The antithrombotic activity of the active fractions from the fruits of Celastrus orbiculatus Thunb through the anti-coagulation, anti-platelet activation and anti-fibrinolysis pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine Celastrus orbiculatus Thunb (C. orbiculatus) with peel and seeds is mainly composed of flavonoids, sesquiterpenes and tripenes. According to the Traditional Chinese medicine standard of Liaoning province (2009), it has been long used to invigorate blood circulation. AIM OF THE STUDY: To identify the antithrombus fraction and components of C. orbiculatus, and to investigate the underlying mechanisms. MATERIALS AND METHODS: The antithrombus effects of C. orbiculatus fractions were evaluated in vitro by plasma recalcification time (PRT). The antithrombus effect of NST-50, the most effective fraction, was further investigated in acute pulmonary embolism (APE) mice and FeCl3-induced carotid arterial thrombus rats. Bleeding assessment was also carried out to assess the side effects of NST-50. In addition, the content of total flavonoids and active components of NST-50 was also quantified. RESULTS: Nine flavonoids were detected in NST-50 as main components with the content of 44.70%. Next, NST-50 was found with significant anticoagulation activity by prolonging the plasma recalcification time (PRT), activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) and decreasing the content of fibrinogen (FIB). Furthermore, NST-50 administration markedly suppressed the level of TXB2 and PAI-1, while significantly up-regulated the level of 6-keto-PGF1a and t-PA (p < 0.05). CONCLUSION: The results demonstrated that NST-50 could be valuable in clinical application against acute coronary syndrome, venous thromboembolisms and cerebrovascular thrombosis. It was possible that the anticoagulation action of NST-50 could be related to the regulation of TXA2 - PGI2 and t-PA - PAI-1 pairs.

Correlation of benign prostatic obstruction-related complications with clinical outcomes in patients after transurethral resection of the prostate.

We aim to investigate the correlation of benign prostatic obstruction (BPO)-related complications with clinical outcomes in patients after transurethral resection of the prostate in China. We reviewed the medical history of all patients who underwent surgery from 1992 to 2013. We assessed the preoperative clinical profile, clinical management, and operative complications. Overall, 2271 patients were enrolled in the study. Of these patients, 1193 (52.5%) had no BPO-related complications and 1078 (46.3%) had BPO-related complications. Compared with patients without BPO-related complications, those with BPO-related complications were older (p = 0.001) and usually had other urologic comorbidities (p = 0.003). Additionally, they tended to have more tissue resected (p < 0.001), a higher American Society of Anesthesiologists grade (p = 0.002), and larger prostates (p < 0.001). Nonetheless, there was no obvious difference in surgical complications between both groups (p > 0.05). Among patients with BPO-related complications, compared with the bladder stone group, only the bladder stone+ group tended to have a greater urinary infection risk after transurethral resection of the prostate. Compared with patients with one or two BPO-related complications, those with three BPO-related complications tended to have a higher risk of pulmonary embolism and acute coronary syndrome (p < 0.05). Despite the widespread use of medication, patients with BPO-related complications were older and had larger prostates; however, transurethral resection of the prostate is still considered a safe and recommended surgical treatment. Nevertheless, those with three or more complications were at a higher risk of severe complication after surgery, and active surgical intervention is needed once BPO-related complications develop.

Acute eosinophilic pneumonia masquerading as multiple pulmonary embolisms.

A 47-year-old previously healthy man was admitted to the hospital with a 5-day history of fever, dry cough, and dyspnoea. Thoracic radiographs and CT scan showed extensive bilateral consolidation predominantly involving the central portions of the upper lung lobes, along with multiple scattered nodules. On taking a thorough history, it was found that the patient had visited a gritty 100-year-old Japanese folk house 1 week ago. An urgent bronchoscopy was performed, and the results were consistent with the findings of acute eosinophilic pneumonia (AEP). The patient's respiratory distress resolved within 10 days without treatment. Hence, even in an AEP case with atypical radiological presentations, careful history taking can lead to a rapid diagnosis.

Antithrombotic and antiplatelet activities of small-molecule alkaloids from Scolopendra subspinipes mutilans.

