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PubMedDate not supplied

[Cerebral ischaemia secondary to non-bacterial thrombotic endocarditis as the presenting symptom of an ovarian tumour].

INTRODUCTION: In cancer patients, cerebrovascular accidents (CVA) are the most common complication occurring in the central nervous system after metastasis. One of its causations is non-bacterial thrombotic endocarditis (NBTE), which appears on rare occasions as the first symptom of the tumour. The clinical manifestations of NBTE are the result of multiple systemic embolism. Emboli consist of platelets and strands of fibrin that are deposited in the valves of the heart, within a context of a state of hypercoagulability secondary to the tumour. The tumours that are most frequently associated to NBTE are mucin-secreting adenocarcinomas. Cases of ovarian cancer with NBTE are rare in the different series reported in the literature. CASE REPORT: We describe the case of a 58-year-old female, previously asymptomatic, who suddenly showed a lowered level of consciousness, hemiplegia on the right-hand side and motor aphasia. A computerised axial tomography scan taken at 48 hours showed two acute ischaemic lesions in the left hemisphere. Magnetic resonance imaging of the brain with diffusion sequences revealed multiple ischaemic lesions in different arterial territories. Transthoracic echocardiography at 24 hours showed a vegetation on the posterior leaflet of the mitral valve. The patient was treated with intravenous sodium heparin and no new CVA appeared. The valve injuries disappeared after treatment. In a study conducted to search for occult neoplasia, a tumour was found in the right ovary. CONCLUSIONS: NBTE must be taken into account in cases of cerebral embolism due to unknown causes. The results of the analyses of most patients reveal chronic disseminated intravascular coagulation. The most valuable diagnostic tests are the transesophageal echocardiogram and magnetic resonance imaging of the brain with diffusion sequences. Preferred treatment is with heparin.

Brain Ischemia↗
PubMed1980

Mucin-producing adenocarcinomas and nonbacterial thrombotic endocarditis: pathogenetic role of tumor mucin.

The clinicopathologic data of 5 patients who died of nonbacterial thrombotic endocarditis (NBTE) and disseminated thrombosis and multiple infarcts associated with mucin-producing adenocarcinomas were presented. Histochemical studies on the valvular vegetations and thrombi revealed that histochemically stainable mucinous substance was an integral part. In 1 patient, circulating mucinous substance was found prior to the development of NBTE and disseminated thrombosis, and the identical mucinous substance was found in the tumor tissue, indicating a possible pathogenetic role of tumor mucin in NBTE-associated mucin-producing adenocarcinomas. Our observations and reports of others suggest that intravascular mucin may be responsible for the clinical syndromes of mucinous malignancies, venous thrombosis, and NBTE with emboli.

Adenocarcinoma↗
PubMed2005

Surgical treatment of nonbacterial thrombotic endocarditis presenting with stroke.

BACKGROUND: Necropsy studies have shown that nonbacterial thrombotic endocarditis (NBTE) may be associated with cerebral infarctions and antemortem diagnosis is now possible. However, the best treatment for patients with NBTE presenting with stroke is not known. We describe three patients presenting with an acute embolic stroke secondary to large,mobile vegetations detected by transthoracic (one case) or transesophageal echocardiography (two cases). All patients underwent surgery for removal of the vegetations to prevent recurrent embolic events; valve replacement was necessary in two cases. The sterile nature of the vegetations was confirmed by pathological examination and negative stains and cultures of the surgical samples. A previously unrecognized hypercoagulable condition was diagnosed in all patients (antiphospholipid antibody syndrome in two cases and disseminated adenocarcinoma in one case). CONCLUSION: NBTE should be considered among the possible causes of embolic stroke even in the absence of history of cancer, hypercoagulability, or previous embolic manifestations. If NBTE is diagnosed, the possibility of underlying thrombophilia should be thoroughly investigated. Valvular surgery represents a valuable therapeutic alternative in patients with large mobile vegetations, valvular dysfunction or recurrent embolic events despite anticoagulation.

Adult↗
PubMed2006

Nonbacterial thrombotic endocarditis with recurrent embolic events as manifestation of ovarian neoplasm.

