Blood Cell Count; Blood Circulation; Blood Coagulation; Blood Coagulation Disorders; Blood Platelets; Blood Transfusion; Factor V; Factor VIII; Fibrin; Fibrinogen; Fibrinolysis; Humans; Infusions, Parenteral; Pediatrics; Prothrombin; Shock, Hemorrhagic; Shock, Traumatic; Thrombocytopenia; Wounds and Injuries

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Fibrin; Hepatitis A; Humans; Liver Cirrhosis; Prothrombin; Time Factors

The subunit structure of fibrinogen Baltimore and fibrin formed from this inherited dysfibrinogenemia was analyzed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. The molecular weights of the alpha-, b- and gamma-chains of fibrinogen Baltimore were found to be identical to those of normal fibrinogen. Noncross-linked fibrin formed from both purified fibrinogen Baltimore as well as normal fibrinogen contained two alpha-monomers (alpha1 and alpha2). alpha2 was presumed to be alpha-monomer from which fibrinopeptide A had been released. The evolution of alpha2 during clotting of fibrinogen Baltimore was delayed and appeared to be quantitatively reduced when compared to normal. Crosslinked fibrin formed from fibrinogen Baltimore possessed an abnormal subunit structure. alpha-polymers were not generated in thrombin-induced, factor XIII-rich clots of fibrinogen Baltimore under conditions of pH and calcium concentration suitable for complete alpha-polymerization in normal fibrin. If clotting was carried out with calcium concentrations twice that required for normal clots or at pH 6.4, fibrin from fibrinogen Baltimore was completely cross-linked. These structural analyses of fibrin formed from fibrinogen Baltimore substantiate earlier findings that indicate a defect in the alpha-chain of this dysfibrinogenemia.

Topics: Blood Coagulation Disorders; Blood Protein Electrophoresis; Electrophoresis, Polyacrylamide Gel; Factor XIII; Fibrin; Fibrinogen; Fibrinolysis; Humans; Molecular Weight; Polymers; Thrombin

Topics: Ancrod; Blood Coagulation Disorders; Endopeptidases; Fibrin; Fibrinogen; Humans; Solubility; Thrombosis

The maximal rate of change in optical density (Vmax-deltaOD)of plasma clots forming in the activated partial thromboplastin time test (APTT) may be significantly influenced by reductions in factor VIII activity insufficient to also cause a distinctly abnormal timed clotting endpoint. Analysis of relationships between Vmax-deltaOD of clotting plasma in the APTT, prothrombin time, and thrombin time tests provides a basis for increasing the screening value of the APTT in suggesting intrinsic system abnormalities. Three illustrative case reports support the added benefit of thrombokinetics in the detection of mild factor VIII deficiency in hemophilia A and in von Willebrand's disease.

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Tests; Factor VIII; Fibrin; Hemophilia A; Humans; Kinetics; Male; Middle Aged; Prothrombin; Prothrombin Time; Thrombin; Thromboplastin

Several coagulation factors were studied in twenty children less than 16 years old, bearing nephrotic syndrome. Four of them were in remission. In nephrotic syndrome there is hypercoagulability. Coagulations factors such as fibrinogen, platelet factor III, prothrombin time, and factor V are markedly altered, and to a lesser degree, total number of platelets. Fibrin degradation products factors II, VII, X and VIII are also altered. During remission, all of them improve or become normal. In no case fibrin breakdown products were found in the blood. However, if found in urine, they would be considered as a pronostic index in nephropaties. Although etiologic factors remain unknown for most of the above-mentioned alterations, increased fibrinogen synthesis, decreased fibrinolytic plasms activity and renal damage have been demonstrated.

Topics: Adolescent; Age Factors; Biopsy; Blood Coagulation Disorders; Blood Coagulation Tests; Child; Child, Preschool; Fibrin; Fibrinolysis; Humans; Kidney; Microscopy, Electron; Nephrotic Syndrome

Topics: Blood Coagulation Disorders; Chromatography, Agarose; Diagnosis, Differential; Disseminated Intravascular Coagulation; Female; Fibrin; Humans; Pregnancy; Pregnancy Complications, Hematologic

Topics: Adult; Blood Coagulation Disorders; Female; Fibrin; Hemostasis; Hepatitis A; Humans; Male

The quantitative estimation of soluble fibrin monomer complexes (SFMC) was applied to evaluate the state of hypercoagulability during pregnancy and delivery. Blood samples from 67 healthy primi and multiparae, 6 to 40 weeks pregnant, and from a group of 8 women in labour and after delivery of the placenta were examined. Fibrinogen and SFMC were precipitated from plasma by precipitation with beta-alanine. Gel filtration (4% agarose) of the redissolved precipitate resulted in a separation of SFMC and fibrinogen. This enabled a quantitative estimation of the SFMC concentration (with-in assay precision: coefficient of variation=8%). The % amount SFMC of the total fibrinogen content increased from 2.6 +/- 0.4 to 4.9 +/- 1.3% (mean and standard deviation) to week 40 of pregnancy. During delivery an additional statistically significant increase occurred. Chain analysis of SFMC showed a decreased amount of alpha-chain indicating plasmin activity. gamma-gamma-dimers as residuals of intermolecular covalent bonding were not observed. The quantitative estimation of SFMC during pregnancy and delivery demonstrates that a state of hypercoagulability during gestation can be evaluated by measuring the catabolic products of fibrinogen. This may lead to a differentiation from severe intravascular coagulation and to an early diagnosis of thromboembolic disease or consumption coagulopathy.

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Blood Specimen Collection; Chromatography, Gel; Female; Fibrin; Fibrinogen; Humans; Pregnancy; Pregnancy Complications, Hematologic

Topics: Afibrinogenemia; Blood Coagulation Disorders; Blood Coagulation Tests; Brain Injuries; Cerebral Hemorrhage; Disseminated Intravascular Coagulation; Factor V; Factor VIII; Fibrin; Fibrinogen; Humans; Plasma Substitutes

Topics: Anticoagulants; Antithrombins; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Cell Aggregation; Ethanol; Fibrin; Fibrinolysis; Gels; Humans; Postoperative Care; Prognosis; Thrombelastography; Thrombin; Thromboembolism; Thrombosis

Topics: Animals; Aspirin; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Chickens; Factor XII; Fibrin; Fibrinolysin; Fibrinolysis; Humans; Plasminogen; Serum Globulins; Streptokinase; Urokinase-Type Plasminogen Activator

Topics: Acute Kidney Injury; Anemia; Basement Membrane; Blood Coagulation Disorders; Capillaries; Epithelial Cells; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Hematuria; Histocytochemistry; Humans; Immunoglobulins; Kidney; Kidney Glomerulus; Kidney Tubules; Microscopy, Electron; Prognosis; Proteinuria; Statistics as Topic

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Factor IX; Factor V; Factor VII; Factor VIII; Factor X; Fibrin; Humans; Infections; Kidney Diseases; Phospholipids; Shock, Septic

Topics: Blood Coagulation Disorders; Electrophoresis, Polyacrylamide Gel; Factor XIII; Fibrin; Fibrinogen; Humans; Molecular Weight; Peptides; Sodium Dodecyl Sulfate

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Diagnosis, Differential; Fibrin; Fibrinogen; Humans; Immunoassay; In Vitro Techniques; Latex Fixation Tests

Topics: Adult; Blood Coagulation; Blood Coagulation Disorders; Clinical Enzyme Tests; Coagulase; Female; Fibrin; Fibrinogen; Heparin; Humans; Methods; Obstetric Labor Complications; Pregnancy; Pregnancy Complications, Hematologic; Prothrombin Time; Streptokinase; Thrombin; Time Factors

Topics: Adult; Anti-Glomerular Basement Membrane Disease; Blood Coagulation Disorders; Female; Ferritins; Fibrin; Glomerulonephritis; Hemorrhagic Disorders; Humans

