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Os anticoagulantes e antiagregantes plaquetários são medicamentos utilizados por uma grande parcela da população mundial. Eles são utilizados para prevenir que pacientes de risco desenvolvam doenças cardiovasculares, como o infarto agudo do miocárdio (IAM) ou o acidente vascular cerebral (AVC). Por serem muito utilizados, constantemente o cirurgião-dentista poderá se deparar em sua rotina clínica, com pacientes usuários de anticoagulantes ou antiagregantes. Neste caso, o profissional precisará estar ciente das normas mais atuais de manejo com cada um dos tipos de medicamentos, para que o tratamento seja realizado com sucesso. No presente trabalho, é proposto um Protocolo Operacional Padrão (POP), que pode ser seguido no momento de realizar cirurgias orais em pacientes em uso de Varfarina, Ácido Acetil Salicílico, Heparina de Baixo Peso Molecular, Heparina Não Fracionada, Rivaroxabana e Clopidogrel.
Anticoagulants and antiplatelet agents are drugs used by a large portion of the world population. They are used to prevent at-risk patients from developing cardiovascular diseases, such as acute myocardial infarction (AMI) or stroke (stroke). Because they are widely used, the dental surgeon may constantly encounter patients using anticoagulants or anti-aggregating agents in their clinical routine. In this case, the professional will need to be aware of the most current management standards with each type of medication, so that the treatment is carried out successfully. In the present work, a Standard Operational Protocol (POP) is proposed, which can be followed when performing oral surgeries on patients using Warfarin, Acetyl Salicylic Acid, Low Molecular Weight Heparin, Unfractionated Heparin, Rivaroxaban and Clopidogrel.
Subject(s)
Platelet Aggregation Inhibitors , Clinical Protocols , Dentists , Anticoagulants , Surgery, OralABSTRACT
Objective:To evaluate the safety and efficacy of argatroban applied as alternative anticoagulant in critical illness patients underwent extracorporeal membrane oxygenation (ECMO) with contraindications of unfractionated heparin (UFH), and to further explore the effective dose of argatroban.Methods:From July 1, 2013 to February 28, 2022, there were 14 patients who admitted in the respiratory intensive care unit (RICU) of Beijing Chao-Yang Hospital received ECMO and used argatroban for anticoagulation (argatroban group). Two of them received argatroban as the initial anticoagulant. The remaining 12 patients used UFH at first, and then switched to argatroban. UFH group included 28 patients who received UFH for anticoagulation after matching the demographic characteristics. Primary endpoint was the prevalence of ECMO-related thrombotic events. Secondary endpoints included the type of thrombotic events, prevalence of ECMO-related major bleeding events, bleeding sites, ICU mortality, mortality during ECMO, liver and kidney function, thrombelastogram, blood transfusion, dosage of argatroban, the dynamic changes of coagulation variables 4 days before and 7 days after argatroban treatment.Results:In argatroban group, there were 8 patients received veno-venous ECMO (VV-ECMO), 2 patients with veno-arterial ECMO (VA-ECMO), and 4 patients with veno-arterio-venous ECMO (VAV-ECMO). In UFH group, VV-ECMO was applied in 23 patients, VA-ECMO and VAV ECMO was established in 3 patients and 2 patients, respectively. In endpoint events, the incidence of ECMO related thrombotic events in argatroban group was slightly higher than that in UFH group (28.6% vs. 21.4%). The ECMO running time in argatroban group was slightly longer than that in UFH group [days: 16 (7, 21) vs. 13 (8, 17)]. The incidence of ECMO-related bleeding events (28.6% vs. 32.1%) and mortality during ECMO (35.7% vs. 46.4%) in argatroban group were slightly lower than those in UFH group. However, the differences were not statistically significant (all P < 0.05). The platelet transfusion in argatroban group was significantly higher than that in UFH group [U: 7.7 (0, 10.0) vs. 0.8 (0, 1.0)]. The coagulation reaction time (R value) in thrombelastography in argatroban group was significantly longer than that in UFH group [minutes: 9.3 (7.2, 10.8) vs. 8.8 (6.3, 9.7)]. The maximum width value [MA value, mm: 48.4 (40.7, 57.9) vs. 52.6 (45.4, 61.5)] and blood clot generation rate [α-Angle (deg): 54.1 (45.4, 62.0) vs. 57.9 (50.2, 69.0)] in the argatroban group were significantly lower than those in the UFH group (all P < 0.05). The activated partial thromboplastin time (APTT) was prolonged after changing from UFH to argatroban in the argatroban group [seconds: 63.5 (58.4, 70.6) vs. 56.7 (53.1, 60.9)]. The PLT level showed a decreasing trend during UFH anticoagulation therapy, and gradually increased after changing to argatroban. D-dimer level was 19.1 (7.0, 28.7) mg/L after switching to argatroban, and then no longer showed an increasing trend. The level of fibrinogen (FIB) showed a decreasing trend during the anticoagulant therapy of UFH (the lowest was 23.6 g/L), and fluctuated between 16.8 and 26.2 g/L after changing to argatroban. The median initial dose of argatroban was 0.049 (0.029, 0.103) μg·kg -1·min -1, which the highest dose was in VV-ECMO patients of [0.092 (0.049, 0.165) μg·kg -1·min -1]. The initial dose of VAV-ECMO was the lowest [0.026 (0.013, 0.041) μg·kg -1·min -1], but without significant difference ( P > 0.05). The maintenance dose of argatroban was 0.033 (0.014, 0.090) μg·kg -1·min -1, VV-ECMO patients was significantly higher than those in VA-ECMO and VAV-ECMO patients [μg·kg -1·min -1: 0.102 (0.059, 0.127) vs. 0.036 (0.026, 0.060), 0.013 (0.004, 0.022), both P < 0.05]. Conclusion:Argatroban appears to be a feasible, effective and safety alternative anticoagulant for patients with contraindications to UFH who undergoing ECMO support.