We describe the case of a 43-year-old woman with transient ischemic neurologic deficits and recurrent systemic and pulmonary emboli in whom infectious work-up and extensive thrombophilic evaluation were unremarkable. Transesophageal echocardiography (TEE) established the diagnosis of nonbacterial thrombotic endocarditis (NBTE). This is a rare condition often associated with hypercoagulable states or advanced malignancy such as adenocarcinomas, characterized by cardiac vegetations along valvular coaptation lines without destruction of leaflets. In our patient, we diagnosed an ovarian clear cell adenocarcinoma, a malignant disorder that has been rarely reported in association with NBTE. This case illustrates that NBTE can present as an atypical manifestation of malignancy and must be distinguished from infective endocarditis, which implies a different therapeutic strategy. When confronted with findings of NBTE without a clear etiology, an occult neoplasm must be excluded. Anticoagulant therapy is the mainstay of treatment. However, cardiac vegetations may require surgical intervention in rare instances.

Adenocarcinoma, Clear Cell↗
PubMed1992

Nonbacterial thrombotic endocarditis. Assessment by transesophageal echocardiography.

Nonbacterial thrombotic endocarditis (NBTE) is difficult to detect antemortem and is often not suspected until embolic events occur. Transthoracic echocardiography is useful in diagnosing NBTE, but it may be limited by suboptimal imaging and resolution. Herein we describe the first reported case of NBTE diagnosed by transesophageal echocardiography. As early detection and treatment may avert significant embolic complications, transesophageal echocardiography should be strongly considered if other techniques are nondiagnostic and clinical suspicion of NBTE remains high.

Echocardiography↗
PubMed1998

Fatal non-bacterial thrombotic endocarditis following viperine bite.

Non-bacterial thrombotic endocarditis (NBTE) commonly occurs in patients with wasting disease (e.g. malignancy) or with valves damaged following trauma due to intra-cardiac foreign body, scarring or marked turbulence. Although disseminated intravascular coagulation (DIC) is well documented following viperine bite and the underlying mechanism of NBTE is thought to be DIC, there is no report of NBTE in humans following snake bite. We report a young male who following viperine bite developed local swelling, superficial gangrene of tissues at the site of bite, and oliguria and died following multiple cerebral infarcts and acute renal failure. The post-mortem examination showed NBTE of the aortic valve, multiple embolic infarcts of brain, spleen and kidneys, acute tubular necrosis and features of DIC in the brain in the form of fibrin thrombi in the capillaries, perivascular hemorrhages and necrosis.

Adult↗
PubMed1985

Microbial adhesion to fibronectin in vitro correlates with production of endocarditis in rabbits.

Microbial adhesion to the constituents of nonbacterial thrombotic endocarditis (NBTE) is an important early event in the pathogenesis of infective endocarditis. Fibronectin is a ubiquitous mammalian glycoprotein with diverse functions which binds to certain bacteria but not to others. In this study, we determined that fibronectin is present on the surface of NBTE (after catheter-induced aortic valve trauma) but not on normal rabbit cardiac valvular endothelium. The adhesion of various bacteria and yeasts to human fibronectin in tissue culture wells was then measured. Microorganisms with a high isolation frequency from endocarditis cases (Staphylococcus aureus, Candida tropicalis, C. albicans, Streptococcus faecalis, S. sanguis) bound significantly better (P less than 0.01) to fibronectin in vitro than other organisms (Escherichia coli, C. krusei, Pseudomonas aeruginosa) rarely implicated in this disease. Microbial adhesion to fibronectin correlated closely with the propensity of each organism to produce endocarditis in rabbits (e.g., ID50) with preexistent NBTE. A similar distribution was noted after binding of soluble radiolabeled fibronectin to bacteria in suspension. The results suggest that fibronectin, expressed on the surface of NBTE, may mediate microbial adhesion of circulating organisms to initiate colonization during the early pathogenesis of infective endocarditis.

Animals↗
PubMed2005

Factors associated with non-bacterial thrombotic endocarditis: case report and literature review.

The case is reported of non-bacterial thrombotic endocarditis (NBTE) in a patient with giant cell arteritis and prostate cancer, and the relevant literature reviewed. To the present authors' knowledge, this is the first case to be reported where NBTE coexists with both arteritis and cancer. NBTE is difficult to diagnose if the underlying disease is accompanied by fever. If a diagnosis of probable infective endocarditis is established, the cultures and serology are negative, and there is no response to antibiotic treatment, then NBTE should be considered.

