RESUMO
Drug-induced bleeding disorders contribute to substantial morbidity and mortality. Antithrombotic agents that cause unintended bleeding of obvious cause are relatively easy to control. However, the mechanisms of most drug-induced bleeding disorders are poorly understood, which makes intervention more difficult. As most bleeding disorders are associated with the dysfunction of coagulation factors, we adapted our recently established cell-based assay to identify drugs that affect the biosynthesis of active vitamin K-dependent (VKD) coagulation factors with possible adverse off-target results. The National Institutes of Health (NIH) Clinical Collection (NCC) library containing 727 drugs was screened, and 9 drugs were identified, including the most commonly prescribed anticoagulant warfarin. Bleeding complications associated with most of these drugs have been clinically reported, but the pathogenic mechanisms remain unclear. Further characterization of the 9 top-hit drugs on the inhibition of VKD carboxylation suggests that warfarin, lansoprazole, and nitazoxanide mainly target vitamin K epoxide reductase (VKOR), whereas idebenone, clofazimine, and AM404 mainly target vitamin K reductase (VKR) in vitamin K redox cycling. The other 3 drugs mainly affect vitamin K availability within the cells. The molecular mechanisms underlying the inactivation of VKOR and VKR by these drugs are clarified. Results from both cell-based and animal model studies suggest that the anticoagulation effect of drugs that target VKOR, but not VKR, can be rescued by the administration of vitamin K. These findings provide insights into the prevention and management of drug-induced bleeding disorders. The established cell-based, high-throughput screening approach provides a powerful tool for identifying new vitamin K antagonists that function as anticoagulants.
Assuntos
Anticoagulantes/isolamento & purificação , Anticoagulantes/farmacologia , Transtornos Hemorrágicos/induzido quimicamente , Ensaios de Triagem em Larga Escala/métodos , Vitamina K/metabolismo , 4-Hidroxicumarinas/efeitos adversos , 4-Hidroxicumarinas/isolamento & purificação , 4-Hidroxicumarinas/farmacologia , Animais , Anticoagulantes/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Técnicas de Cultura de Células/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Células HEK293 , Células Hep G2 , Humanos , Indenos/efeitos adversos , Indenos/isolamento & purificação , Indenos/farmacologia , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Uso Off-Label , Vitamina K/efeitos adversos , Vitamina K/antagonistas & inibidores , Vitamina K/isolamento & purificação , Vitamina K/farmacologia , Vitamina K Epóxido Redutases/antagonistas & inibidores , Vitamina K Epóxido Redutases/metabolismoRESUMO
Hemoperitoneum due to ruptured retroperitoneal varices is an extremely rare condition and a poor prognostic sign with a catastrophic and life-threatening situation. Early recognition affords appropriate management and urgent surgical intervention in order to favor the survival rate. In this case report we accurately describe the complex clinical course of a 56-year old woman with retroperitoneal varices, who few months earlier had a chest trauma with multiple left lower rib fractures and 10 years earlier she underwent to ovarian hyperstimulation for an ovulation induction. She was taken to the emergency room for a fainting episode with signs of a clear hemodinamic shock without a present history of trauma. The intricacy of this case was mostly due to the choice of the correct management, where the damage control resuscitation turned out to have an important role.
