fibrin and Endocarditis

This paper reviews the current evidence on the pathogenesis, clinical manifestations, diagnosis and management of cancer-associated non-bacterial thrombotic endocarditis (NBTE). NBTE is an underdiagnosed condition characterized by sterile valvular vegetations composed of platelets and fibrin which are susceptible to systemic embolization. Cancer is a leading cause of NBTE and should be excluded in NBTE cases without a clear etiology. Malignancies most frequently associated with NBTE are mucin-releasing adenocarcinomas of the lung, ovary, biliary system, pancreas, breast and stomach. NBTE carries a high risk of arterial thromboembolism, while cardiac valvular dysfunction is much less frequent. NBTE appears to be an important underdiagnosed cause of cancer-associated embolic stroke of undetermined source. Characteristics associated with cancer-associated NBTE include elevated D-dimer, visceral infarcts, cerebral infarcts in multiple vascular territories, transcranial doppler microembolic signals, disseminated cancer and adenocarcinoma histology. Transesophageal echocardiography is the diagnostic test of choice, and all suspected cases should be evaluated for the presence of elevated D-dimers and disseminated intravascular coagulation. Long-term anticoagulation with low molecular weight heparin should be strongly considered, and surgical intervention is usually not needed. Underlying cancer must be diagnosed swiftly (if previously undiagnosed) and anti-cancer treatment should be initiated as soon as possible. The paucity of data regarding all aspects of NBTE, and the severe clinical consequences of untreated NBTE, are an urgent call for future research.

Topics: Adenocarcinoma; Anticoagulants; Endocarditis; Endocarditis, Non-Infective; Female; Fibrin; Heart Diseases; Heparin, Low-Molecular-Weight; Humans; Mucins

Topics: Animals; Anti-Bacterial Agents; Endocarditis; Fibrin; Humans

Topics: Animals; Antibodies, Bacterial; Bacteria; Blood Platelets; Coronary Disease; Endocarditis; Endocarditis, Bacterial; Endocarditis, Subacute Bacterial; Fibrin; Heart Failure; Heart Valves; Humans; Platelet Aggregation; Prognosis; Rupture, Spontaneous; Sepsis; Thrombosis

Topics: Animals; Antibodies; Arteries; Blood Platelets; Capillaries; Coronary Disease; Coronary Vessels; Cortisone; Dogs; Endocarditis; Fibrin; Graft Rejection; Heart Failure; Heart Transplantation; Hemorrhage; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Infections; Kidney Transplantation; Male; Microscopy, Electron; Middle Aged; Myocarditis; Myocardium; Necrosis; Rabbits; Shwartzman Phenomenon; Time Factors; Transplantation Immunology; Transplantation, Homologous

Expression of bacteriophage lysin

Topics: Binding Sites; Endocarditis; Fibrin; Fibrinogen; Fibrinolysis; Humans; Plasminogen; Protein Binding; Streptococcus; Streptococcus Phages; Virulence

This report suggests a strong association between coagulase-negative Staphylococcus simulans and endocarditis in broiler chickens of a single flock. Clinical signs included increased mortality and lameness, and some dead chickens were found on their backs. Lesions included cauliflower-like, fibrinous vegetative lesions on the left atrioventricular valve; cream-coloured, necrotic foci of varying size in the liver; and necrosis of the femoral head. Histopathological examination of the heart revealed multifocal conglomerates of bacterial colonies attached to the valvular endocardium, threads of fibrin, and inflammatory cells with the presence of heterophils. S. simulans strains were first identified by API ID32, and then confirmed with Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry and by partial sequencing of the rpoB and dnaJ genes. These bacteria were resistant to methicillin but sensitive to vancomycin and characterized by slime production and protease activity.

Topics: Animals; Anti-Infective Agents; Chickens; Drug Resistance, Bacterial; Endocarditis; Fibrin; Methicillin; Necrosis; Staphylococcal Infections; Staphylococcus; Vancomycin; Virulence Factors

