fibrin and Acute-Disease

Pleural and parenchymal lung injury have long been characterized by acute inflammation and pathologic tissue reorganization, when severe. Although transitional matrix deposition is a normal part of the injury response, unresolved fibrin deposition can lead to pleural loculation and scarification of affected areas. Within this review, we present a brief discussion of the fibrinolytic pathway, its components, and their contribution to injury progression. We review how local derangements of fibrinolysis, resulting from increased coagulation and reduced plasminogen activator activity, promote extravascular fibrin deposition. Further, we describe how pleural mesothelial cells contribute to lung scarring via the acquisition of a profibrotic phenotype. We also discuss soluble uPAR, a recently identified biomarker of pleural injury, and its diagnostic value in the grading of pleural effusions. Finally, we provide an in-depth discussion on the clinical importance of single-chain urokinase plasminogen activator (uPA) for the treatment of loculated pleural collections.

Topics: Acute Disease; Animals; Biomarkers; Blood Coagulation; Epithelium; Fibrin; Fibrinolysis; Humans; Inflammation; Lung; Lung Injury; Pleura; Pleural Effusion; Receptors, Urokinase Plasminogen Activator; Thrombolytic Therapy; Urokinase-Type Plasminogen Activator

Coagulation factor XIII (FXIII) is converted by thrombin into its active form, FXIIIa, which crosslinks fibrin fibers, rendering clots more stable and resistant to degradation. FXIII affects fibrin clot structure and function leading to a more prothrombotic phenotype with denser networks, characterizing patients at risk of venous thromboembolism (VTE). Mechanisms regulating FXIII activation and its impact on fibrin structure in patients with acute VTE encompassing pulmonary embolism (PE) or deep vein thrombosis (DVT) are poorly elucidated. Reduced circulating FXIII levels in acute PE were reported over 20 years ago. Similar observations indicating decreased FXIII plasma activity and antigen levels have been made in acute PE and DVT with their subsequent increase after several weeks since the index event. Plasma fibrin clot proteome analysis confirms that clot-bound FXIII amounts associated with plasma FXIII activity are decreased in acute VTE. Reduced FXIII activity has been associated with impaired clot permeability and hypofibrinolysis in acute PE. The current review presents available studies on the role of FXIII in the modulation of fibrin clot properties during acute PE or DVT and following these events. Better understanding of FXIII's involvement in the pathophysiology of acute VTE might help to improve current therapeutic strategies in patients with acute VTE.

Topics: Acute Disease; Anticoagulants; Blood Coagulation; Factor XIII; Fibrin; Fibrinolysis; Genetic Variation; Humans; Models, Cardiovascular; Venous Thromboembolism

Thrombectomy is a technique that has completely changed the management of acute stroke and current devices have shown that they can achieve upwards of 90% successful recanalization in selected cohorts. However, despite the effectiveness of these devices, there are a proportion of patients who still fail to achieve reperfusion of the affected vascular territory and an even larger portion of patients who have poor functional outcomes in spite of successful recanalization. There are no guidelines on how to treat these patients when such failures occur. In an effort to understand the underpinnings of how failed thrombectomy occurs, we extensively reviewed the current literature in clot properties, vascular access problems, stroke pathogenic mechanisms, embolic complications, failed procedures and pre-procedural imaging. A short summary of each of these contentious areas are provided and the current state of the art. Together these elements give a cohesive overview of the mechanisms of failed thrombectomy as well as the controversies facing the field. New techniques and devices can then be developed to minimize such factors during stroke thrombectomy.

Topics: Acute Disease; Angiography, Digital Subtraction; Cerebral Angiography; Cerebral Arteries; Cerebral Veins; Erythrocytes; Fibrin; Humans; Leukocytes; Mechanical Thrombolysis; Organ Specificity; Reperfusion; Stroke; Thrombosis; Treatment Failure; Vascular Patency; Vertebrobasilar Insufficiency

Fibrin, a natural hydrogel, is the end product of the physiological blood coagulation cascade and naturally involved in wound healing. Beyond its role in hemostasis, it acts as a local reservoir for growth factors and as a provisional matrix for invading cells that drive the regenerative process. Its unique intrinsic features do not only promote wound healing directly via modulation of cell behavior but it can also be fine-tuned to evolve into a delivery system for sustained release of therapeutic biomolecules, cells and gene vectors. To further augment tissue regeneration potential, current strategies exploit and modify the chemical and physical characteristics of fibrin to employ combined incorporation of several factors and their timed release. In this work we show advanced therapeutic approaches employing fibrin matrices in wound healing and cover the many possibilities fibrin offers to the field of regenerative medicine.

Topics: Acute Disease; Animals; Chronic Disease; Drug Delivery Systems; Fibrin; Humans; Hydrogels; Wound Healing

Strong experimental evidence indicates that components of the hemostatic system, including thrombin, exacerbate diverse features of experimental liver disease. Clinical studies have also begun to address this connection and some studies have suggested that anticoagulants can improve outcome in patients with liver disease. Among the evidence of coagulation cascade activation in models of liver injury and disease is the frequent observation of thrombin-driven hepatic fibrin(ogen) deposition. Indeed, hepatic fibrin(ogen) deposition has long been recognized as a consequence of hepatic injury. Although commonly inferred as pathologic due to protective effects of anticoagulants in mouse models, the role of fibrin(ogen) in acute liver injury and chronic liver disease may not be universally detrimental. The localization of hepatic fibrin(ogen) deposits within the liver is connected to the disease stimulus and in animal models of liver toxicity and chronic disease, fibrin(ogen) deposition may not always be synonymous with large vessel thrombosis. Here, we provide a balanced review of the experimental evidence supporting a direct connection between fibrin(ogen) and liver injury/disease pathogenesis, and suggest a path forward bridging experimental and clinical research to improve our knowledge on the nature and function of fibrin(ogen) in liver disease.

Topics: Acute Disease; Animals; Chronic Disease; Disease Models, Animal; Fibrin; Fibrinogen; Humans; Liver Diseases; Mice

Topics: Acute Disease; Aged; Chlamydophila Infections; Chlamydophila pneumoniae; Cryptogenic Organizing Pneumonia; Fatal Outcome; Female; Fibrin; Humans; Multiple Organ Failure; Pneumonia, Bacterial; Pulmonary Alveoli; Respiratory Insufficiency

Acute inflammatory and chronic interstitial lung diseases are characterized by excessive and persistent fibrin deposition in the lung. Intraalveolar fibrin accumulation, observed under these conditions, arises from a leakage of plasma proteins (including fibrinogen) into the alveolar space in combination with a disbalance of alveolar haemostasis. Tissue factor in association with factor VIIa and inhibition of urokinase by plasminogen activator inhibitor-1 are major factors that are responsible for the procoagulant and antifibrinolytic state. In addition, in acute respiratory distress syndrome (ARDS) patients, factor VII-activating protease and extracellular RNA, which may be released into the extracellular milieu from damaged cells during lung injury, may contribute to fibrin formation as well. Fibrin itself can increase vascular permeability, influence the expression of inflammatory mediators and alter the migration and proliferation of various cell types. Additionally, fibrin may inactivate pulmonary surfactant and provide a matrix on which fibroblasts can migrate and produce collagen. Furthermore, cellular activities of haemostatic proteases may also contribute to proinflammatory and fibrotic processes in the lung. The application of coagulation inhibitors, like tissue factor pathway inhibitor, active site-inactivated factor VIIa, activated protein C, antithrombin, heparin or hirudin turned out to be beneficial in experimental models of acute and chronic lung injury. However, the ability of anticoagulant and profibrinolytic agents to improve clinical outcome remains to be elucidated. In the current article, the role of the alveolar coagulation and fibrinolysis systems in acute inflammatory and chronic interstitial lung diseases is discussed with regard to pathomechanisms and modalities of intervention.

Topics: Acute Disease; Animals; Anticoagulants; Blood Coagulation; Blood Coagulation Factors; Chronic Disease; Fibrin; Fibrinolysis; Fibrinolytic Agents; Humans; Lung Diseases, Interstitial; Pneumonia; Pulmonary Alveoli

Topics: Acute Disease; Blood Platelets; Cardiovascular Diseases; Education, Medical, Continuing; Fibrin; Humans; Platelet Aggregation Inhibitors

Coronary thrombosis is an important determinant of prognosis in patients with acute coronary syndromes (ACS). However, the identification of patients at high-risk for progression of coronary thrombosis is difficult in part because we currently lack clinically meaningful laboratory methods for its detection. The most promising approaches involve the measurement in plasma of markers of fibrin formation and degradation. Thrombin activity, as reflected by plasma or urine concentrations of fibrinopeptide A, is increased in patients with ACS and is associated with adverse outcome. However, the use of fibrinopeptide A as a marker of fibrin formation is limited by the very short half-life of the compound, by artifact due to sample acquisition, and by extremely long turnaround times. To overcome these limitations, measurement of soluble fibrin has been proposed. We have recently explored the prognostic value of a new fibrin-specific ELISA assay for soluble fibrin in patients with ACS and found that patients with highest levels had a twofold increased risk of early and late cardiac events. Increases in plasma concentrations of cross-linked fibrin degradation products (XL-FDPs), which reflect increased fibrin turn-over, are a marker of risk for complications of myocardial infarction. However, until recently, assays for XL-FDPs lacked specificity, because they did not distinguish between fibrin and fibrinogen degradation products. Recently, fibrin-specific ELISAs have been described and a rapid whole blood assay for D-dimer has been developed. We recently validated the prognostic value of this whole blood agglutination assay in patients with ACS. The results suggest that: (1) the detection of significant activation of the coagulation and/or fibrinolytic system may be important for rapid risk stratification of patients with ACS; (2) patients with biochemical evidence of ongoing coronary thrombosis may particularly benefit from aggressive antithrombotic strategies; (3) sequential measurements of these markers may be useful to guide antithrombotic treatment during the unstable phase of coronary artery disease.

Topics: Acute Disease; Biomarkers; Coronary Disease; Fibrin; Hemostasis; Humans; Prognosis

Soluble fibrin detected in clinical plasma samples includes a variety of complexes consisting of fibrin monomer units, fibrinogen, and various proteolytic derivatives of fibrinogen and fibrin. The advantage of measuring soluble fibrin over fibrinopeptide A to detect thrombin action on fibrinogen is the considerably longer half-life of soluble fibrin in the circulation. Soluble fibrin can be detected by a variety of methods, including paracoagulation and precipitation assays, adsorption of fibrin monomer to insolubilized fibrinogen, functional assays based on the cofactor activity of some soluble fibrin compounds in t-PA-induced plasminogen activation, and by using fibrin-specific antibodies. Fibrin-specific antibodies may react with epitopes generated directly by fibrinopeptide A or B release or with epitopes generated by fibrin polymerization. Epitopes dependent on fibrinopeptide A release are often not accessible in native fibrin complexes and require the disaggregation of fibrin compounds to be reactive, whereas epitopes dependent on fibrinopeptide B release or fibrin polymerization are accessible to the monoclonal antibodies in nondenatured fibrin. Since soluble fibrin assays detect different structural or functional properties of soluble fibrin, no common calibrator for all soluble fibrin assays and, often, little correlation between different assay systems in clinical evaluations exist. Clinical applications of soluble fibrin assays include diagnosis and treatment monitoring of intravascular coagulation processes and prethrombotic states, monitoring anticoagulant treatment, and biocompatibility investigations. Some soluble fibrin assays have been demonstrated to be extremely sensitive indicators of acute fibrin formation. For the exclusion of venous thrombosis, D-dimer assays appear to be more sensitive than current soluble fibrin assays, since D-dimer assays detect freshly formed fibrin and proteolytic fragments of particulate clots. Further clinical studies are needed to establish the clinical utility of specific, soluble fibrin assays. The development of rapid, quantitative soluble fibrin assays for clinical routine use should be encouraged.

Topics: Acute Disease; Animals; Blood Coagulation; Chronic Disease; Disseminated Intravascular Coagulation; Epitopes; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Plasminogen; Thrombophilia; Venous Thrombosis

Topics: Acute Disease; Brain Ischemia; Fibrin; Fibrinolysis; Glycoproteins; Humans; Plasminogen; Protein C; Protein C Deficiency; Proteins

Topics: Acute Disease; Adolescent; Adult; Child; Child, Preschool; Chronic Disease; Female; Fibrin; Fibrinogen; Glomerulonephritis; Hemolytic-Uremic Syndrome; Humans; Immune Complex Diseases; Immunoglobulin A; Immunoglobulin G; Kidney Diseases; Lupus Erythematosus, Systemic; Male; Middle Aged; Nephritis; Nephrosis; Nephrotic Syndrome; Purpura; Streptococcal Infections

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: 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

Our objective was to demonstrate the effects of platelet-rich fibrin (PRF) for the healing of acute ear drum perforation.. Thirty-two patients with acute traumatic ear drum perforations were randomly separated into 2 groups. In group 1 (n = 14), PRF was used for the repair of ear drum perforation; in group 2 (n = 18), we did not make any intervention.. At initial inspection, perforation sizes were measured as 10.93 ± 3.58 mm in group 1 and 10.05 ± 4.02 mm in group 2. After 1 month, perforation sizes were 1.35 ± 2.53 mm in group 1 and 4.44 ± 3.34 mm in group 2 (P < 0.01). In the study group, the rate of ear drum closure was 64.3% and in the control group it was 22.2% (P < 0.05).. Here we found that PRF is a biomaterial that quickens the healing of ear drum which is autogenous and simply prepared.

Topics: Acute Disease; Adult; Blood Platelets; Female; Fibrin; Humans; Male; Middle Aged; Prospective Studies; Tympanic Membrane Perforation; Wound Healing; Young Adult

Carbon monoxide (CO) poisoning is a leading cause of unintentional poisoning deaths in many countries. In ex vivo studies, CO released from carbon monoxide-releasing molecules has been shown to attenuate fibrinolysis via increased alpha-2-antiplasmin activity. Hypofibrinolysis is associated with coronary ischaemia, which is also commonly observed in CO poisoning. We examined fibrin clot properties in acutely poisoned CO patients. Ex vivo plasma fibrin clot permeability, turbidimetry and efficiency of fibrinolysis were investigated in 48 patients and controls matched for age and sex. CO-poisoned patients had 11.6% longer clot lysis time than the controls (p < 0.0001). No intergroup differences in clot permeability or turbidimetric variables were observed. Plasma tissue-type plasminogen antigen (tPA), plasminogen activator inhibitor-1 (PAI-1) antigen and activity and F1.2 prothrombin fragments were higher in the patients than in the controls (all p < 0.0001). Plasma tPA activity was lower in the CO-poisoned group. Multiple linear regression showed that a thrombin generation marker, F1.2, is the strongest predictor of clot lysis time, followed by PAI-1 activity and carboxyhaemoglobin levels. In conclusion, this report is the first to demonstrate that acute CO poisoning in human beings is linked to increased thrombin generation and impaired fibrinolysis, which might contribute to ischaemic complications.

Topics: Acute Disease; Adult; Blood Coagulation Tests; Carbon Monoxide Poisoning; Female; Fibrin; Fibrinolysis; Humans; Male; Peptide Fragments; Permeability; Plasminogen Activator Inhibitor 1; Prothrombin; Thrombin; Tissue Plasminogen Activator

Few data exist on the effects of n-3 polyunsaturated fatty acids (PUFAs) on the initiators and endstage products of coagulation following an acute myocardial infarction (MI). We assessed the long-term effects of n-3 PUFAs on postinfarct variations of tissue factor (TF), activated factor XII (FXIIa) and fibrin monomer (FM), and expected additional statin treatment to modify thrombogenicity. Acute MI patients (n = 300) were randomly allocated to a high dose of n-3 PUFAs or corn oil for at least one year. Plasma concentrations of TF, FXIIa and FM were unaffected by n-3 PUFAs as compared to corn oil, and were uninfluenced by additional statin treatment in subgroup analyses. TF decreased (p = 0.0001), while FXIIa increased during the first 6 weeks (p = 0.001). FM remained essentially unchanged during the entire observation period. In conclusion, TF, FXIIa and FM were unaffected by long-term treatment with high- dosed n-3 PUFAs and by additional statin treatment.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Blood Coagulation; Cholesterol; Corn Oil; Double-Blind Method; Factor XIIa; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Female; Fibrin; Humans; Lipid Metabolism; Male; Middle Aged; Models, Statistical; Myocardial Infarction; Prospective Studies; Random Allocation; Thromboplastin; Triglycerides

Diagnosis of acute coronary syndromes (ACS) is a major challenge for emergency physicians. Because soluble fibrin (sF) has been suggested as a potential early marker of impending myocardial ischemia, we were interested whether a sF bedside test could help in early identification of patients with ACS in the emergency department.. We evaluated plasma coagulation markers, including a newly developed sF bedside test, prothrombin fragment (F(1+2)), sF, and D-dimer, in a cross-sectional trial with 184 patients suggestive of ACS.. Whereas 76% (13 of 17) of patients with unstable angina pectoris (UAP) had a positive sF bedside test, only 10 of 33 patients (30%) with non-ST-segment-elevation myocardial infarction and 10 of 44 patients (23%) with ST-elevation myocardial infarction tested positive. Three percent of controls (1 of 33) and 11% of patients (6 of 57) with preexisting stable angina had a positive sF bedside test (P <0.001 for noncardiac chest pain vs ACS), yielding an overall specificity of 92% and a sensitivity of 35%. The sensitivity of the established coagulation markers was significantly less to detect ACS (11% for F(1+2), 20% for thrombus precursor protein, and 18% for D-dimer; P <0.02 vs sF bedside test). The sF bedside test presented the earliest objective indicator of impending myocardial damage in the majority (10 of 13) of ACS patients with a normal or nondiagnostic electrocardiogram (ECG).. A sF bedside test offers a specific tool for early identification of patients with ACS in an emergency department setting, although its sensitivity seems sufficient only for the early identification of patients with UAP. A sF bedside test could be useful, particularly in UAP patients with a nondiagnostic ECG.

