Asunto(s)
Anticoagulantes/agonistas , Warfarina/administración & dosificación , Hidrocarburo de Aril Hidroxilasas/genética , Fibrilación Atrial/sangre , Fibrilación Atrial/tratamiento farmacológico , Ensayos Clínicos como Asunto , Citocromo P-450 CYP2C9 , Monitoreo de Drogas , Genotipo , Humanos , Relación Normalizada Internacional , Tromboembolia Venosa/sangre , Tromboembolia Venosa/tratamiento farmacológico , Vitamina K Epóxido Reductasas/genéticaRESUMEN
BACKGROUND AND PURPOSE: Warfarin use has rapidly increased with the aging of the population. We investigated the temporal trends in the incidence and outcome of warfarin-related intracerebral hemorrhages (ICHs) in a defined population. METHODS: We identified all subjects with first-ever primary ICH during 1993 to 2008 among the population of Northern Ostrobothnia, Finland. The number of warfarin users was obtained from the national register of prescribed medicines kept by the Social Insurance Institution of Finland. We calculated the annual incidence of warfarin-related ICHs, 28-day case fatality, and deaths from the primary bleed. RESULTS: The proportion of warfarin users among the population increased 3.6-fold from 0.68% in 1993 to 2.28% in 2008. Of a total of 982 patients with ICH, 182 (18.5%) had warfarin-related ICH. One-year survival rate after onset of stroke was 35.2% among warfarin users and 67.9% among nonusers. The annual incidence (P=0.062) and 28-day case fatality of warfarin-related ICHs (P=0.002) decreased during the observation period. Warfarin users were older (mean difference 6.6; 95% CI, 5.0 to 8.1; P<0.001) than nonusers. Admission international normalized ratio values above the therapeutic range (2.0 to 3.0) decreased through the observation period, suggesting improved control of anticoagulant therapy over time. CONCLUSIONS: The annual incidence and case fatality of warfarin-related ICHs decreased, although the proportion of warfarin users almost quadrupled in our population.
Asunto(s)
Anticoagulantes/agonistas , Hemorragia Cerebral/inducido químicamente , Hemorragia Cerebral/mortalidad , Warfarina/efectos adversos , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Femenino , Finlandia/epidemiología , Humanos , Incidencia , Relación Normalizada Internacional/efectos adversos , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Warfarina/administración & dosificaciónRESUMEN
The recent health care changes and approval of a generic low-molecular-weight heparin (LMWH) by the US Food and Drug Administration (FDA) merit a review of the facts regarding the new and generic anticoagulants. Fatal hypotension from anaphylactoid type reactions following heparin administration was responsible for more than 149 deaths all over the world. Researchers detected a heparin-like semisynthetic contaminant, over-sulfated chondroitin sulfate (OSCS), that appeared to be intentional. Low-molecular-weight heparins are produced using unfractionated heparin and OSCS has been found in various batches of LMWHs. Some newer anticoagulants are claiming to be free from the need to monitor for therapeutic effect and bleeding risk. Therefore, monitoring assays are not being developed and there is no antidote to reverse bleeding. In addition, there are concerns about reproducibility, product variation, and quality. In conclusion, although the generic LMWHs and newer anticoagulants may appear to be effective for qualified indications, their safety remains to be a concern.
Asunto(s)
Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Contaminación de Medicamentos , Medicamentos Genéricos/efectos adversos , Medicamentos Genéricos/uso terapéutico , Heparina de Bajo-Peso-Molecular/efectos adversos , Heparina de Bajo-Peso-Molecular/uso terapéutico , Anafilaxia/inducido químicamente , Anafilaxia/mortalidad , Animales , Anticoagulantes/agonistas , Sulfatos de Condroitina/efectos adversos , Sulfatos de Condroitina/análisis , Sulfatos de Condroitina/farmacología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Medicamentos Genéricos/análisis , Hemorragia/tratamiento farmacológico , Heparina de Bajo-Peso-Molecular/análisis , Humanos , Hipotensión/inducido químicamente , Hipotensión/mortalidad , Monitoreo Fisiológico/métodos , Estados Unidos , United States Food and Drug AdministrationRESUMEN
TLR2 activation induces cellular and organ inflammation and affects lung function. Because deranged endothelial function and coagulation pathways contribute to sepsis-induced organ failure, we studied the effects of bacterial lipoprotein TLR2 agonists, including peptidoglycan-associated lipoprotein, Pam3Cys, and murein lipoprotein, on endothelial function and coagulation pathways in vitro and in vivo. TLR2 agonist treatment induced diverse human endothelial cells to produce IL-6 and IL-8 and to express E-selectin on their surface, including HUVEC, human lung microvascular endothelial cells, and human coronary artery endothelial cells. Treatment of HUVEC with TLR2 agonists caused increased monolayer permeability and had multiple coagulation effects, including increased production of plasminogen activator inhibitor-1 (PAI-1) and tissue factor, as well as decreased production of tissue plasminogen activator and tissue factor pathway inhibitor. TLR2 agonist treatment also increased HUVEC expression of TLR2 itself. Peptidoglycan-associated lipoprotein induced IL-6 production by endothelial cells from wild-type mice but not from TLR2 knockout mice, indicating TLR2 specificity. Mice were challenged with TLR2 agonists, and lungs and plasmas were assessed for markers of leukocyte trafficking and coagulopathy. Wild-type mice, but not TLR2 mice, that were challenged i.v. with TLR2 agonists had increased lung levels of myeloperoxidase and mRNAs for E-selectin, P-selectin, and MCP-1, and they had increased plasma PAI-1 and E-selectin levels. Intratracheally administered TLR2 agonist caused increased lung fibrin levels. These studies show that TLR2 activation by bacterial lipoproteins broadly affects endothelial function and coagulation pathways, suggesting that TLR2 activation contributes in multiple ways to endothelial activation, coagulopathy, and vascular leakage in sepsis.