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RESUMEN Objetivo Identificar el fenómeno procoagulante en pacientes SARS-CoV- 2 y proponer orientación terapéutica sostenible para países de bajos ingresos. Método Se realizó una revisión sistemática que identificó cinco estudios observacionales de un escrutinio a partir de 78 resultados. Se examinaron 712 pacientes y los resultados fueron agrupados según mortalidad y severidad. La comparación de los grupos se interpretó mediante estadística descriptiva. Resultado Los valores del dímero D se asociaron significativamente en todas las observaciones a mayor severidad y mortalidad. La protrombina se asoció, en algunas observaciones, a mayor mortalidad; en cuanto a severidad, los resultados fueron inconclusos. Conclusión El COVID-19 tiene importante actividad procoagulante y su tratamiento oportuno puede alterar el pronóstico. La evidencia explorada avala métodos sostenibles. Se necesita más evidencia para mejorar el manejo. Se recomienda un abordaje sistemático temprano de los pacientes con medidas terapéuticas sostenibles a la medida del sistema de salud.
ABSTRACT Objective To identify the procoagulant phenomenon in SARS-CoV-2 patients and propose sustainable therapeutic guidance for low-income countries. Methods A systematic review was conducted. It identified 5 observational studies from a scrutiny from 78 results. 712 patients were examined and the results were grouped according to mortality and severity. The comparison of the groups was interpreted using descriptive statistics. Results D-dimer values were significantly associated with greater severity and mortality. Prothrombin was associated in some observations with higher mortality, but in terms of severity it was inconclusive. Conclusion COVID-19 disease has significant procoagulant activity and its timely treatment can alter the prognosis. The explored evidence supports sustainable methods. More evidence is needed to improve management. An early systematic approach to patients with sustainable therapeutic measures tailored to the health system is recommended.
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Back Ground: Heparin induced thrombocytopenia (HIT) isthrombocytopenia or thrombosis with one or more positivetests for HIT antibodies. To diagnose HIT, platelet countmonitoring; at least every other day until hospital discharge forday 14 (whichever occurs sooner). A platelet count fall of 50%or greater from baseline or any thrombosis occurs 5 to 10 daysafter heparin starting with exclusion or other causes ofthrombocytopenia are highly suggestive of HIT. Laboratoryconfirming assays are helpful as platelet activations assay.Management of HIT includes discontinuing of any type ofheparin and using an alternative anticoagulant as DTIs(liperudin, argatropan, bivalerudin). Warfarin should be delayedpending substantial recovery of the platelet account.Methods: This study was conducted to 100 patients receivingheparin in a variety of clinical settings to assess the prevalenceof HIT trying to identify clinical predictors of such complication.To all these patients platelet count every other day from baseline to day 14 was done then the 4T score system was appliedto all patients.Results: Only 6 patients developed HIT; 4 of them developedthrombosis and 3 patients died in hospital due to thesethromboembolic events. UFH, surgical treatment and firstheparin exposure were the clinical predictors of HIT.Conclusion: HIT is a serious and life threatening complicationof heparin therapy that should be early diagnosed and properlymanaged to prevent its thromboembolic complications.
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Objective To observe the damage of high mobility group box 1 (HMGB1) on human umbilical vein endothelial cell (HUVEC) barrier permeability and the protective effect of unfractionated heparin (UFH), and to explore the down-regulated protection effect mechanism of UFH on HMGB1-mediated vascular endothelial cadherin (VE-cadherin) expression. Methods The trypsin-digested HUVEC were subcultured in culture flasks. When the cells were grown to 80%, they were randomly divided into four groups: phosphate buffer (PBS) control group (200 μL PBS), recombinant human high mobility group box 1 (rhHMGB1) treatment group (100 μg/L rhHMGB1), UFH control group (10 kU/L UFH), and UFH pretreatment group (10 kU/L UFH+100 μg/L rhHMGB1). The cells in each group were challenged with different reagent for 24 hours, and the activity of endothelial cells was determined by methyl thiazolyl tetrazolium (MTT) colorimetric assay. The permeability of endothelial cells was measured by Transwell method, and the expression and distribution of VE-cadherin was observed by immunofluorescence. The protein expressions of VE-cadherin and phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK) were determined by Western Blot. Results After treatment with 100 μg/L rhHMGB1 for 24 hours, the activity of endothelial cells was not significantly different from that of the PBS control group (A value: 0.230±0.004 vs. 0.255±0.006, P > 0.05), but the permeability was significantly increased (glucan FD40 fluorescence intensity: 11.05±0.12 vs. 6.34±0.39, P < 0.05). Compared with PBS control group, the fluorescence microscopy showed that the VE-cadherin membrane localization was reduced, the distribution was loose, and there were obvious fissures between cells in rhHMGB1 treatment group, and quantitative analysis showed the protein expression of VE-cadherin was decreased significantly (VE-cadherin/β-actin: 0.16±0.04 vs. 0.31±0.03, P < 0.05), and the expression of p-p38MAPK protein was significantly increased (p-p38MAPK/β-actin: 0.79±0.03 vs. 0.26±0.05, P < 0.05). UFH pretreatment could protect HMGB1-mediated endothelial cell injury, cell permeability was significantly reduced (glucan FD40 fluorescence intensity: 9.11±0.23 vs. 11.05±0.12), fluorescence expression of VE-cadherin was enhanced, membrane localization was significantly increased, quantitative analysis showed that VE-cadherin protein expression was significantly up-regulated (VE-cadherin/β-actin: 0.24±0.02 vs. 0.16±0.04), and p38MAPK phosphorylation level was significantly decreased (p-p38MAPK/β-actin: 0.54±0.05 vs. 0.79±0.03), the difference was statistically significant as compared with rhHMGB1 treatment group (all P < 0.05). There was no significant difference in all parameters between PBS control group and UFH control group. Conclusions UFH can protect the endothelial cell barrier from the HMGB1 by regulating the expression and distribution of VE-cadherin. The mechanism may be related to the inhibition of p38MAPK phosphorylation by UFH.