Topics: Acute Disease; Angina, Unstable; Biomarkers; Blood Coagulation Tests; Emergency Medical Services; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Point-of-Care Systems; Sensitivity and Specificity

Echis carinatus is the most important cause of morbidity and mortality from snake bite in Nigeria and in many other parts of the world. Forty-six patients with systemic poisoning by this snake were given echis antivenom made either by the South African Institute for Medical Research (S.A.I.M.R.) or by Behringwerke (North and West African polyvalent antivenom). A simple test of blood coagulability was used to assess whether an adequate neutralizing dose of antivenom had been given. An average of 15.2 ml S.A.I.M.R. antivenom restored normal coagulability permanently in all 23 patients in one group, but in the other group receiving an average dose of 37.9 ml Behringwerke antivenom normal clotting resulted in only 18 out of 23 patients. Local tissue swelling was similar in both groups, but local necrosis occurred in three patients treated with Behringwerke antivenom and in none given S.A.I.M.R. antivenom.

Topics: Acute Disease; Anemia; Antivenins; Blood Coagulation; Cerebral Hemorrhage; Codeine; Epinephrine; Fibrin; Fibrinogen; Hematocrit; Histamine H1 Antagonists; Humans; Hydrocortisone; Nigeria; Prednisone; Shock; Snake Bites; Snake Venoms

Topics: Acute Disease; Anemia, Sickle Cell; Anticoagulants; Bicarbonates; Child; Child, Preschool; Female; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Glucose; Humans; Plasminogen; Time Factors; Venoms

Lipopolysaccharide (LPS) can traverse the intestinal barrier and enter bloodstream, causing endotoxemia and triggering inflammation. Increased circulating LPS was reported in arterial thromboembolism. We investigated whether increased LPS levels occur in acute pulmonary embolism (PE) and if it is associated with a prothrombotic state.. We studied 120 normotensive PE patients (aged 59 [48-68] years) on admission, after 5-7 days, and after a 3-month anticoagulation. Serum LPS levels, along with zonulin, a marker of gut permeability, endogenous thrombin potential (ETP), fibrin clot permeability (K. Median LPS concentration on admission was 70.5 (61.5-82) pg/mL (min-max, 34-134 pg/mL), in association with C-reactive protein (r = 0.22, p = 0.018), but not with fibrinogen, D-dimer or platelet markers. Patients with more severe PE had higher LPS levels compared with the remainder. Median zonulin level was 3.26 (2.74-4.08) ng/mL and correlated with LPS (r = 0.66, p < 0.0001). Patients with baseline LPS levels in the top quartile (≥82 pg/mL; n = 29) compared to lower quartiles had 18.6 % increased ETP, 14.5 % reduced K. Low-grade endotoxemia is detectable in patients with acute PE and may contribute to increased thrombin generation and PAI-1-mediated hypofibrinolysis.

Topics: Acute Disease; Anticoagulants; Endotoxemia; Fibrin; Fibrin Clot Lysis Time; Fibrinolysis; Humans; Lipopolysaccharides; Phenotype; Plasminogen Activator Inhibitor 1; Pulmonary Embolism; Thrombin; Thrombosis

Prothrombotic fibrin clot properties, including increased clot density, are in part genetically determined. We investigated whether fibrinogen alpha-chain gene (FGA) c.991A>G (rs6050), fibrinogen beta chain gene (FGB) -455G>A (rs1800790) and factor XIII gene (F13) c.103G>T (rs5985) polymorphisms affect plasma fibrin clot properties in patients with acute pulmonary embolism (PE).. As many as 126 normotensive patients with PE, free of cancer, were genotyped by TaqMan assay. Fibrin clot permeability (K. The minor allele frequencies were as follows: FGA rs6050 (n = 62, 0.31), FGB rs1800790 (n = 40, 0.17) and F13 rs5985 (n = 49, 0.23). There were no differences related to any of the polymorphisms with regard to demographic, clinical and laboratory data, except for fibrinogen concentration, which was higher in carriers of F13 rs5985 polymorphism (p = .024), and PE combined with deep-vein thrombosis, which was less prevalent in FGB rs1800790 polymorphism carriers (p = .004). Carriers of FGB rs1800790 A allele and F13 rs5985 T allele had lower K. Our study showed that FGB rs1800790 and F13 rs5985 polymorphisms contribute to the prothrombotic fibrin clot phenotype and these effects are strong enough to be observed in the acute phase of PE.

Topics: Acute Disease; Aged; Blood Coagulation; Factor XIII; Female; Fibrin; Fibrinogen; Humans; Male; Middle Aged; Polymorphism, Genetic; Pulmonary Embolism

 Prothrombotic fibrin clot properties are associated with higher early mortality risk in acute pulmonary embolism (PE) patients. It is unknown whether different types of PE are associated with particular clot characteristics..  We assessed 126 normotensive, noncancer acute PE patients (median age: 59 [48-70] years; 52.4% males), who were categorized into central versus peripheral PE with or without concomitant deep vein thrombosis (DVT). Plasma fibrin clot permeability (.  Patients with central PE (.  Our findings suggest that looser fibrin networks composed of thicker fibers with increased susceptibility to lysis characterize patients with central PE, suggesting that fibrin clot phenotype affects the size of thrombi occluding the pulmonary arteries, highlighting the role of fibrin structures in thrombus formation and stability.

Topics: Acute Disease; Aged; Female; Fibrin; Fibrinolysis; Humans; Male; Microscopy, Electron, Scanning; Middle Aged; Phenotype; Pulmonary Embolism

In late December 2019 an outbreak of a novel coronavirus (SARS-CoV-2) causing severe pneumonia (COVID-19) was reported in Wuhan, Hubei Province, China. A common finding in most COVID-19 patients is high D-dimer levels which are associated with a worse prognosis. We aimed to evaluate coagulation abnormalities via traditional tests and whole blood thromboelastometry profiles in a group of 22 (mean age 67 ± 8 years, M:F 20:2) consecutive patients admitted to the Intensive Care Unit of Padova University Hospital for acute respiratory failure due to COVID-19. Cases showed significantly higher fibrinogen and D-dimer plasma levels versus healthy controls (

Topics: Acute Disease; Aged; Area Under Curve; Betacoronavirus; Blood Coagulation; Blood Coagulation Tests; Coronavirus Infections; COVID-19; Critical Care; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Intensive Care Units; Italy; Male; Middle Aged; Pandemics; Pneumonia, Viral; Prognosis; Respiration Disorders; SARS-CoV-2; Thrombelastography; Thrombophilia; Treatment Outcome

Chronic massive rotator cuff tears heal poorly and often retear. This study investigated the effect of adipose-derived stem cells (ADSCs) and transforming growth factor-β3 (TGF-β3) delivered in 1 of 2 hydrogels (fibrin or gelatin methacrylate [GelMA]) on enthesis healing after repair of acute or chronic massive rotator cuff tears in rats.. Adult male Lewis rats underwent bilateral transection of the supraspinatus and infraspinatus tendons with intramuscular injection of botulinum toxin A (n = 48 rats). After 8 weeks, animals received 1 of 8 interventions (n = 12 shoulders/group): (1) no repair, (2) repair only, or repair augmented with (3) fibrin, (4) GelMA, (5) fibrin + ADSCs, (6) GelMA + ADSCs, (7) fibrin + ADSCs + TGF-β3, or (8) GelMA + ADSCs + TGF-β3. An equal number of animals underwent acute tendon transection and immediate application of 1 of 8 interventions. Enthesis healing was evaluated 4 weeks after the repair by microcomputed tomography, histology, and mechanical testing.. Increased bone loss and reduced structural properties were seen in chronic compared with acute tears. Bone mineral density of the proximal humerus was higher in repairs of chronic tears augmented with fibrin + ADSCs and GelMA + ADSCs than in unrepaired chronic tears. Similar improvement was not seen in acute tears. No intervention enhanced histologic appearance or structural properties in acute or chronic tears.. Surgical repair augmented with ADSCs may provide more benefit in chronic tears compared with acute tears, although there was no added benefit to supplementing ADSCs with TGF-β3.

Topics: Acute Disease; Adipose Tissue; Animals; Bone Density; Chronic Disease; Fibrin; Humerus; Hydrogels; Male; Methacrylates; Orthopedic Procedures; Rats; Rats, Inbred Lew; Rotator Cuff Injuries; Stem Cell Transplantation; Transforming Growth Factor beta3; Wound Healing; X-Ray Microtomography

Cultured epithelial autografts (CEAs) represent a life-saving surgical technique for full-thickness skin burns covering more than 60% total body surface area. However, CEAs present numerous drawbacks leading to heavy cosmetic and functional sequelae. In our previous study, we showed that human plasma-based fibrin matrices (hPBM) could improve the reparative potential of CEAs. Therefore, in the present work, we sought to investigate the role of hPBM compared with fibrin from purified fibrinogen (FPF) or plastic support on epidermal substitute formation and engraftment. The use of hPBM for epidermal substitute culture improved keratinocyte migration, proliferation, and epidermal substitute organization to a better extent than FPF in vitro. Both fibrin matrices favored greater dermal-epidermal junction protein deposition and prevented their degradation. Keratinocyte differentiation was also decreased using both fibrin matrices. Basement membrane protein deposition was mainly influenced by matrix whereas growth factors released from fibrin especially by hPBM were shown to enhance in vitro keratinocyte migration, proliferation, and epidermal substitute organization. Ultimately, epidermal substitutes grown on hPBM displayed better engraftment rates than those cultured on FPF or on plastic support in a NOD-SCID model of acute wound with the formation of a functional dermal-epidermal junction. Together, these results show the positive impact of fibrin matrices and their released growth factor on epidermal substitute phenotype and grafting efficiency. Fibrin matrices, and especially hPBM, may therefore be of interest to favor the treatment of full-thickness burn patients.

Topics: Acute Disease; Animals; Basement Membrane; Cell Differentiation; Cell Movement; Cell Proliferation; Cells, Cultured; Epidermis; Female; Fibrin; Humans; Keratinocytes; Membrane Proteins; Mice, Inbred NOD; Mice, SCID; Phenotype; Skin Transplantation; Skin, Artificial; Tissue Engineering

In unenhanced computed tomography (CT) of acute ischemic stroke, the density of occluding clots is associated with the content of red blood cells and successful recanalization with stent thrombectomy. However, no CT marker for fibrin content is established. In order to improve clot diagnostics, we conducted an in vitro study to investigate thrombus composition of histologically defined ovine blood clots with unenhanced and contrast-enhanced CT using spectral detector CT (SDCT).. Ovine blood clot types containing defined amounts of red blood cells (RBC; pure fibrin clots: RBC 0% ± 0, fibrin 100% ± 0), mixed clots (RBC 35.1% ± 4.11, fibrin 79.2% ± 5.6) and red clots (RBC 99.05% ± 1.14, fibrin 0.95% ± 1.14) were scanned in a SDCT (IQon®, Philips, Amsterdam, The Netherlands) (a) in a tube containing saline, (b) 5 min and (c) 3 days after exposure to a 1:50 dilution of iohexol (Accupaque-350®, GE-Healthcare, Boston, MA, USA). The attenuation of the clots was measured in Hounsfield units (HU) in conventional CT datasets as well as virtual noncontrast reconstructions (VNC) of nonenhanced and contrast-enhanced SDCT in a blinded and randomized fashion. Statistical analysis was conducted with ANOVA, Spearman's correlation, linear and multivariable regression models.. In unenhanced scans, clots differed in density with linear interrelation (fibrin 23.6 ± 1.1, mixed 34.9 ± 1.6, red 46.7 ± 1.6, mean HU ± SD). The blood clots did not show any overlap of density in the native scans and VNC at different time points (p < 0.0001 for each setting and clot type). However, they could not be differentiated after initial contrast exposure (fibrin 108.5 ± 7.8, mixed 105.3 ± 3.5, red 104.8 ± 3.8, mean HU ± SD). After prolonged exposure, the fibrin rich clots showed a significant increase of density due to further uptake of contrast medium (fibrin 163.6 ± 3.6, mixed 138.3 ± 4.1, red 109.6 ± 5.4, mean HU ± SD). In multivariable models, native CT density and contrast enhancement were independent variables associated with thrombus type (p < 0.01 each).. The fibrin content in blood clots is strongly associated with contrast uptake. As previously shown, the density of the clot formations in native CT scans is dependent on the RBC. Our data show that CT density and relative enhancement of clots are independent determinants of clot composition. Using both variables in the CT workup of acute ischemic stroke has the potential to have a decisive impact on patient stratification for treatment.

Topics: Acute Disease; Animals; Cattle; Correlation of Data; Erythrocyte Count; Fibrin; Humans; Image Enhancement; Image Interpretation, Computer-Assisted; In Vitro Techniques; Intracranial Thrombosis; Tomography, X-Ray Computed

Venous thromboembolism (VTE) is a common complication in patients who have undergone major orthopedic surgery, but there are few predictors of VTE after major orthopedic surgery treated with an anticoagulant. We measured levels of fibrin-related markers (FRMs), such as D-dimer, soluble fibrin (SF), and fibrinogen and fibrin degradation products (FDPs) in 66 patients with acute-phase VTE, and 367 patients undergoing major orthopedic surgery. Plasma FDP, D-dimer, and SF levels were significantly higher in patients with acute VTE, but only FDP and D-dimer levels were significantly higher in subclinical VTE. Adequate cut-off levels of D-dimer were 2.2 μg/ml for diagnosing acute VTE and 1.5 μg/ml for diagnosing subclinical VTE. D-dimer of less than 1.9 or 0.7 μg/ml ruled out acute VTE or subclinical VTE. D-dimer of more than 1.3 μg/ml preoperatively showed a moderate risk for postoperative VTE. Measurement of FRMs is useful for evaluating the risk of subclinical or postoperative VTE in patients with major orthopedic surgery. In particular, FDP is the most valuable marker for diagnosing acute VTE, whereas D-dimer is the most valuable for diagnosing subclinical VTE or predicting VTE.

Topics: Acute Disease; Aged; Biomarkers; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Male; Middle Aged; Orthopedic Procedures; Venous Thromboembolism; Young Adult

The present study evaluates the in vitro, in vivo, and ex vivo antithrombotic and anticoagulant effect of two flavonoids: quercetin and quercetin-3-O-β-d-glucoside (isoquercetin). The present results have shown that quercetin and isoquercetin inhibit the enzymatic activity of thrombin and FXa and suppress fibrin clot formation and blood clotting. The prolongation effect of quercetin and isoquercetin against epinephrine and collagen-induced platelet activation may have been caused by intervention in intracellular signaling pathways including coagulation cascade and aggregation response on platelets and blood. The in vivo and ex vivo anticoagulant efficacy of quercetin and isoquercetin was evaluated in thrombin-induced acute thromboembolism model and in ICR mice. Our findings showed that in vitro and in vivo inhibitory effects of quercetin were slightly higher than that of quercetin glucoside, whereas in vitro and ex vivo anticoagulant effects of quercetin were weaker than that of quercetin glucoside because of their structural characteristics.

Topics: Acute Disease; Animals; Blood Coagulation; Blood Platelets; Collagen; Disease Models, Animal; Epinephrine; Factor Xa; Fibrin; Fibrinolytic Agents; Flavonoids; Glucosides; Male; Mice; Mice, Inbred ICR; Platelet Activation; Primary Cell Culture; Quercetin; Rats, Sprague-Dawley; Signal Transduction; Thrombin; Thromboembolism

The presence and amount of the proteins within a plasma clot may influence clot properties, like susceptibility to fibrinolysis, however, the clot proteome has not yet been extensively described. The aim of the study was to investigate the protein composition of clots of four patients with acute myocardial infarction (AMI) in two time points: in the acute ischemic phase and two months later during the standard therapy.. Shotgun proteomic method (2DLC-MS/MS) was used to investigate time-dependent protein composition changes of clots prepared ex vivo from citrated plasma of the peripheral blood of patients with AMI.. Proteomic analysis revealed a total number of 62 proteins identified in all 8 samples grouping into several distinct functional clusters (e.g. cholesterol transporter activity, immunoglobulin binding and peptidase regulatory activity). The protein signatures of clots differed significantly depending on time after ACS, showing 30% greater variability in protein composition of the clots prepared in the plasma two months after the onset of AMI. Several proteins potentially involved in clot formation and resolution showed an interesting pattern of changes over time.. We provided the first qualitative analysis of proteomes of fibrin clots generated ex vivo in plasma taken from patients with AMI showing differences between clots generated in the acute ischemic phase and those prepared two months later. It might be hypothesized that differences involving proteins of potential influence on within-clot fibrinolysis and clot stability may partially explain time-dependent changes in the clots structure and firmness in patients with AMI.