Aged↗
PubMed1991

Non-bacterial thrombotic endocarditis in cancer patients.

A total of 10 cases of non-bacterial thrombotic endocarditis (NBTE) were found among 1640 adult patients, autopsied in a 24-year period. Eight out of 10 patients had an underlying malignant tumor, NBTE was more common in cancer patients than in patients without malignancy (1.25% vs 0.2%, P less than 0.05). Patients with adenocarcinoma were at higher risk than patients with other malignant processes (2.70% vs 0.47%, P less than 0.05); especially in cases of pancreatic cancer in comparison with other kinds of adenocarcinoma (10.34% vs 1.55%, P less than 0.05). Systemic embolization was the main cause of morbidity. Any thromboembolic event in cancer patients should prompt a search for NBTE. NBTE may be present in undisseminated cancers in otherwise curable patients.

Adenocarcinoma↗
PubMed1993

[Nonbacterial thrombotic endocarditis--a study of 171 case reports].

A descriptive term nonbacterial thrombotic endocarditis (NBTE) is used currently instead of the former name marantic endocarditis. The study describes 171 cases of NBTE encountered in autopsies over a period of 22 years (an incidence of 0.93% in adults). Malignancy was present in 59% of cases. Tumors relatively most frequently associated with NBTE were carcinomas of the ovaries, biliary system, pancreas, lung, and stomach. The vegetations were located mostly on the left-sided valves (mitral 64%, aortic 24%, both 9%). The involved valves were otherwise normal in 82%, and they were previously damaged in 18%. Systemic emboli from valvular vegetations occurred in 41% of patients, with splenic, cerebral, and renal circulations being most frequently affected. Pulmonary embolism was noted in 43%. The state of nutrition at autopsy was within normal limits in 35%; there was undernourishment or cachexia in 40%, and overweight or obesity in 22% of patients. The main pathogenetic factor in NBTE seems to be a state of hypercoagulation.

Adult↗
PubMed1976

Cerebral embolism, marantic endocarditis, and cancer.

Two subjects with cerebral embolism were found at autopsy to have marantic (nonbacterial thrombotic) endocarditis (NBTE) and an unsuspected carcinoma. A additional 16 subjects with marantic endocarditis and cancer were found on reviewing the autopsy records of 22 subjects with NBTE. Of these 18 subjects with NBTE and cancer, eight developed a stroke during their illness, in five as the initial manifestation of cancer. Although the association of cancer and marantic endocarditis is generally well recognized, cerebral embolism from this source should be more seriously considered as one of the "remote effects" of cancer on the nervous system.

Carcinoma↗
PubMed1997

Hypercoagulable state in a hypobaric, hypoxic environment causes non-bacterial thrombotic endocarditis in rats.

High-altitude hypoxia causes polycythaemia and a hypercoagulable state in humans and animals. This study examines the effects of a hypobaric, hypoxic environment (HHE) on the blood coagulation system in rats. A total of 170 male Wistar rats were housed in a chamber at the equivalent of 5500 m in altitude for 1-12 weeks. After 2 weeks of exposure to HHE, platelet counts decreased significantly; after 4 weeks, the prothrombin and activated partial thromboplastin times were significantly prolonged, compared with those of control rats. In addition, individual coagulation factors (VII, IX, X, XI, and XII) were significantly decreased at 8 weeks (P < 0.05). Levels of anti-thrombin III and alpha 2-plasmin inhibitor also decreased (between 4 and 8 weeks). After 4-12 weeks of exposure to HHE, 30 of 56 rats (54 per cent) developed (i) non-bacterial thrombotic endocarditis (NBTE) or (ii) infarction of the myocardium or kidney, or both (i) and (ii). The incidence of NBTE increased from 33 per cent (5/15 rats) at 4 weeks to 100 per cent (7/7 rats) at 12 weeks. Electron microscopy showed detached endothelial cells in the mitral valves at 1 week; platelets adhered to the subendocardial matrix and platelet aggregation with thrombus formation was seen at 2 weeks of exposure. The results suggest that exposure to HHE induces a hypercoagulable state and causes an NBTE in rats that may result in consumption coagulopathy.