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Fibrin; Fibrinogen; Humans; Molecular Conformation

Topics: Animals; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Factor XI; Factor XII; Fibrin; Humans; Rabbits; Surface-Active Agents

Topics: Adult; Antigens; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Graft Rejection; Humans; Kidney Transplantation; Male; Middle Aged; Thromboplastin; Transplantation, Homologous

Topics: Aged; Batroxobin; Blood Coagulation; Blood Coagulation Disorders; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Immunoelectrophoresis; Male; Thrombin; Time Factors

Topics: Abortion, Induced; Amniotic Fluid; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Factor VIII; Female; Fibrin; Fibrinogen; Humans; Hypertonic Solutions; Plasminogen; Pregnancy; Serum Globulins; Sodium Chloride; Solubility; Thromboplastin; Time Factors; Uterine Hemorrhage

Topics: Adolescent; Adult; Aged; Blood Coagulation Disorders; Blood Pressure; Female; Fibrin; Fibrinogen; Humans; Hypertension; Male; Middle Aged; Solubility

Topics: Blood Coagulation Disorders; Fibrin; Humans

Topics: Animals; Blood; Blood Coagulation Disorders; Blood Coagulation Factors; Chromatography; Dextrans; Dogs; Fibrin; Fibrinogen; Hemostasis; Protamines; Solubility; Thrombosis

Topics: Aged; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Dysgerminoma; Female; Fibrin; Humans; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms; Prostatic Neoplasms; Stomach Neoplasms; Testicular Neoplasms; Thrombophlebitis

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Brain; Cerebrovascular Disorders; Cholesterol; Fibrin; Fibrinogen; Fibrinolysis; Humans; Ischemia; Plasminogen; Triglycerides

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Factors; Female; Fibrin; Fibrinogen; Hemorrhagic Disorders; Humans; Hysterectomy; Molecular Conformation; Plasma; Prothrombin Time; Thrombin

Discrimination between the physiological cleavage fragments of fibrinogen and fibrin offers an approach to differentiation between fibrinogenolytic processes and fibrinolysis after coagulation. By use of the cleavage-associated neoantigen of fibrinogen (fg-D(neo)) as a molecular marker, characteristic differences between the D regions of fibrinogen derivatives and fibrin derivatives can be demonstrated. The expression of fg-D(neo) by X, Y, D:E complex, and D-fragments of fibrinogen or fibrin is shown to be quantitative and unitary. Characteristic differences between fg-D(neo) sites present on fibrinogen cleavage fragments, as contrasted to fibrin cleavage fragments, are indicated by different competitive inhibition slopes, and appear to reflect differential binding affinity of selected anti-fg-D(neo) antibodies for the specific molecular site. There is a linear relationship between the slope of quantitative competitive inhibition and the relative molar ratio of fibrinogen and fibrin derivatives. Identical immunochemical expressions are observed in vitro and in vivo, and support the thesis that cleavage in vivo is produced by plasmin. The differential immunochemical features of fg-D(neo) expression may be the result of stable conformational and/or subtle structural differences between the D region of fibrinogen and fibrin cleavage fragments and suggest that precise changes in the D region are associated with the fibrin transition. These molecular features not only provide additional insight into the molecular immunology and structure of fibrinogen, but also appear to offer a new molecular approach to discrimination between fibrinogenolytic mechanisms as contrasted to fibrinolysis secondary to coagulation.

Topics: Abruptio Placentae; Acute Kidney Injury; Adenocarcinoma; Binding Sites, Antibody; Binding, Competitive; Blood Coagulation Disorders; Epitopes; Female; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Humans; Immune Sera; Iodine Isotopes; Male; Melanoma; Meningococcal Infections; Peritonitis; Pregnancy; Prostatic Neoplasms; Radioimmunoassay; Structure-Activity Relationship

Topics: Adult; Alpha-Globulins; Aminocaproates; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Esophageal and Gastric Varices; Factor V; Factor VII; Factor X; Female; Fibrin; Fibrinolysin; Fibrinolysis; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Macroglobulins; Male; Middle Aged; Plasminogen; Protamines

Topics: Adenocarcinoma; Adult; Aged; Alpha-Globulins; Blood Coagulation Disorders; Blood Protein Electrophoresis; Bronchial Neoplasms; Carcinoma; Carcinoma, Bronchogenic; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Heparin; Humans; Infusions, Parenteral; Lung Neoplasms; Macroglobulins; Male; Middle Aged; Time Factors

Topics: Blood Cells; Blood Coagulation Disorders; Cell Nucleus; Cerebrovascular Disorders; Disseminated Intravascular Coagulation; Fibrin; Humans; Lung; Malaria; Male; Middle Aged; Staining and Labeling

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelet Disorders; Blood Platelets; Cell Aggregation; Cell Count; Factor V; Factor VII; Factor X; Fibrin; Fibrinolysin; Humans; Plasminogen; Time Factors; Transfusion Reaction; Wounds and Injuries

Topics: Adult; Antibodies; Antibodies, Anti-Idiotypic; Blood Cell Count; Blood Coagulation; Blood Coagulation Disorders; Blood Platelet Disorders; Clot Retraction; Erythrocytes; Factor X; Female; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Humans; Male; Plasminogen; Platelet Adhesiveness; Pulmonary Embolism; Stimulation, Chemical; Thrombin; Thrombophlebitis; Thrombosis

Topics: Angiotensin II; Arginine; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Proteins; Caseins; Chromatography, Gel; Chymotrypsinogen; Enzyme Activation; Esters; Fibrin; Fibrinogen; Hemoglobins; Humans; Hydrolysis; Macroglobulins; Pancreatitis; Protein Binding; Protein Denaturation; Thrombin; Trypsin; Trypsin Inhibitors; Trypsinogen; Vasopressins

Topics: Aminocaproates; Animals; Aprotinin; Blood Coagulation Disorders; Fibrin; Fibrinogen; Fibrinolysis; Hirudins; Iodine Radioisotopes; Protamines; Prothrombin Time; Shwartzman Phenomenon; Streptokinase; Thrombin; Time Factors

Topics: Adolescent; Adult; Aprotinin; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Child; Child, Preschool; Disseminated Intravascular Coagulation; Extracorporeal Circulation; Factor V; Factor VII; Fibrin; Fibrinolysis; Heart-Lung Machine; Heparin; Humans; Middle Aged; Protamines; Prothrombin; Time Factors

Topics: Blood Coagulation Disorders; Child, Preschool; Disseminated Intravascular Coagulation; Fibrin; Heparin; Humans; Male; Meningococcal Infections; Prognosis; Sepsis

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Diagnosis, Differential; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinolysis; Humans; Infant; Male; Syndrome

Topics: Agglutination Tests; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Hemagglutination Inhibition Tests; Humans; Liver Cirrhosis; Neoplasms; Staphylococcus

Topics: Anemia, Hemolytic; Animals; Blood Cell Count; Blood Coagulation Disorders; Blood Urea Nitrogen; Carcinoma 256, Walker; Disseminated Intravascular Coagulation; Factor VIII; Female; Fibrin; Fibrinogen; Half-Life; Hematocrit; Hemoglobinometry; Hypercalcemia; Iodine Isotopes; Neoplasm Transplantation; Plasminogen; Platelet Adhesiveness; Rats; Serum Globulins; Thrombelastography; Transplantation, Homologous

Topics: Adolescent; Adult; Aged; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Complement System Proteins; Creatinine; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Fibrinolysis; Glomerulonephritis; Humans; Kidney Diseases; Kidney Glomerulus; Lupus Erythematosus, Systemic; Male; Middle Aged; Proteinuria; Prothrombin Time

Topics: Blood Coagulation Disorders; Blood Platelet Disorders; Blood Platelets; Fibrin; Humans; Phospholipids; Platelet Adhesiveness; Thrombophlebitis; Thrombosis