The aim of this study was to discover small-molecule anticoagulants from Scolopendra subspinipes mutilans (SSM). A new acylated polyamine (1) and a new sulfated quinoline alkaloid (2) were isolated from SSM. Treatment with the new alkaloids 1, 2, and indole acetic acid 4 prolonged the activated partial thromboplastin time and prothrombin time and inhibited the activity and production of thrombin and activated factor X. Furthermore, compounds 1, 2, and 4 inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In accordance with these potential in vitro antiplatelet activities, compounds 1, 2, and 4 showed enhanced antithrombotic effects in an in vivo pulmonary embolism and arterial thrombosis model. Compounds 1, 2, and 4 also elicited anticoagulant effects in mice. Collectively, this study may serve as the groundwork for commercializing SSM or compounds 1, 2, and 4 as functional food components for the prevention and treatment of pathogenic conditions and serve as new scaffolds for the development of anticoagulants.

Antithrombotic Activity of a New Hypoglycemic Compound Limiglidole in Mouse Model of Cell Thrombosis.

Antithrombotic activity of hypoglycemic compound limiglidole that exhibits antiplatelet activity 2-fold exceeded activity of antiplatelet agent acetylsalicylic acid in the mouse model of systemic collagen-epinephrine thrombosis. Limiglidole signifi cantly reduced the relative and mean area of blood clots in the sections of mouse lungs.

New oral anticoagulants for the treatment of venous thromboembolism.

New oral anticoagulants, acting either as direct factor-Xa or thrombin inhibitors, have been evaluated for the acute and long-term treatment of venous thromboembolism (VTE). Dabigatran and rivaroxaban are as effective as conventional therapy (heparin/vitamin K antagonists) without safety concerns. Rivaroxaban allows a single-drug regimen even in patients with pulmonary embolism, while dabigatran requires 5-7 days of initial heparin treatment. The results of clinical trials with apixaban and edoxaban will become available in the coming months. Rivaroxaban, apixaban and dabigatran are more effective than placebo for the extended treatment of VTE. Apixaban is effective in both therapeutic and prophylactic doses. Considering both efficacy and bleeding complications, all these agents have a favorable net clinical benefit. Dabigatran is as effective and safe as warfarin for the extended treatment of VTE. It is conceivable that the new oral anticoagulants will become the standard therapy for VTE in the next years.

Novel oral anticoagulants for thromboprophylaxis after orthopaedic surgery.

The direct thrombin inhibitor, dabigatran, and the selective factor Xa inhibitors, rivaroxaban and apixaban, are new oral anticoagulants that are approved in many countries for prevention of venous thromboembolism in patients undergoing elective hip or knee arthroplasty. All have a rapid onset of action, a low potential for food and drug interactions and a predictable anticoagulant effect that obviates the need for routine coagulation monitoring. These agents offer a convenient alternative to conventional anticoagulant drug regimens, including parenteral low-molecular-weight heparins and fondaparinux, and oral adjusted-dose vitamin K antagonists, for the prevention of venous thromboembolism in this surgical setting. This review summarizes the pharmacology, clinical trial results, bleeding risk and practical use of these new oral anticoagulants in clinical orthopaedic practice. Potential issues to be considered when using these oral anticoagulants include renal impairment, potential drug interactions, neuraxial anaesthesia and management of bleeding.

NOACs for thromboprophylaxis in medical patients.

The risk of venous thrombosis extends for an indeterminate length of time following admission to hospital with a medical or surgical condition. Observational studies in surgery show this risk extends for months and perhaps more than one year, for medical patients the risk extends for at least several weeks. Large bodies of evidence support the heightened risk status of hospitalised surgical and medical patients, and that prophylactic measures significantly reduce the risk of thrombosis. Extending thromboprophylaxis for 4-6 weeks with anticoagulants both old and new has been shown to be efficacious and safe in surgical patients. However in populations of medical patients although prolonged anticoagulant thromboprophylaxis has been shown to be efficacious it also results in more bleeding and the risk benefit is not clear. Hence no therapies are approved for prolonged thromboprophylaxis in medical patients. In this area there have been one phase III study of low molecular weight heparin and two completed phase III studies of NOACs. This article briefly summarises our understanding of the background to preventing venous thromboembolism in hospitalised medical patients and reviews the details of the studies using NOACs.

Cerebral and pulmonary embolisms after transcatheter arterial chemoembolization for hepatocellular carcinoma.