Topics: Acute Disease; Fibrin; Humans; Middle Aged; Myocardial Infarction; Proteomics

The primary limitation of thrombolytic treatment of ischemic stroke with tissue plasminogen activator (tPA) is the hemorrhagic risk. We tested AcSDKP (N-acetyl-seryl-aspartyl-lysyl-proline), as an auxiliary therapeutic agent, to reduce blood-brain barrier (BBB) disruption in a combination tPA thrombolytic treatment of stroke. Wistar rats subjected to embolic stroke were randomly assigned to either the tPA monotherapy group (n=9) or combination of tPA and AcSDKP treatment group (n=9) initiated at 4 h after ischemia. Magnetic resonance imaging (MRI) measurements were performed before and after the treatments. Immunohistochemical staining and measurements were performed to confirm MRI findings. Longitudinal MRI permeability measurements with gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) demonstrated that combination treatment of acute embolic stroke with AcSDKP and tPA significantly reduced BBB leakage, compared to tPA monotherapy, at 3 and 6 days (18.3±9.8 mm3 vs. 65.0±21.0 mm3, p<0.001) after the onset of stroke, although BBB leakage was comparable between the two groups prior to the treatments (6.8±4.4 mm3 vs. 4.3±3.3 mm3, p>0.18). The substantial reduction of BBB leakage observed in the combination treatment group was closely associated with reduced ischemic lesions measured by T2 maps (113.6±24.9 mm3 vs. 188.1±60.8 mm3, p<0.04 at 6 days). Histopathological analysis of the same population of rats showed that the combination treatment significantly reduced parenchymal fibrin deposition (0.063±0.059 mm2 vs. 0.172±0.103 mm2, p<0.03) and infarct volume (146.7±35.9 mm3 vs. 199.3±60.4 mm3, p<0.05) compared to the tPA monotherapy at 6days after stroke. MRI provides biological insight into the therapeutic benefit of combination treatment of stroke with tPA and AcSDKP 4h after onset, and demonstrates significantly improved cerebrovascular integrity with neuroprotective effects compared with tPA monotherapy.

Topics: Acute Disease; Animals; Blood-Brain Barrier; Brain; Capillary Permeability; Contrast Media; Disease Models, Animal; Drug Therapy, Combination; Fibrin; Fibrinolytic Agents; Gadolinium DTPA; Immunohistochemistry; Infarction, Middle Cerebral Artery; Longitudinal Studies; Magnetic Resonance Imaging; Male; Neuroprotective Agents; Oligopeptides; Rats, Wistar; Tissue Plasminogen Activator

Topics: Acute Disease; Adult; Extracorporeal Membrane Oxygenation; Fibrin; Humans; Male; Microscopy, Electron; Myocarditis; Oxygenators, Membrane; Polypropylenes

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

We investigated whether markers of platelet, neutrophil and endothelial activation, plasma fibrin clot properties and patient clinical profile may characterize coronary thrombus composition in ST-segment elevation myocardial infarction (STEMI) patients.. A total of 40 intracoronary thrombi obtained 4.0-16.5 h since chest pain onset by manual aspiration during primary coronary intervention (PCI) were assessed using scanning electron microscopy. Plasma fibrin clot permeation coefficient (Ks) and clot lysis time (CLT), together with platelet and endothelial activation, fibrinolysis, and inflammation markers, were measured ex vivo in 16 patients on admission (pre-PCI group) and on the next morning in 24 patients (post-PCI group).. Fibrin, erythrocyte, platelet and white blood cell content in the thrombi were estimated at 49.1%, 24.2%, 11.6% and 3.7% respectively. In the pre-PCI group, in addition to fibrinogen, P-selectin and plasminogen activator inhibitor-1 were positively correlated with thrombus fibrin content. In the post-PCI group, in addition to von Willebrand factor antigen (vWF:Ag), soluble CD40 ligand and myeloperoxidase (MPO) were positively correlated with thrombus fibrin content. After adjustment for fibrinogen and onset-to-thrombectomy time circulating vWF:Ag in both groups, and MPO and P-selectin in the pre-PCI group were the independent predictors of fibrin-rich intracoronary thrombus presence. Other predictors were renal impairment, arterial hypertension and time from symptom onset to thrombus aspiration in all patients.. In STEMI patients coronary thrombus composition is partly characterized by plasma markers of platelet, neutrophil and endothelial activation, with a varying contribution of these factors over time.

Topics: Acute Disease; Aged; Blood Coagulation; Blood Platelets; Coronary Vessels; Endothelial Cells; Endothelium, Vascular; Female; Fibrin; Fibrinogen; Humans; Inflammation; Male; Microscopy, Electron, Scanning; Middle Aged; Neutrophils; P-Selectin; Percutaneous Coronary Intervention; Plasminogen Activator Inhibitor 1; Platelet Activation; Prospective Studies; Thrombosis; Treatment Outcome

Human induced pluripotent stem cells (hiPSCs) hold promise for myocardial repair following injury, but preclinical studies in large animal models are required to determine optimal cell preparation and delivery strategies to maximize functional benefits and to evaluate safety. Here, we utilized a porcine model of acute myocardial infarction (MI) to investigate the functional impact of intramyocardial transplantation of hiPSC-derived cardiomyocytes, endothelial cells, and smooth muscle cells, in combination with a 3D fibrin patch loaded with insulin growth factor (IGF)-encapsulated microspheres. hiPSC-derived cardiomyocytes integrated into host myocardium and generated organized sarcomeric structures, and endothelial and smooth muscle cells contributed to host vasculature. Trilineage cell transplantation significantly improved left ventricular function, myocardial metabolism, and arteriole density, while reducing infarct size, ventricular wall stress, and apoptosis without inducing ventricular arrhythmias. These findings in a large animal MI model highlight the potential of utilizing hiPSC-derived cells for cardiac repair.

Topics: Acute Disease; Animals; Apoptosis; Cell Differentiation; Cell Lineage; Cells, Cultured; Disease Models, Animal; Endothelial Cells; Fibrin; Heart Ventricles; Humans; Induced Pluripotent Stem Cells; Insulin-Like Growth Factor I; Microspheres; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Myocytes, Smooth Muscle; Recovery of Function; Stem Cell Transplantation; Swine

Emerging evidence indicates that various haemostatic components can regulate the progression of liver disease. Thrombin-activatable fibrinolysis inhibitor (TAFI) possesses anti-inflammatory properties besides its anti-fibrinolytic function. Here, we investigated the contribution of TAFI to the progression of disease in murine models of chronic and acute liver failure. Chronic carbon tetrachloride (CCL4) administration induced liver damage and fibrosis both in TAFI knockout (TAFI-/-) mice and wild-type controls. Smooth muscle actin-α (α-SMA) content of liver tissue was significantly increased after 1 and 3 weeks, and pro-collagen α1 expression was significantly increased after 3 and 6 weeks in TAFI-/- mice. TAFI-/- mice showed significantly elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) after 3 weeks of CCL4. Neutrophil influx was significantly increased in TAFI-/- mice after 6 weeks of CCL4. No difference in hepatic fibrin deposition between TAFI-/- and wild-types was observed. After acetaminophen intoxication, necrosis was significantly increased in TAFI-/- mice at 24 hours (h) after injection. AST and ALT levels were decreased at 2 and 6 h after acetaminophen injection in TAFI-/- mice, but were significantly higher in the TAFI-/- mice at 24 h. Similarly, hepatic fibrin deposition was decreased at 6 h in TAFI-/- mice, but was comparable to wild-types at 24 h after injection. In conclusion, TAFI deficiency results in accelerated fibrogenesis and increased liver damage in murine models of chronic and acute liver disease, which may be related to increased inflammation.

Topics: Acetaminophen; Actins; Acute Disease; Alanine Transaminase; Animals; Aspartate Aminotransferases; Carbon Tetrachloride; Carboxypeptidase B2; Chemical and Drug Induced Liver Injury; Chronic Disease; Collagen Type I; Collagen Type I, alpha 1 Chain; Fibrin; Gene Expression Regulation; Liver; Liver Cirrhosis, Experimental; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Necrosis; Neutrophil Infiltration; RNA, Messenger; Time Factors

Skin injury is followed by accumulation of a fibrin based provisional matrix which normally drives the process of wound repair. Exogenous fibrin with extra cellular matrix (ECM) components can also favor the wound healing process. In a preliminary study we found that lyophilized fibrin sheet (FS) arrest bleeding from rabbit skin wound but it remained dry during the repair period and did not accelerate the healing process better than untreated control. In the current study, hyaluronic acid (HA) was incorporated into FS and the resultant HA-FS promoted water retention and improved wound healing process. Gross-morphology, histopathology and histomorphometry were employed to compare qualitative and quantitative difference of wound healing in treated group against controls. In experimental sites (HA-FS), re-epithelialization was completed by 14 days with neo-vascularization and deposition of wavy bundles of collagen in the treated sites. Rate of healing process was different in treated and untreated wounds and most striking difference was the appearance of appendages, sebaceous gland and hair follicle at some locations in HA-FS treated sites. Therefore, HA with fibrin can create an effective wound care matrix which promotes water retention and wound healing potential.

Topics: Acute Disease; Animals; Extracellular Matrix; Fibrin; Hyaluronic Acid; Neovascularization, Physiologic; Rabbits; Skin; Skin, Artificial; Tissue Scaffolds; Wound Healing; Wounds and Injuries

Mechanical behavior of the thromboembolus is one of the key factors that determine the efficacy of thrombectomy devices for revascularization in AIS. We characterized the mechanical properties and composition of thromboemboli from clinical cases and compared them with commonly used EAs.. Thromboemboli were obtained from patients with AIS by using aspiration devices and from carotid atherosclerotic plaques harvested during endarterectomy. In the laboratory, common EAs were created by varying blood donor species (human, porcine, and bovine), thrombin concentration, and presence of barium sulfate. Stiffness and elasticity of the specimens were measured with DMA. Scanning electron microscopy and histology were used to investigate the ultrastructure and composition of all specimens.. Red thromboemboli from patients composed mainly of fibrin and erythrocytes were much softer than the calcified and cholesterol-rich material. Of the EAs created in the laboratory, those made from bovine blood presented the highest stiffness that was independent of thrombin concentration. Addition of thrombin increased the stiffness and elasticity of human and porcine EAs (P < .05). The presence of barium sulfate significantly reduced the elasticity of all EAs (P < .05).. Endovascular device testing and development requires realistic EAs. The stiffness and elasticity of the cerebral thromboemboli analyzed in this study were closely matched by recalcified porcine EAs and thrombin-induced human EAs. Stiffness of the thrombus extracted from carotid endarterectomy specimens was similar with that of the thrombin-induced bovine and porcine EAs.

Topics: Acute Disease; Aged; Animals; Barium Sulfate; Biomechanical Phenomena; Brain Ischemia; Cattle; Elasticity; Erythrocytes; Fibrin; Humans; Infarction, Middle Cerebral Artery; Male; Species Specificity; Stress, Mechanical; Swine; Thrombectomy; Thrombin; Thromboembolism

We sought to investigate whether patients with in-stent thrombosis (IST) display altered plasma fibrin clot properties.. We studied 47 definite IST patients, including 15 with acute, 26 subacute and 6 late IST, and 48 controls matched for demographics, cardiovascular risk factors, concomitant treatment and angiographic/stent parameters. Plasma clot permeability (K(s)), which indicates a pore size, turbidity (lag phase, indicating the rate of fibrin clot formation, DeltaAbs(max), maximum absorbance of a fibrin gel, reflecting the fiber thickness), lysis time (t(50%)) and maximum rate of D-dimer release from clots (D-D(rate)) were determined 2 to 73 (median 14.7) months after IST. Patients with IST had 21% lower K(s), 14% higher DeltaAbs(max), 11% lower D-D(rate), 30% longer t(50%) (all P<0.0001) and 5% shorter lag phase compared to controls (P=0.042). There were no correlations between clot variables and the time of IST or that from IST to blood sampling. Multiple regression analysis showed that K(s) (odds ratio=0.36 per 0.1 microm(2), P<0.001), D-D(rate) (odds ratio=0.16 per 0.01 mg/L/min, P<0.001) and stent length (odds ratio=1.1 per 1 mm, P=0.043) were independent predictors of IST (R(2)=0.58, P<0.001).. IST patients tend to form dense fibrin clots resistant to lysis, and altered plasma fibrin clot features might contribute to the occurrence of IST.

Topics: Acute Disease; Aged; Angioplasty, Balloon, Coronary; Case-Control Studies; Coronary Angiography; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Humans; Kinetics; Logistic Models; Male; Middle Aged; Nephelometry and Turbidimetry; Odds Ratio; Permeability; Platelet Aggregation Inhibitors; Prosthesis Design; Retrospective Studies; Risk Assessment; Risk Factors; Stents; Thrombosis; Treatment Outcome

Hypercoagulable state occurs in patients with acute vascular events. We wondered whether clot structure/function is altered in acute ischemic stroke (AIS), like in acute myocardial infarction.. In 45 consecutive patients with AIS (24M, 21F), aged 67.4+/-10.9 years, and 45 healthy controls matched for age and sex, we investigated plasma fibrin clot structure/function by permeation, turbidity, and efficiency of fibrinolysis.. Compared to controls, AIS patients produced clots that had 30.5% less porous network (p<0.0001), were less susceptible to fibrinolysis (10.8% longer lysis time, p=0.001), were 20.5% more compact (p<0.0001), had 17.1% higher clot mass (p<0.0001), and showed increased (by 10.2%) overall fiber thickness (p<0.0001) with 8% shorter lag phase of fibrin formation (p=0.0002). Maximum rate of D-dimer release from clots was similar. Multiple regression analyses for all subjects (n=90) showed that being a stroke patient (p<0.0001), fibrinogen (p<0.0001) and lipoprotein(a) (p=0.0075) were independent predictors of clot permeability (model R2 0.79). Only fibrinogen (p<0.0001) and lipoprotein(a) (p=0.0026) predicted lysis time. All other fibrin parameters were predicted only by being a stroke patient. Clot compaction was associated with neurological deficit on admission (r=-0.81; p<0.0001) and at discharge (r=-0.69; p<0.0001). Patients with 0 or 1 point in the modified Rankin scale (n=19) had 13.3% higher clot permeability compared to the remainder (p=0.02).. This study is the first to show that AIS is associated with unfavorably altered fibrin clot properties that might correlate with neurological deficit.

Topics: Acute Disease; Aged; Blood Coagulation Tests; Family; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Humans; Intracranial Thrombosis; Ischemia; Male; Middle Aged; Permeability; Stroke; Thrombosis

Acute fibrinous and organizing pneumonia (AFOP) is a disease of the small airways that is characterized by deposition of fibrin within the alveolar spaces. The histological pattern is described as a variant of cryptogenic organizing pneumonia (COP). Although COP has been occasionally described in patients with HIV infection, the variant form, AFOP, has not been previously reported in such patients. This report describes an intriguing case of AFOP in a patient with HIV infection and Pneumocystis jiroveci pneumonia. AFOP was diagnosed after tapering of corticosteroid therapy. This case illustrates that non-infectious pulmonary infiltrates should be considered in the differential diagnosis of lung disease in patients with HIV infection.

Topics: Acute Disease; Adult; AIDS-Related Opportunistic Infections; Cryptogenic Organizing Pneumonia; Diagnosis, Differential; Fibrin; HIV Infections; Humans; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisone; Treatment Outcome

To enable outpatient treatment of a selected group of patients with pulmonary embolism (PE), insight in the determinants of adverse clinical outcome is warranted. We have identified risk factors for serious adverse events (SAE) within the first 10 days of acute PE. We have retrospectively analysed data of 440 consecutive patients with acute PE. Collected data included age, gender, medical history, blood pressure, pulse rate and D-dimer concentration. The variables associated with SAE in the first 10 days in univariate analysis (p<0.15) have been included in a multivariate logistic regression model (backward conditional, p out >0.10). In 440 patients with acute PE, 20 SAEs occurred in a 10-day follow-up period. Pulse rate > or = 100 beats per minute (bpm) (OR, 6.85; 95%CI 1.43-32.81) and D-dimer concentration > or = 3,000 microg/ml (OR, 5.51; 95%CI 0.68-44.64) were significantly related to the SAEs. All SAEs were predicted by a pulse rate > or = 100 bpm and/or a D-dimer concentration > or = 3,000 microg/ml. Older age, gender, history of venous thromboembolism (VTE), heart failure, chronic obstructive pulmonary disease, cancer or a systolic blood pressure < 90 mm Hg had no significant influence on short term SAEs. Pulse rate and D-dimer concentration can be used to identify patients with acute PE, who are at risk for adverse clinical outcome during the first 10 days of hospitalisation. Outpatient treatment of PE-patients with a pulse rate > or = 100 bpm and/or a D-dimer concentration > or = 3,000 microg/ml has to be discouraged.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Disease Progression; Female; Fibrin; Follow-Up Studies; Heart Rate; Humans; Male; Middle Aged; Netherlands; Predictive Value of Tests; Pulmonary Embolism; Retrospective Studies; Risk Factors; Sensitivity and Specificity

Acute hyperglycemia on admission for acute coronary syndrome worsens the prognosis in patients with and without known diabetes. Postulated mechanisms of this observation include prothrombotic effects. The aim of this study was to evaluate the effect of elevated glucose levels on blood clotting in acute coronary syndrome patients.. We studied 60 acute coronary syndrome patients within the first 12 h after pain onset, including 20 subjects with type 2 diabetes, 20 subjects with no diagnosed diabetes but with glucose levels >7.0 mmol/l, and 20 subjects with glucose levels <7.0 mmol/l. We determined generation of thrombin-antithrombin complexes (TATs) and soluble CD40 ligand (sCD40L), a platelet activation marker, at the site of microvascular injury, together with ex vivo plasma fibrin clot permeability and lysis time.. The acute coronary syndrome patients with no prior diabetes but elevated glucose levels had increased maximum rates of formation and total production of TATs (by 42.9%, P < 0.0001, and by 25%, P < 0.0001, respectively) as well as sCD40L release (by 16.2%, P = 0.0011, and by 16.3%, P < 0.0001, respectively) compared with those with normoglycemia, whereas diabetic patients had the highest values of TATs and sCD40L variables (P < 0.0001 for all comparisons). Patients with hyperglycemia, with no previously diagnosed diabetes, had longer clot lysis time (by approximately 18%, P < 0.0001) similar to that in diabetic subjects, but not lower clot permeability compared with that in normoglycemic subjects.. Hyperglycemia in acute coronary syndrome is associated with enhanced local thrombin generation and platelet activation, as well as unfavorably altered clot features in patients with and without a previous history of diabetes.