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Disseminated Intravascular Coagulation; Factor VIII; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemagglutination Inhibition Tests; Humans; Liver Cirrhosis; Male; Plasminogen; Thromboplastin

Topics: Adolescent; Adult; Aged; Arteriosclerosis; Blood Coagulation Disorders; Blood Coagulation Tests; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Fibrin; Fibrinogen; Half-Life; Humans; Iodine Radioisotopes; Middle Aged

Topics: Acute Kidney Injury; Basement Membrane; Blood Coagulation Disorders; Diabetic Nephropathies; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Fibrinolysis; Glomerulonephritis; Hemagglutination Tests; Hemolytic-Uremic Syndrome; Humans; Ischemia; Kidney; Kidney Diseases; Male; Middle Aged; Pre-Eclampsia; Pregnancy; Thrombosis; Urokinase-Type Plasminogen Activator

Topics: Acute Disease; Blood Coagulation Disorders; Blood Urea Nitrogen; Factor VIII; Fibrin; Fibrinolysin; Fibrinolysis; Glomerulonephritis; Humans; Thromboplastin; Time Factors

Topics: Blood Coagulation Disorders; Cell Membrane; Fibrin; Fibrinogen; Fibrinolysin; Graft Rejection; Humans; Kidney Transplantation; Liver; Methods; Mononuclear Phagocyte System; Peptide Hydrolases; Transplantation, Homologous

Topics: Aminocaproates; Blood Coagulation; Blood Coagulation Disorders; Fibrin; Fibrinolysin; Fibrinolysis; Hematuria; Humans; Male; Middle Aged; Urinary Tract; Urinary Tract Infections

Topics: Aminocaproates; Animals; Blood Coagulation; Blood Coagulation Disorders; Chlorides; Densitometry; Disseminated Intravascular Coagulation; Dogs; Endotoxins; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Humans; Mercury; Methods; Myocardial Infarction; Protamines; Rabbits; Sulfates; Thromboembolism

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Carcinoma, Hepatocellular; Chromatography, Gel; Female; Fibrin; Fibrinogen; Humans; Liver Neoplasms; Middle Aged; Prothrombin Time

Topics: Amines; Binding Sites; Blood Coagulation; Blood Coagulation Disorders; Cadaverine; Chemical Phenomena; Chemistry; Cyclohexanecarboxylic Acids; Dansyl Compounds; Enzyme Activation; Factor XIII; Fibrin; Fibrinolysis; Glutamine; Humans; Methylamines; Naphthalenes; Structure-Activity Relationship; Sulfonamides; Thrombosis; Transferases

Topics: Antigens; Blood Coagulation Disorders; Fibrin; Humans; Immune Sera; Immunoelectrophoresis

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Evaluation Studies as Topic; Factor XIII; Fibrin; Humans

Topics: Amino Acid Sequence; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Fibrin; Fibrinogen; Humans

Topics: Absorption; Animals; Anticoagulants; Barium Sulfate; Binding Sites; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Viscosity; Calcium; Cattle; Fibrin; Hot Temperature; Humans; Immunoelectrophoresis; Immunoglobulin A; Immunoglobulin G; Iodine Isotopes; Myeloma Proteins; Peptides; Polymers; Protamines; Rabbits; Spectrophotometry

Topics: Afibrinogenemia; Blood Coagulation Disorders; Blood Coagulation Factors; Factor IX; Factor VII; Factor VIII; Factor X; Factor XIII; Fibrin; Fibrinogen; Hemophilia A; Hemophilia B; Humans; Prothrombin; Thrombin; Vitamin K

Topics: Blood Coagulation Disorders; Fibrin; Fibrinogen; Humans; Liver Cirrhosis

Topics: Afibrinogenemia; Blood Coagulation Disorders; Fibrin; Fibrinogen; Humans; Methods; Time Factors

Topics: Animals; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Disease Models, Animal; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Male; Papain; Prothrombin Time; Rabbits; Thrombin

Topics: Acute Disease; Adolescent; Adult; Aged; Blood Coagulation Disorders; Blood Coagulation Tests; Child; Child, Preschool; Exchange Transfusion, Whole Blood; Factor V Deficiency; Factor VII Deficiency; Female; Fibrin; Fibrinolysis; Hemorrhage; Hemostasis; Hepatitis A; Humans; Hypoprothrombinemias; Liver Diseases; Liver Function Tests; Male; Middle Aged; Plasminogen; Prothrombin Time

Topics: Anemia, Hemolytic; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Fibrin; Hemangiosarcoma; Humans; Male; Middle Aged; Phagocytosis; Splenectomy; Splenic Neoplasms; Thrombocytopenia

Topics: Arterial Occlusive Diseases; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Blood Transfusion; Factor XIII; Femoral Artery; Fibrin; Humans; Male; Microscopy, Electron; Middle Aged

Topics: Apgar Score; Birth Weight; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Disseminated Intravascular Coagulation; Female; Fibrin; Gestational Age; Humans; Hypothermia; Infant, Newborn; Infant, Newborn, Diseases; Male

Topics: Alpha-Globulins; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Child; Female; Fibrin; Fibrinogen; Genes, Dominant; Humans; Immunoelectrophoresis; Male; Microscopy, Electron; Prothrombin Time; Thrombin

Topics: Animals; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelet Disorders; Blood Platelets; Coagulase; Disease Models, Animal; Dogs; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Mice; Rabbits; Rats; Streptodornase and Streptokinase; Thrombin; Thrombosis; Venoms

Topics: Animals; Blood Coagulation Disorders; Chemical Precipitation; Fibrin; Fibrinogen; Humans; In Vitro Techniques; Indicator Dilution Techniques; Protamines; Rabbits; Streptokinase; Thrombin; Vascular Diseases

Topics: Angiography; Animals; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Embolism, Fat; Escherichia coli Infections; Female; Fibrin; Infarction; Kidney; Kidney Cortex Necrosis; Kidney Diseases; Kidney Glomerulus; Lipids; Rabbits; Shwartzman Phenomenon; Toxemia; Triglycerides

The formation of human fibrin from fibrinogen has been examined by polyacrylamide gel electrophoresis in sodium dodecyl sulfate, a method which separates a mixture of proteins on the basis of differences in molecular weight. It has been found that the plasma from a patient with a congenital deficiency of fibrin-stabilizing factor forms clots lacking the cross links among the alpha- and gammachains found in normal, cross-linked human fibrin. The addition of purified fibrin-stabilizing factor or normal plasma to the deficient plasma results in extensive cross-linking of the chains. Thus, the fibrinogen in the fibrin-stabilizing factor deficient plasma appears to be normal and forms fibrin which contains dimeric, cross-linked gamma-chains and polymeric, high molecular weight forms of alpha-chains. By the use of these electrophoretic methods, it has also been possible to develop a highly sensitive method for measuring the content of fibrin-stabilizing factor in plasma. This method depends upon the use of urea-treated fibrinogen, which is completely devoid of fibrin-stabilizing factor, but which forms the usual cross-linked subunits after conversion to fibrin by thrombin in the presence of fibrin-stabilizing factor.