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<p><b>Background</b>Unfractionated heparin (UFH), despite its limitations, has been used as the primary anticoagulant alternative during the percutaneous coronary intervention (PCI). Some studies indicated that intravenous enoxaparin could be an effective and safe option. Our team used enoxaparin alone at one time according to the guidelines (Class IIA) and found a little catheter thrombosis during PCI. We recommend a new anticoagulation strategy using enoxaparin in combination with UFH. Enoxaparin has a more predictable anticoagulant response with no need of repeatedly monitoring anticoagulation during PCI. This retrospective study aimed to evaluate the efficacy and safety of using enoxaparin in combination with UFH in PCI patients with complex coronary artery disease.</p><p><b>Methods</b>Between January 2015 and April 2017, 600 PCI patients who received intravenous UFH at an initial dose of 3000 U plus intravenous enoxaparin at a dose of 0.75 mg/kg (observation group) and 600 PCI patients who received UFH at a dose of 100 U/kg (control group) were consecutively included in this retrospective study. The endpoints were postoperative 48-h thrombolysis in myocardial infarction (TIMI) bleeding and transfusion and 30-day and 1-year major adverse cardio-cerebrovascular events (MACCE).</p><p><b>Results</b>Baseline clinical, angiographic, and procedural characteristics were similar between groups, except there was less stent implantation per patient in the observation group (2.13 vs. 2.25 in the control group, P = 0.002). TIMI bleeding (3.3% vs. 4.7%) showed no significant difference between the observation group and control group. During the 30-day follow-up, the rate of MACCE was 0.9% in the observation group and 1.5% in the control group. There was no significant difference in the rates of MACCE, death, myocardial infarction, target vessel revascularization, cerebrovascular event, and angina within 30 days and 1 year after PCI between groups as well as in the subgroup analysis of transfemoral approach.</p><p><b>Conclusions</b>UFH with sequential enoxaparin has similar anticoagulant effect and safety as UFH in PCI of complex coronary artery disease.</p>
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<p><b>Background</b>Despite its limitations, unfractionated heparin (UFH) has been the standard anticoagulant used during percutaneous coronary intervention (PCI). This study compared the safety of low-dose UFH with sequential enoxaparin with that of UFH in patients with diabetes mellitus (DM) and complex coronary artery disease receiving elective PCI.</p><p><b>Methods</b>In this retrospective study, 514 consecutive patients with atherosclerotic cardiovascular diseases and type 2 DM were admitted to the hospital and received selective PCI, from January 2013 to December 2015. All patients with PCI received low-dose UFH with enoxaparin (intraductal 50 U/kg UFH and 0.75 mg/kg enoxaparin, n = 254; UFH-Enox group) or UFH only (intraductal 100 U/kg UFH, n = 260; UFH group). The study endpoints were major adverse cardiac events (MACEs), namely death, myocardial infarction (MI), stroke, target-vessel immediate revascularization (TVR), and thrombolysis in MI (TIMI) major bleeding, within 30 days and 1 year after PCI. Any catheter thrombosis during the procedure was recorded.</p><p><b>Results</b>Only one patient had an intraductal thrombus in the UFH group. At the 30-day follow-up, no MACE occurred in any group; seven and five cases of recurrent angina and/or rehospitalization were reported in the UFH-Enox and UFH groups, respectively; there was no significant difference between the two groups (χ = 0.11, P = 0.77). There was no TIMI major bleeding in the groups. With respect to the 1-year endpoint, two cases of recurrent MI and two of TVRs were reported in the UFH-Enox group, whereas in the UFH group, one case of recurrent MI and three of TVRs were reported; no significant difference existed between the two groups (χ = 0, P = 0.99). There were 30 and 25 recurrent angina and/or rehospitalizations in the UFH-Enox and UFH groups, respectively; there was no significant difference between the two groups (χ = 0.37, P = 0.57).</p><p><b>Conclusion</b>In elective PCI, low-dose UFH with sequential enoxaparin has similar effects and safety to the UFH-only method.</p>
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Anticoagulants , Therapeutic Uses , Coronary Artery Disease , Drug Therapy , General Surgery , Diabetes Mellitus , Drug Therapy , General Surgery , Enoxaparin , Therapeutic Uses , Heparin , Therapeutic Uses , Percutaneous Coronary Intervention , Methods , Retrospective StudiesABSTRACT
The article analyzed an anticoagulant treatment regimen for a patient with acute pulmonary embolism and discussed the drug treatment strategy when the patient had renal insufficiency and thrombocytopenia. After fully evaluating the advantages and disad-vantages, unfractionated heparin was firstly applied under the monitoring of activate partial thrombin time, platelet counts and hemor-rhage. When the renal function was improved, low molecular weight heparin replaced unfractionated heparin. Finally, long-term warfa-rin therapy was conducted. The efficacy monitoring included symptoms, thrombosis,respiratory cycle indicators and indicators of extra-pulmonary organ function, such as serum creatinine, transaminases and pro-brain natriuretic peptides. Adverse reaction monitoring in-cluded bleeding and assessing the risk of heparin-related thrombocytopenia based on the characteristics of reduced platelet counts. After the adequate anticoagulant therapy, the patient's symptoms were relieved, liver and kidney functions were improved without significant bleeding and heparin-related thrombocytopenia. When patients have a variety of complications resulting in increased risk of drug treat-ment, the treatment regimen should be based on drug efficacy and adverse reaction characteristics. Assessing patients' prognosis and choosing a controllable treatment regimen are the keys to reducing treatment risk.