Assuntos
Emergências , Hemoperitônio/etiologia , Síncope/etiologia , Varizes/complicações , Consumo de Bebidas Alcoólicas/efeitos adversos , Transfusão de Componentes Sanguíneos , Terapia Combinada , Embolização Terapêutica , Evolução Fatal , Feminino , Hemoperitônio/cirurgia , Hemoperitônio/terapia , Transtornos Hemorrágicos/induzido quimicamente , Técnicas Hemostáticas , Hemostáticos/uso terapêutico , Humanos , Hipertensão Intra-Abdominal/etiologia , Laparotomia , Falência Hepática/etiologia , Pessoa de Meia-Idade , Síndrome de Hiperestimulação Ovariana/complicações , Síndrome de Hiperestimulação Ovariana/fisiopatologia , Complicações Pós-Operatórias/etiologia , Ressuscitação/métodos , Espaço Retroperitoneal , Salpingectomia , Choque Séptico/etiologia , Aderências Teciduais/etiologia , Técnicas de Fechamento de Ferimentos/efeitos adversosRESUMO
BACKGROUND: The aim of this study was to evaluate the modulatory effect of S-allyl cysteine against cyclophosphamide-induced changes in uroplakin IIIa, CCL11 and TNF-α. METHODS: Mice were treated with cyclophosphamide (200mg/kg×7 d, ip). S-allyl cysteine (150mg/kg×7d, ip), and comparator compound mesna (40mg/kg×7d, ip) were administered 1h before and 4h after each cyclophosphamide dose. The urinary bladder was analysed for mRNA and protein changes in uroplakin IIIa (UPIIIa), CCL11 and TNF-α and histopathological findings. RESULTS: Cyclophosphamide caused hemorrhagic cystitis formation and downregulation of UPIIIa. These changes were accompanied by upregulation of CCL11 and TNF-α. S-allyl cysteine attenuated these changes including protection at histological level. Mesna which was used as a comparator drug also showed protection. However, relatively S-allyl cysteine showed a stronger protective effect than mesna. CONCLUSION: These findings highlight a correlation between downregulaion of UPIIIa and enhanced production of inflammatory biomarkers and protective effects of S-allyl cysteine which has been reported to be a potent uroprotective agent. The present study strengthens its role which could be clinically exploited in chemotherapy regimen.
Assuntos
Quimiocina CCL11/metabolismo , Ciclofosfamida/antagonistas & inibidores , Cisteína/análogos & derivados , Fator de Necrose Tumoral alfa/metabolismo , Bexiga Urinária/metabolismo , Uroplaquina III/biossíntese , Animais , Ciclofosfamida/efeitos adversos , Cisteína/farmacologia , Cistite/induzido quimicamente , Cistite/prevenção & controle , Regulação para Baixo , Transtornos Hemorrágicos/induzido quimicamente , Transtornos Hemorrágicos/prevenção & controle , Masculino , Mesna/farmacologia , Camundongos , Substâncias Protetoras/farmacologia , Bexiga Urinária/patologiaRESUMO
BK virus-associated hemorrhagic cystitis (BK-HC) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HCT), with incidences up to 70%. Cidofovir is an antiviral agent with growing evidence as a therapeutic intervention. To assess the safety profile and efficacy of intravenous and intravesical cidofovir in allo-HCT patients with BK-HC, a retrospective study was undertaken of the allo-HCT cohort who received cidofovir for symptomatic BK-HC (hematuria with BK viruria or viremia) from January 2010 until March 2017 in a single transplant center in Ontario, Canada. The primary outcome measure was a reduction in BK-HC severity (graded from 1 to 4); secondary outcomes included overall survival, BK virus titers, and the onset of acute kidney injury. Twelve allo-HCT patients received cidofovir for BK-HC, with pretreatment clinical severity of 3 (50%) or 4 (50%). Cidofovir was administered via intravenous (33%), intravesical (58%), or both modalities (8%). After a median cumulative dose of 10 mg/kg (range, 1 to 37), mean BK-HC grade decreased significantly by 1.8 (3.5 precidofovir, 1.7 postcidofovir, P < .01). Sixty-six percent of patients had at least partial response to cidofovir, with similar response rates between intravenous (66%) and intravesical (62%) administration. Sixty-seven percent of patients died, and 33% of patients experienced renal toxicity, including 2 patients receiving intravesical therapy. In this retrospective series, there was a significant reduction in BK-HC severity after cidofovir administration; most patients achieved at least partial response after cidofovir administration. Even with intravesical instillation, acute kidney injury remains a potential complication of cidofovir. Although cidofovir may be an efficacious therapy for BK-HC, albeit with potential demonstrated toxicities, further prospective trials are needed.