Topics: Acetates; Blood Coagulation Disorders; Blood Protein Electrophoresis; Ethylmaleimide; Factor XIII; Fibrin; Fibrinogen; Guanidines; Humans; Methods; Molecular Weight; Urea

Topics: Adrenal Glands; Asphyxia Neonatorum; Blood Cell Count; Blood Coagulation Disorders; Blood Platelets; Disseminated Intravascular Coagulation; Embryonic and Fetal Development; Fibrin; Fibrinogen; Hemorrhage; Humans; Hypothermia; Infant, Newborn; Liver; Respiration, Artificial; Thromboembolism; Vitamin K Deficiency

Topics: Blood Coagulation Disorders; Fibrin; Fibrinogen; Genetic Code; Hemostasis; Humans

Topics: Acute Disease; Blood Coagulation Disorders; Chromatography; Fibrin; Fibrinogen; Humans; Myocardial Infarction; Thrombosis

Topics: Aminocaproates; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Diagnosis, Differential; Fibrin; Fibrinogen; Fibrinolysis; Hemostatics; Heparin; Humans; Injections, Intravenous; Intrinsic Factor; Perfusion; Prothrombin Time

Topics: Animals; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Group Incompatibility; Dogs; Female; Fibrin; Fibrinogen; Fibrinolysis; Heparin; Immunoelectrophoresis; Male; Rats; Shock; Thrombelastography; Transfusion Reaction

Fibrin clots formed in normal plasma contained about 6 mol of epsilon-(gamma-glutamyl)lysine per mol of fibrin, whereas those formed in plasma from individuals with Factor XIII deficiency contained little or none of this crosslink (0.02-0.64 mol/mol of fibrin). Partial supplementation of the plasma with Factor XIII, at a single concentration tested, commensurately increased the number of crosslinks.

Topics: Blood Coagulation Disorders; Factor XIII; Fibrin; Glutamates; Humans; Lysine; Methods; Peptides

Topics: Adolescent; Adult; Blood Coagulation Disorders; Bone Marrow; Brain; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Hemorrhage; Humans; Kidney Glomerulus; Leukemia, Myeloid, Acute; Liver; Lymph Nodes; Male; Middle Aged; Pulmonary Edema; Skin; Spleen

Topics: Aprotinin; Blood Coagulation Disorders; Fibrin; Fibrinolysis; Heparin; Humans

Topics: Abortion, Septic; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Ethanol; Female; Fibrin; Hematoma; Humans; Leukemia; Liver Cirrhosis; Methods; Neoplasms; Phlebitis; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications, Hematologic; Sepsis

Topics: Agar; Blood Coagulation Disorders; Blood Coagulation Tests; Female; Fibrin; Fibrinolysis; Humans; Methods; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications, Hematologic; Serologic Tests

Topics: Autopsy; Blister; Blood Coagulation Disorders; Duodenal Ulcer; Fibrin; Hemorrhage; Histocytochemistry; Humans; Infant; Kidney Glomerulus; Lung Diseases; Male; Mast Cells; Peptic Ulcer Hemorrhage; Shock, Hemorrhagic; Skin; Thrombosis; Urticaria Pigmentosa

Topics: Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Fibrin; Humans; Hyaline Membrane Disease; Infant, Newborn; Infant, Premature; Renal Veins; Thrombophlebitis

Topics: Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Factor V; Fibrin; Fibrinogen; Fibrinolysis; Humans

Topics: Blood; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Humans; Infant, Newborn; Thrombin; Thromboplastin; Umbilical Cord

Topics: Adult; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemagglutination Inhibition Tests; Humans; Male; Methods; Middle Aged; Staphylococcus

Topics: Adult; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Embolism, Amniotic Fluid; Factor IX; Factor V; Factor VIII; Factor X; Female; Fibrin; Fibrinogen; Haptoglobins; Hemoglobinometry; Humans; Plasminogen; Pregnancy; Prothrombin; Prothrombin Time; Serum Globulins; Time Factors

Topics: Anemia, Hemolytic; Animals; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Blood Vessels; Carcinoma 256, Walker; Female; Fibrin; Fibrinogen; Hematocrit; Hemoglobins; Hypercalcemia; Iodine Isotopes; Plasminogen; Rats

Topics: Adult; Afibrinogenemia; Blood Coagulation Disorders; Blood Coagulation Tests; Chemical Precipitation; Female; Fibrin; Fibrinogen; Humans; Immunoelectrophoresis; Prothrombin Time; Thrombelastography; Thrombin

Topics: Autopsy; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Fibrin; Fibrinogen; Fibrinolysis; Hemorrhage; Hepatitis A; Humans; Thrombocytopenia

Topics: Abortion, Septic; Animals; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Female; Fibrin; Heparin; Humans; Pregnancy; Rabbits; Shock, Septic

Topics: Adolescent; Adult; Anemia, Hemolytic; Blood Coagulation Disorders; Blood Pressure; Child, Preschool; Desoxycorticosterone; Erythrocytes; Female; Fibrin; Glomerulonephritis; Humans; Hypertension, Malignant; Kidney Diseases; Male; Middle Aged; Necrosis; Nephrectomy; Urea; Vascular Diseases

Topics: Amines; Blood Coagulation Disorders; Factor XIII; Fibrin; Fibrinolysis; Fibrinolytic Agents; Fluorescence; Humans; Kinetics; Naphthalenes; Plasminogen; Polyamines; Serum Globulins; Spectrophotometry; Sulfonic Acids; Thrombin; Time Factors

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Chemical Precipitation; Diagnosis, Differential; Fibrin; Fibrinogen; Fibrinolysis; Immunodiffusion; Immunoelectrophoresis

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Vessels; Capillaries; Fibrin; Heart Massage; Humans; Kidney; Kidney Glomerulus; Lung; Myocardial Infarction; Staining and Labeling; Time Factors

Topics: Adult; Agglutination Tests; Arthritis, Rheumatoid; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Contraceptives, Oral; Erythrocytes; False Negative Reactions; False Positive Reactions; Female; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Hemagglutination Inhibition Tests; Hodgkin Disease; Humans; Immunoassay; Immunodiffusion; Kidney Diseases; Liver Cirrhosis; Lymphoma, Non-Hodgkin; Male; Methods; Middle Aged; Myocardial Infarction; Neoplasms; Plasminogen; Staphylococcus

Topics: Animals; Blood; Blood Coagulation Disorders; Blood Coagulation Factors; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Fibrinolysin; Humans; Male; Microscopy, Electron; Plasma; Rabbits; Serum Globulins; Spectrophotometry; Thrombelastography; Thrombin; Thrombosis

Topics: Acute Kidney Injury; Animals; Aprotinin; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinolysis; Fibrinolytic Agents; Kidney; Kidney Function Tests; Kidney Glomerulus; Liver; Lung; Rabbits; Sodium Chloride; Spleen; Thrombelastography; Thrombin

Topics: Adenocarcinoma; Anemia, Hemolytic; Blood Coagulation Disorders; Diagnostic Techniques, Surgical; Erythrocytes; Fibrin; Humans; Lung; Male; Microscopy, Electron; Microscopy, Electron, Scanning; Middle Aged; Postmortem Changes; Stomach Neoplasms

Topics: Autopsy; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Cytopathogenic Effect, Viral; Erythrocytes; Fibrin; Fibrinogen; Hemorrhage; Herpes Simplex; Humans; Infant, Newborn; Infant, Newborn, Diseases; Prothrombin Time

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Caseins; Chromosome Aberrations; Chromosome Disorders; Consanguinity; Factor XIII; Female; Fibrin; Fluorometry; Genes, Recessive; Humans; Male; Pedigree; Sex Chromosome Aberrations; Sex Factors

Disseminated intravascular coagulation occurred in dogs given scorpion venom subcutaneously in doses of 3 mg./kg. body weight. Treatment with heparin reversed the coagulation abnormality of the syndrome and 10 out of 12 dogs survived. Necropsy findings in human patients stung by scorpions suggest that this syndrome also occurs in man.