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Objective To study unfractionated heparin (UFH) effect on the expression of HOXA9 in activation of human umbilical vein endothelial cells (HUVECs) induced by lipopolysaccharide (LPS). Methods HUVECs were cultured and they were randomly divided into four groups (n = 5) for the challenge respectively: ① control group (with an equal volume of phosphate buffer saline); ② LPS group (LPS 10 mg/L); ③UFH group (UFH 10 kU/L);④ UFH+LPS group (10 kU/L UFH 30 minutes + LPS 10 mg/L). After treatment for 3 hours, the expressions of HOXA9, E-selectin and nuclear factor-κB (NK-κB) in endothelial cells were detected by Western Blot. Results Compared with the control group, the expression of HOXA9 in LPS group was significantly decreased, the expressions of E-selectin and NF-κB were significantly increased (HOXA9/β-actin: 0.082±0.009 vs. 0.199±0.067, E-selectin/β-actin:0.113±0.055 vs. 0.047±0.030, NF-κB/β-actin: 0.845±0.025 vs. 0.664±0.092, all P < 0.05). Compared with LPS group, the expression of HOXA9 in UFH+LPS group was significantly increased, the expressions of E-selectin and NF-κB were significantly decreased (HOXA9/β-actin: 0.190±0.096 vs. 0.082±0.009, E-selecin/β-actin: 0.057±0.017 vs. 0.113±0.055, NF-κB/β-actin: 0.544±0.060 vs. 0.845±0.025, all P < 0.05). Each protein expression of UFH group were in accordance with the control group. Conclusions In LPS stimulated endothelial cells, HOXA9 expression is down regulated, E-expression is reduced, and endothelial cell activation is inhibited. UFH can inhibit the activation of endothelial cells by decreasing the degree of HOXA9 reduced expression.
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Objective To investigate the effect of high mobility group box-1 protein (HMGB1) on the permeability of human umbilical vein endothelial cells, and the protective effect of unfractionated heparin on HMGB1-mediated, endothelial cell tightly junction-related protein Claudin-5. Methods The human umbilical vein endothelial cells after trypsin digestion were subcultured in culture flasks and divided into 4 groups: blank control group (addition of PBS equivalent), rhHMGB1 treatment group (100 ng/mL), unfractionated heparin control group (UFH, 10 U/mL) and rhHMGB1+ unfractionated heparin-treated group (100 ng/mL rhHMGB1 + UFH 10 U/mL). After human umbilical vein endothelial cells were cultured: the viability of endothelial cells was determined by MTT assay; transwell method was used to measure the permeability of endothelial cells; the expression and distribution of Claudin-5 were determined by immunofluorescence; and Claudin-5 protein expression was detected by Western blotting. Results After treated with rhHMGB1 (100 ng/mL), the viability of endothelial cells was notsignificantly different from that of the blank control group (P> 0.05). After treated with rhHMGB1 (100 ng/mL) for 3 and 6 h respectively, the permeability of endothelial cells was not significantly different from that of the blank control group (P> 0.05). After 12 h and 24 h treatment of rhHMGB1, the permeability of endothelial cells was significantly increased compared with the blank control group (P< 0.05). However, after endothelial cells were incubated with unfractionated heparin and rhHMGB1 for 12 and 24 h, the permeability of endothelial cell was lower than that of rhHMGB1 treatment group (P< 0.05). Immunofluorescence and Western-blot showed that after treatment of rhHMGB1 for 24 h, the distribution and expression of claudin-5, a tightly junction-associated protein, was decreased. After incubation with unfractionated heparin and rhHMGB1, the expression of tightly junction-associated protein Claudin-5 was increased, as well as the fluorescence intensity of Claudin-5. Conclusions HMGB1 can increase the permeability of endothelial cells by mediating the abnormal distribution and decreased expression of Claudin-5. Unfractionated heparin can improve the expression and distribution of Claudin-5, improving the permeability of endothelial cells.
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Objective:To evaluate the efficacy and safety of low molecular weight heparin and unfarction heparin in patients with coronary heart disease during percutaneous coronary intervention by investigating the MACE beteewn the percutaneous coronary intervention procedure and post percutaneous coronary intervention 72 hours.Methods:200 patients with coronary heart disease who accepted percutaneous coronary intervention were investigated in this study.According to the anticoagulants,these patients were divided into LMWH subgroup(117 cases) and UFH subgroup(83 cases).According to conventional method,the MACE what happened during percutaneous coronary intervention procedure and post percutaneous coronary intervention 72 hours come from each group of patients was investigated and these statistics were analysised so that evaluate the efficacy and safety of low molecular weight heparin and unfarction heparin.Results:(1) There were no statistical significance in baseline characteristics between the each group (P＞0.05).(2) There were statistical significance in the incidence of TIMI flow slows between the each group (P＜0.05),low molecular weight heparin is superior to unfarction heparin in terms of efficacy.(3)There were no statistical significance in death between the each group (P＞0.05),but there were statistical significance in bleeding / hematoma complications,and other (pericardial tamponade,chest pain,cardiogenic shock,cardiac rapture,ventricular septal perforation,ventricular tachycardia,ventricular fibrillation,cardiac arrest,Aspen attack,stent thrombosis and so on) between the each group (P＜0.05),low molecular weight heparin less adverse reactions,higher safety.Conclusion:Low molecular weight heparin in the percutaneous coronary intervention effect is more significant,and less than UFH adverse reactions and high safety,more suitable for percutaneous coronary intervention anticoagulant therapy.