Topics: Acute Coronary Syndrome; Acute Disease; Aged; Blood Coagulation; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Fibrin; Fibrinolysis; Humans; Hyperglycemia; Hypoglycemic Agents; Male; Middle Aged; Myocardial Infarction; Platelet Activation; Prognosis; Thrombin

In previous studies, (99m)Tc-recombinant tissue plasminogen activator (rt-PA) imaging has had a high sensitivity and specificity for the detection of deep vein thrombosis (DVT). In this technique, the plasminogen activation site of rt-PA undergoes inactivation but fibrin binding is retained. Uptake of (99m)Tc-rt-PA into DVT relies on binding of C-terminal lysine residues on fibrin. It is postulated that as the thrombus ages, fewer fibrin sites are available for (99m)Tc-rt-PA and that there should be a progressive decrease in (99m)Tc-rt-PA uptake in old thrombi as compared with fresh thrombi. The ability to differentiate fresh from old thrombus would have significant clinical implications in the objective diagnosis of recurrent DVT. Our aim was to examine the relative uptake of (99m)Tc-rt-PA in acute DVT over the first 30 d after diagnosis.. Seventy-four patients with acute symptomatic DVT were entered into the study. Patients underwent ultrasound and (99m)Tc-rt-PA imaging on days 1, 7, and 30.. Residual thrombus was detected by ultrasonography in 46 (84%) of 55 patients on day 7 and in 29 (66%) of 44 patients on day 30. Of the persisting thrombi on day 7, 72% (33/46) showed (99m)Tc-rt-PA uptake. Of the persisting thrombi on day 30, 0% (0/29) showed (99m)Tc-rt-PA uptake.. Uptake of (99m)Tc-rt-PA into DVT was absent 30 d after diagnosis. This finding suggests that this imaging technique can distinguish fresh from old thrombus.

Topics: Acute Disease; Female; Fibrin; Humans; Leg; Male; Middle Aged; Mucoproteins; Plasminogen Activators; Protein Binding; Radionuclide Imaging; Radiopharmaceuticals; Recombinant Proteins; Recurrence; Technetium; Thigh; Time Factors; Ultrasonography; Veins; Venous Thrombosis

The aim of this study was to report a case of severe bilateral fibrinous anterior uveitis following pamidronate therapy in a patient on latanoprost.. This study is presented as an interventional case report.. Clinical examination showed bilateral severe fibrinous uveitis following an intravenous infusion of disodium pamidronate. Ocular signs and symptoms responded to stopping latanoprost and treatment with oral prednisolone (60 mg) and hourly topical prednisolone acetate 1%. The reintroduction of latanoprost resulted in a recurrence, which was stopped with subsequent improvement.. Mild anterior uveitis is an unfamiliar adverse effect of pamidronate therapy. However, severe fibrinous uveitis has not been previously described. This may be due to the compounding effect of latanoprost. This case highlights the importance of history taking and awareness of the otherwise uncommon side effect of this commonly prescribed medication.

Topics: Acute Disease; Administration, Topical; Aged, 80 and over; Anti-Inflammatory Agents; Bone Density Conservation Agents; Diphosphonates; Drug Interactions; Female; Fibrin; Glaucoma, Open-Angle; Humans; Infusions, Intravenous; Latanoprost; Osteoporosis, Postmenopausal; Pamidronate; Prednisolone; Prostaglandins F, Synthetic; Recurrence; Uveitis, Anterior

While coagulation often causes pathology during infectious disease, we recently demonstrated that fibrin, a product of the coagulation pathway, performs a critical protective function during acute toxoplasmosis (L. L. Johnson, K. N. Berggren, F. M. Szaba, W. Chen, and S. T. Smiley, J. Exp. Med. 197:801-806, 2003). Here, we investigate the mechanisms regulating the formation of this protective fibrin. Through comparisons of Toxoplasma-infected wild-type and cytokine-deficient mice we dissociate, for the first time, the relative fibrin-regulating capacities of pathogen products, host cytokines, and infection-stimulated hemorrhage. Remarkably, neither the pathogen burden nor hemorrhage is a primary regulator of fibrin levels. Rather, two type 1 cytokines exert dominant and counterregulatory roles: tumor necrosis factor alpha (TNF-alpha), acting via the type 1 TNF-alpha receptor, promotes fibrin deposition, while gamma interferon (IFN-gamma), acting via STAT1 and IFN-gamma receptors expressed on radioresistant cells, suppresses fibrin deposition. These findings have important clinical implications, as they establish that cytokines known to regulate pathological coagulation also dictate levels of protective fibrin deposition. We present a novel model depicting mechanisms by which the immune system can destroy infected tissue while independently restraining hemorrhage and promoting tissue repair through the deliberate deposition of protective fibrin.

Topics: Acute Disease; Animals; Fibrin; Gene Expression Regulation; Hemorrhage; Humans; Interferon-gamma; Mice; Mice, Inbred C57BL; Toxoplasma; Toxoplasmosis; Tumor Necrosis Factor-alpha

Homocysteine (Hcy) is a risk factor for thrombosis. We investigated a hypothesis that the clot permeability and its resistance to fibrinolysis is associated with plasma total Hcy (tHcy) in human subjects.. We studied healthy men not taking any medication (n=76), male patients with advanced coronary artery disease (CAD) taking low-dose aspirin (n=33), men with diabetes mellitus diagnosed recently (median hemoglobin A(1c) 7.65%; n=16), and patients with isolated hypercholesterolemia (>7.0 mmol/L; n=15). We assessed clot permeability and turbidimetric lysis time as the determinants of fibrin clot structure. In a regression model, including age and fibrinogen, plasma tHcy was an independent predictor of clot permeation and fibrinolysis time in healthy subjects (R2=0.88, P<0.0001 and R2=0.54, P<0.0001, respectively). In CAD patients, tHcy and fibrinogen were stronger predictors of the permeation coefficient (R2=0.84; P<0.0001) than was fibrinogen alone (R2=0.66; P<0.0001), whereas tHcy was the only predictor of lysis time (R2=0.69; P<0.0001). Elevated tHcy levels observed after methionine load were not associated with any of the fibrin clot properties. In patients with diabetes or hypercholesterolemia, the influence of Hcy on permeation and, to a lesser extent, on the lysis time was obscured by dominant effects of glucose and cholesterol. In 20 asymptomatic men with hyperhomocysteinemia treated with folic acid, reduction in tHcy levels resulted in increased clot permeability (P=0.0002) and shorter lysis time (P<0.0001).. Our results indicate that plasma tHcy predicts clot permeation and susceptibility to fibrinolysis in healthy men and CAD patients. Our data are consistent with a mechanism of thrombosis in hyperhomocysteinemia, which involves modification of fibrinogen by Hcy-thiolactone.

Topics: Acute Disease; Adult; Aged; Blood Coagulation; Case-Control Studies; Coronary Artery Disease; Diabetes Mellitus; Drug Resistance; Fibrin; Fibrinolytic Agents; Folic Acid; Hematinics; Homocysteine; Humans; Hypercholesterolemia; Hyperhomocysteinemia; Male; Middle Aged; Permeability; Recombinant Proteins; Tissue Plasminogen Activator

To study the optical coherence tomography (OCT) pattern of the fluorescein angiographic leakage in acute central serous chorioretinopathy (CSCR).. This is a non-interventional pilot case study. OCT line scan was performed over the fluorescein angiographic leak site in eyes clinically diagnosed acute CSCR. Clinical fundus photograph, site of leakage on fundus fluorescein angiography and corresponding OCT were analysed.. The mean age of 10 consecutive patients was 38.8 +/- 6.9 years. Six patients were male and the mean duration of symptom was 7 days. Six eyes (60%) showed a characteristic dipping pattern of neurosensory retina with intervening hyper-reflective echoes suggestive of fibrin over the leakage site. All these eyes had ink-blot leak and subretinal fibrin.. Ink-blot leak in acute CSCR with subretinal fibrin generates a dipping morphological pattern on OCT.

Topics: Acute Disease; Adult; Capillary Permeability; Choroid Diseases; Exudates and Transudates; Female; Fibrin; Fluorescein Angiography; Humans; Male; Middle Aged; Pilot Projects; Retinal Diseases; Retinal Vessels; Tomography, Optical Coherence

The liver can be injured and its functions altered by activation of the coagulation and inflammatory processes in sepsis. The objective of the present study was to investigate the pattern of protease- activated receptors (PARs) over time in a model of acute liver injury induced by lipopolysaccharide (LPS); and whether PARs play a role in this process and exert their effects through inflammation and coagulation. Levels of tumor necrosis factor-a (TNF-a) were significantly expressed 1 h after LPS administration followed by: i) an increase in levels of tissue factor, factor VIIa, thrombin and plasminogen activator inhibitor-1; ii) unchanged or steady levels of tissue factor pathway inhibitor; and iii) subsequent deposition of fibrin in the liver tissue, that led to the elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which are associated with liver injury. The expression of all PAR isoforms (1-4) was elevated, and each isoform had a distinct cellular localization (hepatocytes, Kupffer cells, the portal triad area, and central veins) and a time-dependent pattern of expression. The immuno-reactivity of PAR2 and 4 in Kupffer cells was intense. Interestingly, PAR2 blocking peptide improved the healing of liver injuries, an effect that was associated with suppression of TNF-a elevation, and normalization of coagulation and fibrinolysis. This ultimately led to decreased fibrin formation in the injured liver. The present study reveals a distinct chronological expression and cellular localization of PARs in LPS-mediated liver injury and shows that blockade of PAR2 may play a crucial role in treating liver injury, via normalization of inflammation, coagulation and fibrinolytic pathways.

Topics: Acute Disease; Animals; Blood Coagulation; Blood Coagulation Factors; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Fibrin; Fibrinolysis; Humans; Lipopolysaccharides; Liver; Liver Diseases; Peptides; Protein Isoforms; Rats; Rats, Wistar; Receptor, PAR-1; Receptor, PAR-2; Receptors, Proteinase-Activated; Receptors, Thrombin; RNA, Messenger; Sepsis; Time Factors; Tumor Necrosis Factor-alpha

The purpose of the study was to determine the level of thrombus precursor protein (TrP) in patients with acute coronary syndrome (ACS). Twenty-six patients with ACS and anginal pain experienced during 2 to 12 hours (7.2 +/- 1.3 hours), admitted to cardiological intensive care unit, were enrolled in the study. Five ml of blood were sampled from a cubital vein of all the patients during the phase of the most intensive pain. TrP blood levels were measured with ELISA, Enzyme-Linked Immunoadsorbent Assay. The control group consisted of 29 healthy volunteers and 22 patients with stable exertional stenocardia. A significant increase in TpR (7.2 +/- 1.45 mcg/ml) was noted in the ACS patients as early as during the first 6 hours, vs. the healthy controls (1.01 +/- 0.12 mcg/ml) and the patients with stable stenocardia (1.21 +/- 0.06 mcg/ml), p < 0.01. A high level of TrP in the ACS patients could be noted earlier than a diagnostically significant increase in creatine phosphokinase level. No direct correlation was observed between the TrP level and the dynamics of such indices of the procoagulatory hemocoagulation chain as fibrinogen, prothrombin index, and active partial thromboplastin time. The results of the study demonstrate that the measurement of TrP level is highly informative when the intensity of intravascular blood coagulation in ACS patients is to be evaluated, which can be used to clarify indications to anticoagulation therapy. The enzyme immune method of TrP detection in the plasma of ACS patients can be recommended for clinical application.

Topics: Acute Disease; Biomarkers; Coronary Disease; Enzyme-Linked Immunosorbent Assay; Female; Fibrin; Follow-Up Studies; Humans; Male; Middle Aged; Prognosis; Severity of Illness Index; Syndrome

Deep venous thrombosis and pulmonary thromboembolism are common within weeks of spinal cord injury (SCI) but clinically uncommon in the chronically paralyzed. Fibrinogen half-life (FHL) and fibrin uptake of the legs (FUT), as indicators of an active thrombotic process, have been used to test this clinical impression.. Data from the use of autologous preparations of radioiodinated fibrinogen to determine FHL and FUT in 17 men paralyzed at cervical (6), thoracic (10), and lumbar levels (1), at ASIA grades A (15) and C (2) in 1974 to 1976 were reviewed. Group A consisted of 12 subjects 29 +/- 8 years of age and paralyzed 1 week to 5 months (median, 1 month). Group B consisted of 5 subjects 46 +/- 17 years of age and paralyzed 24 to 96 months (median, 36 months). Group B subjects were older and paralyzed longer than Group A. Group C consisted of 4 able-bodied control subjects enrolled at the same time for FHL studies, and these subjects were 34 to 38 years of age.. FHL was 61 +/- 14 hours for all SCI subjects and 95 +/- 23 hours for Group C (P = 0.001). Group A FHL was 59 +/- 16 hours, and FUT was positive in 8 of 12 subjects. Group B FHL was 66 +/- 7 hours, and FUT was positive in 3 of 4 subjects (1 FUT not done; P = 0.30 and 1.0, respectively).. Fibrinogen metabolism was abnormal in patients with acute SCI at high risk for pulmonary thromboembolism (PE) but continued to be abnormal beyond the high risk period for PE, possibly because of the greater age of the patients in the long-term paralysis group.

Topics: Acute Disease; Adult; Case-Control Studies; Chronic Disease; Disease Progression; Fibrin; Fibrinogen; Half-Life; Humans; Iodine Radioisotopes; Male; Middle Aged; Paralysis; Pulmonary Embolism; Risk Factors; Spinal Cord Injuries; Time Factors; Venous Thrombosis

Considerable confusion exists regarding the proper classification of idiopathic eosinophilic pneumonia (IEP). Furthermore, there are no reports describing the clinicopathological differences between the various forms of eosinophilic pneumonias.. The histological findings in acute eosinophilic pneumonia (AEP) and chronic eosinophilic pneumonia (CEP) were examined and the clinical and radiological features were contrasted with them.. Radiologically, ground glass opacity and interlobular septal thickening were characteristic of the AEP cases, while air space consolidation was seen in all CEP cases. Histologically, interstitial oedema and fibrin deposition were prominent in the AEP cases. Type II cells were detached from the alveolar walls, although the basal lamina was predominantly intact. In CEP, in addition to cellular infiltration, there was prominent intraluminal fibrosis. Disruption of the basal lamina was observed and nests of intraluminal fibrosis were directly adjacent and connected to the alveolar walls.. An essential histological difference between AEP and CEP is the severity of basal lamina damage and the amount of subsequent intraluminal fibrosis. In AEP particularly, these findings explain the radiographical findings, as well as the rapid and complete improvement noted in such cases.

Topics: Acute Disease; Adolescent; Adult; Aged; Basement Membrane; Biopsy; Bronchoalveolar Lavage; Chronic Disease; Female; Fibrin; Humans; Lung; Male; Middle Aged; Pulmonary Alveoli; Pulmonary Edema; Pulmonary Eosinophilia; Pulmonary Fibrosis; Radiography, Thoracic; Retrospective Studies; Tomography, X-Ray Computed

To describe an unusual ocular manifestation of a patient with acute myeloid leukemia (AML).. Observational case report.. A 59-year-old woman with a history of preleukemic myelodysplastic syndrome (MDS) and status post bone marrow transplant (BMT) complained of a sudden onset of poor vision associated with a corneal pseudomembrane. Ocular graft vs host disease was suspected, and the pseudomembrane was excised for histopathologic examination.. The pseudomembrane showed myeloblasts admixed with an acute inflammatory response suggestive of the development of AML, a complication of MDS. Bone marrow examination confirmed the diagnosis of relapsing AML.. Acute myeloid leukemia could present as a pseudomembrane; thus, examination of relevant ocular tissue is recommended.

