Thromboembolic and hemorrhagic complications in patients with prosthetic heart valves cared for in a tertiary care center. What have we learned?

BACKGROUND: Heart valve replacement surgery with mechanical or biological prostheses entails a risk of thromboembolism and bleeding complications. OBJECTIVE: To determine the complications related to complementary anticoagulation therapy and the probability of risk. METHODS: One-hundred and sixty-three patients who underwent heart valve replacement between 2002 and 2016 with either mechanical or biological prostheses, and who received vitamin K antagonists after hospital discharge, were studied. Anticoagulation therapy was categorized into optimal and non-optimal according to INR values prior to the development of complications. Patients with comorbidities and other risk factors for thrombosis and/or bleeding were excluded. RESULTS: In total, 68.7 % of patients received mechanical prostheses, and 31.3 %, biological prostheses (p ≤ 0.001); 25.2 % experienced the complications that motivated the study (p ≤ 0.001), which were hemorrhagic in 48.8 %, thromboembolic in 26.8 %, and of both types in 24.4 % (relative risk = 4.229). Among the patients with complications, 95.1 % received mechanical prostheses, and 4.9 %, biological (p = 0.005); non-optimal INR was identified in 49.7 % (p ≤ 0.001). CONCLUSIONS: Given the high risk of thromboembolic and hemorrhagic complications, valve prostheses must be carefully chosen, and care priorities should include prevention and follow-up, especially in those patients who require anticoagulation therapy.

ANTECEDENTES: El reemplazo valvular por prótesis mecánicas o biológicas implica riesgo de tromboembolismo y complicaciones hemorrágicas. OBJETIVO: Determinar las complicaciones relacionadas con la terapia de anticoagulación complementaria y la probabilidad de riesgo en pacientes portadores de prótesis valvulares del corazón. MÉTODOS: Se estudiaron 163 pacientes entre 2002 y 2016, portadores de prótesis mecánicas y biológicas, quienes recibieron antagonistas de la vitamina K posterior al egreso hospitalario. La terapia de anticoagulación se categorizó en óptima y no óptima conforme a los valores de INR previos a las complicaciones. Fueron excluidos los pacientes con comorbilidades y otros factores de riesgo de trombosis y/o sangrado. RESULTADOS: a 68.7 % de los pacientes se les colocó prótesis mecánica y a 31.3 %, biológica (p ≤ 0.001); 25.2 % presentó las complicaciones motivo de estudio (p ≤ 0.001), hemorrágicas en 48.8 %, tromboembólicas en 26.8 % y de ambos tipos en 24.4 % (riesgo relativo = 4.229); a 95.1 % de los pacientes con complicaciones se les colocó prótesis mecánica y a 4.9 %, biológica (p = 0.005); 49.7 % presentó INR no óptimo (p ≤ 0.001). CONCLUSIONES: Ante riesgo alto de complicaciones tromboembólicas y hemorrágicas, la elección de las prótesis valvulares, la prevención y el seguimiento son prioridades, principalmente en quienes requieren terapia de anticoagulación.

Complicaciones tromboembólicas y hemorrágicas en pacientes portadores de prótesis valvulares del corazón en un centro de tercer nivel. ¿Qué hemos aprendido? / Thromboembolic and hemorrhagic complications in patients with prosthetic heart valves at third level care center. What have we learned?

Resumen Antecedentes: El reemplazo valvular por prótesis mecánicas o biológicas implica riesgo de tromboembolismo y complicaciones hemorrágicas. Objetivo: Determinar las complicaciones relacionadas con la terapia de anticoagulación complementaria y la probabilidad de riesgo en pacientes portadores de prótesis valvulares del corazón. Métodos: Se estudiaron 163 pacientes entre 2002 y 2016, portadores de prótesis mecánicas y biológicas, quienes recibieron antagonistas de la vitamina K posterior al egreso hospitalario. La terapia de anticoagulación se categorizó en óptima y no óptima conforme a los valores de INR previos a las complicaciones. Fueron excluidos los pacientes con comorbilidades y otros factores de riesgo de trombosis y/o sangrado. Resultados: a 68.7 % de los pacientes se les colocó prótesis mecánica y a 31.3 %, biológica (p ≤ 0.001); 25.2 % presentó las complicaciones motivo de estudio (p ≤ 0.001), hemorrágicas en 48.8 %, tromboembólicas en 26.8 % y de ambos tipos en 24.4 % (riesgo relativo = 4.229); a 95.1 % de los pacientes con complicaciones se les colocó prótesis mecánica y a 4.9 %, biológica (p = 0.005); 49.7 % presentó INR no óptimo (p ≤ 0.001). Conclusiones: Ante riesgo alto de complicaciones tromboembólicas y hemorrágicas, la elección de las prótesis valvulares, la prevención y el seguimiento son prioridades, principalmente en quienes requieren terapia de anticoagulación.