Streptococcus mutans, the predominant bacterial species associated with dental caries, can enter the bloodstream and cause infective endocarditis. The aim of this study was to investigate S. mutans biofilm formation and adherence to endothelial cells induced by human fibrinogen. The putative mechanism by which biofilm formation is induced as well as the impact of fibrinogen on S. mutans resistance to penicillin was also evaluated. Bovine plasma dose dependently induced biofilm formation by S. mutans. Of the various plasma proteins tested, only fibrinogen promoted the formation of biofilm in a dose-dependent manner. Scanning electron microscopy observations revealed the presence of complex aggregates of bacterial cells firmly attached to the polystyrene support. S. mutans in biofilms induced by the presence of fibrinogen was markedly resistant to the bactericidal effect of penicillin. Fibrinogen also significantly increased the adherence of S. mutans to endothelial cells. Neither S. mutans cells nor culture supernatants converted fibrinogen into fibrin. However, fibrinogen is specifically bound to the cell surface of S. mutans and may act as a bridging molecule to mediate biofilm formation. In conclusion, our study identified a new mechanism promoting S. mutans biofilm formation and adherence to endothelial cells which may contribute to infective endocarditis.

Topics: Animals; Biofilms; Cattle; Cell Line; Endocarditis; Endothelial Cells; Fibrin; Fibrinogen; Humans; Mutation; Streptococcus

Bacteria within endocarditis vegetations are encased in fibrin matrix that is resistant to resolution. We have previously shown that FSS2 Challisin, a serine protease from Streptococcus gordonii, is able to hydrolyse the Aα and Bβ chains of fibrinogen and has potent angiotensin converting enzyme (ACE) activity. The alteration in the structure of fibrin formed from FSS2 Challisin-degraded fibrinogen may therefore contribute to the resistant fibrin matrix. To this end, we have investigated the specific interactions of FSS2 Challisin with fibrinogen. FSS2 Challisin extensively degrades the αC region of fibrinogen Aα chains, hydrolysing both the αC-domain and αC-connnector. Additionally, the N-terminal region of the Bβ chains is cleaved twice, at Leu19 and Ser28, removing the B fibrinopeptides and 'B' knobs. Substrate analysis indicates FSS2 Challisin has specific requirement for proline two residues before the cleavage point and a neutral or basic un-branched amino acid preceding the cleavage point. Fibrin formation by thrombin was modified and the initiation of fibrinolysis extended, in FSS2 Challisin-treated plasma clots. Digestion of fibrinogen by FSS2 Challisin prior to thrombin action increased fiber density and fiber branch point density. The velocity of fibrinolysis was significantly slower for fibrin formed from FSS2 Challisin-treated fibrinogen but was faster when data was normalised for the increased fibrin density. Thromboelastography of whole blood treated with FSS2 Challisin indicated reduced clot coagulation time and increased shear resistance. Combined ACE and fibrinogenase activities of FSS2 Challisin suggest a pro-coagulant effect of this virulence factor which is conserved in the viridans streptococci.

Topics: Amino Acid Sequence; Bacterial Proteins; Blood Coagulation; Coagulants; Endocarditis; Fibrin; Fibrinogen; Humans; Molecular Sequence Data; Peptide Fragments; Proline; Protein Binding; Protein Structure, Tertiary; Serine Proteases; Streptococcus gordonii; Substrate Specificity; Thrombosis; Virulence Factors

Topics: Adult; Endocarditis; Fibrin; Heart Ventricles; Humans; Male; Neutrophils; Radiography; Treatment Outcome

Topics: Antigens, CD34; Cell Adhesion Molecules; Endocarditis; Fibrin; Histiocytes; Humans; Monocytes

The stentless xenograft with its favorable hemodynamic performance on the left side of the heart seems an attractive, readily available alternative for the reconstruction of the right ventricular outflow tract in children.. To assess its function in a preclinical animal investigation, we replaced the pulmonary root with a Freestyle stentless aortic xenograft in 18 piglets of 26.6 +/- 3.2 kg weight. The animals were allowed to grow as much as possible and slaughtered when symptoms of heart failure developed or body weight reached more than 160 kg. All valve explants were analyzed by gross examination and photography and, in 4 representative pigs, by histologic examination.. Fourteen animals died prematurely after 2 weeks to 11 months. Twelve xenograft explants showed thick, immobilized, large nodular structures as cuspal remnants causing significant stenosis. At microscopy, large cuspal masses of degenerating collagen and fibrin and various inflammatory cells were frequently found. In the growing pig, most of the xenografts implanted in the pulmonary position showed early degeneration causing severe stenosis.. Use of this valve for right ventricular outflow tract reconstruction in children cannot be recommended.

