The effect of hirudin on antagonisting thrombin induced apoptosis of human microvascular endothelial cells

Abstract Purpose: To investigate whether hirudin exerts its antithrombin action to decrease the ratio of Human Microvascular Endothelial Cells (HMVECs) apoptosis. Methods: Human microvascular endothelial cells (HMVECs) cultured in the third and fifth generations were used. HMVECs were divided into normal group, thrombin group (T group), natrual hirudin group (H group), thrombin + natrual hirudin group (T + H group), AG490 group, thrombin + AG490 group (T + AG490 group), natrual hirudin + AG490 group (H + AG490 group), thrombin + natural hirudin + AG490 (T + H + AG490 group).Apart from the normal group, the other groups were exposed to the relevant drugs for 24 hours.HMVEC apoptosis was assessed by flow cytometric and double Immunofluorescence of phosphorylation of JAK (P-JAK2) and TUNEL assay. Results: Compared with the normal group, in thrombin group the HMVECs apoptosis rate were significantly increased (P<0.05).The results indicated that the index of apoptosis and the apoptosis rate were improved in cultures treated by natural hirudin (T + H group), relative to cultures with thrombin only (T group). We found that the index of apoptosis and the apoptosis rate in the AG490 + thrombin group were higher than that in the hirudin + thrombin group (P<0.05). Double Immunofluorescence of p-JAK2 and TUNEL assays showed that cells were double positive for P-JAK2 uptake and TUNEL detection liquid binding. Conclusion: The natural hirudin and JAK2/STATs signal inhibitor AG490 could block the effects of thrombin. Natural hirudin could attenuate HMVECs apoptosis via antagonizing thrombin and it is suggested that this effect may occur by blocking the JAK2/STATs signaling pathway and this signaling pathways appears to be not the only pathway.

Factibilidad del uso de bivalirudina como anticoagulante en soporte vital extracorpóreo / Experience with anticoagulation with bivalirudin during extracorporeal membrane oxygenation

Background: Extracorporeal membrane oxygenation (ECMO) is used with increasing frequency in patients with respiratory and cardiac failure. The achievement of an adequate anticoagulation is critical to avoid patient and circuit complications. Aim: To assess the feasibility and safety of anticoagulation with bivalirudin, as an alternative to unfractionated heparin (UFH), in patient with ECMO. Material and Methods: Observational study, which included all patients receiving anticoagulation with bivalirudin during ECMO, according to a standardized protocol, between august 2015 to May 2016. Results: Bivalirudin was used in 13 out 70 patients connected to ECMO. Ten procedures were for cardiac support and three for respiratory support. Mortality was 43%. ECMO lasted 31 ± 31 days. The time of UFH use before changing to bivalirudin was 7 ± 7 days. The reasons to change to bivalirudin were inadequate levels of partial thromboplastin time (PTT) in nine patients, and heparin induced thrombocytopenia (HIT) in four patients. The time of bivalirudin use was 24 ± 33 days. Per patient, a mean of 2.7 ± 4 oxygenators were changed. These had a useful life of 11.4 and 19.1 days during UFH and bivalirudin use, respectively. The mean bivalirudin dose was 0.08 ± 0.04 mg/kg/h. There was no significant bleeding, thrombosis or circuit obstruction during its use. PTT levels (p < 0.01) and platelet count (p < 0.01) increased significantly after the start of bivalirudin use in patients with UHF resistance and HIT, respectively. Conclusions: Bivalirudin was a safe and efficient drug for anticoagulation during ECMO. It is important to have an alternative drug for anticoagulation in ECMO patients.