Altitude Sickness↗
PubMed2005

Recurrent embolism in the course of marantic endocarditis.

Marantic or nonbacterial thrombotic endocarditis (NBTE) associated with systemic embolism is usually a complication of advanced or terminal malignancies. We report on the case of a 46-year-old woman in whom nonbacterial thrombotic endocarditis (NBTE)-related cerebral embolism was the first clinical sign of ovarian neoplasm, which was diagnosed after cardiac surgery. Marantic endocarditis should alert the physician to make every effort to diagnose the possible background of this clinical phenomenon. Early identification of NBTE, treatment of the underlying disease, and the associated coagulopathy could possibly prevent cardiac surgery.

Blood Coagulation Disorders↗
PubMed1987

Nonbacterial thrombotic endocarditis in an adolescent with Hodgkin disease.

Nonbacterial thrombotic endocarditis (NBTE) is one of several coagulopathies common in patients with cancer. It is rare in children; only four cases have been reported in children with cancer. Five other cases have occurred in bone marrow transplant patients. We report an adolescent who died from cerebral infarction and was found on autopsy to have NBTE of the mitral valve. We review the signs and symptoms, pathology, mortality, diagnostic and therapeutic approaches associated with NBTE. We wish to call attention to this disorder among those who treat children with cancer.

Adolescent↗
PubMed1978

Bacterial adherence in the pathogenesis of endocarditis. Interaction of bacterial dextran, platelets, and fibrin.

The role of dextran in the pathogenesis of bacterial endocarditis was investigated by studying the adherence of dextran producing oral streptococci to the constituents of nonbacterial thrombotic endocarditis (NBTE) in vitro and in vivo. The adherence of Streptococcus sanguis to fibrin and platelets was determined in an in vitro assay system simulating nonbacterial thrombotic endocarditis. Adherence was increased when the organisms were grown in sucrose-supplemented media (adherence ratio X 10(4), 177 +/- 6 in 5% sucrose vs. 140 +/- 7 in 0.5% sucrose, P less than 0.001), and decreased by incubating the organisms in dextranase (adherence ratio X 10(4), 117 +/- 16, P less than 0.001), an effect which was nullified by heat inactivating this enzyme (adherence ratio X 10(4), 192 +/- 7, P less than 0.001). The amount of dextran produced in broth by three different oral streptococci correlated directly with the adherence observed to fibrin and a fibrin-platelet matrix in vitro (P less than 0.001). These organisms adhered more readily to a fibrin-platelet matrix than to fibrin alone (adherence ratio X 10(4), 455 +/- 30 vs. 177 +/- 6, respectively, P less than 0.001). The role of dextran formation was also examined in vivo in rabbits with preexisting NBTE. After injection of 10(7) S. sanguis, 12 of 17 animals developed endocarditis. In contrast, when the organisms were pretreated with dextranase (an enzyme that removes dextran from the bacterial cell surface), the same inoculum resulted in endocarditis in only 5 of 19 animals (P less than 0.05). In addition, a fresh strain of S. sanguis that produced high levels of dextran (1,220 +/- 50 microgram/ml) and adhered avidly to fibrin (adherence ratio X 10(4), 220 +/- 11) produced endocarditis in 12 of 18 rabbits after injection of 10(7) organisms. Another isolate of the same strain that had been passed repeatedly in the laboratory produced less dextran (400 +/- 30 microgram/ml), adhered poorly to fibrin (adherence ratio X 10(4), 140 +/- 7), and produced endocarditis in only 3 of 14 rabbits under identical conditions (P less than 0.05). This study demonstrates that dextran production is important in the adherence of oral streptococci to the constituents of NBTE and may play a role in the pathogenesis of bacterial endocarditis by oral streptococci.

Animals↗
PubMed1981

Bacterial adhesion in the pathogenesis of infective endocarditis. Effect of subinhibitory antibiotic concentrations on streptococcal adhesion in vitro and the development of endocarditis in rabbits.