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Objective To investigate the effect of unfractionated heparin on the expression of serum and liver tissue heparanase (HPA) in mice with liver injury induced by sepsis. Methods Forty-eight healthy male C57BL/6 mice aged 6-8 weeks were divided into groups according to random number table method. Twenty-four septic mice models (CLP group) were established by cecal ligation and puncture (CLP); the other 24 mice underwent sham operation (sham group), only laparotomy and abdominal closure were performed without ligation. Twelve mice in sham group and CLP group received heparin pretreatment (sham+UFH group, CLP+UFH group), and 8 U heparin unfractionated heparin (diluted to 200 μL) was injected into the tail vein of the mice at 30 minutes and 12 hours after operation respectively. The other 12 mice were injected with the same amount of normal saline. The serum and liver tissues of mice were collected at 4 and 24 hours after CLP. The levels of serum HPA, interleukin (IL-6, IL-1β), tumor necrosis factor-α (TNF-α), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured by enzyme linked immunosorbent assay (ELISA). The pathological changes of liver tissue were observed with hematoxylin eosin (HE) staining. The expression of HPA in liver tissue was detected by immunohistochemistry. Results Compared with the sham group, the levels of serum HPA, IL-6, IL-1β, TNF-α, ALT and AST in the CLP group were increased significantly, and increased further over time. The histopathology examination was performed, and abnormal structure, inflammatory cell infiltration, liver cell necrosis could be found in the tissue. The expression level of HPA in liver tissue was detected by immunohistochemistry, which was increased after CLP. This indicated that the animal model of sepsis was successfully prepared. Compared with CLP group, serum HPA, inflammatory factors and transaminase levels were significantly decreased at 4 hours after operation in group CLP+UFH [HPA (ng/L): 76.72±2.75 vs. 101.55±7.54, IL-6 (ng/L): 51.16±5.68 vs. 63.89±3.26, IL-1β (ng/L): 31.53±2.90 vs. 40.87±2.88,TNF-α (ng/L): 171.76±5.60 vs. 194.62±14.13, ALT (μg/L): 0.26±0.09 vs. 0.62±0.17, AST (μg/L): 1.03±0.22 vs. 1.45±0.08, all P < 0.05]. At 24 hours, it was significantly higher than that of 4 hours, but they were significantly lower than those in CLP group [HPA (ng/L): 125.30±7.80 vs. 302.50±17.81, IL-6 (ng/L): 81.16±4.54 vs. 176.56±5.45, IL-1β (ng/L): 61.13±2.80 vs. 113.73±3.96, TNF-α (ng/L): 328.47±10.79 vs. 599.62±10.20, ALT (μg/L): 0.38±0.17 vs. 0.91±0.26, AST (μg/L): 1.16±0.15 vs. 1.88±0.08, all P < 0.05]. It was shown by HE staining that the edema of liver tissue decreased and inflammatory cell infiltration decreased. It was shown by immunohistochemistry that the expression level of HPA in liver tissue was significantly decreased [A value (×10-3): 2.49±0.93 vs. 6.05±1.22 at 4 hours, 1.86±0.77 vs. 7.55±0.35 at 24 hours, both P < 0.05]. There was no significant difference in indexes between the sham+UFH group and the sham group. Conclusions The expression of HPA was significantly increased during sepsis in mice. Unfractionated heparin may mitigate liver injury by inhibiting HPA.
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Objective To observe the anticoagulant efficacy and safety of argatroban and unfractionated heparin (UFH) in continuous blood purification (CBP) treatment and provide the theoretical basis for optimizing the anticoagulant mode of CBP treatment in critically ill patients. Methods Sixty patients treated with CBP in Binhai Hospital of General Hospital of Tianjin Medical University from September 2015 to October 2016 were enrolled, and they were divided into two groups by random number table method, each group 30 cases. Before CBP therapy, the patients in argatroban group were treated with argatroban for anti-coagulation, the first dose was 250 μg/kg, the additional dose was 1 μg·kg-1·min-1 continuously infused before sustained filtration, and 20-30 minutes before the end of the CBP treatment, the dose added was stopped; the patients in UFH group were treated with UFH before CBP treatment, the first dose was 0.3-0.5 mg/kg, the additional dose was 5-10 mg/h, and 30 minutes before the end of CBP treatment the dose added was stopped. The changes of activated partial thromboplastin time (APTT) were monitored, before and after the end of CBP treatment, the coagulation of blood in the CBP filter/circuit and bleeding tendency of patients in two groups were observed, and the differences in platelet (PLT) counts were compared between the two groups before and after CBP treatment. Results The APTT of the two groups were significantly longer at 3 hours after treatment and before the end of treatment than those before treatment [UFH group (s): 64.96±7.35, 64.33±6.27 vs. 37.77±5.23; argatroban group (s):70.19±6.18, 72.03±6.39 vs. 40.10±5.11], and at 1 hour after the end of treatment, APTT basically returned to baseline level in argatroban group (s: 39.6±5.06), while in the UFH group APTT was still higher than that before treatment (s: 64.17±6.59). There were no statistical significant differences in the blood coagulation score of the CBP filter/circuit and bleeding score and gradation of patients between the two groups (both P > 0.05). After treatment the PLT levels of the two groups were significantly lower than those before treatment, but the level of PLT in the argatroban group was significantly higher than that in the UFH group (×109/L: 192.20±50.05 vs. 160.00±57.12, P < 0.05). Conclusion In comparison, argatroban has a better anticoagulant effect in CBP treatment for critically ill patients, argatroban is superior to UFH in controllability, so that using the former one can lower the incidence of thrombocytopenia and risk of bleeding.