Terapia adjunta após intervenções coronárias / Adjuntive therapeutics following percutaneous coronary interventions

Atualmente, a terapia farmacológica adjunta é essencial para a obtenção de bons resultados com o tratamento percutâneo. Destacam-se os agentes antiagregantes plaquetários, que reduziram a taxa de trombose subaguda dos stents coronários para valores inferiores a 1 por cento. Nas síndromes coronárias agudas, os inibidores da glicoproteína Ilb/llla proporcionaram evolução mais favorável, principalmente para os pacientes de médio e alto riscos. O adequado manuseio clínico e os grandes avanços na terapêutica contra a reestenose coronária, demonstrados em recentes estudos com os stents recober- tos, proporcionarão evolução clínica altamente favorável para a maioria dos pacientes portadores de doença obstrutiva arterial coronária...

Aplicaçöes clínicas dos novos antitrombóticos / Clinical use of new antithrombotics

Os autores discutem os novos antitrombóticos descrevendo suas vantagens e desvantagens, ainda com muitas dúvidas quanto ao seu uso e segurança nas síndromes isquêmicas coronarianas, além de outras condiçöes.

La trombina: ¿Un nuevo factor útil en el diagnóstico temprano de metástasis pulmonar? / The trombin: Anew useful factor in the early diagnosis of pulmonary metastasis?

Los eventos celulares tempranos que inducen una metástasis pulmonar son desconocidos. La trombina, componente clave de las cascada de la coagulación, podría estar involucrada en el desarrollo de este padecimiento, ya que incrementa la adhesión plaquetas-células tumorales in vitro y el número de metástasis in vivo. Para evaluar si la trombina podría ser considerada como un marcador en su diagnóstico, mediamos los niveles de trombina en elevados broncoalveolares (LBA) de 20 pacientes con dicho padecimiento y los comparamos frente a los de 20 pacientes con cáncer de pulmón y 20 controles. La mediana de la concentración de trombina en los lavados de los pacientes con metástasis fue 5.4 x 10-9 M (2.5 x 10-9 M - 13 x 10-9 M). Esto presentó un incremento de 10 y 100 vece en los niveles de trombina, en comparación con los encontrados en los lavados de pacientes con cáncer de pulmón (0.6 x 10-9 M; 0.2 x 10-9 M-2.2 x 10-9 M) y los controles (0.06 x 10-9 M; 0.02 x 10-9 M - 0.4 x 10-9 M), respectivamente (p < 0.02). Lavados de pacientes con metástasis y cáncer de pulmón incrementaron la proliferación celular en un 34.9 por ciento (1.5 - 58.3 por ciento) (p< 0.02). La hurudina, un inhibidor de la trombina, disminuyó únicamente la proliferación inducida por los lavados brincoalveolares de pacientes con metástasis en un 63.8 por ciento (p < 0.05). Estos resultados demuestran que la trombina está presente en forma selectiva en los pulmones de pacientes con metástasis pulmonar, y que podría estar involucrada en el desarrollo de este padecimiento

Fibrilación auricular no reumática y stroke: su terapéutica actual / Atrial fibrillation nonrheumatic and stroke: current therapeutics

La fibrilación auricular no reumática afecta al 1,7 por ciento de las personas entre 60 y 64 años y al 11,6 por ciento de los mayores de 75 años. El riesgo de ictus aumenta con la edad, la fibrilación auricular es la causa más frecuente de embolismo cerebral. Los objetivos terapéuticos incluyen: alivio sintomático, mejoría de los índices hemodinámicos, prevención de la disfunción ventricular progresiva y prevención de embolias. El análisis combinado de 5 ensayos pone de manifiesto que, en pacientes con fibrilación auricular no reumática la warfarina redujo la incidencia de ictus isquémicos o embolias del 4,5 por ciento al 1,4 por ciento anual (reducción de riesgo del 69 por ciento ó 31 episodios por 1000 pacientes tratados). El consenso actual luego de los resultados del SPAF III, es que la utilización de dosis habituales de warfarina demostró ser más eficaz que las bajas dosis de warfarina más aspirina. Como conclusión final y teniendo en cuenta la gran incidencia de stroke asociado a la fibrilación auricular, es recomendable anticoagular a todos los pacientes con fibrilación auricular no reumática, y factores de riesgo excepto que presenten contraindicaciones que no permitan su segura utilización.