Topics: Animals; Blood Coagulation Disorders; Cortisone; Dogs; Fibrin; Fibrinogen; Heparin; Humans; Scorpions; Venoms

Topics: Aminocaproates; Animals; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Chickens; Comb and Wattles; Disseminated Intravascular Coagulation; Fibrin; Hemorrhage; Heparin; Influenza in Birds; Liver; Lung; Myocardium; Spleen; Thrombelastography; Virus Diseases

Topics: Adenocarcinoma; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelet Disorders; Blood Protein Disorders; Carcinoma; Colonic Neoplasms; Fibrin; Hemostatics; Humans; Immunoelectrophoresis; Kidney Neoplasms; Male; Middle Aged; Multiple Myeloma; Papain; Plasmapheresis

Topics: Accidents, Traffic; Aged; Autopsy; Blood Coagulation Disorders; Embolism, Fat; Female; Femoral Fractures; Fibrin; Fracture Fixation, Intramedullary; Fractures, Bone; Humans; Intracranial Embolism and Thrombosis; Lipids; Lung; Male; Middle Aged; Pelvic Bones; Pulmonary Artery; Pulmonary Embolism; Pulmonary Veins; Tibial Fractures; Time Factors; Wounds and Injuries

Topics: Antigens; Blood Cell Count; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Disseminated Intravascular Coagulation; Fibrin; Hemostasis; Humans; Meningococcal Infections; Sepsis; Thrombin

Serum levels of fibrinogen/fibrin degradation products, measured in African women, were significantly higher in pre-eclamptic toxaemia than in normal pregnancy, and were significantly higher with eclampsia than with toxaemia. These findings are in accord with the hypothesis that eclampsia and toxaemia are associated with disseminated intravascular coagulation, which may be responsible for certain clinical manifestations of these conditions.

Topics: Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Eclampsia; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Postpartum Period; Pre-Eclampsia; Pregnancy

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Cysteine; Factor XIII; Female; Fibrin; Fibrinogen; Humans; Male; Methods; Solubility; Time Factors

Topics: Adult; Blood Coagulation Disorders; Diagnosis, Differential; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Pregnancy; Pregnancy Complications, Hematologic

Topics: Anemia, Hemolytic; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Blood Transfusion; Child; Diagnosis, Differential; Disseminated Intravascular Coagulation; Factor V; Factor VIII; Fibrin; Fibrinolysis; Hemorrhagic Disorders; Heparin; Hepatitis; Humans; Infections; Pediatrics; Uremia

Topics: Adult; Arteriosclerosis; Blood Coagulation Disorders; Coronary Disease; Diffuse Cerebral Sclerosis of Schilder; Fibrin; Fibrinolysis; Genetic Diseases, Inborn; Germany, East; Humans; Intracranial Arteriosclerosis; Male; Middle Aged

Topics: Animals; Blood Coagulation Disorders; Enzyme Activation; Female; Fibrin; Fibrinogen; Fibrinolysis; Injections, Intravenous; Plasminogen; Rabbits; Thrombin; Thromboplastin

Topics: Adult; Afibrinogenemia; Blood Coagulation Disorders; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Plasminogen; Pregnancy; Pregnancy Complications, Hematologic; Puerperal Disorders; Thrombin

Topics: Acute Disease; Acute Kidney Injury; Adult; Aged; Amylases; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Female; Fibrin; Humans; Kidney; Kidney Failure, Chronic; Kidney Glomerulus; Male; Middle Aged; Pancreas; Pancreatitis

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Cerebral Arterial Diseases; Chromatography; Chromatography, Gel; Diagnosis, Differential; Fibrin; Fibrinogen; Hematoma, Subdural; Humans; Infant; Iodine Radioisotopes; Male; Middle Aged; Molecular Weight; Postoperative Complications; Thromboembolism; Thrombosis

Topics: Abortion, Septic; Adolescent; Adult; Anticoagulants; Antithrombins; Blood; Blood Coagulation Disorders; Blood Coagulation Factors; Child; Disseminated Intravascular Coagulation; Encephalitis; Encephalitis Viruses; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemorrhagic Disorders; Humans; Liver; Male; Necrosis; Pituitary Gland; Pregnancy; Prostatic Neoplasms; Prothrombin; Sepsis; Shock, Septic; Spleen; Streptokinase

Topics: Afibrinogenemia; Blood Coagulation Disorders; Female; Fetal Death; Fibrin; Humans; Hysterectomy; Pregnancy; Pregnancy Complications, Hematologic

Topics: Antibodies; Antibody Specificity; Antigens; Blood Coagulation Disorders; Erythrocytes; Factor XIII; Fibrin; Fibrinogen; Hemagglutination Inhibition Tests; Humans; Immune Sera; Immunoelectrophoresis; Neutralization Tests

Topics: Afibrinogenemia; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Dextrans; Female; Fibrin; Fibrinolysis; Hemostasis; Heparin; Humans; Hysterectomy; Pregnancy; Pregnancy Complications, Hematologic; Thrombosis

Topics: Animals; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Embolism, Fat; Endotoxins; Fibrin; Lipids; Lipopolysaccharides; Mice; Rabbits; Sulfonic Acids; Trypsin

Topics: Adult; Blood Coagulation Disorders; Clot Retraction; Factor XIII; Fibrin; Humans; Male; Thrombelastography

Topics: Adolescent; Adult; Anemia, Hemolytic; Beta-Globulins; Blood Coagulation Disorders; Blood Coagulation Tests; Child; Child, Preschool; Complement System Proteins; Female; Fibrin; Fluorescent Antibody Technique; Heparin; Humans; Kidney Diseases; Lupus Erythematosus, Systemic; Male; Nephritis; Nephrotic Syndrome; Purpura; Uremia; Urinary Tract Infections

Topics: Aminocaproates; Antifibrinolytic Agents; Benzoates; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelet Disorders; Cyclohexanecarboxylic Acids; Factor V; Factor V Deficiency; Factor VIII; Fibrin; Fibrinolysis; Hemagglutination Tests; Hemorrhage; Heparin; Humans; Immunodiffusion; Immunoelectrophoresis; Plasminogen; Streptokinase; Thrombocytopenia

Topics: Abruptio Placentae; Animals; Blood Coagulation; Blood Coagulation Disorders; Female; Fibrin; Fibrinogen; Fibrinolysin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Pregnancy; Pregnancy Complications, Hematologic; Rabbits

Topics: Adolescent; Adult; Age Factors; Aged; Animals; Anticoagulants; Arthritis, Rheumatoid; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Cardiovascular Diseases; Cattle; Child; Child, Preschool; Dogs; Electrophoresis; Female; Fibrin; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Hemorrhage; Hemorrhagic Disorders; Humans; Infant; Male; Menstruation; Methods; Middle Aged; Neoplasms; Plasminogen; Pregnancy; Rabbits; Sex Factors; Thromboembolism; Thrombosis; Uremia

Topics: Blood Coagulation Disorders; Densitometry; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Humans; Methods; Protamines; Thrombin

Topics: Adult; Afibrinogenemia; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Carcinoma, Hepatocellular; Diagnosis, Differential; Female; Fibrin; Fibrinogen; Heparin; Hepatic Encephalopathy; Humans; Liver Neoplasms; Pregnancy; Pregnancy Complications; Prothrombin Time; Spectrophotometry; Thrombin

Topics: Animals; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Dogs; Factor V; Factor VIII; Fibrin; Fibrinogen; Fibrinolysis; Graft vs Host Reaction; Histocompatibility; Kidney; Kidney Transplantation; Platelet Adhesiveness; Prothrombin Time; Swine; Time Factors; Transplantation Immunology; Transplantation, Heterologous

Topics: Animals; Blood Coagulation Disorders; Blood Pressure; Body Temperature; Carbon Dioxide; Diuresis; Endotoxins; Escherichia coli; Female; Fibrin; Hemodynamics; Histocytochemistry; Hydrogen-Ion Concentration; Injections, Intravenous; Kidney; Kidney Cortex Necrosis; Kidney Function Tests; Kidney Glomerulus; Lactates; Liver; Lung; Osmolar Concentration; Rabbits; Respiration; Shock, Septic; Spleen

Topics: Angiography; Blood Coagulation; Blood Coagulation Disorders; Blood Proteins; Cerebral Arteries; Contrast Media; Fibrin; Humans; Microscopy, Electron; Microscopy, Phase-Contrast; Solubility; Spectrophotometry; Urea