Asunto(s)
Anticoagulantes/fisiología , Coagulación Sanguínea/inmunología , Endotelio Vascular/fisiología , Proteínas de Escherichia coli/fisiología , Lipoproteínas/fisiología , Peptidoglicano/farmacología , Transducción de Señal/inmunología , Receptor Toll-Like 2/agonistas , Animales , Anticoagulantes/agonistas , Anticoagulantes/farmacología , Permeabilidad Capilar/inmunología , Línea Celular , Endotelio Vascular/citología , Endotelio Vascular/inmunología , Proteínas de Escherichia coli/agonistas , Humanos , Inmunofenotipificación , Lipoproteínas/agonistas , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptor Toll-Like 2/deficiencia , Receptor Toll-Like 2/fisiología , Regulación hacia Arriba/inmunologíaAsunto(s)
Bebidas/efectos adversos , Citrus paradisi/efectos adversos , Interacciones Alimento-Droga , Anticoagulantes/agonistas , Benzodiazepinas/agonistas , Bloqueadores de los Canales de Calcio/sangre , Citocromo P-450 CYP3A , Inhibidores Enzimáticos del Citocromo P-450 , Humanos , Warfarina/agonistasRESUMEN
The pathophysiology of acute renal failure in sepsis is complex and includes intrarenal vasoconstriction, infiltration of inflammatory cells in the renal parenchyma, intraglomerular thrombosis, and obstruction of tubuli with necrotic cells and debris. Attempts to interfere pharmacologically with these dysfunctional pathways, including inhibition of inflammatory mediators, improvement of renal hemodynamics by amplifying vasodilator mechanisms and blocking vasoconstrictor mechanisms, and administration of growth factors to accelerate renal recovery, have yielded disappointing results in clinical trials. Interruption of leukocyte recruitment is a potential promising approach in the treatment of septic acute renal failure, but no data in humans are presently available. Activated protein C and steroid replacement therapy have been shown to reduce mortality in patients with sepsis and are now accepted adjunctive treatment options for sepsis in general.
Asunto(s)
Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/etiología , Sepsis/complicaciones , Anticoagulantes/agonistas , Anticoagulantes/uso terapéutico , Antineoplásicos/antagonistas & inhibidores , Antitrombinas/uso terapéutico , Endotelinas/antagonistas & inhibidores , Sustancias de Crecimiento/uso terapéutico , Humanos , Interleucina-8/uso terapéutico , Lipoproteínas/uso terapéutico , Péptidos Natriuréticos/uso terapéutico , Óxido Nítrico Sintasa/antagonistas & inhibidores , Factor de Activación Plaquetaria/antagonistas & inhibidores , Proteína C/uso terapéutico , Esteroides/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
Despite approximately 40 years of experience with oral anticoagulant drugs, controversy still exists about the safety of dental treatment in a patient receiving this therapy. The authors review the topic in depth and offer detailed recommendations for the dental management of patients receiving coumarin anticoagulant therapy.