Topics: Animals; Aortic Valve; Bioprosthesis; Body Weight; Calcinosis; Cardiac Output, Low; Cause of Death; Collagen; Constriction, Pathologic; Disease Models, Animal; Endocarditis; Fibrin; Growth; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Prosthesis Design; Prosthesis Failure; Pulmonary Valve; Surface Properties; Swine

The uptake of a 111In labelled antifibrin antibody was studied in left ventricle endocarditis on a rabbit model. The immunospecificity of the antibody for the cardiac vegetations is favorable, exhibiting an uptake at least 4 times that of blood, or myocardium. A planar scintigraphy of the opened left ventricle showed a radionuclide imaging of vegetations, according to anatomical lesions. The use of antifibrin monoclonal antibodies could prove helpful to improve the specificity of valvular lesions visualized by echocardiography, or to detect the small vegetations at the early stage of acute endocarditis.

Topics: Animals; Antibodies, Monoclonal; Disease Models, Animal; Endocarditis; Female; Fibrin; Indium Radioisotopes; Rabbits; Radionuclide Imaging

The adherence of six Candida species to fibrin clots was studied using a simple, in vitro technique. Yeast suspensions were incubated with fibrin clots and the number of adherent organisms quantified as follows: after washing, the clots were subjected to vortex mixing and the number of CFU's which subsequently grew on Sabourauds medium were counted. Adhesion was directly proportional to the concentration of Candida species in the suspension (r = 0.99 p less than 0.001). C. albicans and C. tropicalis exhibited marked adherence whereas C. krusei, C. gulliermondi and C. glabrata adhered less readily. C. parapsilosis was intermediate in its ability to adhere.

Topics: Candida; Candida albicans; Cell Adhesion; Endocarditis; Fibrin; Humans; In Vitro Techniques; Thrombosis

Invasive resuscitative and supportive therapy subsequent to accidental trauma, assault, or medical mishap may create lesions that forensic pathologists must interpret. Pulmonary valve nonbacterial endocarditis sometimes complicates placement of flow-directed pulmonary artery (Swan-Ganz) catheters. We examined ten cases of endocarditis from patients dying 0-10 days after removal of a Swan-Ganz catheter, and compared the natural evolution of vegetations in critically ill patients with the reported evolution of similar vegetations in experimental animals in the Freedman model. There was wide variation in macroscopic, as well as in the light- and scanning electron-microscopic, appearances in our cases and we could not establish a direct relationship between vegetation structure and time elapsed after removal of the catheter. These findings suggest that parameters related to critical illness and species account for the differences between this disease in human and animal models.

Topics: Catheterization, Swan-Ganz; Endocarditis; Endothelium; Fibrin; Heart Valve Diseases; Humans; Microscopy, Electron, Scanning; Pulmonary Valve; Tricuspid Valve

The influence of preformed antibody on the induction of experimental Candida albicans endocarditis was investigated by both in vitro and in vivo techniques. Preincubation of C. albicans with immune serum (raised in rabbits by intravenous injection of Formalin-killed yeast cells) decreased adhesion to the constituents of nonbacterial thrombotic endocarditis, e.g., fibrin plus platelets, in vitro. Two different methods, with radiolabeled or viable yeast cells, were confirmatory and demonstrated decreased adhesion of immune serum-treated C. albicans cells to 0 to 7.8% of control values (P less than 0.001). These results correlated with protection from the development of C. albicans endocarditis in the immunized rabbits. The mean (+/- standard deviation) infectious dose for 50% of the animals was 10(5.29) +/- 10(0.07) in 48 control animals versus 10(7.11) +/- 10(0.22) in 37 immunized rabbits (P less than 0.001). These studies suggest that humoral antibody may protect against C. albicans endocarditis, perhaps through inhibition of adhesion, a crucial early step in the pathogenesis of endocarditis.

Topics: Adhesiveness; Animals; Antibodies, Fungal; Blood Platelets; Candida albicans; Candidiasis; Endocarditis; Fibrin; Humans; Immunization; Rabbits

Endocardial lesions in acute serum sickness in rabbits were studied with the aid of scanning electron microscopy (SEM). Prominent inflammation developed most often in the ventricular (pocket) side of the mitral valve and was confined to a hollowed area formed between valvular ridges. The early lesion consisted of swelling of endothelial cells with monocytic attachments. Subsequently, frequent endothelial perforations occurred, through which a number of monocytes emigrated into the subendothelial space. Focal or diffuse endothelial desquamation then followed. SEM revealed that the denuded basement membrane also had many perforations enabling monocytic emigration into the deeper valve layer. The accumulated monocytes and proliferating mesenchymal cells produced a granulomatous focus in the valvular tissue in which some monocytes were observed to convert to Anitschkow cells. Infiltration by polymorphs was minimal. Deposition of fibrin occurred in the more severe valvulitic lesions, but no verrucous vegetation formation was observed. The inflammatory process regressed rapidly, leaving focal areas of fibrosis. A possible pathogenesis is discussed in connection with the pathophysiologic conditions of the mitral valve pocket.