A cerebral lipiodol embolism is an extremely rare complication of transcatheter arterial chemoembolization for hepatocellular carcinoma. We present a case of cerebral lipiodol embolism that occurred after the third arterial chemoembolization, report the clinical and radiological findings, and review the medical literature.

Sudden death during worker transportation due to massive pulmonary thromboembolism: a case report.

This is a report on a 30-year-old black man who suddenly died in the worker transportation vehicle in which he had been quietly sitting for thirty minutes. No information about his medical or surgical history or any family history has been obtained. This case is intended to highlight the fact that forensic autopsy is a valuable tool to recognize the cause of death and that fatal pulmonary thromboembolism still remains a post-mortem diagnosis. In this case report, the autopsy found a fresh saddle pulmonary thromboembolus associated with partially organized thrombi of the inferior vena cava. Can a prolonged seated position encourage thrombus formation? We think that seat-related factors and especially patient-related factors intervene together in the development of thromboembolic events. In our medico-legal unit, having no means to search for these factors, we speculated on the various causes that could be involved in the occurrence of venous thromboembolism in our subject. We emphasize the importance of focusing research on genetic factors and the impact of traditional medicine in African people.

Relationship between pulmonary fat embolism and core body temperature in rats with a severe fatty liver.

We previously demonstrated that pulmonary fat embolism was induced by elevation of the core body temperature, in rats with a fatty liver. The aim of the present examination was to investigate the core body temperature at which pulmonary fat embolism developed capillaries through exposure to a high temperature, in rats with a fatty liver. Following heat stress, pulmonary fat embolism was observed to a slight degree at a core body temperature of 41 and 42 degrees C, whereas the severity of pulmonary fat embolism was greatly increased and was classified as severe at a core body temperature of 43 degrees C. Moreover, the concentrations of aspartate aminotransferase and alanine aminotransferase within plasma were significantly increased at a core body temperature of 43 degrees C. These results clearly indicate that the development of pulmonary fat embolism could be related to hyperthermia at above 42 degrees C following heat stress, and that fat emboli may be derived from the fatty liver itself. It is thus likely that pulmonary fat embolism can be considered as one form of evidence of hyperthermia in an individual with a fatty liver.

Culture-positive and culture-negative endocarditis in patients with cancer: a retrospective observational study, 1994-2004.

Endocarditis is uncommon in patients with cancer. The characteristics of culture-positive (CPE) and culture-negative endocarditis (CNE) in high-risk cancer patients are not known; therefore we sought to evaluate the disease characteristics in patients with endocarditis at a comprehensive cancer center. We retrospectively reviewed the transthoracic (TTE) and transesophageal (TEE) echocardiograms obtained from 654 consecutive cancer patients in whom endocarditis was suspected between 1994 and 2004. Endocarditis was confirmed in 45 (7%) of 654 patients using modified Duke University criteria based on information obtained from hospital records and computerized data systems. In 21 (95%) of 22 cases, TEE examinations were diagnostic, and 16 (42%) of 38 patients with initially nondiagnostic TTE studies had the diagnosis confirmed by TEE study; this difference between diagnostic TEE and initial nondiagnostic TTE was significant (p < 0.0001). Among the 26 (58%) patients with CPE, Staphylococcus aureus (35%) was the most common organism isolated, followed by coagulase-negative Staphylococcus species (23%). Eighteen (78%) of 23 patients with a central venous catheter had CPE, whereas only 8 (36%) of 22 patients without a central venous catheter had CPE (odds ratio [OR], 6.3; 95% confidence interval [CI], 1.69-23.53; p < 0.006). Vegetations were larger in patients with CPE than in patients with CNE (median +/- standard deviation, 10 +/- 8.8 vs. 8.7 +/- 3.9 mm). Fifteen patients (58%) with CPE and 10 (53%) with CNE had embolic complications. We note that cutaneous and septic pulmonary emboli were more common in patients with CPE than in patients with CNE (31% vs. 11% and 15% vs. 0%, respectively), whereas embolic cerebrovascular and fatal embolic coronary events were more common in patients with CNE than in those with CPE (37% vs. 12% and 21% vs. 0%, respectively; p = 0.026). The 4-week endocarditis-attributable death rate did not differ significantly between the groups (CPE, 15% vs. CNE, 32%; p = 0.28). On stepwise multivariate regression analysis, patients with neutropenia (OR, 22.52; 95% CI, 2.25-225.48; p < 0.008) and those with embolic cerebrovascular events (OR, 17.07; 95% CI, 1.63-178.45; p < 0.01) had an increased probability of death due to endocarditis. The clinical spectrums of CPE and CNE differed in these patients with cancer. In patients with CNE, embolic cerebrovascular and fatal myocardial infarction were relatively common.