Asunto(s)
Anticoagulantes , Cumarinas , Atención Dental para Enfermos Crónicos/métodos , Anticoagulantes/administración & dosificación , Anticoagulantes/agonistas , Anticoagulantes/antagonistas & inhibidores , Anticoagulantes/química , Protocolos Clínicos , Cumarinas/administración & dosificación , Cumarinas/agonistas , Cumarinas/antagonistas & inhibidores , Cumarinas/química , Interacciones Farmacológicas , Monitoreo de Drogas/normas , Hemorragia Bucal/prevención & control , Hemorragia Posoperatoria/prevención & control , Tiempo de Protrombina , Estándares de ReferenciaRESUMEN
Cultured peritoneal macrophages (M phi) of GK rats, a non insulin-dependent diabetes mellitus model established from normal Wistar rats, increased the tube formation of aortic endothelial cells (EC). A polyclonal anti-platelet-derived growth factor (PDGF)-BB (0.21-3.3 micrograms/ml) inhibited (by 66.5 +/- 6.6%) the tube-forming activity of conditioned medium (CM) from M phi in diabetic GK rats, but not that in age-matched normal Wistar rats. A polyclonal anti-interleukin (IL)-1 alpha (0.16-0.33%) also inhibited (by 37.7 +/- 5.8%) the activity of diabetic M phi-CM, and its inhibitory effect was smaller than that of anti-PDGF-BB. A monoclonal anti-basic fibroblast growth factor (bFGF) (0.6-60 ng/ml) inhibited the activities of CM from both M phi, respectively. The tube-forming activity of the normal M phi-CM was increased by the serum isolated from the diabetic GK rat more than by that from the age-matched normal Wistar rat. The activity of normal M phi-CM was also increased by 16.7-50 mM glucose-exposed serum. These tube-forming activities of the CM of M phi stimulated by diabetic serum and by the high concentration of glucose-treated serum were completely inhibited by anti-PDGF-BB. In conclusion, PDGF-BB was selectively released from the diabetic state-modified M phi in the GK rat to increase tube formation, suggesting a key role in the cause of angiogenesis. The diabetic state-induced activation may depend on advanced glycosylation endproducts produced in the serum in the diabetic rat.
Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Endotelio Vascular/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Neovascularización Patológica/etiología , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Factor de Crecimiento Derivado de Plaquetas/fisiología , Animales , Anticoagulantes/agonistas , Aorta Torácica/patología , Becaplermina , Células Cultivadas , Medios de Cultivo Condicionados , Glucosa/farmacología , Masculino , Ratones , Proteínas Proto-Oncogénicas c-sis , Ratas , Ratas WistarRESUMEN
We have produced recombinant human Protein C (rHPC) in the milk of transgenic swine. After purification, we have analyzed the interaction of teh zymogen with Protac, thrombin/thrombomodulin and thrombin alone. The amidolytic and anticoagulant activities of rAPC after Protac activation were approximately 80% those of its human plasma counterpart. Upon the excision of the activation peptide by thrombin/thrombomodulin complex, both the natural and recombinant activation products had similar enzymatic and biological activities. This observation can be attributed to the difference in the mechanism of action between the two activators and structural differences between HPC and rHPC.
Asunto(s)
Anticoagulantes/metabolismo , Proteína C/metabolismo , Animales , Animales Modificados Genéticamente , Anticoagulantes/agonistas , Anticoagulantes/farmacología , Humanos , Péptidos y Proteínas de Señalización Intercelular , Péptidos/farmacología , Proteína C/agonistas , Proteína C/farmacología , Proteínas Recombinantes/agonistas , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacología , Porcinos , Trombina/química , Trombomodulina/químicaRESUMEN
The activated protein C (APC)-resistance test is a simple and reliable method for detecting reduced sensitivity to the anticoagulant action of this protein. We investigated the sensitivity to APC in 180 Japanese controls and in 96 Japanese patients with venous and arterial thrombosis (28 with deep vein thrombosis; 13 with pulmonary thromboembolism; 41 with cerebral infarction; and 14 with coronary artery disease). All of the patient groups showed significantly reduced sensitivity to APC, reflected by the lower normalized APC-sensitivity ratio (n-APC-SR), as compared with healthy control. The APC-sensitivity ratio was negatively correlated with plasma activated factor VII levels. These results suggest that the low n-APC-SR is related to venous or arterial thrombotic disease. The APC resistance may serve as a potential marker for assessing the hypercoagulable state.
Asunto(s)
Anticoagulantes/farmacología , Trastornos de la Coagulación Sanguínea/diagnóstico , Proteína C/farmacología , Tromboflebitis/sangre , Trombosis/sangre , Adulto , Anciano , Anticoagulantes/agonistas , Biomarcadores/sangre , Trastornos de la Coagulación Sanguínea/sangre , Estudios de Casos y Controles , Resistencia a Medicamentos/genética , Factor VIIa/metabolismo , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Mutación , Valor Predictivo de las Pruebas , Proteína C/agonistas , Reproducibilidad de los Resultados , Factores de RiesgoRESUMEN
Treatment plans for patients taking anticoagulants can become complicated. Anticoagulants predispose a patient to bleeding problems. Many drugs used in dentistry cannot be taken concomitantly with these medications.