Topics: Acute Disease; Bone Marrow; Bone Marrow Transplantation; Corneal Diseases; Female; Fibrin; Graft vs Host Disease; Humans; Leukemia, Myeloid; Membranes; Middle Aged; Neoplasm Recurrence, Local

Topics: Acute Disease; Blood Coagulation; Brain Ischemia; Drug Interactions; Female; Fibrin; Humans; Male; Nicotiana; Plasminogen; Smoking; Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator

Plaque rupture leading to thrombosis and occlusion is a major source of acute coronary syndromes. Methods for accurate detection of thrombosis in veins or arteries may expand our capacity to predict clinical complications and guide therapeutic decisions. We sought to demonstrate the feasibility of in vivo acute thrombus detection using a fibrin-targeted gadolinium based magnetic resonance contrast agent (EP-1242).. Carotid thrombosis was induced in 12 guinea pigs by external injury and blood stasis. MR images were obtained after thrombus formation pre- and post- EP-1242 injection, using a T1-weighted high-resolution fast spin-echo sequence.. An occlusive fibrin-rich thrombus was achieved in all animals. Correlation for thrombus location was excellent between MRI and histology (R=0.94; P<0.001). Contrast-enhanced MRI significantly improved thrombus detection when compared to non contrast-enhanced MRI (100% versus 41.6%; p<0.001). In addition, thrombus signal intensity (SI) was significantly increased after injection (SI(30 min-post)=4.39+/-0.12 versus 1.0; p<0.001). Contrast-to-noise ratio (CNR) was 43.8+/-7.2, 30 min post-injection (P<0.001). No enhancement was seen in the uninjured control arteries.. We demonstrate the feasibility of in vivo MRI for carotid thrombus detection using a novel fibrin-targeted contrast agent. This technique significantly improves detection of small size thrombi in an animal model of occlusive fibrin-rich thrombosis.

Topics: Acute Disease; Animals; Carotid Artery Thrombosis; Contrast Media; Disease Models, Animal; Fibrin; Guinea Pigs; Magnetic Resonance Imaging; Peptides, Cyclic

Plaque rupture with subsequent thrombosis is recognized as the underlying pathophysiology of most acute coronary syndromes and stroke. Thus, direct thrombus visualization may be beneficial for both diagnosis and guidance of therapy. We sought to test the feasibility of direct imaging of acute and subacute thrombosis using MRI together with a novel fibrin-binding gadolinium-labeled peptide, EP-1873, in an experimental animal model of plaque rupture and thrombosis.. Fifteen male New Zealand White rabbits (weight, approximately 3.5 kg) were made atherosclerotic by feeding a high-cholesterol diet after endothelial aortic injury. Plaque rupture was then induced with the use of Russell's viper venom (RVV) and histamine. Subsequently, MRI of the subrenal aorta was performed before RVV, after RVV, and after EP-1873. Histology was performed on regions suggested by MRI to contain thrombus. Nine rabbits (60%) developed plaque rupture and thrombus, including 25 thrombi visually apparent on MRI as "hot spots" after injection of EP-1873. Histological correlation confirmed all 25 thrombi (100%), with no thrombi seen in the other regions of the aorta. In the remaining 6 rabbits (control) without plaque rupture, no thrombus was observed on the MR images or on histology.. We demonstrate the feasibility of in vivo "molecular" MRI for the detection of acute and subacute thrombosis using a novel fibrin-binding MRI contrast agent in an animal model of atherosclerosis and acute/subacute thrombosis. Potential clinical applications include thrombus detection in acute coronary syndromes and stroke.

Topics: Acute Disease; Animals; Arteriosclerosis; Binding, Competitive; Contrast Media; Fibrin; Gadolinium DTPA; Magnetic Resonance Imaging; Male; Peptides; Rabbits; Thrombosis; Time Factors

This study objectively compares efficacy of dexamethasone Na phosphate 0.1%, fluorometholone 0.1% (FML), loteprednol etabonate 0.5% (Lotemax [LE]; Bausch & Lomb Pharmaceuticals, Inc., Tampa, FL), prednisolone acetate 1% (Pred Forte [PRED F]; Allergan Pharmaceuticals, Irvine, CA), and generic prednisolone acetate 1% (PRED A). These steroids were administered for 24 hours or 72 hours to New Zealand white rabbits with endotoxin-induced uveitis. Intraocular pressure (IOP), slit-lamp examination, and confocal microscopy were performed daily. Internalization of the glucocorticoid receptor (GC) was assayed in iris tissue by Western blot, and protein in aqueous humor by Bradford assay. Only LE and PRED F treatments significantly internalized GC receptor after 72 hours of treatment. Only LE and PRED A reduced protein concentration between 24 hours and 72 hours of treatment. All drugs improved clinical signs after 24 hours of treatment. None of the steroids promoted return of the inflammation-induced corneal thickness to baseline. While none returned IOP to baseline, LE was most effective. Confocal microscopy indicated that only treatment with LE reverted the abnormal endothelial-cell shape to normal. In conclusion, all steroid treatments reduced uveitis to some degree but LE was consistently effective. A longer observation period may be required to document the return of IOP and corneal thickness to baseline values.

Topics: Acute Disease; Administration, Topical; Androstadienes; Animals; Aqueous Humor; Blotting, Western; Conjunctiva; Corneal Stroma; Dexamethasone; Endothelium, Corneal; Eye Proteins; Fibrin; Fluorometholone; Glucocorticoids; Intraocular Pressure; Lipopolysaccharides; Loteprednol Etabonate; Male; Particle Size; Prednisolone; Rabbits; Receptors, Glucocorticoid; Suspensions; Time Factors; Uveitis, Anterior; Vitreous Body

Topics: Acute Disease; Echo-Planar Imaging; Female; Fibrin; Humans; Magnetic Resonance Imaging; Magnetic Resonance Imaging, Cine; Middle Aged; Pericarditis; Pericardium

The alveolar fibrinolytic system is altered in acute lung injury (ALI). Levels of the fibrinolytic protease inhibitor, plasminogen activator inhibitor-1 (PAI-1), are too low in bronchoalveolar lavage to address its prognostic significance. This study was performed to assess whether PAI-1 antigen in undiluted pulmonary edema fluid levels can identify patients with ALI and predict their outcome. PAI-1 antigen levels in both plasma and edema fluid were higher in ALI compared with hydrostatic edema, and edema fluid PAI-1 values identified those with ALI with high sensitivity and specificity. Both the high plasma and edema fluid PAI-1 antigen values were associated with a higher mortality rate and fewer days of unassisted ventilation in patients with ALI. Differences in PAI-1 activity were concordant with levels of PAI-1 antigen. Although the fibrin-derived alveolar D-dimer levels were strikingly similar in both groups, ALI patients had a higher relative proportion of D-monomer. In conclusion, PAI-1 levels in edema fluid and plasma identify those with ALI that have a poor prognosis. The data indicate that fibrin turnover in early ALI is a consequence of a rapid fibrinogen influx and fractional fibrinolytic inhibition.

Topics: Acute Disease; Adult; Aged; Enzyme-Linked Immunosorbent Assay; Extravascular Lung Water; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Humans; Hydrostatic Pressure; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Predictive Value of Tests; Prognosis; Pulmonary Edema; Sepsis

Circulating D-dimer and thrombomodulin (TM) levels are now routinely measured in clinical laboratories. Plasma levels of D-dimer are used as a marker of fibrin formation and degradation, and serum TM is used to assess the state of endothelial cell injuries. While the levels of circulating D-dimer and TM have been investigated in many diseases, to our knowledge they have not been studied in patients with measles. We measured circulating levels of D-dimer in patients with measles to discuss whether fibrin formation and degradation occur and TM whether endothelial injury occur.. The plasma levels of D-dimer and serum levels of alanine aminotransferase (ALT) and creatinine were measured of 14 adolescent and adult Japanese patients with measles, and the serum or plasma levels of TM of 10 of these 14 patients were measured in the acute febrile phase and convalescent afebrile phase with commercially available kits.. Plasma D-dimer levels were significantly higher in the acute febrile phase than in the convalescent afebrile phase in patients with measles, and no significant difference was shown in serum and plasma TM levels between the two phases. Plasma D-dimer levels were not correlated with serum or plasma TM levels in either phase. No significant differences were identified in the serum ALT and creatinine levels between the acute febrile and convalescent afebrile phases, and the levels of plasma D-dimer were not significantly correlated with the serum ALT levels.. Our results indicate that while clot formation and fibrinolysis may tend to occur in patients with the acute febrile phase of measles, there may be little risk that such patients will suffer endothelial injury.

Topics: Acute Disease; Acute-Phase Reaction; Adolescent; Adult; Alanine Transaminase; Convalescence; Creatinine; Endothelium; Fever; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Measles; Morbillivirus; Thrombomodulin

Acute vascular or humoral rejection, a vexing outcome of organ transplantation, has been attributed by some to activation and by others to apoptosis of endothelial cells in the graft. We asked which of these processes causes acute vascular rejection by tracing the processes during the development of acute vascular rejection in porcine cardiac xenografts performed in baboons. Apoptosis, assayed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), expression of activated caspase-3, and proapoptotic genes Bax and Bcl-x(L), was not detected until acute vascular rejection was well advanced, and even then, apoptosis was largely confined to myocytes. Activation of the endothelium, as evidenced by expansion of rough endoplasmic reticulum and increased ribosomal antigen and phospho-p70 S6 kinase, occurred early in the course of acute vascular rejection and progressed through the disease process. These findings suggest that acute vascular rejection is caused by an active metabolic process and not by apoptosis in the endothelium.

Topics: Acute Disease; Animals; Antibody Formation; Apoptosis; Blood Vessels; CD59 Antigens; Disease Models, Animal; Disease Progression; Endothelium, Vascular; Fibrin; Gene Expression; Graft Rejection; Guinea Pigs; Heart Transplantation; Humans; In Situ Nick-End Labeling; Myocardium; Necrosis; Papio; Rats; Rats, Inbred Lew; Swine; Transplantation, Heterologous

Increased vascular permeability is an important event during the initial process of Kawasaki disease (KD). One potential responsible candidate for the induction of vascular hyperpermeability is vascular endothelial growth factor (VEGF).. We investigated the expression of VEGF and its receptors (flt-1, KDR) in acute KD tissues at 7 days to 5 weeks of illness. Neuropilin-1, which enhances the binding of VEGF(165) to KDR, was also studied. Abundant expression of VEGF and flt-1 was documented immunohistochemically in many organs from acute KD, including heart and lung. VEGF and flt-1 were colocalized in all vessels that showed edema. These molecules resided in endothelium and vascular media and also in migrating smooth muscle cells in neointima and infiltrating macrophages. Compared with controls, coronary vessels of acute KD had upregulation of VEGF and flt-1 but not KDR or neuropilin-1. KDR was expressed by vessels at 7 days of illness but not later in the illness. Plasma proteins were more extensively bound to the extracellular matrix in coronary vessels in acute KD than controls. Furthermore, elevation of serum VEGF levels was correlated with low serum albumin in acute KD (n=220, r=-0.53, P<0.001).. These findings suggest that VEGF and flt-1 are upregulated in blood vessels in many organs of acute KD. Expression of KDR was limited to the early stage of acute KD. The roles of VEGF in acute KD may involve promotion of vascular permeability and macrophage activation. Low serum albumin may indicate overproduction of VEGF in acute KD.

Topics: Acute Disease; Aneurysm; Asian People; Blood Vessels; Child; Child, Preschool; Coronary Vessels; Edema; Endothelial Growth Factors; Fibrin; Fibrinogen; Humans; Immunohistochemistry; Infant; Japan; Lymphokines; Mucocutaneous Lymph Node Syndrome; Nerve Tissue Proteins; Neuropilin-1; Organ Specificity; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases; Receptors, Growth Factor; Receptors, Vascular Endothelial Growth Factor; Reference Values; Serum Albumin; Up-Regulation; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factors; White People

It is not known why acute pancreatitis in Soweto, South Africa, pursues an aggressive course. We sought clues from circulating trypsinogen load at admission as marker of initial acinar injury, trypsinogen activation using the carboxypeptidase B activation peptide as surrogate, proteinase inhibitors, the coagulation-fibrinolysis axis, indicators of inflammation, oxidative stress markers, and antioxidant status. This article reports on the first four aspects.. The study involved 24 consecutive patients with a first attack. All of them were admitted within 24 h, and 22 were alcoholic. Urine was analyzed for anionic trypsinogen and the carboxypeptidase B activation peptide. Serum was tested for anionic and cationic trypsinogen, alpha1 proteinase inhibitor and alpha2 macroglobulin. Plasma from a subset was assayed for soluble fibrin, cross-linked fibrin degradation products (surrogates for thrombin and plasmin activity, respectively), and tissue-type plasminogen activator and inhibitor.. Soweto controls had higher serum anionic trypsinogen (p = 0.004) and plasminogen activator:inhibitor ratio (p = 0.047) than U.K. controls. The outcome of acute pancreatitis was mild in 17 but severe in seven with three deaths, two on day 2. In mild pancreatitis, intense plasmin activity (p < 0.001) accompanied the surge in trypsinogen, especially anionic (p < 0.001), but without increased thrombin activity and in five patients without trypsinogen activation. In severe pancreatitis, further significant increments in plasmin activity and trypsinogens were accompanied by increased thrombin activity (p = 0.013) and trypsinogen activation (p = 0.046). There was no correlation between surrogates of plasmin and thrombin activity, or between either and the carboxypeptidase B activation peptide, which showed a curvilinear relationship to total serum trypsinogen.. The aggressive nature of alcoholic acute pancreatitis in Soweto seems to reflect early profound fibrinolysis, which precedes coagulation and is initially independent of trypsin. Subclinical acinar-cell injury and a profibrinolytic diathesis in outwardly healthy Sowetans may predispose to this problem.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Female; Fibrin; Fibrinolysis; Humans; Male; Middle Aged; Pancreatitis, Alcoholic; Protease Inhibitors; Severity of Illness Index; South Africa; Trypsinogen

Tissue repair requires an adequate cellular proliferation coordinated with the timely proteolysis of matrix elements. Based on the properties of plasminogen activators in liver cell proliferation and tissue proteolysis, we explored the regulatory role of tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) in liver repair. Using carbon tetrachloride (CCl(4)) intoxication as a model of acute liver injury, we found that tPA-deficient mice displayed a mild defect in hepatic repair, whereas livers of uPA-deficient mice had a more substantial delay in repair, with injury of centrilobular hepatocytes persisting up to 14 days after CCl(4). Notably, functional cooperativity between plasminogen activators was strongly inferred from the profound reparative defect in livers of mice lacking tPA and uPA simultaneously, with persistence of centrilobular injury as far out as 35 days. The defective repair was not because of increased susceptibility of experimental mice to the toxin or to inadequate cellular proliferation. Instead, lack of plasminogen activators led to the accumulation of fibrin and fibronectin within injured areas and poor removal of necrotic cells. These data demonstrate that tPA and uPA play a critical role in hepatic repair via proteolysis of matrix elements and clearance of cellular debris from the field of injury.

Topics: Acute Disease; Animals; Carbon Tetrachloride; Cell Division; Extracellular Matrix Proteins; Fibrin; Gene Targeting; Liver; Liver Diseases; Liver Regeneration; Mice; Mice, Mutant Strains; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator

We report a case of crescentic glomerulonephritis that presented with extensive crescent formation and fibrinoid necrosis in the glomeruli. Immunofluorescence staining was strongly positive for linear and pseudolinear staining of the capillary walls for immunoglobulin G (IgG) in the absence of significant mesangial staining. Histologic examination and immunofluorescence staining suggested a diagnosis of anti-glomerular basement membrane disease. However, electron microscopy showed the presence of numerous fibrillary deposits in the subepithelial areas of the glomerular capillary walls, supporting the diagnosis of fibrillary glomerulonephritis. Test results for circulating anti-glomerular basement membrane antibodies were negative. We report this interesting case to illustrate the point that fibrillary glomerulonephritis should be considered in the differential diagnosis of crescentic glomerulonephritis with linear and pseudolinear IgG deposits within the capillary walls. In such cases, electron microscopy is critical in differentiating the cause of crescentic glomerulonephritis.

Topics: Acute Disease; Anti-Glomerular Basement Membrane Disease; Capillaries; Diagnosis, Differential; Fibrin; Glomerulonephritis; Humans; Immunoglobulin G; Kidney Glomerulus; Male; Microscopy, Fluorescence; Middle Aged

In two young patients with an elevated temperature, a girl aged 6 months and a boy aged 10 months, purpura and oedema were noticed on the face, ears, arms and legs. On one occasion the boy lost blood anally. A histopathological examination revealed leucocytoclastic vasculitis with fibrin deposits. The diagnosis was 'acute haemorrhagic oedema of infancy' (AHOI), a relatively unknown variant of palpable purpura due to leucocytoclastic vasculitis affecting infants and young children (up to two years of age). AHOI is characterised clinically by marked oedema and fever as well as large palpable purpuric and ecchymotic skin lesions in a target-like pattern mainly on the face, ears and extremities. The skin lesions heal spontaneously within one to three weeks and internal organs are rarely affected. This is in contrast to Henoch-Schönlein purpura, which was observed in a 5-year old boy suffering from similar skin lesions on the legs as well as painful joints, in whom IgA deposits were found in the vasculitis. Henoch-Schönlein purpura is clinically characterised by palpable purpura on the extensor surfaces of the legs and on the buttocks, whereas in AHOI larger purpura and ecchymoses are found on the face, ankles and wrists, with far more extensive oedema. There are also histological differences: in AHOI there is more extensive vasculitis with fibrin deposits and IgA deposits are seen in a minority of cases. Awareness of this relatively unknown form of leucocytoclastic vasculitis will assist in making an early diagnosis possible, thereby avoiding unnecessary treatment and concern.