Assuntos
Antivirais/uso terapêutico , Vírus BK/patogenicidade , Cidofovir/uso terapêutico , Cistite/induzido quimicamente , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transtornos Hemorrágicos/induzido quimicamente , Condicionamento Pré-Transplante/efeitos adversos , Adulto , Idoso , Antivirais/farmacologia , Cidofovir/farmacologia , Cistite/tratamento farmacológico , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Transtornos Hemorrágicos/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Condicionamento Pré-Transplante/métodosRESUMO
Chemotherapy-induced hemorrhagic cystitis (CHC) can be difficult to manage. Prior work suggests that IL-4 alleviates ifosfamide-induced hemorrhagic cystitis (IHC), but systemically administered IL-4 causes significant side effects. We hypothesized that the Schistosoma hematobium homolog of IL-4-inducing principle from Schistosoma mansoni eggs (H-IPSE), would reduce IHC and associated bladder pathology. IPSE binds IgE on basophils and mast cells, triggering IL-4 secretion by these cells. IPSE is also an "infiltrin," translocating into the host nucleus to modulate gene transcription. Mice were administered IL-4, H-IPSE protein or its nuclear localization sequence (NLS) mutant, with or without neutralizing anti-IL-4 antibody, or 2-mercaptoethane sulfonate sodium (MESNA; a drug used to prevent IHC), followed by ifosfamide. Bladder tissue damage and hemoglobin content were measured. Spontaneous and evoked pain, urinary frequency, and bladdergene expression analysis were assessed. Pain behaviors were interpreted in a blinded fashion. One dose of H-IPSE was superior to MESNA and IL-4 in suppressing bladder hemorrhage in an IL-4-dependent fashion and comparable with MESNA in dampening ifosfamide-triggered pain behaviors in an NLS-dependent manner. H-IPSE also accelerated urothelial repair following IHC. Our work represents the first therapeutic exploitation of a uropathogen-derived host modulatory molecule in a clinically relevant bladder disease model and indicates that IPSE may be an alternative to MESNA for mitigating CHC.-Mbanefo, E. C., Le, L., Pennington, L. F., Odegaard, J. I., Jardetzky, T. S., Alouffi, A., Falcone, F. H., Hsieh, M. H. Therapeutic exploitation of IPSE, a urogenital parasite-derived host modulatory protein, for chemotherapy-induced hemorrhagic cystitis.
Assuntos
Cistite/tratamento farmacológico , Proteínas do Ovo/farmacologia , Proteínas de Helminto/farmacologia , Hemorragia/tratamento farmacológico , Transtornos Hemorrágicos/tratamento farmacológico , Parasitos/metabolismo , Animais , Antineoplásicos/efeitos adversos , Basófilos/efeitos dos fármacos , Cistite/induzido quimicamente , Feminino , Hemorragia/induzido quimicamente , Transtornos Hemorrágicos/induzido quimicamente , Imunoglobulina E/metabolismo , Interleucina-4/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Schistosoma haematobium/metabolismo , Schistosoma mansoni/metabolismo , Bexiga Urinária/efeitos dos fármacosRESUMO
INTRODUCTION: Endoscopic lung volume reduction coil (LVRC) treatment is an option for selected patients with severe emphysema. This study was conducted to determine the incidence of bleeding complications after LVRC treatment, to identify risk factors and to discuss treatment options in case of hemoptysis which does not resolve spontaneously. METHODS: Retrospective observational study conducted in the Department of Respiratory Medicine at the University Medical Center Hamburg-Eppendorf in all subjects in whom LVRC treatment was performed between April 1, 2012 and September 30, 2015. RESULTS: During the study period, 101 LVRC procedures were performed in 62 subjects. Early post-procedural bleeding was encountered in 65.3% of cases. Hemoptysis was significantly more likely to occur in patients receiving acetylsalicylic acid (P=.005). Hemoptysis resolved spontaneously in 98.5% of cases. In the one case (1.5%) with persistent hemoptysis, bronchial artery embolization was successful in terminating bleeding. Hospital stay was significantly prolonged in subjects with hemoptysis (P=.01). No significant differences were found between subjects with or without hemoptysis in terms of chronic obstructive pulmonary disease exacerbations within four weeks after LVRC treatment (P=.18). Late bleeding complications were observed in 3 subjects (3.0%). In 2 of these cases, bronchial artery embolization was performed and bleeding was successfully terminated. CONCLUSIONS: Self-limiting low volume bleeding is a common finding in the first days after LVRC treatment. However, persistent bleeding may occur in the early post-procedural phase and late after LVRC treatment. In these cases, bronchial artery embolization was a feasible and successful approach to terminating bleeding.