[Pulmonary lesions and total parenteral nutrition in children admitted to a pediatric intensive care unit]. / Lesões pulmonares e nutrição parenteral total em crianças internadas em unidade de terapia intensiva pediátrica.

OBJECTIVE: To describe lung injuries in autopsied pediatric patients (neonates through 15 years old) subjected or not to total parenteral nutrition, in an intensive care unit. METHODS: Sections from six paraffin-embedded lung fragments, from 114 children were studied by routine staining. Demographic, clinical and therapeutic data were retrieved from the records. Statistical analysis was performed using Statistical Package for the Social Sciences. RESULTS: The 114 patients were divided in two groups: 50 who were treated with total parenteral nutrition with lipid emulsion and 64 who did not receive total parenteral nutrition. The two groups did not differ in gender (p = 0.654), age (p = 0.682) or body weight (p = 0.175), but duration of hospital stay (p = 0.000), prematurity (p = 0.008) and treatment with blood products (p = 0.009) were all higher in the group treated with total parenteral nutrition. All patients received mechanical ventilation during hospitalization. Chi-square comparisons showed that diffuse alveolar injury (p = 0.022), pulmonary fibrosis (p = 0.019), pneumocyte hyperplasia (p = 0.004), microthromboembolism (p = 0.047) and thrombophlebitis (0.033) all exhibited a significant relationship with total parenteral nutrition. However, a multivariate analysis by logistic regression, taking into account prematurity and duration of hospital stay, demonstrated that total parenteral nutrition was an independent factor only with respect of pulmonary fibrosis. CONCLUSION: Although lung injuries were significantly more frequent in children who had received total parenteral nutrition, it was impossible to conclude that the lipid infusion had a direct relationship with these injuries, because prematurity and duration of hospital stay were significant co-factors.

Lesões pulmonares e nutrição parenteral total em crianças internadas em unidade de terapia intensiva pediátrica / Pulmonary lesions and total parenteral nutrition in children admitted to a pediatric intensive care unit

OBJETIVO: Descrever as lesões pulmonares em uma série de necropsias de pacientes com idade de até 15 anos, falecidos em unidade de terapia intensiva, submetidos ou não à nutrição parenteral total. MÉTODOS: Seis fragmentos de cada pulmão de 114 crianças foram corados por métodos de rotina. Dos prontuários foram obtidas informações referentes aos dados demográficos, clínicos e de terapêutica. Para a análise estatística, foi utilizado o Programa Statistical Package for the Social Sciences. RESULTADOS: Os 114 pacientes foram separados em dois grupos: 50 foram tratados com NPT contendo emulsão de lipídios e os 64 restantes, sem nutrição parenteral total. Os grupos eram semelhantes em relação ao sexo (p = 0,654), à idade (p = 0,682) e ao peso (p = 0,175), e apresentavam diferenças significativas no que tange às seguintes variáveis: tempo de internação (p = 0,000), prematuridade (p = 0,008) e tratamento com hemoderivados (p = 0,009). Todos foram submetidos à ventilação mecânica durante o período de internação. Na análise univariada, as lesões relacionadas à nutrição parenteral total foram: dano alveolar difuso (p = 0,022), fibrose pulmonar (p = 0,019), hiperplasia de pneumócitos (p = 0,004), microtromboembolismo (p = 0,047) e tromboflebite (p = 0,033). A análise multivariada, levando em consideração a prematuridade, o tempo de internação e a idade, mostrou que apenas a fibrose estava relacionada, de modo independente, ao uso da nutrição parenteral total. CONCLUSAO: Embora as lesões pulmonares tenham sido mais freqüentes em pacientes tratados com nutrição parenteral total, não foi possível concluir que essa tenha sido diretamente responsável pela origem das lesões, tendo em vista que co-fatores como prematuridade e tempo de internação influenciaram significativamente no seu aparecimento.