Abstract Background: Heart valve replacement surgery with mechanical or biological prostheses entails a risk of thromboembolism and bleeding complications. Objective: To determine the complications related to complementary anticoagulation therapy and the probability of risk. Methods: One-hundred and sixty-three patients who underwent heart valve replacement between 2002 and 2016 with either mechanical or biological prostheses, and who received vitamin K antagonists after hospital discharge, were studied. Anticoagulation therapy was categorized into optimal and non-optimal according to INR values prior to the development of complications. Patients with comorbidities and other risk factors for thrombosis and/or bleeding were excluded. Results: In total, 68.7 % of patients received mechanical prostheses, and 31.3 %, biological prostheses (p ≤ 0.001); 25.2 % experienced the complications that motivated the study (p ≤ 0.001), which were hemorrhagic in 48.8 %, thromboembolic in 26.8 %, and of both types in 24.4 % (relative risk = 4.229). Among the patients with complications, 95.1 % received mechanical prostheses, and 4.9 %, biological (p = 0.005); non-optimal INR was identified in 49.7 % (p ≤ 0.001). Conclusions: Given the high risk of thromboembolic and hemorrhagic complications, valve prostheses must be carefully chosen, and care priorities should include prevention and follow-up, especially in those patients who require anticoagulation therapy.

Antiproliferative activity of standardized herbal phytopreparation from Asclepias subulata.

Background: Several studies have shown that active compounds of Asclepias subulata (cardenolides) have antiproliferative effect on human cancer cells. Cardenolides isolated from A. subulata can be used as active chemical markers to elaborate phytopharmaceutical preparations. To evaluate the antiproliferative effect of a standardized extract of the aerial parts, based on Asclepias subulata cardenolides. Methods: Four standardized extracts were prepared by HPLC-DAD depending on the concentration of calotropin and the antiproliferative activity was measured for the MTT assay, on the A549, MCF-7, HeLa, PC3 and ARPE cell lines. The concentrations of calotropin used for the standardization of the extracts were 10, 7.6, 5 and 1 mg/dL. Results: Standardization of the A. subulata extract based on calotropin at 7.6 mg/g dry weight was achieved and the antiproliferative activity was evaluated over A549, HeLa and MCF-7 cell lines, obtaining proliferation percentages of 3.8 to 13.4% . Conclusions: The standardized extracts of A. subulata at different concentrations of calotropin showed antiproliferative activity against all the cell lines evaluated. The greatest effect was observed against the HeLa cell line.

Antiproliferative and Apoptotic Activities of the Medicinal Plant Ziziphus obtusifolia.

BACKGROUND: Ziziphus obtusifolia is a spiny shrub found in Northwest Mexico desert, with traditional medicinal use to treat several diseases including cancer. OBJECTIVE: The aims of the present study were to evaluate the antiproliferative and apoptotic activities of the aerial parts of this plant. MATERIALS AND METHODS: The methanol extract and its fractions were prepared using several solvents. The antiproliferative activity was evaluated by the (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium) (MTT) assay on HeLa, A549, RAW 264.7, M12.C3.F6, and L-929 cell lines, and the apoptotic activity using Annexin V and (5,50,6,60-tetra-chloro-1,10,3,30-tetra-ethylbenzimidazol-carbocyanine iodide) staining. The most active fraction was further separated by column chromatography. RESULTS: The most active fraction was hexane with an IC50 of 90.4 µg/mL against RAW 264.7, 94 µg/mL against M12.C3.F6, 165.5 µg/mL against HeLa and 187.7 µg/mL against A549 cell lines. In apoptotic activity assays the methanol extract and its n-hexane fraction were found to induce mitochondrial depolarization in HeLa cells (83 and 87% respectively), and both induced the externalization of the phosphatidylserine increasing the percentage of cells in early apoptosis from 1.4% in untreated control cells, to 1.9% and 3.5% for methanol extract and n-hexane fraction-treated cells, respectively, statistically different for the total percentage of apoptotic cells (P < 0.05). CONCLUSIONS: These results show that Z. obtusifolia has antiproliferative and apoptotic activities in vitro and confirms its use in traditional medicine. SUMMARY: The methanol extract and its fractions using several solvents were evaluated in the antiproliferative activity by the MTT assay on HeLa, A549, RAW 264.7, M12.C3.F6, and L-929 cell lines, and the apoptotic activity using Annexin V and (5,50,6,60-tetra-chloro-1,10,3,30-tetra-ethylbenzimidazol-carbocyanine iodide) staining. The most active fraction against cell lines was hexane. In apoptotic activity assays, the methanol extract and its n-hexane fraction were found to induce mitochondrial depolarization. This results we showed that Ziziphus obtusifolia has antiproliferative and apoptotic activities in vitro.Abbreviations Used: DMEM: Dulbecco's modified eagle's medium, DMSO: Dimethyl sulfoxide, MTT: (3-4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium), JC-1: (5,50,6,60-tetra-chloro-1,10,3,30-tetra-ethylbenzimidazol-carbocyanine iodide), FBS: Fetal bovine serum, CAPE: Caffeic acid phenethyl ester, PBS: Phosphate-buffered saline.