不稳定型心绞痛使用伊诺肝素后凝血及血浆抗Xa活性的性别差异

目的研究不同性别不稳定型心绞痛(UAP)者使用伊诺肝素后,血液凝血指标及血浆抗Xa活性的性别差异。方法 UAP者男、女两组各40例,年龄28～75岁。给予伊诺肝素1mg/kg,腹壁皮下注射,每12h1次,疗程7d,于末次用药后12h抽静脉血检测血浆凝血酶原时间(PT)、活化部分凝血酶原时间(APTT)及血浆抗Xa活性,观察治疗期间男、女两组出血事件发生情况。结果用药后男、女两组PT、APTT均轻度延长,两组之间无明显差异(P>0.05);血浆抗Xa活性均增高,女性明显高于男性(P<0.05);女性组出血事件发生率明显高于男性组(P<0.05)。结论伊诺肝素采用1mg/kg给药治疗不同性别UAP者均可获得满意的抗凝效果,对PT、APTT影响较小,且无明显性别差异,无需实验室检测。两组均可达到有效血浆抗Xa活性,女性显著高于男性。出血事件发生率女性明显高于男性。

Effects of aspirin and enoxaparin in a rat model of liver fibrosis

AIM To examine the effects of aspirin and enoxaparin on liver function, coagulation index and histopathology in a rat model of liver fibrosis.METHODS Forty-five male Sprague-Dawley rats were randomly divided into the control group(n = 5) and model group(n = 40). Thioacetamide(TAA) was used to induce liver fibrosis in the model group. TAA-induced fibrotic rats received TAA continuously(n = 9), TAA + low-dose aspirin(n = 9), TAA + high-dose aspirin(n = 9) or TAA + enoxaparin(n = 9) for 4 wk. All rats were euthanized after 4 wk, and both hematoxylin-eosin and Masson staining were performed to observe pathological changes in liver tissue. RESULTS Liver fibrosis was assessed according to the METAVIR score. Compared with untreated cirrhotic controls, a significant improvement in fibrosis grade was observed in the low-dose aspirin, high-dose aspirin and enoxaparin treated groups, especially in the high-dose aspirin treated group. Alanine aminotransferase and total bilirubin were higher, albumin was lower and both prothrombin time and international normalized ratio were prolonged in the four treatment groups compared to controls. No significant differences among the four groups were observed.CONCLUSION Aspirin and enoxaparin can alleviate liver fibrosis in this rat model.

Efficacy and safety of fondaparinux versus enoxaparin in patients undergoing percutaneous coronary intervention treated with the glycoprotein IIb/IIIa inhibitor tirofiban

Background: In worldwide, the mortality rate of acute myocardial infarction(AMI) raises year by year. Although the applications of percutaneous coronary intervention(PCI) and anticoagulants effectively reduce the mortality of patients with acute coronary syndrome(ACS), but also increase the incidence of bleeding. Therefore, drugs with stable anticoagulant effects are urgently required.Methods: We enrolled 894 patients with acute coronary syndrome who underwent percutaneous coronary intervention in Shenyang Northern Hospital from February 2010 to May 2012; 430 patients were included in the fondaparinux group(2.5mg/d), and 464 were included in the enoxaparin group(1mg/kg twice daily). Fondaparinux and enoxaparin were applied for 3–7 days. All patients were treated with tirofiban [10μg/kg for 3min initially and 0.15μg/(kg·min) for 1 to 3 days thereafter]. The primary efficacy endpoint was the incidence of a major adverse cerebrovascular or cardiovascular event. The primary safety endpoint was bleeding within 30 days and 1 year after percutaneous coronary intervention.Results: One-year data were available for 422 patients in the fondaparinux group and for 453 in the enoxaparin group. The incidence of a major adverse cerebrovascular or cardiovascular event(10.9% vs 12.6%, P=0.433) and cardiac mortality(0.5% vs 1.5%, P=0.116) were generally lower in the fondaparinux group than in the enoxaparin group, although the differences were not significant. Compared with the enoxaparin group, the fondaparinux group had a significantly decreased rate of bleeding at 30 days(0.9% vs 2.9%, P=0.040) and 1 year(2.4% vs 5.5%, P=0.018). In addition, the rate of major bleeding events was lower in the fondaparinux group, but this difference was not significant(0.2% vs 0.9%, 0.2% vs 1.1%).Conclusion: In tirofiban-treated patients with acute coronary syndrome undergoing percutaneous coronary intervention, fondaparinux presented similar efficacy for ischemia events as enoxaparin. However, fondaparinux significantly decreased the incidence of bleeding, thus providing safer anticoagulation therapy.