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Objective To observe the anticoagulant efficacy and safety of argatroban and unfractionated heparin (UFH) in continuous blood purification (CBP) treatment and provide the theoretical basis for optimizing the anticoagulant mode of CBP treatment in critically ill patients. Methods Sixty patients treated with CBP in Binhai Hospital of General Hospital of Tianjin Medical University from September 2015 to October 2016 were enrolled, and they were divided into two groups by random number table method, each group 30 cases. Before CBP therapy, the patients in argatroban group were treated with argatroban for anti-coagulation, the first dose was 250 μg/kg, the additional dose was 1 μg·kg-1·min-1 continuously infused before sustained filtration, and 20-30 minutes before the end of the CBP treatment, the dose added was stopped; the patients in UFH group were treated with UFH before CBP treatment, the first dose was 0.3-0.5 mg/kg, the additional dose was 5-10 mg/h, and 30 minutes before the end of CBP treatment the dose added was stopped. The changes of activated partial thromboplastin time (APTT) were monitored, before and after the end of CBP treatment, the coagulation of blood in the CBP filter/circuit and bleeding tendency of patients in two groups were observed, and the differences in platelet (PLT) counts were compared between the two groups before and after CBP treatment. Results The APTT of the two groups were significantly longer at 3 hours after treatment and before the end of treatment than those before treatment [UFH group (s): 64.96±7.35, 64.33±6.27 vs. 37.77±5.23; argatroban group (s):70.19±6.18, 72.03±6.39 vs. 40.10±5.11], and at 1 hour after the end of treatment, APTT basically returned to baseline level in argatroban group (s: 39.6±5.06), while in the UFH group APTT was still higher than that before treatment (s: 64.17±6.59). There were no statistical significant differences in the blood coagulation score of the CBP filter/circuit and bleeding score and gradation of patients between the two groups (both P > 0.05). After treatment the PLT levels of the two groups were significantly lower than those before treatment, but the level of PLT in the argatroban group was significantly higher than that in the UFH group (×109/L: 192.20±50.05 vs. 160.00±57.12, P < 0.05). Conclusion In comparison, argatroban has a better anticoagulant effect in CBP treatment for critically ill patients, argatroban is superior to UFH in controllability, so that using the former one can lower the incidence of thrombocytopenia and risk of bleeding.
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OBJECTIVE: To evaluate the efficacy and safety of rivaroxaban in the treatment of deep venous thrombosis(DVT). METHODS: PubMed, Embase, Cochrane Library, Web of Science, Clinical Trials, CNKI, CBM and WANFANG database were systematically searched. All databases had been searched from up to August 2016. All randomized controlled trials (RCTs) of rivaroxaban therapy in patients with deep venous thrombosis were selected. Meta-analysis was carried out by using RevMan 5.3 software. The incidence of recurrent DVT, recurrent VTE, DVT, pulmonary embolism(PE), major bleeding, clinical relevant non-major bleeding(CRNMB) and all-cause mortality after the treatment were compared and the results were presented with risk ratio (RR) with 95% confidence interval (CI). RESULTS: Total 5 RCTs of 4 737 cases were included in this study, including 1 605 cases accepted rivaroxaban (treatment group), other of 3 132 cases accepted other drugs (control group). The results of Meta-analysis were as follows the incidence of recurrent DVT in the rivaroxaban group was lower than that in the unfractionated heparin/low molecular heparin+ vitamin K antagonists (UFH/LMWH+VKA) group (P=0.002). There was no significant difference in the incidence of pulmonary embolism, venous thromboembolism, major bleeding, CRNMB and all-cause mortality between the treatment and control group (P>0.05). CONCLUSION: In the treatment of DVT, rivaroxban shows better efficacy than that of traditional anticoagulant therapy (UFH/LMWH+VKA) and it will not increase the risk of adverse events such as bleeding and death.
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Unfractionated heparin is the most commonly used anticoagulant for hemodialysis (HD). It is well-known that heparin can cause immune-mediated thrombocytopenia due to immunoglobulin antibody formation against the complex of platelet factor 4 (PF4) and heparin. Heparin may also contribute to HD-associated platelet activation, thrombocytopenia, and increased PF4 release from platelets during a heparin dialytic session. The present study was conducted to study the effect of unfraction heparin as anticoagulant in newly treatment hemodialysis patients. Material and method: A sample of 72 people were selected, 32 patients on dialysis for first time from unite of kidney dialysis. At the same time a group of 40 randomly selected healthy adults to participate in the study as control. By Automated cell counter (sysmex X 21) platelets from all patients on dialysis before starting heparin and after one month later were estimated. Result: The mean value of platelets in patients after treated with heparin was significant lower (192.3 ± 20.7 ) × 109/l as compare before treated with heparin 203 ± 20.7 × 109/l ( P = 0.001). Conclusion: From this study, heparin as anti-coagulant has effect on decrease platelets count but still patients have no thrombocytopenia platelets level ≥ 150 × 109/l.