Assuntos
Broncoscopia/efeitos adversos , Enfisema/cirurgia , Hemoptise/etiologia , Pneumopatias/etiologia , Pneumonectomia/efeitos adversos , Hemorragia Pós-Operatória/etiologia , Idoso , Aspirina/efeitos adversos , Artérias Brônquicas , Broncoscopia/métodos , Embolização Terapêutica , Feminino , Fluoroscopia , Hemoptise/epidemiologia , Hemoptise/terapia , Transtornos Hemorrágicos/induzido quimicamente , Técnicas Hemostáticas , Humanos , Hipertensão Pulmonar/complicações , Tempo de Internação/estatística & dados numéricos , Pneumopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/efeitos adversos , Pneumonectomia/instrumentação , Pneumonectomia/métodos , Hemorragia Pós-Operatória/epidemiologia , Hemorragia Pós-Operatória/terapia , Radiografia Intervencionista , Estudos Retrospectivos , Fatores de RiscoRESUMO
In the Digestive Disease Week in 2015 there have been some new contributions in the field of gastrointestinal bleeding that deserve to be highlighted. Treatment of celecoxib with a proton pump inhibitor is safer than treatment with nonselective NSAID and a proton pump inhibitor in high risk gastrointestinal and cardiovascular patients who mostly also take acetylsalicylic acid. Several studies confirm the need to restart the antiplatelet or anticoagulant therapy at an early stage after a gastrointestinal hemorrhage. The need for urgent endoscopy before 6-12 h after the onset of upper gastrointestinal bleeding episode may be beneficial in patients with hemodynamic instability and high risk for comorbidity. It is confirmed that in Western but not in Japanese populations, gastrointestinal bleeding episodes admitted to hospital during weekend days are associated with a worse prognosis associated with delays in the clinical management of the events. The strategy of a restrictive policy on blood transfusions during an upper GI bleeding event has been challenged. Several studies have shown the benefit of identifying the bleeding vessel in non varicose underlying gastric lesions by Doppler ultrasound which allows direct endoscopic therapy in the patient with upper GI bleeding. Finally, it has been reported that lower gastrointestinal bleeding diverticula band ligation or hemoclipping are both safe and have the same long-term outcomes.
Assuntos
Hemorragia Gastrointestinal , Anemia/etiologia , Anemia/terapia , Anti-Inflamatórios não Esteroides/uso terapêutico , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Transfusão de Sangue , Celecoxib/uso terapêutico , Quimioterapia Combinada , Endoscopia Gastrointestinal , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Transtornos Hemorrágicos/induzido quimicamente , Técnicas Hemostáticas , Humanos , Ligadura , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Trombofilia/tratamento farmacológicoRESUMO
Mesonordihydroguaiaretic acid (NDGA) extends murine lifespan. The studies reported here describe its dose dependence, effects on body weight, toxicity-related clinical chemistries, and mortality-related pathologies. In flies, we characterized its effects on lifespan, food consumption, body weight, and locomotion. B6C3F1 mice were fed AIN-93M diet supplemented with 1.5, 2.5, 3.5, or 4.5 g NDGA/kg diet (1.59, 2.65, 3.71 and 4.77 mg/kg body weight/day) beginning at 12 months of age. Only the 3.5 mg/kg diet produced a highly significant increase in lifespan, as judged by either the Mantel-Cox log-rank test (p = .008) or the Gehan-Breslow-Wilcoxon test (p = .009). NDGA did not alter food intake, but dose-responsively reduced weight, suggesting it decreased the absorption or increased the utilization of calories. NDGA significantly increased the incidence of liver, lung, and thymus tumors, and peritoneal hemorrhagic diathesis found at necropsy. However, clinical chemistries found little evidence for overt toxicity. While NDGA was not overtly toxic at its therapeutic dosage, its association with severe end of life pathologies does not support the idea that NDGA consumption will increase human lifespan or health-span. The less toxic derivatives of NDGA which are under development should be explored as anti-aging therapeutics.
Assuntos
Antioxidantes/farmacologia , Drosophila/fisiologia , Metabolismo Energético/efeitos dos fármacos , Transtornos Hemorrágicos/induzido quimicamente , Homeostase/efeitos dos fármacos , Longevidade/efeitos dos fármacos , Masoprocol/farmacologia , Camundongos/fisiologia , Neoplasias/induzido quimicamente , Neoplasias/mortalidade , Animais , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ingestão de Alimentos/efeitos dos fármacos , MasculinoRESUMO
Although drugs are the most powerful therapeutic tools we have for improving the quality of life of the population, their use is not free of adverse effects. Today there are many polymedicated patients, and it is difficult to find the cause of their adverse effects that increase exponentially when more than 4 drugs are combined. There are a large number of drugs that can result in numerous adverse effects in the oral cavity. The most common are xerostomia, altered taste, gingival enlargement and mucositis caused by cancer treatment. We also review other disorders of the salivary glands, oral mucosal changes, pigmentations, halitosis, osteonecrosis, opportunistic infections and bleeding diathesis.