Topics: Animals; Basement Membrane; Endocarditis; Endocardium; Endothelium; Fibrin; Microscopy, Electron, Scanning; Mitral Valve; Monocytes; Rabbits; Serum Sickness

Gross anatomic, histologic, and transmission and scanning electron microscopic observations were made of 29 bioprosthetic valves that had been implanted in patients for up to 115 months. On the basis of these morphologic data, no significant evidence of tissue rejection was seen. However, the durability of these valve bioprostheses is still questionable. Our observation primarily emphasize three factors: (1) disruption of the endothelial cell barrier and the lack of significant host endothelialization even 115 months after transplantation; (2) increased permeability that eased diffusion of circulating host plasma proteins into valve tissue, and increased activity of infiltration processes, eg. calcification and lipid accumulation; and (3) biodegradation of the collagen framework. Each of these factors may contribute further to valve dysfunction. Development of an intimal fibrous sheath seems to occur in porcine bioprostheses that have been implanted for the longest periods of time, but the rate of host tissue ingrowth varies.

Topics: Adolescent; Adult; Aged; Aldehydes; Aortic Valve; Bioprosthesis; Calcinosis; Child; Collagen; Connective Tissue; Endocarditis; Endothelium; Evaluation Studies as Topic; Female; Fibrin; Glutaral; Heart Valve Diseases; Heart Valve Prosthesis; Humans; Male; Mediastinitis; Methods; Microscopy, Electron, Scanning; Middle Aged; Mitral Valve

The coronary microcirculation was examined for platelet and fibrin thrombi in hearts from 21 normal subjects and 244 cardiac patients, including 168 with ischemic heart disease (IHD) and 76 with other types of heart disease. Seventy-seven cases were sudden cardiac death (SCD). No microthrombi were present in any of the normal hearts, whereas platelet and fibrin thrombin were present in the coronary microcirculation in 32 of 244 cardiac cases (13.1%), including 19 with IHD and 13 with other types of heart disease and after cardiac surgery. The microthrombi were either embolic or represented in situ thrombosis, depending upon the underlying pathologic process. There was no significant difference in the incidence of microthrombi in SCD patients, with IHD (10 of 50, 20%) compared with patients who survived longer (nine of 93, 10%). In SCD patients, however, platelet microthrombin were more frequent in patients less than 45 years of age compared with those older than 45 years of age (p = 0.0002). We concluded that coronary microcirculatory thrombi are not uncommon in heart disease. A subgroup of SCD in young patients with IHD has been identified in whom microcirculatory platelet thrombosis is the main cardiac pathologic process. The significance of this process is emphasized by the associated myocardial damage.

Topics: Adult; Aged; Blood Platelets; Cardiac Surgical Procedures; Coronary Circulation; Coronary Disease; Death, Sudden; Endocarditis; Female; Fibrin; Humans; Male; Microcirculation; Middle Aged; Myocardium; Thromboembolism

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: Blood Platelets; Endocarditis; Fibrin; Humans; Infant, Newborn; Mitral Valve; Myocardium

Topics: Adams-Stokes Syndrome; Cardiac Catheterization; Endocarditis; Fibrin; Fibrinolysis; Humans; Male; Middle Aged; Pacemaker, Artificial; Tissue Adhesions; Tricuspid Valve

Topics: Animals; Endocarditis; Fibrin; Haplorhini; Humans; Male; Myocarditis; Rheumatic Diseases; Rheumatic Heart Disease; Streptococcus; Toxins, Biological

Topics: Adenosine Triphosphatases; Blood Platelets; Colitis; Colitis, Ulcerative; Dihydrolipoamide Dehydrogenase; Endocarditis; Fibrin; Geriatrics; Glomerulonephritis; Histocytochemistry; Humans; Mitral Valve; Pathology; Polysaccharides; Rheumatic Heart Disease; Thrombosis