Topics: Acute Disease; Child, Preschool; Diagnosis, Differential; Ecchymosis; Edema; Female; Fever; Fibrin; Humans; IgA Vasculitis; Immunoglobulin A; Infant; Male; Purpura; Skin; Syndrome; Vasculitis, Leukocytoclastic, Cutaneous

To report the use of intracameral tissue plasminogen activator to dissolve fibrinous membranes and break posterior synechiae in patients with acute HLA-B27-positive iridocyclitis with impending pupillary block.. Two patients with severe acute fibrinous iridocyclitis and seclusio pupillae were identified. Because of the concern of impending pupillary block, intracameral tissue plasminogen activator (12.5 microg in 0.1 ml, Activase; Genentech, Inc, South San Francisco, California) was injected with a 25-gauge needle through the corneal limbus.. Both patients showed complete dissolution of fibrin with disruption of posterior synechiae. There were no adverse events after injection. Neither patient required further invasive intervention, and both fully recovered with medical management.. Intracameral tissue plasminogen activator is a safe and effective agent for patients with severe acute iridocyclitis and pupillary seclusion. Patients with clinical signs suggestive of impending pupillary block glaucoma may be considered for tissue plasminogen activator injection to avoid the possible need for emergency surgical iridectomy and synechiolysis.

Topics: Acute Disease; Adult; Fibrin; Fibrinolysis; Fibrinolytic Agents; Glaucoma; HLA-B27 Antigen; Humans; Iridocyclitis; Male; Pupil Disorders; Tissue Plasminogen Activator

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

Topics: Acute Disease; Animals; Complement Inactivator Proteins; Elapid Venoms; Fibrin; Graft Rejection; Guinea Pigs; Heart Transplantation; Male; Rats; Rats, Inbred Lew; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Thromboplastin; Transcription, Genetic

Thrombolytic therapy in acute myocardial infarction (AMI) is hampered by a considerable reocclusion rate. Thrombin activity is enhanced, and contact-system activation via plasminemia might be possible. Prospectively we examined the contact phase and the kallikrein-kinin system and additional molecular markers of hemostasis and fibrinolysis in AMI. In 22 patients with AMI, blood sampling was performed at admission and < or =10 days afterward. Eleven patients received 1.5 Mio U streptokinase (group A) and were compared with 11 AMI patients without thrombolytic therapy (group B). All patients had systemic heparinization (5,000 IU bolus, i.v.; 1,000 IU/h, i.v.). In group A (vs. group B), the kallikrein-factor XII system was significantly activated (3 h after start of therapy): kallikrein activity 140 +/- 41 (vs. 43 +/- 8) U/L (p < 0.05); kallikrein inhibition 87 +/- 9 (vs. 113 +/- 7%; p < 0.05), and factor XII 70 +/- 14 (vs. 94 +/- 6%). C1 inhibitor and factor XII inhibition were decreased. High-molecular-weight kininogen consumption indicating bradykinin generation was enhanced (p < 0.01). In group A, thrombin activity (TAT) was increased, and a hypercoagulative state with increased fibrin degradation products (d-dimer) was found. Plasmin activation in group A was reflected by decreased plasminogen and antiplasmin levels (p < 0.01). The findings indicate that streptokinase induces activation of the contact phase-kinin system in vivo associated with a consecutive increase of thrombin and bradykinin generation. Activation of this pathway might substantially contribute to reocclusion after initially successful thrombolytic therapy and to hypotensive reactions observed after streptokinase.

Topics: Acute Disease; Aged; Analysis of Variance; Factor XII; Female; Fibrin; Humans; Kallikrein-Kinin System; Kallikreins; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Streptokinase; Thrombin

We investigated the distribution and frequency of microthromboemboli (MTE) in acute infarcts in humans and determined whether MTE in the contralateral circulation resulted in histological changes.. Forty patients dying within the first month after unilateral infarct were investigated. Infarct etiology was determined mainly on the pathological findings. Whole brain sections from the region of maximal necrosis were stained for fibrin. Fibrin-containing MTE were transferred to a schematic drawing and counted. Sections from 20 patients without infarcts served as controls.. Infarct sections had significantly more MTE than controls. Infarcts of thrombotic (n=6) and thromboembolic (n=21) origin had more MTE than infarcts of embolic origin (n=13). Thromboembolic infarcts had the highest number of MTE within the region assumed to be the ischemic penumbra, other arterial territories, and the contralateral hemisphere. Patients with large infarcts and those with short clinical courses had a higher number of MTE. Sixteen patients had recent micronecroses in the contralateral hemisphere.. There seems to be a pattern of MTE in acute infarcts that is dependent on cause, size, and clinical duration. Our findings of contralateral micronecroses emphasize that acute infarcts may result in more widespread cerebral injury than clinically expected. Given the many variables influencing stroke and death in humans, the results have to be interpreted with caution.

Topics: Acute Disease; Aged; Autopsy; Brain; Cause of Death; Cerebral Arteries; Cerebral Infarction; Cerebrovascular Circulation; Cerebrovascular Disorders; Coloring Agents; Female; Fibrin; Humans; Intracranial Embolism and Thrombosis; Male; Necrosis

The activity of several proteins involved in fibrinolysis and the morphological changes in the blood vessel walls of pigs infected with highly virulent (Malawi'83) and moderately virulent (Dominican Republic '78-DR'78) ASF virus isolates were determined. Pigs infected with the Malawi'83 virus developed an increased fibrinolytic activity due to high plasma levels of tissue-plasminogen activator (t-PA) of 71.3 +/- 22.8 IU/ml (mean +/- SD), which correlated well with an increased activation of interstitial capillary endothelial cells and high levels of 1150 +/- 73.6 nM of fibrin monomer in the circulation. Animals infected with DR'78 virus, in contrast, showed an inhibition of fibrinolysis in the late stages of disease with almost a 5-fold increase of plasminogen activator inhibitor (PAI) activity of 196.0 AU/ml. These results suggest that activation of the fibrinolytic system in pigs infected with the Malawi'83 virus is probably due to increased formation and deposition of fibrin in the circulation, contributing to an increased bleeding tendency and higher mortality. On the contrary, animals infected with DR'78 virus developed an inhibition of fibrinolysis and thus a reduction in bleeding.

Topics: Acute Disease; African Swine Fever; African Swine Fever Virus; Animals; Edema; Fibrin; Fibrinolysis; Hemorrhage; Kidney; Liver; Plasminogen Inactivators; Swine; Syndrome; Thrombosis; Tissue Plasminogen Activator; Virulence

The weight gain of IVOX devices removed from the first 49 human clinical trials patients after from 1 to 29 days of implantation into the venae caval blood stream has been assessed. Each patient had received sufficient systemic heparin to maintain activated clotting times between 150 and 200 s while the IVOX device was indwelling. The nature of the material accumulating on the IVOX device was documented histologically as being thrombus in various stages of development. The weight gain findings indicate that an average of 2.0 g of thrombus accumulates per 24 h on IVOX devices indwelling in the venous blood stream of moderately anticoagulated human acute respiratory failure patients. The rate of weight gain per 24 h of the IVOX device was more rapid during the first 96 h after its implantation than during its second, third, or fourth week of implantation. The accumulated thrombus on the IVOX hollow fibers was associated with a small but measurable decrease (approximately 1%/day) in gas transfer efficiency of the implanted device. The data support the conclusion that IVOX can function effectively and safely without major thrombus formation for up to 29 days in moderately anticoagulated human acute respiratory failure patients.

Topics: Acute Disease; Blood Platelets; Carbon Dioxide; Clinical Trials as Topic; Fibrin; Heparin; Humans; Oxygenators; Prostheses and Implants; Respiratory Insufficiency; Surface Properties; Thrombosis; Time Factors; Venae Cavae

In a prospective study, all patients with peptic ulcer bleeding were documented between February 1984 and April 1992. A total of 227 patients were treated by local injection of epinephrine followed by laser application and injection of polidocanol or fibrin tissue adhesive. In five of these patients, intramural hematomas developing at the former bleeding site one to three days after endoscopic treatment were observed. The presenting symptoms were abdominal pain, nausea, and vomiting. The diagnosis was established by endoscopy, abdominal ultrasound, computed tomography, or laparotomy. In four of our five patients, the bleeding site and hematoma were located in the duodenum. All patients suffered from severe underlying diseases, and showed a clear disturbance of coagulation parameters. In three patients, acute pancreatitis occurred concurrently with the hematoma, probably due to obstruction of the papilla of Vater or compression of the pancreas caused by the hematoma.

Topics: Acute Disease; Adult; Aged; Duodenal Diseases; Endoscopy, Gastrointestinal; Epinephrine; Female; Fibrin; Hematoma; Humans; Injections, Intralesional; Male; Middle Aged; Pancreatitis; Peptic Ulcer Hemorrhage; Polidocanol; Polyethylene Glycols; Prospective Studies; Tissue Adhesives

To examine the vascular changes occurring in three archival cases of acute multiple sclerosis, and to provide immunohistochemical evidence of early endothelial cell activation and vascular occlusion in this condition.. Central nervous system tissues from three cases of acute active multiple sclerosis and six non-inflammatory controls were stained using the following methods: haematoxylin and eosin, Luxol fast blue, cresyl violet, Bielschowsky's silver, and reticulin. Tissues were also immunostained with specific antibodies against collagen type IV, factor XIIIa, class II antigens, glial fibrillary acidic protein, and fibrinogen.. Early vascular endothelial cell activation which may progress to vasculitis and vascular occlusion including class II antigen expression and fibrin deposition were identified. The vascular changes were seen prior to cerebral parenchymal reaction and demyelination, and were not seen in control cerebral tissues.. It is proposed that vascular endothelial cell activation may be an early and pivotal event in the evolution of multiple sclerosis, and that demyelination may have an ischaemic basis in this condition. The vascular endothelium may contain an early element in the evolution of multiple sclerosis.

Topics: Acute Disease; Adolescent; Adult; Brain; Endothelium, Vascular; Female; Fibrin; HLA-D Antigens; Humans; Immunoenzyme Techniques; Male; Microcirculation; Multiple Sclerosis; Thrombosis; Vascular Diseases; Vasculitis

Topics: Acute Disease; Animals; Dog Diseases; Dogs; Female; Fibrin; Hemoptysis; Male; Nocardia asteroides; Nocardia Infections; Pneumonia

The bone marrow of a 53-year-old woman with acute myeloid leukemia (AML) with disseminated intravascular coagulation was investigated by transmission electron microscopy. The patient had a preceding granulocytic sarcoma, and subclinical disseminated intravascular coagulation occurred concomitantly with the development of AML. Ultrastructural findings of the bone marrow at the onset of AML revealed the following: (1) The cytoplasm of the leukemic cells showed frequent fragmentation, resulting in the formation of abundant cytoplasmic fragments. (2) These cytoplasmic fragments were surrounded by abundant fibrin fibers, forming the fibrin-cytoplasmic fragment complex (FCF complex). (3) Slight fibrin deposition was seen around the leukemic cells and in the intercellular space of the bone marrow. Fibrin deposition in the bone marrow is thought to represent morphologic evidence of disseminated intravascular coagulation. The damage on the leukemic cell surface due to the cytoplasmic fragmentation seems to be closely related to the development of disseminated intravascular coagulation.

Topics: Acute Disease; Antigens, CD; Blood Coagulation Tests; Bone Marrow; Cytoplasm; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Humans; Leukemia, Myeloid; Middle Aged

Plasma crosslinked fibrin polymers (XLFP) are formed as a result of in vivo hemostatic activation and are elevated in thrombotic disease. We have investigated the plasmic degradation of plasma XLFP in vitro to provide information regarding the pattern of crosslinking and the composition of degradation products. Plasma XLFP were identified by sodium dodecyl sulfate (SDS)-agarose electrophoresis and Western blotting and quantitated by gel scanning. D-dimer was measured by enzyme-linked immunosorbent assay and the results were verified by SDS-polyacrylamide gel electrophoresis and Western blotting of the digests. Complete degradation of XLFP occurred only after supplementation of plasma with plasminogen (5 U/mL) and incubation with recombinant tissue plasminogen activator (rt-PA), indicating that the normal plasma plasminogen concentration limits plasmic degradation in vitro. Gel electrophoresis showed that the principal terminal degradation products of XLDP were fragments D, DD, and E, indicating that crosslinking occurred primarily through gamma chain dimers. After adding a low concentration of thrombin to plasma in vitro, XLFP increased progressively before clotting, and the concentration correlated with the increase in the D-dimer concentration after degradation (r = .98). Plasma XLFP and D-dimer concentrations in plasmic digests were significantly elevated in patients with stroke (150 +/- 83 micrograms/mL and 88 +/- 32 micrograms/mL), myocardial infarction (217 +/- 110 micrograms/mL and 84 +/- 30 micrograms/mL), and venous thrombosis (187 +/- 80 micrograms/mL and 86 +/- 19 micrograms/mL) compared with normals (28 +/- 12 micrograms/mL and 25 +/- 7 micrograms/mL). There was a strong correlation between the plasma concentration of XLFP and the D-dimer immunoreactivity of plasma after plasmic degradation (r = .87). The results indicate that XLFP in plasma are crosslinked primarily through gamma chains and degrade to fragment DD with plasminogen activation. Also, the immunoreactivity of in vitro plasmic digests of plasma reflects the concentration of XLFP and may provide a useful indirect measure of in vivo hemostatic activation in patients with thrombotic disease.

Topics: Acute Disease; Blotting, Western; Cerebrovascular Disorders; Electrophoresis, Agar Gel; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Fibrin; Fibrinolysin; Humans; Macromolecular Substances; Molecular Weight; Reference Values; Thrombosis; Tissue Plasminogen Activator

Fibrin ring granuloma is characterized by a fibrinous ring surrounding a central fat vacuole. It has been found in the liver and bone marrow of patients with Q fever, and occasionally with visceral leishmaniasis, cytomegalovirus, Epstein-Barr virus, Staphylococcus epidermidis infections, Hodgkin's lymphoma, and hypersensitivity to allopurinol. We describe a case of serologically confirmed viral hepatitis A with this lesion in the liver biopsy. A false positive anti-hepatitis A virus IgM result has been excluded. This is, to our knowledge, the second reported case of type A hepatitis with hepatic fibrin ring granulomas. It confirms that hepatitis A should be included in the differential diagnosis of this lesion.

Topics: Acute Disease; Female; Fibrin; Granuloma; Hepatitis A; Humans; Liver; Liver Diseases; Middle Aged; Q Fever

Blood coagulation, fibrinolytic and unspecific proteolytic parameters were investigated in 34 patients with acute myeloid leukemia. An increased activity of the coagulation system, documented by elevated thrombin-antithrombin III-complex (TAT) plasma levels, was found in 91% of the patients; 50% had increased elastase plasma levels. Hyperfibrinolysis, as shown by elevated fibrin split-product D-Dimer plasma levels, was detected in 91% of AML patients. Activation of these enzyme systems was not associated with relevant defects in blood coagulation or fibrinolysis in the majority of the patients investigated. In selected cases of promyelocytic M3 and monoblastic M5 leukemia, however, hypofibrinogenemia and alpha 2-plasmininhibitor deficiency was found, most likely due to depletion of these proteins in the course of disseminated intravascular coagulation and secondary hyperfibrinolysis. Significant correlations were calculated between TAT and fibrinogen (r = -0.57, P less than 0.005), TAT and D-Dimer (r = 0.89, P less than 0.0005), and D-Dimer and alpha 2-plasmininhibitor (r = -0.77, P less than 0.0005) levels. Indications of a pathogenetic importance of primary hyperfibrinolysis or unspecific proteolysis for hypofibrinogenemia and alpha 2-PI deficiency were not found.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; alpha-2-Antiplasmin; Antithrombins; Blood Coagulation; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemostasis; Humans; Leukemia, Myeloid; Male; Middle Aged; Peptide Hydrolases; Reference Values; Thrombin

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

Acute hematomas can appear hypointense on T2-weighted magnetic resonance (MR) images at field strengths as low as 0.35 T. Using Raman spectroscopy to measure blood oxygenation and taking T2 measurements at 2.1 and 9.4 T, the authors examined the relaxation mechanisms acting during deoxygenation, increases in hematocrit, and fibrin-clot formation and retraction. Individual contributions to overall T2 from deoxyhemoglobin and the interactions of water with protein hydration layers in hemoglobin, plasma proteins, and fibrin were measured. Overall T2 values estimated by summing individual relaxation rates were in reasonable agreement with the T2 values of clotted blood. Results suggest that deoxygenation may be most important in T2 shortening, followed by increased hematocrit. T2 shortening from fibrin polymerization was minimal at the field strengths used. Effects of deoxygenation and increasing hematocrit are more sensitive to field strength than fibrin T2 shortening. Effects of fibrin may be more significant at middle and low field strengths.