Assuntos
Doenças da Boca/induzido quimicamente , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Suscetibilidade a Doenças , Doenças da Gengiva/induzido quimicamente , Halitose/induzido quimicamente , Transtornos Hemorrágicos/induzido quimicamente , Humanos , Imunossupressores/efeitos adversos , Doenças da Boca/patologia , Infecções Oportunistas/etiologia , Transtornos da Pigmentação/induzido quimicamente , Doenças das Glândulas Salivares/induzido quimicamente , Sialometaplasia Necrosante/induzido quimicamente , Estomatite/induzido quimicamente , Estomatite/etiologia , Distúrbios do Paladar/induzido quimicamente , Doenças da Língua/induzido quimicamente , Vasoconstritores/efeitos adversos , Xerostomia/induzido quimicamenteAssuntos
Hemorragia Bucal/etiologia , Púrpura Trombocitopênica Idiopática/diagnóstico , Idoso , Equimose/etiologia , Transtornos Hemorrágicos/induzido quimicamente , Humanos , Masculino , Mucosa Bucal/irrigação sanguínea , Inibidores da Agregação Plaquetária/efeitos adversos , Púrpura Trombocitopênica Idiopática/complicações , Telangiectasia/etiologiaRESUMO
BACKGROUND AND OBJECTIVE: Antiphospholipid syndrome (APS) is characterized by the presence of antiphospholipid antibodies (aPL) and thrombotic and/or obstetric manifestations. Patients without another associated autoimmune disease are considered to have primary APS. Some patients develop thrombosis recurrence despite anticoagulant treatment and some clinical features do not respond to standard therapy. Rituximab may be an alternative in these cases. We review the published scientific evidence on the use of rituximab in the treatment of primary APS. PATIENTS AND METHODS: Description of a case and review of the literature with descriptive analysis of the demographic, clinical, and immunologic features, treatment and outcome of patients. RESULTS: We identified 24 patients (15 women [62.5%]), with a mean age of 37.0 ± 13.4 years. The reasons for the use of rituximab were thrombocytopenia (41.7%), skin involvement (33.3%), neurologic and heart valve involvement (12.5%), hemolytic anemia (8.3%) and pulmonary and renal involvement (4.2%). Lupus anticoagulant was present in 72.7% of the cases, the IgG and IgM isotypes of anticardiolipin antibodies in 75 and 50%, respectively, and the anti-ß2GPI (IgG e IgM) antibodies in 80% of patients. Thirteen (54.1%) patients received 2 doses of 1,000 mg of rituximab fortnightly, 10 (41.7%) 4 doses of 375 mg/m(2) weekly and one (4.2%) 8 doses of 375 mg/m(2) weekly. Eleven (45.8%) patients presented a complete clinical response, 7 (29.2%) a partial response and 6 (25%) did not respond to rituximab. Four patients with clinical improvement presented with aPL titer decrease and in one patient, aPL levels did not change. In one patient without clinical response, aPL remained positive. A clinical-immunologic dissociation existed in 2 additional cases. CONCLUSIONS: The results obtained suggest a possible potential benefit of rituximab in the treatment of some clinical manifestations of primary APS such as thrombocytopenia, skin and heart valve involvement.