A case of portal vein thrombosis associated with acute cholecystitis/pancreatitis or coincidence

BACKGROUND: Portal vein thrombosis (PVT) is complex and risk factors include local precipitating factors and acquired and inherited factors. It occurs secondary to abdominal malignancy, infection or surgical intervention. PVT is commonly forgotten as a possible cause of abdominal pain. The clinical picture may vary but abdominal pain and low grade fever are the most characteristic picture. METHODS: A 58-year-old male patient was admitted to our hospital complaining of abdominal pain for three days. CT scan revealed an edematous area around the portal vein. Doppler ultrasonography showed evidence of a portal vein thrombosis. RESULTS: PVT can be diagnosed with CT and Doppler ultrasonography. Fresh thrombus can be undetected by sonography because of the low echogenity but can be recognised by color Doppler ultrasonography. Treatment ranges from observation and bowel rest to surgical resection of bowel. CONCLUSIONS: When we suspect a case of PVT, it should be treated at an early stage to prevent being lost in a diagnostic dilemma. The immediate use of anticoagulant could be important in preventing serious consequences of PVT.

Effect of low molecular weight heparin (enoxaparin) on congenital cataract surgery

AIM: To assess the efficacy of intracameral enoxaparin (a low-molecular-weight heparin) infusion, in variable doses on postoperative inflammatory response in congenital cataract surgery.METHODS: It is a prospective, randomized controlled trial. Eighty eyes of 53 children with congenital cataract were enrolled in this study. Every eye had primary posterior capsulorrhexis and intraocular lens (IOL) implantation after lens aspiration. The eyes were divided into 4 equal groups. In group 1 balanced salt solution (BSS) without enoxaparin was used as an irrigation solution. Whereas in group 2, 3 and 4, 40mg, 20mg and 10mg enoxaparin in 500mL BSS was used respectively. The inflammatory response in the anterior chamber was compared among the groups with slit-lamp biomicroscopy.RESULTS: The mean follow-up period was (17.75±3.95) months in group 1, (18.00±5.15) months in group 2, (19.20±5.47) months in group 3 and (18.65±5.16) months in group 4. Mean number of inflammatory cells in the anterior chamber in group 1 was significantly higher than that of group 2, 3, 4 (P <0.001). There was fibrin formation in the anterior chambers of 3 eyes in group 1 and one eye in group 4. There was synechiae formation in 3 eyes of group 1 and one eye of group 4. There was no significant difference among the groups by means of fibrin or synechiae formation (P>0.05). There were IOL precipitates in 4 eyes of group 1 and 2 eyes of group 4. IOL precipitate formation was significantly higher in group 1 than that of group 2 and 3 in which there was no IOL precipitate (P=0.048). There was IOL subluxation in only one eye of group 1, 3 and 4 while no subluxation was observed in group 2 (P>0.05). There was no statistically significant difference detected about IOL subluxation occurance in all 4 groups (P>0.05). CONCLUSION: Complications of cataract surgery in congenital cataract patients associated with postoperative inflammatory response found to be decreased with the use of enoxaparin in intraocular infusion solutions. Furthermore according to our results the anti-inflammatory effect of enoxaparin was dose dependant.

Dose-dependent neuroprotective effect of enoxaparin on cold-induced traumatic brain injury

Recent evidence exists that enoxaparin can reduce brain injury because of its anticoagulant activity. To investigate the potential therapeutic effect of enoxaparin on cold-induced traumatic brain injury, at 20 minutes after modeling, male BALB/c mouse models of cold-induced traumatic brain injury were intraperitoneally administered 3 and 10 mg/kg enoxaparin or isotonic saline solution. Twenty-four hours later, enoxaparin at 10 mg/kg greatly reduced infarct volume, decreased cell apoptosis in the cortex and obviously increased serum level of total antioxidant status. By contrast, administration of enoxaparin at 3 mg/kg did not lead to these changes. These findings suggest that enoxaparin exhibits neuroprotective effect on cold-induced traumatic brain injury in a dose-dependent manner.

Fondaparinux:A cornerstone drug in acute coronary syndromes

In acute coronary syndrome(ACS),the use of anticoagulants in conjunction with antiplatelet agents in the acute phase has resulted in reduced ischemic events and is more effective than either class of drug used alone.Though parenteral anticoagulation is essential at the time of diagnosis,a balance must be made between ischemic benefit and the increased risk of bleeding when prescribing anticoagulants.Adverse events associated with anticoagulants,such as heparin-induced thrombocytopenia,bleeding problems,and the need for close monitoring of anticoagulant activity,have contributed to finding agents that reduce these limitations.Studies like the Organization to Assess Strategies in Ischemic Syndromes 5 and 6 and their meta-analysis have proven the efficacy of Fondaparinux over the entire ACS spectrum.The convenience of administration(once daily),lack of monitoring,reduction in mortality,and better safety profile make Fondaparinux a simple and effective anti-coagulant for the management of ACS.