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Objective To determine the effect of unfractionated heparin (UFH) on lipopolysaccharide (LPS)-induced expression of chemokines and nuclear factor-κB (NF-κB) signaling pathway. Methods Human pulmonary microvascular endothelial cells (HPMECs) were cultured in vitro, and the cells between passages 3 and 5 were used in the experiments. The cells were divided into control group, LPS challenge group, 1 kU/L or 10 kU/L UFH+LPS group, and NF-κB inhibitor N-tosyl-L-lysyl chloromethyl-ketone (TLCK) group (TLCK+LPS group). HPMECs in LPS challenge group were treated with 10 mg/L LPS. UFH pretreatment with different dosages groups were treated with 1 kU/L or 10 kU/L UFH 15 minutes before LPS challenge. Cells in the TLCK+LPS group were treated with 10 μmol/L of TLCK 30 minutes before the addition of LPS, and HPMECs in control group were treated with an equal volume of phosphate-buffered saline (PBS) instead. The cells were harvested 1 hour after LPS challenge, and the nuclear translocation of NF-κB was determined by immunofluorescence assay to detect the effect of UFH on NF-κB activation. The levels of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in cell culture supernatants were determined by enzyme linked immunosorbent assay (ELISA) 3 hours and 6 hours after LPS challenge to detect the effect of UFH on LPS induced expression of chemokines and its mechanism of effect on NF-κB signaling pathway in HPMECs. Results ① In the control group, NF-κB was mostly located in the cytosol as shown by immunofluorescence. Treatment of HPMECs with LPS significantly increased the translocation of NF-κB from the cytosol to nucleus. UFH suppressed LPS-induced NF-κB activation both in 1 kU/L and 10 kU/L dosages, and 10 kU/L UFH gave even better results. ② Compared with control group, the levels of IL-8 and MCP-1 in the supernatants in LPS challenge group were significantly increased at 3 hours and 6 hours after LPS challenge [IL-8 (ng/L): 387.1±26.4 vs. 23.8±8.1 at 3 hours, 645.5±69.6 vs. 125.7±18.7 at 6 hours; MCP-1 (ng/L): 3 654.9±467.9 vs. 721.6±61.3 at 3 hours, 8 178.5±792.6 vs. 1 324.7±148.7 at 6 hours, all P < 0.05]. Compared with that of LPS challenge group, in 1 kU/L and 10 kU/L UFH pretreatment groups, the levels of IL-8 and MCP-1 were significantly decreased [IL-8 (ng/L): 315.3±24.8, 275.8±31.1 vs. 387.1±26.4 at 3 hours, 557.8±43.3, 496.9±38.7 vs. 645.5±69.6 at 6 hours; MCP-1 (ng/L): 2 924.1±267.9, 2 668.3±522.6 vs. 3 654.9±467.9 at 3 hours, 7 121.7±557.2, 6 563.9±576.4 vs. 8 178.5±792.6 at 6 hours, all P < 0.05]. The results indicated that 10 kU/L UFH yielded better results. However, inhibition study using the known NF-κB inhibitor TLCK could decrease LPS-induced increase in IL-8 and MCP-1 levels [IL-8 (ng/L): 162.4±21.3 vs. 387.1±26.4 at 3 hours, 274.1±22.6 vs. 645.5±69.6 at 6 hours; MCP-1 (ng/L): 1 478.2±138.5 vs. 3 654.9±467.9 at 3 hours; 3 667.6±259.4 vs. 8 178.5±792.6 at 6 hours, all P < 0.05]. Conclusions The levels of IL-8 and MCP-1 were increased obviously in LPS treated HPMECs. UFH might suppress LPS-activated NF-κB signaling pathway, contributing to the inhibitory effects of chemokines in HPMECs.
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Objective To investigate the effect of unfractionated heparin (UFH) on the expression of heme oxygenase-1 (HO-1) in intestinal mucosa of mice with sepsis.Methods Thirty-six male C57BL/6J mice were randomly divided into sham group,cecal ligation and puncture (CLP) group and UHF group,n =12 in each group.Model of intestinal injury in sepsis was induced by CLP.In sham group,the mice were exposed without ligation of cecum.In UFH group,the mice were treated intravenously with 8 U of UFH via the tail vein half an hour before the operation and 12 hours after the surgery respectively.Six mice in each group were randomly chosen at 4 hours and 24 hours after operation to collect inferior vena venous blood samples and terminalileum tissues.The serum levels of interleukins (IL-1 β,IL-6),and tumor necrosis factor-α (TNF-α) were determined by enzyme linked immunosorbent assay (ELISA).The serum level of D-lactate was determined by colorimetry.Pathological changes of ileum tissue and Chiu score were observed after hematoxylin eosin (HE) staining.The HO-1 expression was detected immunohistochemically.Results In sham group,no significant changes in the serum levels of IL-1 β,IL-6,TNF-α and D-lactate were observed.Twenty-four hours after the operation,the structure of intestinal mucosa was basically normal without obvious pathology change and no HO-1 positive cells were found.The serum levels of IL-1 β,IL-6,TNF-α,and D-lactate in CLP group were gradually increased,and they were significantly increased as compared with sham group [IL-1 β (ng/L):40.87±2.88 vs.22.60±2.05 at 4 hours,113.73±3.96 vs.22.07±2.74 at 24 hours;IL-6 (ng/L):63.89±3.26 vs.44.89±3.38 at 4 hours,176.56±5.45 vs.45.76±4.02 at 24 hours;TNF-α (ng/L):194.62± 14.13 vs.152.05±6.22 at 4 hours,599.62± 10.20 vs.155.90± 14.18 at 24 hours;D-lactate (mmol/L):0.24± 0.02 vs.0.19 ± 0.01 at 4 hours,0.33 ± 0.04 vs.0.20 ± 0.02 at 24 hours,all P ＜ 0.05].Twenty-four hours after the operation,edema and inflammation in ileal mucosa,intestinal villi structural damage were observed,the Chiu score was significantly higher than those in the sham group [4.5 (3.0-5.0) vs.0 (0-1.0),P ＜ 0.05],and a small amount of HO-1 positive cells were localized in the intestinal mucosa.Compared with CLP group,the serum levels of IL-1 β,IL-6,TNF-α,and D-lactate of UFH group were significantly decreased [IL-1 β (ng/L):31.53 ± 2.90 vs.40.87 ± 2.88 at 4 hours,61.13 ± 2.80 vs.113.73 ± 3.96 at 24 hours;IL-6 (ng/L):51.16 ± 5.68 vs.63.89 ± 3.26 at 4 hours,81.16 ± 4.54 vs.176.56 ± 5.45 at 24 hours;TNF-α (ng/L):171.76± 5.60 vs.194.62± 14.13 at 4 hours,328.48 ± 10.79 vs.599.62± 10.20 at 24 hours;D-lactate (mmol/L):0.21 ±0.01 vs.0.24±0.02 at 4 hours,0.24±0.02 vs.0.33±0.04 at 24 hours,all P ＜ 0.05].Twenty-four hours after the operation,intestinal injury was ameliorated,the Chiu score was significantly lower [1.5 (1.0-5.0) vs.4.5 (3.0-5.0),P ＜ 0.05],and HO-1 positive cells in the intestinal mucosa was remarkably increased.Conclusion UFH can enhance the expression of HO-1 in intestinal mucosa,reduce the release of inflammatory factors,ameliorate the intestinal inflammatory response,and thus play a protective role in intestinal tissue in mice with sepsis.