Topics: Animals; Biopsy; Blood Cell Count; Blood Coagulation; Blood Coagulation Disorders; Blood Platelets; Bone Marrow Examination; Dogs; Embolism; Endotoxins; Escherichia coli; Fibrin; Fibrinogen; Fibrinolysis; Fibrinolytic Agents; Fluorescent Antibody Technique; Liver; Microscopy, Electron; Mononuclear Phagocyte System; Neutrophils; Phagocytosis; Platelet Adhesiveness; Precipitin Tests; Protein Denaturation; Spleen; Streptokinase; Thrombin; Thrombosis; Zymosan

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Calcium; Citrates; Enzyme Activation; Factor VIII; Fibrin; Fibrinolysis; History of Medicine; Humans; Lipids; Prothrombin; Sodium; Thrombin; Thromboplastin

Fibrinoligase, the fibrin cross-linking enzyme, transiently appearing during the course of coagulation in normal blood, was shown to catalyze the incorporation of a fluorescent amine, monodansylcadaverine [or N-(5-aminopentyl)-5-dimethylamino-1-naphthalene-sulfonamide] into casein. The reaction provided the basis of a sensitive fluorimetric method for measuring the activity of the enzyme (and also of similar other transpeptidases, such as transglutaminase). In tests involving plasma, certain difficulties had to be overcome which were mainly due to the fact that the enzyme itself does not occur in citrated plasma. Only its precursor (fibrin-stabilizing factor or factor XIII) is present, still requiring limited proteolytic activation by thrombin. Thus, in order to measure amine incorporation with plasma as a source of the factor, thrombin must be added. This necessitated a differential desensitization of the intrinsic fibrinogen so that the latter could not clot and could not thereby interfere with amine incorporation. Also, the thrombin-inactivating capacity of plasma had to be saturated to enable full conversion of the factor to the transpeptidase. Concentrations of casein, monodansylcadaverine, calcium, and hydrogen ions were chosen to permit almost maximal velocity of amine incorporation. A linear relationship with regard to plasma concentration could be obtained only under such conditions. No similar assay is presently available for quantitatively evaluating fibrin-stabilizing factor levels in plasma.The amine incorporation test was applied to a clinical case of hereditary total fibrin-stabilizing factor deficiency. The effect of transfusion therapy was studied, and some of the patient's relatives were examined. Whereas a paternal aunt and uncle gave values well within the normal range, a brother and the mother proved to be partially deficient and could be considered as heterozygous carriers. The father appeared to have a reduced level of fibrin-stabilizing factor, though not quite as low as the other two relatives. Two infusions (1 liter each) of fresh normal plasma, administered about 26 hr apart, brought levels in the patient's plasma close to those found in the mother and brother. The corrective power of the transfusions, however, rapidly declined within 5-6 days. Futility of the last transfusion could be ascribed to the appearance of a neutralizing antibody directed against the precursor stabilizing factor, a serious complication. General diagnost

Topics: Adult; Amines; Antibodies; Blood Coagulation Disorders; Blood Transfusion; Calcium; Caseins; Factor VIII; Female; Fibrin; Humans; Hydrogen-Ion Concentration; Immunodiffusion; Male; Methods; Thrombin

Topics: Aged; Agglutination; Animals; Blood Coagulation Disorders; Blood Platelets; Dogs; Female; Fibrin; Fibrinogen; Haplorhini; Humans; Middle Aged; Necrosis; Shock

Topics: Blood Coagulation Disorders; Dentistry; Fibrin

Topics: Acute Disease; Blood Coagulation Disorders; Blood Platelets; Bone Marrow; Bone Marrow Cells; Cold Temperature; Endoplasmic Reticulum; Female; Fibrin; Fibrinogen; Humans; Leukemia, Myeloid, Acute; Microscopy, Electron

Topics: Abruptio Placentae; Aminocaproates; Animals; Aprotinin; Blood Coagulation Disorders; Blood Transfusion, Intrauterine; Delivery, Obstetric; Extraembryonic Membranes; Female; Fetus; Fibrin; Fibrinogen; Fibrinolysis; Humans; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications, Hematologic; Rabbits; Uterine Diseases; Uterus

Topics: Adsorption; Aprotinin; Blood Coagulation Disorders; Ethanol; Fibrin; Formaldehyde; Microscopy; Mononuclear Phagocyte System; Spleen; Thrombin

Topics: Adolescent; Adult; Age Factors; Blood Coagulation Disorders; Child; Child, Preschool; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemagglutination Inhibition Tests; Humans; Infant; Infant, Newborn; Male

Topics: Blood Chemical Analysis; Blood Coagulation Disorders; Blood Coagulation Tests; Fibrin; Fibrinogen; Humans; Methods

Topics: Abortion, Septic; Abruptio Placentae; Antibodies; Antigens; Blood Coagulation Disorders; Eclampsia; Embolism, Amniotic Fluid; Female; Fetal Death; Fibrin; Fibrinogen; Fibrinolysis; Hemostasis; Humans; Immunoelectrophoresis; Kidney Glomerulus; Lung; Pregnancy; Pregnancy Complications, Hematologic; Spleen; Thrombelastography

Topics: Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Duodenal Ulcer; Fibrin; Fibrinolysis; Heparin Antagonists; Humans; Postoperative Complications; Solubility; Stomach Ulcer; Wound Healing

Topics: Animals; Benzopyrans; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelet Disorders; Budd-Chiari Syndrome; Coronary Disease; Female; Fibrin; Fibrinogen; Fibrinolysis; Heparin; Mice; Microscopy; Microscopy, Electron; Placenta; Placenta Diseases; Pregnancy; Pregnancy Complications; Pulmonary Embolism; Renal Veins; Thrombosis; Veins

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Diagnosis, Differential; Fibrin; Humans; Serologic Tests; Time Factors

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Fibrin; Fibrinogen; Hemagglutination Inhibition Tests; Humans; Immunoassay; Methods; Time Factors

Topics: Blood Coagulation Disorders; Fibrin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Thrombocytopenia

Topics: Blood Coagulation Disorders; Ethanol; Fibrin; Gels; Humans

Topics: Animals; Anticoagulants; Blood Coagulation Disorders; Bone Marrow; Fibrin; Fibrinogen; Iodine Isotopes; Kidney; Liver; Lung; Male; Rabbits; Thrombin; Thrombosis; Venoms

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Female; Fibrin; Fibrinogen; Fibrinolysis; Heparin; Humans; Middle Aged; Purpura, Thrombocytopenic; Thrombophlebitis; Thromboplastin

Topics: Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Blood Transfusion; Child, Preschool; Factor XIII; Female; Fibrin; Genes, Recessive; Hemoglobinometry; Humans; Pedigree; Prothrombin Time

Topics: Animals; Blood Coagulation Disorders; Blood Platelets; Busulfan; Fibrin; Fibrinogen; Hemolysis; Injections, Intravenous; Kidney Glomerulus; Models, Biological; Neoplasms; Platelet Adhesiveness; Purpura; Rabbits; Sepsis; Shock; Shwartzman Phenomenon; Sulfonic Acids; Thrombocytopenia

Lewis et al. recently reported on a patient who died of hemorrhages attributable to an acquired inhibitor of fibrin-stabilizing factor. They indicated that the inhibitor was associated with the immune globulins. Using the postmortem serum in the isolated fibrin cross-linking system, we have now further localized the site of inhibition in the scheme of blood coagulation. The interference occurs at the transpeptidation step catalyzed by the thrombin-activated fibrin-stabilizing factor. The patient's serum also uniquely delayed the clotting time of Homarus plasma, a test for specific inhibitors of transpeptidation. Since the inhibitor was effective in two such widely different systems, it probably is not an antibody, but falls into the category of cross-linking inhibitors which we have previously described (4, 5, 10, 12-17). While the exact nature of the inhibitor remains unknown, we raise the question whether some unusual metabolic transformation of isonicotinic acid hydrazide (with which the patient was treated and which itself we found to be a potent inhibitor fibrin cross-linking), in combination with a macromolecule, might not have given rise to an inhibitory compound.