Assuntos
Síndrome Antifosfolipídica/tratamento farmacológico , Imunossupressores/uso terapêutico , Rituximab/uso terapêutico , Aborto Habitual/etiologia , Corticosteroides/uso terapêutico , Adulto , Anticorpos Antifosfolipídeos/sangue , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/imunologia , Avaliação de Medicamentos , Quimioterapia Combinada , Feminino , Morte Fetal/etiologia , Transtornos Hemorrágicos/induzido quimicamente , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Rituximab/efeitos adversos , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Resultado do TratamentoAssuntos
Derivados de Hidroxietil Amido/efeitos adversos , Substitutos do Plasma/efeitos adversos , Transtornos da Coagulação Sanguínea/induzido quimicamente , Estado Terminal/terapia , Medicina Baseada em Evidências/normas , Transtornos Hemorrágicos/induzido quimicamente , Humanos , Derivados de Hidroxietil Amido/uso terapêutico , Hipovolemia/tratamento farmacológico , Hemorragias Intracranianas/induzido quimicamente , Legislação de Medicamentos , Substitutos do Plasma/uso terapêutico , Insuficiência Renal/induzido quimicamente , Fatores de Risco , Sepse/terapia , Reino Unido , Estados Unidos , United States Food and Drug AdministrationRESUMO
This study was undertaken to determine whether there was a correlation between fine particle (PM2.5) levels and hospital admissions for hemorrhagic stroke (HS) in Taipei, Taiwan. Hospital admissions for HS and ambient air pollution data for Taipei were obtained for the period 2006-2010. The relative risk of hospital admissions was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. For the single-pollutant model (without adjustment for other pollutants), increased HS admissions were significantly associated with PM2.5 levels both on warm days (>23°C) and cool days (<23°C), with an interquartile range rise associated with a 12% (95% CI = 7-18%) and 4% (95% CI = 0-8%) elevation in admissions for HS, respectively. In the two-pollutant models, PM2.5 remained significantly high after inclusion of SO2 or O3 on both warm and cool days. This study provides evidence that higher levels of PM2.5 increase the risk of hospital admissions for HS.
Assuntos
Exposição Ambiental/efeitos adversos , Transtornos Hemorrágicos/epidemiologia , Hospitalização/estatística & dados numéricos , Material Particulado/toxicidade , Acidente Vascular Cerebral/epidemiologia , Poluição do Ar/análise , Estudos Cross-Over , Transtornos Hemorrágicos/induzido quimicamente , Humanos , Modelos Logísticos , Ozônio/análise , Tamanho da Partícula , Fatores de Risco , Acidente Vascular Cerebral/induzido quimicamente , Dióxido de Enxofre/análise , Taiwan/epidemiologiaRESUMO
Systemic thrombolysis is a well known treatment for massive pulmonary embolism (PE) but it remains often underutilized in clinical practice because of the risk of major bleeding, especially intracranial hemorrhage. Recently, the use of safe-dose recombinant tissue-type plasminogen activator (rTPA) has been proposed for the treatment of moderate PE demonstrating to be safe and more effective than standard anticoagulation. We report the case of an 83-year-old male patient affected by massive PE associated with high bleeding risk, and treated with half-dose of rTPA that resulted in rapid clinical improvement. This clinical experience led us to focus on the role of reduced doses of rTPA to decrease bleeding risk in patients with PE. We conclude that the new concept of "safe-dose thrombolysis" with rTPA may be considered a reasonable and interesting option in high-bleeding risk patients with massive PE.
Assuntos
Fibrinolíticos/administração & dosagem , Transtornos Hemorrágicos/induzido quimicamente , Embolia Pulmonar/tratamento farmacológico , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/administração & dosagem , Idoso de 80 Anos ou mais , Anemia Hipocrômica/complicações , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Bloqueio de Ramo/complicações , Complicações do Diabetes/tratamento farmacológico , Relação Dose-Resposta a Droga , Enoxaparina/administração & dosagem , Enoxaparina/efeitos adversos , Enoxaparina/uso terapêutico , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , Transtornos Hemorrágicos/etiologia , Transtornos Hemorrágicos/prevenção & controle , Heparina/administração & dosagem , Heparina/efeitos adversos , Heparina/uso terapêutico , Humanos , Hipertensão/complicações , Achados Incidentais , Infusões Intravenosas , Injeções Intravenosas , Nefropatias/complicações , Masculino , Obesidade/complicações , Guias de Prática Clínica como Assunto , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico por imagem , Radiografia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Fatores de Risco , Neoplasias Gástricas/complicações , Neoplasias Gástricas/diagnóstico por imagem , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tecidual/efeitos adversos , Ativador de Plasminogênio Tecidual/uso terapêutico , UltrassonografiaRESUMO
The new oral anticoagulants (NOACs) represent alternative antithrombotic agents for prophylaxis and therapy of thromboembolic diseases. They act either by inhibition of the clotting factor Xa or IIa (thrombin). As a consequence, they influence several coagulation assays (for example prothrombin time, activated partial thromboplastin time). Because of the short half-life of these new agents, these changes show great variations in the course of 24 hours. Furthermore, there are significant differences of laboratory results depending on the used reagents. We explain the influence of apixaban, rivaroxaban (factor Xa inhibitors) and dabigatran (thrombin inhibitor) on the most commonly used coagulation assays. Besides we show that this influence depends on the way of action of the drug as well as on the principle of the coagulation assay. Being aware of this relationships helps to interpret the results of coagulation assays under influence of NOACs correctly.