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BACKGROUND: Unfractionated heparin (UFH) has unstable pharmacokinetics and requires close monitoring. The activated partial thromboplastin time (aPTT) test has been used to monitor UFH therapy for decades in Korea, but its results can be affected by numerous variables. We established an aPTT heparin therapeutic range (HTR) corresponding to therapeutic anti-Xa levels for continuous intravenous UFH administration, and used appropriate monitoring to determine if an adequate dose of UFH was applied. METHODS: A total of 134 ex vivo samples were obtained from 71 patients with a variety of thromboembolisms. All patients received intravenous UFH therapy and were enrolled from June to September 2015 at Gyeongsang National University Hospital. All laboratory protocols were in accordance with the Clinical and Laboratory Standards Institute guidelines and the College of American Pathologist requirements for aPTT HTR. RESULTS: An aPTT range of 87.1 sec to 128.7 sec corresponded to anti-Xa levels of 0.3 IU/mL to 0.7 IU/mL for HTR under our laboratory conditions. Based on their anti-Xa levels, blood specimen distribution were as follows: less than 0.3 IU/mL, 65.7%; 0.3–0.7 IU/mL (therapeutic range), 33.6%; and more than 0.7 IU/mL, 0.7%. No evidence of recurring thromboembolism was observed. CONCLUSION: Using the conventional aPTT target range may lead to inappropriate dosing of UFH. Transitioning from the aPTT test to the anti-Xa assay is required to avoid the laborious validation of the aPTT HTR test, even though the anti-Xa assay is more expensive.
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Humans , Heparin , Korea , Partial Thromboplastin Time , Pharmacokinetics , ThromboembolismABSTRACT
ObjectiveTo determine the effect of unfractionated heparin (UFH) on lipopolysaccharide (LPS)-induced expression of granulocyte colony-stimulating factor (G-CSF), and the role of Toll-like receptor 4 (TLR4) signaling pathway in this process.Methods Human pulmonary microvascular endothelial cells (HPMECs) were cultured in vitro, and the cells between passages 3 and 5 were used in the experiments. ExperimentⅠ: the cells were divided into four groups as follows: control group, LPS stimulation group (LPS 10μg/mL), LPS+ 0.1 U/mL UFH group, and LPS+ 1 U/mL UFH group. HPMECs in UFH groups were treated with 0.1 U/mL or 1 U/mL UFH 15 minutes before LPS stimulation, and HPMECs in control group were treated with an equal volume of phosphate-buffered saline (PBS) instead. The concentrations of interleukin-6 (IL-6) and G-CSF in cell culture supernatants were determined by enzyme linked immunosorbent assay (ELISA) 24 hours after LPS challenge to detect the effect of UFH on HPMECs. ExperimentⅡ: HPMECs were treated with 5μg/mL of rhodobacter sphaeroides LPS (LPS-RS, antagonist for TLR4) 4 hours before the addition of PBS or LPS. The concentrations of IL-6 and G-CSF in cell culture supernatants were determined 24 hours after LPS stimulation to detect the effect of TLR4 on LPS-induced HPMEC injury. ExperimentⅢ: HPMECs were divided into four groups as before: control group, LPS stimulation group, LPS+ 0.1 U/mL UFH group, LPS+ 1 U/mL UFH group. Treatments to cells were the same as experimentⅠ. The protein expression of TLR4 in HPMECs was determined by Western Blot 1 hour after LPS stimulation to detect the effect of UFH on TLR4.Results① Compared with control group, the levels of IL-6 and G-CSF in LPS stimulation group were increased [IL-6 (ng/L): 655.9±58.3 vs. 75.5±18.2, G-CSF (ng/L): 388.7±36.2 vs. 35.3±12.6, both P 0.05].③ Compared with control group, the protein expression of TLR4 (grey value) in LPS stimulation group was significantly upregulated after 1 hour (0.87±0.23 vs. 0.36±0.12,P< 0.05). UFH with 0.1 U/mL and 1 U/mL lowered TLR-4 protein expression induced by LPS (0.68±0.18, 0.62±0.26 vs. 0.87±0.23, bothP< 0.05).ConclusionsThe expressions of IL-6 and G-CSF were increased obviously in LPS treated HPMECs. UFH might take its therapeutic effect through TLR4-dependent pathway.