Enoxaparin dosing errors in the emergency department

BACKGROUND:The study aimed to determine the frequency of enoxaparin dosing errors for patients who had a measured emergency department(ED)weight compared to those who did not have a measured ED weight,and to determine if demographic variables(e.g.,weight,height,age,Englishspeaking,race)impact the likelihood of receiving an inappropriate dose.METHODS:This is a retrospective,electronic chart review of patients who received a dose of enoxaparin in the ED between January 1,2008 and July 1,2013.We identified all patients>18 years who received a dose of enoxaparin while in the ED,were admitted,and had at least one inpatient weight within the first four days of hospitalization.Patients were excluded if they received enoxaparin for prophylaxis or a dose of more than 1.25mg/kg.RESULTS:A total of 1,944 patients were included.Patients were more likely to experience an error if they did not have a measured ED weight.Over-doses of>10mg were more likely to occur in patients without a measured ED weight.Patients with no documented ED weight or with a staffestimated ED weight were more likely to experience a dosing error than those with a patient-stated weight.Patients were more likely to experience an error if their first inpatient weight was more than 96kg,they were more than 175-cm tall,or were English speaking.CONCLUSION:Dosing errors are more likely to occur when patients are not weighed in the ED.Modifications to current workflows to incorporate weighing those patients who receive weightdosed medications may be warranted.

Histopathologic effects of a low molecular weight heparin on bone healing in rats:a promising adjuvant in dacryocystorhinostomy

AIM： To investigate the effect of short -term prophylactic dose of a low molecular weight heparin （LMWH） drug on the bone healing process in an animal model simulating the osteotomy obtained in dacryocystorhinostomy. METHODS： Forty male Wistar albino rats were divided into 2 groups. Subcutaneous injections of enoxaparin 1 mg/kg （enoxaparin-treated group） and saline solution （control group） were performed once daily for 4d, beginning on the first preoperative day. The osteotomy was created at the femoral diaphysis in all animals by using a Kirschner wire. Each group was further divided into 2 subgroups depending on the timing of the second operation, 14 or 21d following initial osteotomy. Patent osteotomy area on the second and the third weeks in each group were calculated by using a computer software on digital micrographs. RESULTS： The patent osteotomy areas at the second and the third weeks were significantly larger in the enoxaparin-treated group than those of the control group （P〈0.001 for each time-period）. In the control group, the patent osteotomy area at the third week of healing was significantly smaller than that of the second week （P=0.003）, whereas there was no significant difference between these two measurements in the enoxaparin-treated group （P=0.185）. CONCLUSION： Short -term administration of enoxaparin resultes in a significant alteration in bone healing at 14 and 21d after injury. LMWHs can be regarded as promising alternative adjuvants in dacryocystorhinostomy after being evaluated with further clinical and animal studies,

Enoxaparin sensitizes human non-small-cell lung carcinomasto gefitinib by inhibiting DOCK1 expression,vimentin phosphorylation,and Akt activation

Gefitinib is widely used for the treatment of lung cancer in patients with sensitizing epidermal growth factor receptor mutations,but patients tend to develop resistance after an average of 10 months.Low molecular weight heparins,such as enoxaparin,potently inhibit experimental metastasis.This study aimed to determine the potential of combined enoxaparin and gefitinib(enoxaparin+gefitinib)treatment to inhibit tumor resistance to gefitinib both in vitro and in vivo.A549 and H1975 cell migration was analyzed in wound closure and Transwell assays.Akt and extracellular signal related kinase 1/2(Erk1/2)signaling pathways were identified,and a proteomics analysis was conducted using SDSPAGE/liquid chromatography-tandem mass spectrometry analysis.Molecular interaction networks were visualized using the cytoscape bioinformatics platform.Protein expression of dedicator of cytokinesis1(DOCK1)and cytoskeleton intermediate filament vimentin were identified using an enzyme-linked immunosorbent assay,Western blotting,and small interfering RNA transfection of A549 cells.In xenograft A549-luc-C8 tumors in nude mice,enoxaparin+gefitinib inhibited tumor growth and reduced lung colony formation compared with gefitinib alone.Furthermore,the combination had stronger inhibitory effects on cell migration than either agent used individually.Additional enoxaparin administration resulted in better effective inhibition of Akt activity compared with gefitinib alone.Proteomics and network analysis implicated DOCK1 as the key node molecule.Western blot verified the effective inhibition of the expression of DOCK1 and vimentin phosphorylation by enoxaparin+gefitinib comparedwith gefitinib alone.DOCK1 knockdown confirmed its role in cell migration,Akt expression,and vimentin phosphorylation.Our data indicate that enoxaparin sensitizes gefitinib antitumor and antimigration activity in lung cancer by suppressing DOCK1 expression,Akt activity,and vimentin phosphorylation.