Assuntos
Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Testes de Coagulação Sanguínea , Hemostasia/efeitos dos fármacos , Tromboembolia/sangue , Tromboembolia/tratamento farmacológico , Administração Oral , Anticoagulantes/farmacocinética , Antígenos , Relação Dose-Resposta a Droga , Inibidores do Fator Xa , Transtornos Hemorrágicos/sangue , Transtornos Hemorrágicos/induzido quimicamente , Humanos , Protrombina/antagonistas & inibidores , Fatores de RiscoRESUMO
BACKGROUND AND PURPOSE: Cyclophosphamide induces urotoxicity characterized by the development of cystitis, which involves bladder overactivity and inflammation. Here, we investigated the roles of chemokine receptor 2 (CXCR2) and transient receptor potential vanilloid 1 (TRPV1) channels in a rat model of cyclophosphamide-induced cystitis. EXPERIMENTAL APPROACH: Cystitis induced by cyclophosphamide in rats was assessed by gross morphology, histology and immunohistochemistry of bladder tissue. mRNA for CXCR2 and TRPV1 channels were measured by RT-PCR. Nociceptive responses in paw and abdomen, along with cystometric measures were recorded. KEY RESULTS: Cyclophosphamide, i.p., induced pain behaviour, bladder inflammation and voiding dysfunction. The CXCR2 antagonist, SB225002, the TRPV1 channel antagonist, SB366791 or their combination reduced the mechanical hypersensitivity of paw and abdominal area and nociceptive behaviour after cyclophosphamide. Cyclophosphamide-induced cystitis was characterized by haemorrhage, oedema, neutrophil infiltration and other inflammatory changes, which were markedly decreased by the antagonists. Up-regulation of CXCR2 and TRPV1 mRNA in the bladder after cyclophosphamide was inhibited by SB225002, SB366791 or their combination. Expression of CXCR2 and TRPV1 channels was increased in the urothelium after cyclophosphamide. Bladder dysfunction was shown by increased number of non-voiding contractions (NVCs) and bladder pressures and a reduction in bladder capacity (BC), voided volume (VV) and voiding efficiency (VE). SB225002 or its combination with SB366791 reduced bladder pressures, whereas SB225002, SB366791 or their combination increased BC, VV and VE, and also reduced the number of NVCs. CONCLUSIONS AND IMPLICATIONS: CXCR2 and TRPV1 channels play important roles in cyclophosphamide-induced cystitis in rats and could provide potential therapeutic targets for cystitis.
Assuntos
Antineoplásicos Alquilantes , Comportamento Animal/efeitos dos fármacos , Ciclofosfamida , Cistite/patologia , Transtornos Hemorrágicos/patologia , Inflamação/patologia , Receptores de Interleucina-8B/metabolismo , Canais de Cátion TRPV/metabolismo , Animais , Cistite/induzido quimicamente , Cistite/tratamento farmacológico , Citocinas/metabolismo , Feminino , Transtornos Hemorrágicos/induzido quimicamente , Transtornos Hemorrágicos/tratamento farmacológico , Hiperalgesia/induzido quimicamente , Hiperalgesia/psicologia , Imuno-Histoquímica , Neutrófilos/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Medição da Dor/efeitos dos fármacos , Peroxidase/metabolismo , Ratos , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Interleucina-8B/antagonistas & inibidores , Canais de Cátion TRPV/antagonistas & inibidores , Bexiga Urinária/patologiaRESUMO
Late-onset hemorrhagic cystitis (LOHC) is a common complication following allogeneic hematopoietic stem cell transplantation (HSCT), but its cause remains obscure. More attention to risk factors for LOHC is needed. We retrospectively analyzed patients with advanced leukemia who had been treated with ATG-containing conditioning regimens to evaluate the influence of different doses of ATG on LOHC after haploidentical HSCT. Seventy-five patients undergoing haploidentical HSCT from January 2003 to February 2011 were evaluated. A total of 39 patients receiving transplantation before June 2008 were treated with high-dose ATG (10 mg/kg), whereas 36 patients received low-dose ATG (6 mg/kg) thereafter. LOHC occurred in 16.7% of the patients with low-dose ATG, and in 38.5% of the patients with high-dose ATG (P = 0.027). Univariate analysis showed high-dose ATG, male gender and cytomegalovirus reactivation to be significant risk factors for LOHC. However, only high-dose ATG (HR 2.96, 95% CI 1.143-7.663, P = 0.025) and male gender (HR 4.033, 95% CI 1.355-12.008, P = 0.012) were independent risk factors, as shown by multivariate analysis. In the setting of haploidentical HSCT, we concluded that LOHC is more prevalent in recipients of high-dose ATG and male patients. Future studies should focus on immune reconstitution and virus infection after haploidentical HSCT with 6 mg/kg or 10 mg/kg ATG.