Topics: Animals; Blood Coagulation Disorders; Cross-Linking Reagents; Fatal Outcome; Fibrin; Hemorrhage; Humans; Nephropidae

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Chromosome Aberrations; Chromosome Disorders; Consanguinity; Female; Fibrin; Genes, Recessive; Humans; Male

Topics: Angiomatosis; Anticoagulants; Arm; Biopsy; Blindness; Blood Coagulation Disorders; Capillaries; Chronic Disease; Factor V; Factor VIII; Female; Fibrin; Fibrinolysin; Humans; Leg Dermatoses; Middle Aged; Pain; Prednisolone; Skin Manifestations; Skin Ulcer; Thrombosis

Topics: Anticoagulants; Antifibrinolytic Agents; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Calcium; Clot Retraction; Fibrin; Fibrinolysis; Fibrinolytic Agents; gamma-Globulins; Humans; Hydrogen-Ion Concentration; Prothrombin Time

Topics: Adrenocorticotropic Hormone; Animals; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Chorionic Gonadotropin; Contraceptives, Oral; Endotoxins; Factor V; Factor VII; Female; Fibrin; Kidney Glomerulus; Lipopolysaccharides; Liver; Lung; Mestranol; Myocardium; Norethynodrel; Pregnancy; Prothrombin; Rabbits; Shwartzman Phenomenon; Spleen; Thromboplastin; Thrombosis

Topics: Blood Coagulation Disorders; Chymotrypsin; Electrophoresis; Fibrin; Fibrinogen; Humans; Immunodiffusion; Immunoelectrophoresis; In Vitro Techniques; Papain; Peptide Hydrolases; Peptides; Plasminogen; Streptokinase; Trypsin

Topics: Agar; Antigen-Antibody Reactions; Aprotinin; Blood Coagulation Disorders; Drainage; Extracorporeal Circulation; Fibrin; Fibrinolysis; Gels; Humans; Streptokinase

Topics: Blood Coagulation Disorders; Fibrin; Fibrinogen; Humans

Topics: Abruptio Placentae; Adult; Animals; Anuria; Bilirubin; Blood Coagulation Disorders; Dogs; Erythrocytes; Female; Fibrin; Fibrinolysis; Hematologic Diseases; Hemolysis; Humans; Mice; Pregnancy; Rabbits; Rats; Shock, Hemorrhagic; Thrombin; Thromboplastin

In chronic renal failure and after acute renal failure, fibrinogen levels are raised and there is diminished fibrinolysis as the result of renal damage. A similar situation is found in nephrosis, possibly due to fibrinolytic inhibitors. Increased levels of cryofibrinogen were found in one quarter of cases of acute nephritis, nephrosis, and acute and chronic renal failure. In addition, after acute renal failure low platelet counts, prolonged thrombin times, and high levels of fibrin degradation products, yet with diminished fibrinolysis, indicate that intravascular coagulation has occurred. A positive result for fibrin degradation products was found in 17 of 20 cases of acute renal failure but in none of 10 cases of chronic uraemia. Intravascular coagulation is a process in which fibrin is deposited in the glomerular filters and may account for anuria, and, in the renal vasculature, where it may cause ischaemic tubular necrosis.

Topics: Acute Kidney Injury; Blood Coagulation Disorders; Blood Coagulation Tests; Fibrin; Fibrinogen; Fibrinolysis; Hemagglutination Inhibition Tests; Humans; Immunoelectrophoresis; Kidney Diseases; Kidney Failure, Chronic; Nephritis; Nephrotic Syndrome; Plasminogen; Uremia

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Cellulose; Chromatography; Factor XIII; Fibrin; Fibrinogen; Fibrinolysis; Humans; Polymers; Streptokinase

Topics: Arteriosclerosis; Blood Coagulation Disorders; Blood Platelets; Fibrin; Humans

Topics: Adult; Anemia, Hemolytic; Animals; Blood Coagulation Disorders; Erythrocytes; Female; Fibrin; Filtration; Hemoglobins; Humans; Models, Biological; Photography; Rabbits; Thrombin; Venoms

Topics: Blood Coagulation Disorders; Fibrin; Fibrinogen; Fibrinolysis; Humans; Immunoelectrophoresis

Topics: Adult; Afibrinogenemia; Blood Coagulation Disorders; Female; Fibrin; Fibrinolytic Agents; Hematuria; Humans

Topics: Adult; Blood Coagulation Disorders; Electrocardiography; Embolism, Amniotic Fluid; Female; Fibrin; Humans; Phenethylamines; Prednisolone; Pregnancy; Pulmonary Heart Disease; Radiography; Shock, Cardiogenic

Topics: Biological Assay; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelet Disorders; Female; Fibrin; Humans; Immunoelectrophoresis; Male; Neoplasms; Thrombin; Thrombocytopenia; Thromboplastin

Topics: Adolescent; Adult; Blood Coagulation Disorders; Blood Coagulation Factors; Extraembryonic Membranes; Female; Fibrin; Fibrinolysis; Heparin; Humans; Kidney; Liver Cirrhosis; Middle Aged; Mononuclear Phagocyte System; Obstetric Labor, Premature; Pituitary Gland; Pregnancy; Sepsis; Shwartzman Phenomenon; Thrombin

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Transfusion; Child, Preschool; Factor XIII; Fibrin; Fibrinogen; Humans; Infusions, Parenteral; Male; Pedigree; Urea

Topics: Aged; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Blood Protein Disorders; Calcium; Collagen; Connective Tissue; Fibrin; Fibrinogen; gamma-Globulins; Hemorrhagic Disorders; Humans; Male; Multiple Myeloma; Nitrogen Mustard Compounds; Plasmapheresis; Prothrombin Time; Thromboplastin; Tryptophan

Topics: Abruptio Placentae; Animals; Blood Coagulation Disorders; Dogs; Embolism, Amniotic Fluid; Female; Fibrin; Humans; Meconium; Mice; Motion Pictures; Photomicrography; Pregnancy; Pulmonary Embolism; Rabbits; Staining and Labeling

Topics: Animals; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Female; Fibrin; Fluorescent Antibody Technique; Male; Mice; Microscopy, Electron; Nephritis; Serum Albumin; Serum Globulins; Staining and Labeling; Warfarin

Topics: Adolescent; Afibrinogenemia; Blood Coagulation Disorders; Bone Marrow Cells; Cardiac Tamponade; Factor V Deficiency; Factor VIII; Fibrin; Hemorrhagic Disorders; Humans; Leukemia, Myeloid, Acute; Male; Pericarditis; Pericardium; Staining and Labeling

Topics: Antifibrinolytic Agents; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Cardiac Surgical Procedures; Extracorporeal Circulation; Fibrin; Fibrinogen; Fibrinolysis; Heart-Lung Machine; Heparin; Humans; Protamines; Thrombelastography

Topics: Adult; Blood Coagulation Disorders; Embolism, Amniotic Fluid; Female; Fibrin; Humans; Lung; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications, Hematologic

Topics: Abortion, Spontaneous; Adult; Blood Coagulation Disorders; Blood Coagulation Tests; Female; Fibrin; Fibrinogen; Fibrinolysis; Heparin; Humans; Immune Sera; Immunoelectrophoresis; Pregnancy; Pregnancy Complications; Shwartzman Phenomenon; Thrombelastography

Topics: Animals; Blood Coagulation Disorders; Capillaries; Dogs; Fibrin; Gastric Mucosa; Heparin; Humans; Kidney Glomerulus; Lung; Male; Middle Aged; Popliteal Vein; Pulmonary Embolism; Rabbits; Rats; Thrombophlebitis; Thrombosis