Acute pulmonary thromboembolism induced by prophylactic heparin use and a heparin-coated catheter: a case of heparin-induced thrombocytopenia and thrombosis syndrome.

Heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) is a potentially life-threatening side effect of heparin therapy, triggered by an immune response, and has been reported to be related not only to the therapeutic use of heparin but also to heparin-coated catheters. A 45-year-old woman with intrapelvic malignancy developed an acute pulmonary thromboembolism (PE) after hysterectomy despite prophylactic heparin use. Subsequent large doses of heparin for treatment of the PE exacerbated the thrombocytopenia and, moreover, a large thrombus formed around the heparin-coated central venous catheter. Anti-heparin-platelet factor 4 complex antibody and heparin-induced platelet aggregation assay were positive, so the diagnosis was HITTS, and heparin was replaced by argatroban after carrying out thrombectomy. This therapy was successful, and the patient made favorable progress.

Pulseless electrical activity with witnessed arrest as a predictor of sudden death from massive pulmonary embolism in outpatients.

BACKGROUND: the objective was to determine clinical characteristics that can quickly distinguish sudden death from massive pulmonary embolism (MPE) from other causes of sudden death. METHODS AND RESULTS: all medical examiner reports from Charlotte, NC from 1992 to 1999 (n=4926) were hand-searched for cases of sudden death which met the inclusion criteria: non-traumatic death, age 18-65 years, transported to an emergency department (ED), and autopsy performed. Supplemental data from ED and prehospital records were retrieved to complete documentation. Data were analyzed by univariate odds ratios (OR) followed by chi-square (chi(2)) recursive partitioning for decision tree construction. Three hundred eighty four cases met inclusion criteria; MPE was the second most frequent cause of cardiac arrest in this cohort (37/384, 9.6%). The mean age of subjects with MPE (40.2+/-11.1 years) was significantly lower compared with non-PE subjects (46.5+/-9.9 years). Pulseless electrical activity was observed as the initial arrest rhythm (primary PEA) in 52/384 (13.5%) subjects. Out of 52 subjects with primary PEA, 28 (53%) died from MPE. Odds ratio data indicated significant association of MPE with female gender, arrest witnessed by medical providers, presence of primary PEA, and return of spontaneous circulation. The most accurate decision rule to recognize MPE consisted of witnessed arrest+primary PEA. This rule generated sensitivity=67.6% and specificity=94.5% and yielded a posttest probability of MPE of 57%. CONCLUSIONS: outpatients with witnessed cardiac arrest and primary PEA carry a high probability of MPE.

Fatal microvascular pulmonary emboli from precipitation of a total nutrient admixture solution.

BACKGROUND: Paroxysmal respiratory failure and death occurred in two young adult females with pelvic infections. Autopsy revealed an amorphous material containing calcium obstructing the pulmonary microvasculature of each patient. Both patients received an identical total nutrient admixture (TNA) solution before their deaths. METHODS: Infusion of TNA into an animal model was undertaken in an effort to reproduce the clinical effect. Laboratory investigation was also performed to isolate a precipitate and identify the factors contributing to precipitation. RESULTS: A nonvisible precipitate containing calcium, phosphorus, and organic material was isolated from the TNA solution. Infusion of the formulation into healthy pigs resulted in sudden death within 4 hours. Alteration of the amino acid component, mix sequence, agitation technique, and mixing container influenced precipitate formation. CONCLUSION: Pulmonary embolization of a precipitate containing calcium phosphate resulted in the death of two patients. The pH of the amino acid component, transient elevation of calcium and phosphorus concentrations during mixing, and the lack of agitation during automated preparation of the formulation were identified as the etiologic factors producing the fatal precipitate.

Clinical features of Kleine-Levin syndrome with localized encephalitis.

We report the clinico-pathological findings regarding a 9 year-old girl with some clinical features of Kleine-Levin syndrome who died suddently as a result of pulmonary embolism in the course of femoro-iliac thrombophlebitis. Neuropathological examination provided evidence of perivascular inflammatory infiltrates and microglial proliferation of nodular type located in the diencephalon and midbrain. These findings suggest that a localized encephalitis may be the underlying condition in Kleine-Levin syndrome.