Bacterial adhesion to the constituents of nonbacterial thrombotic endocarditis (NBTE) is important in the pathogenesis of endocarditis. Subinhibitory concentrations (subMIC) of some antibiotics decrease bacterial adhesion to epithelial cells in vitro. We utilized an in vitro assay system to study the effect of subMIC of various antibiotics on streptococcal adhesion to a fibrin-platelet matrix (simulating NBTE). The results were (a) bacterial adhesion of Streptococcus sanguis and Streptococcus faecalis to NBTE was significantly reduced by vancomycin, penicillin, tetracycline, chloramphenicol and streptomycin (P less than 0.01 vs. controls) but not rifampin or trimethoprimsulfametrole; (b) the effect was dose-dependent and increased with duration of exposure to antibiotic; (c) reduction in bacterial adhesion did not correlate with altered retention by hydrophobic-interaction chromatography. This reduction in adhesion correlated with a diminished capacity of subMIC exposed Streptococcus sanguis (1/4 vancomycin minimum inhibitory concentration (MIC) X 4 h) to produce endocarditis in vivo. After intravenous inoculation of 10(6) colony-forming units of preincubated organisms into rabbits with traumatized aortic valves, 6 of 22 developed endocarditis vs. 17 of 22 controls (P = 0.03). These results may be relevant to prophylaxis of endocarditis since exposure of bacteria to subMIC of various antibiotics may reduce bacterial adherence both, to mucosal surfaces, and to damaged cardiac valves.

Animals↗
PubMed2001

Surgical pathology of nonbacterial thrombotic endocarditis in 30 patients, 1985-2000.

OBJECTIVE: To describe the causes, complications, and histological appearance of nonbacterial thrombotic endocarditis (NBTE) in a surgical population compared with those in previously reported autopsy series. PATIENTS AND METHODS: Cases were identified by reviewing the surgical pathology reports for all cardiac valvular specimens removed at Mayo Clinic, Rochester, Minn., between 1985 and 2000. Archived microscopic slides and medical records were reviewed for each study patient. RESULTS: The study group consisted of 30 patients (20 female and 10 male), with a mean age of 49 years (range, 15-89 years). Of these 30 patients, 28 had single valve involvement (19 mitral, 8 aortic, and 1 tricuspid), and 2 had involvement of both their mitral and aortic valves. An underlying immune-mediated disorder was identified in 18 patients (60%), including primary antiphospholipid syndrome (in 8), rheumatic heart disease (in 6), systemic lupus erythematosus (in 2), and rheumatoid arthritis (in 2), 15 (83%) of whom were women. Of the remaining 12 patients with no autoimmune disease, only 5 (42%) were women. No patient had metastatic malignant disease or disseminated intravascular coagulopathy. Systemic embolization was documented in 10 patients (33%), 8 of whom had cerebral involvement. Valvular vegetations were visualized by echocardiography before surgery in 8 patients and were suspected but not confirmed preoperatively in 1 patient. All vegetations consisted primarily of platelets and fibrin. The site and appearance of vegetations did not vary with the underlying disease state. CONCLUSIONS: In contrast to previously reported autopsy series, NBTE in a surgical population was more commonly associated with autoimmune disorders than malignancy or disseminated intravascular coagulopathy. Women were affected twice as often as men. Systemic embolization, particularly to the brain, was prominent in both surgical and autopsy series. Vegetations had a similar appearance regardless of the specific underlying disease. An antemortem diagnosis of NBTE in a patient with no known risk factors should prompt a search not only for occult malignancy, as suggested by autopsy studies, but also for autoimmune or rheumatic diseases, particularly the antiphospholipid syndrome.

Adolescent↗
PubMed1985

Non-bacterial thrombotic endocarditis associated with malignant disease: a clinicopathological study of 16 cases.

Among 2627 necropsies performed in the Sir Charles Gairdner Hospital, Perth, over a period of 11 years, 16 cases of non-bacterial thrombotic endocarditis (NBTE) were found in patients with cancer (13 adenocarcinomas). The final stay in hospital of seven of these patients was complicated by a major embolic cerebral (six patients), or spinal cord (one patient), stroke. In all cases, the diagnosis of NBTE was made at necropsy. The aortic valve was affected in 10 patients, the mitral valve in five, and both the mitral and tricuspid valves in one. The diagnosis of NBTE should be considered in any patient with a known, or suspected, malignant neoplasm who suffers a stroke or other unexplained embolic events.

Adenocarcinoma↗