Topics: Acute Disease; Blood Coagulation; Fibrin; Hematocrit; Hematoma; Hemoglobins; Humans; In Vitro Techniques; Magnetic Resonance Imaging; Oxygen

Plasmin generation in vivo was assessed by measuring plasma levels of plasmin-a2-plasmin inhibitor complex (PAP) with an ELISA in 42 patients with arterial or venous thromboembolic diseases. Plasma concentration of PAP was markedly elevated in patients with venous thromboembolic diseases during acute illness (3.32 +/- 3.71 ug/ml, mean +/- SD) as compared to healthy subjects (0.24 +/- 0.13 ug/ml, n = 14), while it was nearly normal (0.30 +/- 0.13 ug/ml) in patients with venous thromboembolic diseases in chronic stage. Patients with arterial thromboembolism had modestly elevated PAP; 1.05 +/- 0.77 ug/ml during acute episode, and 0.84 +/- 0.40 ug/ml in chronic stage. These results indicate that excessive activation of fibrinolytic system (plasmin generation in vivo) occurs actually in many patients with thrombotic diseases, especially in venous thromboembolic diseases during acute illness.

Topics: Acute Disease; alpha-2-Antiplasmin; Antifibrinolytic Agents; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Fibrin; Fibrinolysin; Fibrinolysis; Humans; Male; Pancreatitis-Associated Proteins; Thromboembolism; Thrombophlebitis

The validity of the fibrin(ogen) derivatives 'soluble fibrin, D-dimers and fibrin(ogen) degradation products' was compared with other parameters in early and sensitive diagnosing of disseminated intravascular coagulation (DIC). In a clinical study 900 patients' samples from separate, defined groups were examined, including course observations of intensive care patients (n = 38) and patients with acute pancreatitis. The fibrin(ogen) derivatives correlated very well with the degree of blood coagulation disturbances: in particular, D-dimers and soluble fibrin proved to be more sensitive in early diagnosis of DIC than other parameters. The SF-PS-turbidimetry demonstrated a good validity and practicality in the quantitative determination of soluble fibrin, but a suitable analyzer is essential. Determination of D-dimers is preferable to that of fibrin(ogen) degradation products (both in the latex-agglutination test) because of the better sensitivity and practicality; even more sensitive results were provided by the D-dimer-ELISA, which is, however, not practical in acute diagnostics. The decrease in protein C was at least equally sensitive as the antithrombin III-levels in indicating the consumption of the hemostatic potential. The decrease of thrombocyte counts and fibrinogen levels could first be detected in a later stage of DIC. In conclusion, D-dimers and soluble fibrin can improve the DIC diagnostics, making them more reliable; additionally, antithrombin III and possibly protein C deserve further consideration, although the fibrin(ogen) derivatives are apparently of greater importance.

Topics: Acute Disease; Antithrombin III; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Pancreatitis; Platelet Count; Protein C

Cutaneous deposits of fibrinogen activity in lesional skin, plasmatic fibrinolytic activity, and antiplasmin activity (alpha 2 macroglobulin, alpha 1 antitrypsin and antithrombin III) were evaluated in a group of ten patients with atopic dermatitis and in a sex- and age-matched control group. Plasma fibrinolytic activity was increased in the acute phase of the disease (p less than 0.05). The levels of circulating antiplasmins appeared similar in the patients and the control group. Cutaneous fibrinolytic activity was increased in the acute phase of the disease in 5 of 5 cases, suggesting a role of the fibrinolytic system in the amplification of the inflammatory phenomenon in that phase of the disease. In the chronic lichenified phase, CFA was decreased in 3 of 5 cases leading to an excessive deposit of fibrin in the skin. This could be correlated with the abnormal vascular response (blanching phenomenon). On the basis of these data, the therapeutic use of the antifibrinolytic agents only seems rational in the acute phase of the disease.

Topics: Acute Disease; Adolescent; Adult; alpha-2-Antiplasmin; Child, Preschool; Dermatitis, Atopic; Female; Fibrin; Fibrinolysis; Humans; Male; Plasminogen Activators; Skin

Cellular expression and extracellular deposition of fibronectin and fibrin/fibrinogen in experimental allergic encephalomyelitis (EAE) in guinea pigs (GP) were studied by light and electron microscopic immunohistochemistry of the central nervous system (CNS). Normal GPs had few fibronectin+ and fibrin/fibrinogen+ CNS vessels. Positively stained vessels were more numberous in sensitized GPs prior to and after onset of EAE, and there were extracellular deposits of these molecules in inflammatory foci. Staining was greater in EAE-susceptible strain 13 GPs than in sensitized EAE-resistant strain 2 GP. On ultrastructural analysis both molecules were localized on endothelial cell luminal surfaces and on intravascular mononuclear cells. Fibronectin and the macrophage fibronectin receptor (A6F10) were found on mononuclear cells in parenchyma. Endothelial cell luminal surface fibronectin and fibrin/fibrinogen may mark and/or contribute to early immune events in EAE, including mononuclear cell margination and emigration in inflammatory sites. Genetic factors, cytokines, and components of coagulation may regulate these interactions in vivo.

Topics: Acute Disease; Animals; Encephalomyelitis, Autoimmune, Experimental; Fibrin; Fibrinogen; Fibronectins; Immunohistochemistry; Macrophages; Microscopy, Electron; Receptors, Fibronectin; Receptors, Immunologic

The plasma concentrations of protein C, an anticoagulant protein, and fibrinopeptide A were measured in 37 patients with acute hemispheric stroke and in age-matched controls with nonvascular neurologic diseases. In 11 stroke patients who died within 15 days after the onset (nonsurvivors) protein C antigen concentration on admission was lower than in the control group (p less than 0.005), with a mean value of 63% of the concentrations found in the 26 survivors (p less than 0.001). The difference in protein C concentrations was not associated with different prothrombin time ratios and serum albumin concentration in survivors and nonsurvivors of stroke and was independent of the size of the cerebral lesion. Increased fibrinopeptide A concentration on admission was found in all stroke patients (p less than 0.001), but it was higher in nonsurvivors than in survivors (p less than 0.01), suggesting that lower protein C concentrations in nonsurvivors might be due to increased thrombin-dependent protein C activation. In survivors, protein C concentration was slightly but significantly higher than in controls (p less than 0.05) and was unchanged 2 months after stroke, a time when fibrinopeptide A concentrations had returned to normal. These results show that protein C is involved in the hemostatic derangement caused by stroke and provide a rationale for clinical trials evaluating the therapeutic supplementation with protein C of patients with acute ischemic stroke.

Topics: Acute Disease; Aged; Cerebrovascular Disorders; Fibrin; Fibrinopeptide A; Humans; Middle Aged; Protein C

Topics: Acute Disease; Animals; Aorta; Aortic Aneurysm; Aortic Dissection; Dogs; Fibrin; Tissue Adhesives

Fibrin crosslinking was assayed in 22 patients with acute leukemia showing secondary coagulation abnormalities of variable severity. In 9 patients fibrin crosslinking was found to be normal, whereas 10 patients presented impaired polymerization of alpha-chains and 3 of both alpha- and gamma-chains. Only a rough correlation was found between transamidating activity of factor XIII and the fibrin crosslinking pattern in these patients. Moreover, incomplete fibrin crosslinkage occurred at levels of factor XIII far in excess of that required for full polymerization of fibrin in "normal" plasma. This latter finding suggests that, in addition to factor XIII deficiency, other causes are responsible for the high rate of fibrin crosslinking impairment in acute leukemia.

Topics: Acute Disease; Factor XIII; Fibrin; Humans; In Vitro Techniques; Leukemia; Protein Conformation

Using an experimental model of acute pancreatitis in the rat, we have studied changes in the biophysical properties of lungs and intrapulmonary fibrin deposition in this condition. Acute pancreatitis is associated with a significant decrease in pulmonary compliance (p less than 0.01) and a significant increase in lung weight (p less than 0.01) compared with a control sham operation group. These changes are associated with a 24% increase in intrapulmonary 125I fibrinogen deposition (p less than 0.01), and an 18% increase in 125I fibrinogen deposition per gram of lung tissue (p less than 0.05) in acute pancreatitis, compared with a control sham operation group. The increased fibrinogen deposition is abolished by treatment with low dose heparin. Using the same animal model changes in pulmonary ultrastructure are shown using scanning electron microscopy. The results indicate that pulmonary abnormalities are associated with intrapulmonary fibrin deposition in experimental acute pancreatitis and these findings may be relevant to the well described respiratory complications of the condition in man.

Topics: Acute Disease; Animals; Fibrin; Fibrinogen; Lung; Lung Compliance; Microscopy, Electron, Scanning; Pancreas; Pancreatitis; Rats; Rats, Inbred Strains

A case of acute lymphoedema is described. It was caused by a sharply localised, nearly circular, trauma. While there was minimal bruising, the trauma broke enough blood vessels to cause the blockage, by fibrin, of the initial lymphatics and tissue channels. This encircled a region, superficial to the deep fascia, and significantly prevented both the tissue fluid reaching the lymphatics and transport via the system. In addition, there was a short-lived, generalised lymphoedema, presumably caused by damage to the saphenous collecting lymphatics.

Topics: Acute Disease; Fibrin; Humans; Leg Injuries; Lymphatic System; Lymphedema; Male; Wounds, Nonpenetrating

Clinical and autopsy studies have shown an association between pulmonary microembolism and acute respiratory failure after trauma or sepsis. Prophylaxis and treatment with the aim of decreasing the fibrin deposition in the lungs were associated with a decrease in the incidence and death rate of this syndrome. Small fibrin degradation products (peptides) are accumulated in the lungs and are only slowly cleared from this organ, especially during states of fibrinolysis inhibition. These peptides may contribute to the pulmonary damage in several ways. They act by interfering with other vasoactive substances as bradykinin, histamine and products of the arachidonic acid cascade. Products of the cyclooxygenase pathways as thromboxane A2 play a major role in early microembolism whereas lipoxygenase products seem to be involved in delayed microembolism. Pulmonary microembolism thus seems to be one important, but certainly not the only pathogenetic factor in acute "idiopathic" respiratory failure. Other factors such as pulmonary contusion, aspiration of gastric contents or blood, or oxygen toxicity, might well be contributory in some cases. Pulmonary microemboli containing fibrin and leukocytes are probably also involved as contributory agents in some cases in the large group of acute respiratory failure due to "known factors".

Topics: Acute Disease; Animals; Disseminated Intravascular Coagulation; Dogs; Fibrin; Fibrinolysis; Humans; Lung; Pulmonary Embolism; Rats; Respiratory Insufficiency

In summary, this series of 48 patients with acute and chronic DIC demonstrates the reliability of laboratory tests in both aiding a diagnosis of DIC and in offering reasonable predictability of efficacy of therapy, as noted by the correction of abnormalities after delivery of antiprocoagulant therapy for this syndrome. It appears that the diagnostic tests most likely to aid in diagnosis and to reliably inform the clinician when the intravascular clotting process has been stopped are those that determine the antithrombin-III level, the presence of soluble fibrin monomer, and the finding of elevated fibrin(ogen) degradation products, thrombocytopenia and a prolonged thrombin time in the face of the appropriate type of bleeding in the appropriate clinical setting. In addition, it would appear that mini-dose heparin therapy is highly effective in controlling the intravascular clotting process in acute DIC, whereas antiplatelet therapy utilizing two agents is effective in chronic DIC. In addition, in this population, patients with acute disease demonstrated a 74 percent survival rate and those with chronic disease had a 100 percent survival rate from the disseminated intravascular clotting process.

Topics: Acute Disease; Afibrinogenemia; Antacids; Antithrombin III; Chronic Disease; Dipyridamole; Disseminated Intravascular Coagulation; Fibrin; Fibrin Fibrinogen Degradation Products; Heparin; Humans; Partial Thromboplastin Time; Platelet Count; Prothrombin Time; Thrombin Time; Thrombocytopenia

The activity of the inhibitor of activated Stuart factor (anti-Xa) was evaluated together with the activity of the antiactivator of plasminogen (antiplasminogen) and the amount and nature of the fibrinogen/fibrin degradation products (FDP), as indicators of the existence of the risk for hypercoagulability in patients with acute and recent myocardial infarction (AMI and RMI, respectively). The activity of anti-Xa was diminished in the AMI group with a p less than 0.001. The antiplasminogen activity was increased in both groups with a p less than 0.001; on the other hand, the amount of FDP was increased in the AMI patients and they were of the 'early' type, while in the RMI group the increase was not as marked, but the FDP were of the 'late' type. In both groups the euglobulin lysis time was very prolonged, while the plasminogen did not vary significantly. The tests described appear to be valuable tools for studying the status of the cardiovascular system during cardiac rehabilitation.

Topics: Acute Disease; Anticoagulants; Factor X; Factor Xa; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Male; Myocardial Infarction; Plasminogen; Serum Globulins

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

Studies of coagulation were performed prospectively in 41 patients with mild to moderately severe acute pancreatitis. Six patients (15%) presented with coagulation data suggestive of defibrination; two of them had clinical signs of bleeding. No other cause than pancreatitis was found in these 6 patients to account for coagulation abnormalities. Comparing the patients who presented defibrination to those who did not, no difference was observed in clinical course and admission values of serum amylase, fibrinogen, urea, calcium, glucose, transaminase levels, white blood cell count and arterial partial pressure of oxygen. Platelets counts and serum creatinine levels were respectively lower and higher in the first group of patients.

Topics: Acute Disease; Adult; Blood Coagulation Tests; Creatinine; Disseminated Intravascular Coagulation; Fibrin; Humans; Male; Middle Aged; Pancreatitis; Prospective Studies; Thrombocytopenia; Trypsin

The effect of acute haemorrhage on the deposition and clearance of fibrin in the rat lung after thrombin-induced intravascular coagulation was investigated. Haemorrhage was followed by less embolization of fibrin to the lungs and delayed elimination from the lungs. As lung tissue fibrinolysis was not diminished, the peripheral and pulmonary circulatory disturbance was probably in itself responsible for the observed effects.

Topics: Acute Disease; Animals; Female; Fibrin; Fibrinogen; Fibrinolysis; Lung; Pulmonary Circulation; Pulmonary Embolism; Rats; Shock, Hemorrhagic; Thrombin

Injection of approximately 10(6) to 10(9) Escherichia coli into the renal arteries of rabbits resulted in retention of sufficient numbers of organisms in renal vessels to permit study of the mechanism of localization by electron microscopy. After injection of the bacterial suspension, perfusion fixation was used to maintain open vascular contours. Individual organisms were found to adhere to the endothelium of glomerular and intertubular capillaries, and ruthenium red staining demonstrated a close interaction between the largely polysaccharide bacterial microcapsule and the sialoglycoprotein endothelial surface coat. Thus, individual E. coli seem to localize in the rabbit kidney in this model by sticking to the endothelial surfact coat of the renal vessels. After localization, polymorphonuclear leukocytes and monocytes appeared in the capillaries and phagocytosed the bacteria. Phagocytosis of bacteria was evident at 10 minutes and was almost complete at 60 minutes and, although less frequent, were associated with small amounts of fibrin at 60 minutes. This acute inflammation and thrombosis may be mediated by activation of complement through the alternate pathway.

Topics: Acute Disease; Animals; Capillaries; Cell Membrane; Escherichia coli; Female; Fibrin; Kidney Glomerulus; Macrophages; Neutrophils; Phagocytosis; Platelet Aggregation; Pyelonephritis; Rabbits; Sepsis

Topics: Acute Disease; Afibrinogenemia; Chronic Disease; Disseminated Intravascular Coagulation; Fibrin; Hemostatics; Humans; Hypoprothrombinemias; Thrombocytopenia

Acute anterior immunogenic uveitis of varying degree was induced in rabbits by the injection of human serum albumin into the vitreous body. After fixation and drying by the critical point method, the lens, the zonules, the vitreous and, in some specimens, coagulated exudate were removed by careful dissection. The surface of the ciliary body and the posterior surface of the iris were examined by scanning electron microscopy. In moderate uveitis, the ciliary body was covered by a thin layer of leucocytes enmeshed in fibrin strands. Scattered deposits of fibrin and a few leucocytes were also found in the iris. In severe uveitis, the processes of the ciliary body had nearly disappeared because of oedema and exudate, which also contained erythrocytes. The numerous leucocytes had marked excrescences formed by folds of the cell membrane. Fibrin seemed to play a role in the attachment of the leucocytes on the surface of the ciliary body.

Topics: Acute Disease; Animals; Ciliary Body; Fibrin; Iris; Leukocytes; Microscopy, Electron, Scanning; Rabbits; Serum Albumin; Uveitis

Rabbit anti-human fibrin globulin (A.F.G.) was labelled with iodine (131I) and used as a thrombus-detecting agent. 131I-A.F.G. labelled thrombi were displayed by means of a gamma scintillation camera. Normal subjects and patients with thrombophlebitis of legs, acute fibrin depositions other than thrombi, and chronic varicosities were examined. The 131I-A.F.G. technique detected both formed thrombi and those that were forming and could discriminate between acute thrombosis and chronic varicosities. Thrombophlebitis and extravascular fibrin depositions were best demonstrated between 24 and 27 hours of 131I-A.F.G. injection. Radiolabelled A.F.G. in normal veins and chronic varicosities was best displayed within 6 hours of injection.