Topics: Adult; Aged; Blood Coagulation Disorders; Coronary Disease; Female; Fibrin; Humans; Male; Middle Aged

Topics: Blood Coagulation Disorders; Child; Female; Fibrin; Hemorrhage; Humans

Topics: Adolescent; Adult; Aged; Blood Coagulation Disorders; Child; Child, Preschool; Enzymes; Female; Fibrin; Fibrinolysin; Fibrinolysis; Humans; In Vitro Techniques; Infant; Leukemia; Male; Middle Aged

Topics: Anaphylaxis; Animals; Blood Coagulation Disorders; Fibrin; Fibrinogen; Fibrinolysis; Kidney Glomerulus; Liver; Rabbits; Spleen

Topics: Animals; Blood Coagulation Disorders; Blood Vessels; Culture Techniques; Factor XII; Fibrin; Fibrinolysin; Humans; Plasminogen; Rats; Serum Albumin; Thromboplastin

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Tests; Fibrin; Humans; Male

Topics: Animals; Blood; Blood Coagulation Disorders; Cattle; Fibrin; Fibrinogen; Fibrinolysis; Horses; Humans; Immunoelectrophoresis; In Vitro Techniques; Precipitin Tests; Rabbits; Sheep

Topics: Blood Coagulation Disorders; Fibrin; Fibrinolysis; Heparin; Humans; Leukemia; Neoplasms; Thrombosis

Topics: Abortion, Spontaneous; Biopsy; Blood Coagulation; Blood Coagulation Disorders; Female; Fibrin; Humans; Pregnancy; Uterus

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Cerebral Hemorrhage; Child; Diagnosis; Enzymes; Factor XIII; Fibrin; Genetics, Medical; Hemarthrosis; Hematoma; Hematoma, Subdural; Hemorrhagic Disorders; Humans; Knee Joint

Topics: Biophysical Phenomena; Biophysics; Blood Coagulation Disorders; Blood Platelets; Fibrin; Fibrinogen; Humans; Immunoelectrophoresis; Peptides; Polymers; Proteolysis; Research; Spectrophotometry; Thrombelastography; Thrombosis

Topics: Animals; Blood Coagulation Disorders; Electrons; Endotoxins; Fibrin; Liver; Microscopy; Microscopy, Electron; Mononuclear Phagocyte System; Phagocytosis; Pharmacology; Rabbits; Research; Spleen; Thrombin

Topics: Blood Coagulation; Blood Coagulation Disorders; Fibrin; Humans; Physiology; Thrombosis

Topics: Afibrinogenemia; Blood Coagulation Disorders; Coagulants; Fibrin; Fibrinogen; Hematocrit; Hemostatics; Humans; Polycythemia; Polycythemia Vera

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Transfusion; Fibrin; Humans

Topics: Adult; Blood Coagulation Disorders; Fibrin; Fibrinogen; Humans; Immunoelectrophoresis; Male; Microscopy, Electron; Thrombin

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Platelet Disorders; Blood Platelets; Classification; Fibrin; Genetics, Medical; Hemophilia A; Humans; Purpura; Surgery, Oral; Thrombin; Thromboplastin

Topics: Aminocaproates; Aminocaproic Acid; Amniotic Fluid; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Transfusion; Embolism; Embolism, Amniotic Fluid; Female; Fibrin; Fibrinolysin; Fibrinolysis; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Male; Physiology; Plasminogen; Pregnancy; Prostatic Neoplasms

Topics: Adolescent; Adult; Animals; Anticoagulants; Blood Coagulation Disorders; Bone Development; Child; Child, Preschool; Female; Fibrin; Fractures, Bone; Fractures, Ununited; Hematoma; Hemophilia A; Heparin; Humans; Infant; Male; Periosteum; Pseudarthrosis; Rabbits; Radiography; Radius Fractures; Warfarin; Wound Healing

Topics: Afibrinogenemia; Animals; Blood Coagulation Disorders; Blood Coagulation Tests; Dogs; Epinephrine; Fibrin; Fibrinogen; Pharmacology; Postoperative Complications; Reserpine; Shock; Shock, Hemorrhagic; Thrombophilia

Topics: Anticoagulants; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Fibrin; Geriatrics; Heparin; Humans; Pancreatic Neoplasms; Phenindione; Plasma

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Coagulants; Fibrin; Fibrinogen; Fibrinolysis; Hemophilia A; Heparin; History; Humans; Phosphotransferases; Thrombin

Topics: Blood Coagulation Disorders; Fibrin; Fibrinogen; Fibrinolysis; Hemorrhagic Disorders; Humans; Plasma; Polymerization; Thrombolytic Therapy

Topics: Blood Coagulation Disorders; Electrons; Fibrin; Fibrinogen; Fibrinolysis; Hemorrhagic Disorders; Humans; Microscopy; Microscopy, Electron; Thrombolytic Therapy

Topics: Blood Coagulation Disorders; Fibrin; Fibrinogen; Fibrinolysis; Hemorrhagic Disorders; Humans; Plasma; Proteolysis; Thrombolytic Therapy

Topics: Blood Coagulation; Blood Coagulation Disorders; Factor XIII; Fibrin; Hemorrhagic Disorders; Humans; Vascular Diseases

Topics: Blood Coagulation; Blood Coagulation Disorders; Fibrin; Hemorrhagic Disorders; Humans

An investigation of the pulmonary fibrinolytic enzyme system in 31 infants who died with hyaline membrane formation was reviewed. There was complete lack of plasminogen activator activity in the lungs of 84 per cent of these infants. This phenomenon was shown to result from an abnormal inhibitor. A comparable inhibitor was found in normal placental tissue, and it is postulated that this inhibitor is released into the circulating blood as the result of placental infarction. Fibrin, a basic component of the hyaline membrane, is probably precipitated from a physiological capillary transudate associated with the formation of amniotic fluid by the lungs. The presence of an inhibitor of fibrinolysis would then result in the accumulation of intrapulmonary fibrin and the formation of hyaline membranes.

Topics: Amniotic Fluid; Blood Coagulation Disorders; Female; Fibrin; Fibrinolysis; Humans; Hyalin; Hyaline Membrane Disease; Infant; Infant, Newborn; Lung; Placenta; Plasminogen; Pregnancy; Thrombolytic Therapy

A bleeding disorder occurring during labour and affecting mother and foetus is described. All stages of coagulation were normal until the reaction fibrinogen-->fibrin. Either there was some abnormality present in the fibrinogen molecule, or there was an "anticoagulant" acting at this stage. The abnormality was reversible by protamine sulphate and toluidine blue, but in other respects did not resemble hyperheparinaemia. Reversibility of a clotting defect by protamine or toluidine blue is not sufficient evidence on which to make a diagnosis of hyperheparinaemia. Demonstration of a prolonged clotting time occurring in late pregnancy does not necessarily justify the diagnosis of "afibrinogenaemia."

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Female; Fibrin; Fibrinogen; Hemorrhagic Disorders; Humans; Pregnancy

Topics: Blood Coagulation; Blood Coagulation Disorders; Embolism; Female; Fibrin; Hemorrhagic Disorders; Heparin; Humans; Infant, Newborn; Meconium; Placenta; Pregnancy; Shock

Topics: Afibrinogenemia; Blood Coagulation Disorders; Female; Fibrin; Fibrinogen; Humans; Pregnancy

Topics: Blood Coagulation Disorders; Fibrin; Humans

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Fibrin; Fibrinolysis; Herpes Zoster; Humans

Topics: Blood Coagulation Disorders; Fibrin; Hemorrhagic Disorders; Humans; Polycythemia Vera

Topics: Blood; Blood Coagulation Disorders; Fibrin; Humans; Polycythemia