Assuntos
Soro Antilinfocitário/efeitos adversos , Cistite/induzido quimicamente , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transtornos Hemorrágicos/induzido quimicamente , Imunossupressores/efeitos adversos , Leucemia/terapia , Condicionamento Pré-Transplante/efeitos adversos , Adolescente , Adulto , Soro Antilinfocitário/administração & dosagem , Soro Antilinfocitário/uso terapêutico , Criança , China/epidemiologia , Estudos de Coortes , Cistite/epidemiologia , Cistite/imunologia , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Transtornos Hemorrágicos/epidemiologia , Transtornos Hemorrágicos/imunologia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Incidência , Leucemia/imunologia , Leucemia/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos , Adulto JovemRESUMO
Polysulfated glycosaminoglycans (PSGAGs) have been used for decades in a variety of species for the management of osteoarthritic pain. However, reports on the use of PSGAGs in avian species are scarce. In domestic cats and dogs, PSGAG injections have caused prolongation of clotting times but are considered to be an efficacious drug with a wide margin of safety. This publication documents four cases of fatal coagulopathies in different avian species (one coraciiforme, two raptors, and one psittacine) following the intramuscular administration of PSGAG. All affected birds received varying dosages and dosing intervals of PSGAG. Three of the four birds experienced fatal hemorrhage into the pectoral muscle, while the fourth bled continuously from the injection site. Only one bird had chronic, severe pre-existing disease; the remainder were being managed for osteoarthritis. This report highlights the importance of species-specific dosing of PSGAG and warrants further investigation into the etiopathogenesis of this process.
Assuntos
Doenças das Aves/induzido quimicamente , Glicosaminoglicanos/efeitos adversos , Transtornos Hemorrágicos/veterinária , Animais , Aves , Evolução Fatal , Feminino , Glicosaminoglicanos/administração & dosagem , Transtornos Hemorrágicos/induzido quimicamente , MasculinoAssuntos
Transtornos Hemorrágicos/induzido quimicamente , Antitrombinas/efeitos adversos , Aspirina/efeitos adversos , Transtornos da Coagulação Sanguínea/induzido quimicamente , Transtornos Plaquetários/induzido quimicamente , Transtornos Hemorrágicos/diagnóstico , Transtornos Hemorrágicos/tratamento farmacológico , Humanos , Receptores Citoplasmáticos e Nucleares/efeitos dos fármacos , Trombocitopenia/induzido quimicamente , Vitamina K/metabolismoRESUMO
We report the first case of acute subdural hematoma (SDH) developing after tightening the halo of an osteoporotic 61-year-old woman on warfarin therapy for bilateral traumatic vertebral artery dissection. We discuss literature relevant to this case with an emphasis on identifying warning signs, including recurrent pin loosening, especially in patients with compromised bone structure and high risk of bleeding. Our 61-year-old patient presented to neurosurgery clinic for a 2-month follow-up of a type-III odontoid fracture sustained in a motor vehicle accident. The patient had repeatedly loosened halo pins, and shortly after the pins were tightened, the patient had a syncopal event and struck her head. An emergent computed tomography scan revealed acute SDH requiring emergent craniotomy and evacuation. SDH following pin penetration in a patient with bilateral vertebral artery dissection, osteoporosis, and anticoagulation has not been reported as a complication of the use of the halo vest for stabilization of the cervical spine. The risk of this serious complication can be minimized by giving special consideration to patients with comorbidities and by repositioning problematic pins. This case demonstrates the importance of special attention to bone strength, bleeding risk, and recurrent minor complaints with use of the halo vest.