Topics: Acute Disease; Animals; Antibodies; Chronic Disease; Diagnosis, Differential; Female; Fibrin; Humans; Immunodiffusion; Iodine Radioisotopes; Isotope Labeling; Middle Aged; Rabbits; Radionuclide Imaging; Thrombophlebitis; Time Factors; Varicose Veins

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

Forty-two patients underwent open-lung biopsy during the early phase of acute respiratory insufficiency. Correlation between the gross appearance of the lung at operation and the microscopic findings was good. Although only fair correlation was found between lung and tracheal cultures, the findings of two positive cultures in the lung only was of utmost importance. Biopsying multiple areas from the same operation showed identical pathology in 86 per cent of cases. The mortality rate of open-lung biopsy was zero; the morbidity rate was 4 per cent. The over-all survival rate of acute respiratory insufficiency (ARI) due to trauma was 39 per cent; that of pneumonia, 11 per cent. In 17 (33 percent) patients specific diagnoses and/or specific therapies were employed as a direct result of the biopsy or the thoracotomy. The incidence and prognostic implications of fibrosis and microthromboembolism are presented and discussed. Open-lung biopsy has been extremely safe and valuable in characterizing and managing ARI.

Topics: Acute Disease; Biopsy; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Humans; Lung; Pulmonary Embolism; Pulmonary Fibrosis; Respiratory Insufficiency

The fibrinogen related antigens were measured in 22 consecutive patients with acute pancreatitis. During the attack a marked elevation was seen, the values normalizing in the quiet phase. This may be due to either intravascular and/or extravascular degradation of fibrinogen-fibrin. As other authors have demonstrated intravascular coagulation experimentally in animals with pancreatitis, the authors stress that intravascular coagulation may play an important role in the patheogenesis of acute pancreatitis.

Topics: Acute Disease; Adult; Aged; Amylases; Antigens; Bilirubin; Calcium; Fibrin; Fibrinogen; Humans; Middle Aged; Pancreatitis

A new procedure, plasma fibrinogen chromatography, has been utilized, together with other blood coagulation assays, to quantify fibrin formation in 43 children with acute poststreptococcal glomerulonephritis (AGN) from the time of hospitalization until recovery. During the prediuretic phase of AGN, significant evidence for substantial increase in fibrin formation (intravascular coagulation) included gross increase in plasma high molecular weight fibrinogen complexes (HMWFC), the development of either hypo- or hyperfibrinogenemia and gross depression of coagulation factor XIII concentration and of alpha2-macroglobulin concentration. During the diuretic phase of the disease, these abnormalities regressed and evidence of enhanced plasma fibrinolytic activity, documented by an increase in fibrinogen first derivative, was detected. Concomitantly, urinary excretion of fibrin(ogen) degradation products (FDP) underwent substantial increase. With disease recovery, which occurred in all children, urinary FDP excretion ceased and all coagulation findings normalized.

Topics: Acute Disease; Adolescent; Blood Coagulation Factors; Blood Coagulation Tests; Child; Child, Preschool; Chromatography, Gel; Disseminated Intravascular Coagulation; Diuresis; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Glomerulonephritis; Humans; Kidney Function Tests; Molecular Weight; Prognosis; Streptococcal Infections

Topics: Acute Disease; Alpha-Globulins; Antithrombin III; Antithrombins; Biological Assay; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Heparin; Hexadimethrine Bromide; Humans; Liver Cirrhosis; Methods; Myocardial Infarction; Spectrophotometry; Thrombin

The cytotoxicity of peripheral blood leukocytes from normal human donors and from patients with EBV-associated infectious nomonucleosis (IM) has been determined for human lymphoid cell lines (LCL) containing Epstein-Barr virus (EBV) DNA. In a 51Cr release assay, mononuclear leukocytes from all donors are spontaneously cytotoxic. Leukocytes taken from patients within the first 2 weeks of overt IM are significantly more cytotoxic. This increased cytotoxicity declines to the spontaneous level as the disease progesses. The increase shows no correlation with the degree of lymphocytosis but a positive correlation with numbers of circulating atypical cells. The reaction is apparently not directed against histocompatability antigens, known EBV membrane antigens, or other characteristics of fresh human lymphoid cells. Susceptibility to damage is shared by bone marrow-derived (B) cell lines but not thymus derived (T) cell lines. EBV-gene products cannot be soley responsible for expression of the unknown characteristic. Transformation of B cells with EBV in vivo or in vitro, however, may trigger its expression

Topics: Acute Disease; Antigens, Viral; Cell Line; Cell Membrane; Centrifugation, Density Gradient; Chromium Radioisotopes; Cytotoxicity Tests, Immunologic; Fibrin; Fluorescent Antibody Technique; Heparin; Herpesvirus 4, Human; Humans; In Vitro Techniques; Infectious Mononucleosis; Leukocytes; Lymphocyte Activation; Lymphocytes

Evidence of disseminated intravascular coagulation (DIC) was dought in normal baboons infused with autologous hemolyzed whole blood, preceded or followed by infusion of dextran (molecular weight, 70,000). Mean peak plasma hemoglobin following a rapid single injection was 370 mg/100 ml in 2 animals and 1,236 mg/100 ml in 1 animal, while levels during continuous 5 hour infusion in 2 animals averaged 326 and 474 mg/100 ml, respectively. Dextran infusion immediately preceded hemoglobin injection in 2 baboons and followed hemoglobin injection by 1 1/2 and 2 1/2 hours, respectively, in 2 baboons. Coagulation studies showed a moderate although significant fall in platelet count with prolongation of the partial thromboplastin time following hemoglobin infusion, and shortening of the thrombin time after dextran. Fibrin degradation products developed in four of five experiments after hemolysate injection. The induction of acute experimental hemoglobinemia results, therefore, in the development of coagulation changes consistent with milk DIC. Preliminary infusion of dextran (molecular weight, 70,000) may facilitate this response by either initiating the development or impeding the clearance of fibrin degradation products.

Topics: Acute Disease; Animals; Blood Cell Count; Blood Coagulation; Blood Platelets; Dextrans; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Haplorhini; Hemoglobins; Hemolysis; Molecular Weight; Papio; Prothrombin Time; Thrombin; Thromboplastin; Time Factors

Topics: Acute Disease; Adolescent; Adult; Aged; Chronic Disease; Female; Fibrin; Humans; Kidney Diseases; Male; Middle Aged; Nephrotic Syndrome

Topics: Acute Disease; Animals; Babesiosis; Blood Cell Count; Blood Platelets; Clot Retraction; Erythrocytes; Fibrin; Fibrinogen; Hematocrit; Horses

Topics: Acute Disease; Adolescent; Adult; Aged; Fibrin; Fibrinogen; Fibrinolysis; Glucocorticoids; Hepatic Encephalopathy; Hepatitis A; Humans; Middle Aged

Topics: Acute Disease; Antithrombins; Blood Cell Count; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Fibrinolysis; Hemorrhage; Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Liver Cirrhosis; Lymphatic Diseases; Platelet Adhesiveness; Prothrombin Time; Retinal Detachment; Thrombin; Thrombophlebitis

Topics: Acute Disease; Adult; Aged; Alcoholism; alpha 1-Antitrypsin; Alpha-Globulins; Chronic Disease; Fatty Liver; Female; Fibrin; Fibrinogen; Fibrinolysis; Hepatitis; Humans; Liver Cirrhosis; Liver Cirrhosis, Biliary; Macroglobulins; Male; Middle Aged; Plasminogen

Topics: Acute Disease; Adult; Disseminated Intravascular Coagulation; Fatty Liver; Female; Fibrin; Gastrointestinal Hemorrhage; Humans; Jaundice; Liver; Maternal Mortality; Pregnancy; Pregnancy Complications; Time Factors

Twenty-two patients with acute hepatic failure were studied to determine the incidence and magnitude of intravascular coagulation and fibrinolysis and their relation to the severity of bleeding and prognosis. The mean platelet count, Thrombotest, plasminogen activator, and plasminogen were reduced; the reduction in fibrinogen was not statistically significant. Fibrin/fibrinogen degradation products were only moderately increased. Hepatic fibrin deposition was not extensive, being present in 11 of 22 hepatic sections, more in areas of confluent necrosis than in the sinusoids. The combination of increased fibrin/fibrinogen degradation products with decreased plasminogen activator, plasminogen, and thrombocytopenia is consistent with a diagnosis of intravascular coagulation and secondary local fibrinolysis. However, neither of these processes was severe. Severity of bleeding was related only to plasminogen levels and prognosis only to Thrombotest levels. There was no relation between hepatic histological and haematological findings. Heparin therapy is not indicated in the routine management of acute hepatic failure, as intravascular coagulation is not severe and heparin may itself cause massive bleeding.

Topics: Acute Disease; Adolescent; Adult; Aged; Blood Coagulation Tests; Blood Platelet Disorders; Blood Platelets; Child; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemoglobins; Humans; Liver; Liver Diseases; Male; Middle Aged; Plasminogen; Prognosis

Topics: Acute Disease; Adolescent; Adult; Animals; Antibodies, Heterophile; Antibody Specificity; Female; Fibrin; Fibrinogen; Glomerulonephritis; Graft Rejection; Hemagglutination; Humans; Indomethacin; Kidney Transplantation; Male; Middle Aged; Sheep; Transplantation, Homologous

Topics: Acute Disease; Fibrin; Fibrinogen; Graft Rejection; Humans; Kidney; Kidney Glomerulus; Kidney Transplantation; Postoperative Complications; Time Factors; Transplantation, Homologous

Topics: Acute Disease; Blood Cell Count; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemoglobins; Heparin; Humans; Liver Diseases; Male; Methods

Topics: Acute Disease; Animals; Blood Platelets; Cytoplasm; Dogs; Endoplasmic Reticulum; Erythrocytes; Fibrin; Injections; Islets of Langerhans; Ligation; Lipase; Lymphatic System; Lysosomes; Neutrophils; Pancreas; Pancreatic Ducts; Pancreatic Juice; Pancreatitis; Phagocytosis; Phospholipases; Time Factors; Trypsin

Topics: Acute Disease; Disseminated Intravascular Coagulation; Fibrin; Hemorrhagic Disorders; Humans; Liver Diseases; Prothrombin Time

Topics: Acute Disease; Adult; Aged; Angiography; Drug Resistance; Female; Fibrin; Fibrinogen; Heparin; Humans; Infusions, Parenteral; Iodine Radioisotopes; Male; Middle Aged; Plasminogen; Prothrombin Time; Pulmonary Embolism; Radioisotopes; Radionuclide Imaging; Streptokinase; Time Factors

Topics: Acute Disease; Adolescent; Adult; Aged; Blood Coagulation Tests; Diagnosis, Differential; Fibrin; Fibrinogen; Humans; Iodine Radioisotopes; Methods; Middle Aged; Phlebography; Protamines; Pulmonary Embolism; Radionuclide Imaging; Staphylococcus; Thrombophlebitis

Topics: Acute Disease; Adult; Aged; Angiography; Cardiac Catheterization; False Negative Reactions; False Positive Reactions; Fibrin; Humans; Lung; Methods; Middle Aged; Pulmonary Embolism

Topics: Acute Disease; Factor XIII; Fibrin; Humans; Leukemia

Topics: Acute Disease; Adult; Alanine Transaminase; Blood Coagulation Tests; Factor IX; Factor V; Factor VII; Factor VIII; Factor X; Female; Fibrin; Fibrinogen; Hepatic Encephalopathy; Hepatitis A; Humans; Middle Aged; Necrosis; Plasmapheresis; Prothrombin; Time Factors; Vitamin K

A patient with viral hepatitis in the third trimester of pregnancy is described. She developed acute hepatic failure in the postpartum period which was associated with evidence of intravascular coagulation. Following therapy with heparin and fresh-frozen plasma, the patient made a dramatic recovery. Hepatitis developed during the puerperium may predispose to pathological intravascular coagulation and hepatocellular necrosis may thereby be perpetuated.

Topics: Acenocoumarol; Acute Disease; Adult; Alanine Transaminase; Alkaline Phosphatase; Bilirubin; Blood Platelets; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Heparin; Hepatitis A; Humans; Necrosis; Plasma; Postpartum Period; Pregnancy; Pregnancy Complications, Infectious; Time Factors

Topics: Acute Disease; Acute Kidney Injury; Adult; Biopsy; Blood Vessels; Capillaries; Female; Fibrin; Follow-Up Studies; Humans; Kidney; Kidney Glomerulus; Microscopy, Electron; Microscopy, Fluorescence; Pre-Eclampsia; Pregnancy; Prognosis; Proteinuria; Puerperal Disorders

Topics: Acute Disease; Adult; Aged; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Chronic Disease; Disseminated Intravascular Coagulation; Ecchymosis; Ethanol; Female; Fibrin; Fibrinolysis; Hemorrhage; Hemostasis; Humans; Male; Middle Aged; Mucous Membrane; Protamines; Prothrombin Time; Syndrome; Thrombocytopenia

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

Topics: Acute Disease; Age Factors; Aged; Fibrin; Fibrinogen; Humans; Middle Aged; Myocardial Infarction; Serologic Tests; Thrombophlebitis

Topics: Acute Disease; Adenine Nucleotides; Adenosine Diphosphate; Adult; Aged; Blood Platelets; Collagen; Epinephrine; Female; Fibrin; Humans; Kaolin; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Male; Middle Aged; Muramidase; Platelet Adhesiveness; Remission, Spontaneous; Thrombin

Topics: Acute Disease; Arteriosclerosis; Blood Platelets; Cardiac Output; Coronary Disease; Death, Sudden; Erythrocytes; Fibrin; Humans; Leukocytes; Myocardial Infarction

Topics: Acute Disease; Adult; Agar; Aged; Female; Fibrin; Fibrinolysis; Humans; Male; Middle Aged; Myocardial Infarction; Racial Groups

Topics: Acute Disease; Adult; Aged; Blood Coagulation Tests; Diagnosis, Differential; Female; Fibrin; Humans; Male; Middle Aged; Myocardial Infarction; Sex Factors; Shock, Cardiogenic; Time Factors

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: Acute Disease; Child; Fibrin; Fibrinolysis; Glomerulonephritis; Hemostasis; Humans; Kidney Diseases; Pyelonephritis

Topics: Acute Disease; Animals; Antigens; Antigens, Viral; Chronic Disease; Coxsackievirus Infections; Endocarditis; Endocardium; Enterovirus; Fibrin; Fluorescent Antibody Technique; Heart Valve Diseases; Injections, Intraperitoneal; Mice; Myocardium; Rheumatic Heart Disease

Topics: Acute Disease; Blood Coagulation Factors; Blood Urea Nitrogen; Child; Creatinine; Female; Fibrin; Fibrinolysis; Glomerulonephritis; Heparin; Humans; Penicillin V; Prednisolone; Streptococcal Infections; Uremia

It appears that in human renal isografts glomerulonephritis in the transplant may be a recurrence of the original disease. In the allograft, nephritis may be either recurrence, an intrinsic part of the rejection process itself, or acquisition de novo of the disease. A number of parallels to both antiglomerular basement membrane disease and circulating antigen-antibody complex disease in the animal model are suggested, but with the possible exception of an occasional demonstration of anti-GBM disease, proof that such mechanisms operate in the glomerulonephritis developing in the human allograft is at present lacking.

Topics: Acute Disease; Adrenal Cortex Hormones; Antigen-Antibody Complex; Antigens, Bacterial; Antilymphocyte Serum; Autoantibodies; Basement Membrane; Chronic Disease; Disease Models, Animal; Fibrin; Glomerulonephritis; Graft Rejection; Humans; Kidney; Kidney Glomerulus; Kidney Transplantation; Recurrence; Streptococcus; Transplantation, Homologous; Transplantation, Isogeneic; Virus Diseases

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

Topics: Acute Disease; Acute Kidney Injury; Adult; Aged; Agglutination Tests; Arteries; Arteriosclerosis Obliterans; Blood Coagulation Tests; Contraceptives, Oral; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinolysis; Humans; Liver Cirrhosis; Male; Methods; Middle Aged; Neoplasm Metastasis; Protamines; Pulmonary Embolism; Staphylococcus; Sulfates; Thrombosis; Veins

Topics: Acute Disease; Blood Coagulation; Blood Platelets; Chronic Disease; Female; Fibrin; Fibrinolysis; Humans; Male; Myocardial Infarction; Thrombin

Topics: Acute Disease; Acute Kidney Injury; Antifibrinolytic Agents; Blood Cell Count; Blood Coagulation Factors; Blood Platelets; Blood Urea Nitrogen; Chronic Disease; Creatinine; Fibrin; Fibrinolysis; Humans; Immunoelectrophoresis; Plasminogen; Renal Dialysis; Uremia

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: 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: Acute Disease; Animals; Benzenesulfonates; Blood Proteins; Dicumarol; Endopeptidases; Fibrin; Fibrinolytic Agents; Glomerulonephritis; Heparin; Histocytochemistry; Mice; Polymers; Solubility; Streptococcus; Time Factors

Topics: Acute Disease; Animals; Arthritis; Blood Coagulation; Blood Proteins; Chemotaxis; Dogs; Fibrin; Fibrinogen; Humans; Inflammation; Leukocytes; Skin; Skin Window Technique; Synovial Fluid

Topics: Acute Disease; Appendicitis; Blood; Fibrin; Humans; Peritonitis; Thrombolytic Therapy