Current status of COVID-19 treatment:An opinion review

The pandemic severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has garnered the attention of scientists worldwide in the search for an effective treatment while also focusing on vaccine development.Several drugs have been used for the management of coronavirus disease 2019(COVID-19),which has affected many hospitals and health centers worldwide.Statistically significant results are lacking on the effectiveness of the experimented drugs in reducing COVID-19 morbidity or mortality,as there are very few published randomized clinical trials.Despite this,the literature offers some material for study and reflection.This opinion review attempts to address three burning questions on COVID-19 treatment options.(1)What kind of studies are currently published or ongoing in the treatment of patients with COVID-19?(2)What drugs are currently described in the literature as options of treatment for patients affected by the infection?And(3)Are there specific clinical manifestations related to COVID-19 that can be treated with a customized and targeted therapy?By answering these questions,we wish to create a summary of current COVID-19 treatments and the anti-COVID-19 treatments proposed in the recent clinical trials developed in the last 3 mo,and to describe examples of clinical manifestations of the SARS-CoV-2 infection with a cause-related treatment.

A randomized comparative study of using enoxaparin instead of unfractionated heparin in the intervention treatment of coronary heart disease

Background Low molecular weight heparin （LMWH） was more effective than unfractionated heparin （UFH） in treating acute coronary syndrome （ACS）. However, it remains uncertain whether LMWH can be used in patients undergoing percutaneous coronary intervention （PCI） instead of UFH. This study aimed to evaluate the efficacy and safety of using enoxaparin instead of UFH in the intervention treatment of patients with coronary heart disease （CHD） .Methods From October 2003 to Febuary 2005, 966 patients with CHD were enrolled into this study. Among 966 patients, 455 patients received the PCI, including 283 patients with Non-ST segment elevation ACS （NSTEACS）, 511 patients did not received PCI due to mild, moderate lesions or were suitable for coronary artery bypass graft （CABG）. The 966 patients were randomized to enoxaparin group （484 patients） and UFH group （482 patients）. Patients in the enoxaparin group were given enoxaparin at least twice subcutaneously （1 ms/kg, q12 h） before catheterization. Plasma anti-Xa activity was determined 1-8 hours after the last dose of enoxaparin was determined. The catheterization was performed within 8 hours after the last dose of enoxaparin. The sheath was removed immediately after the procedure. Patients in the UFH group were given UFH 25 mg intravenously before coronary angiography. Additional 65 mg was given intravenously if PCI was to be performed. The sheath was removed 4 hours after the procedure. Results A total of 227 patients in the enoxaparin group and 228 patients in the UFH group received PCI. In the enoxaparin group, one patient developed acute thrombosis during PCI and resulted in acute myocardial infarction （AMI）, no acute or subacute thrombosis was found during hospitalization. In the UFH group, no acute or subacute thrombosis occurred during PCI procedure and hospitalization. Therefore, the incidence of major adverse cardiovascular events （MACEs） during the hospitalization was 0.44% in the enoxaparin group and 0 in the UFH group. In the enoxaparin group, the sheath was removed immediately after the procedure and 8 patients had hematoma on the puncture site. In the UFH group, the sheath was removed 4 hours after the procedure and 20 cases had hematoma on the puncture site. The incidence of hematoma on the puncture site was significantly higher in the UFH group than that in the enoxaparin group （P〈0.05）. Anti-Xa activity was determined in 174 patients in LMWH group. The mean anti-Xa activity was （0.87±0.23） U/ml, and 94.8% of them had anti-Xa activity 〉0.5 U/ml and 6.9% of the patient 〉1.2 U/ml. There was no death and AMI occurred in enoxaparin group, but one patient had AMI caused by subacute thrombosis in UFH group during 30-day follow-up. MACE rate at 30-day follow-up was 0 in enoxaparin group and 0.43% in UFH group. Conclusions The results of the study suggest that it is safe and efficient to give enoxaparin at least twice before the PCI procedure, and the sheath can be removed immediately after PCI. For NSTEACS patient who has received enoxaparin more than twice during the hospitalization can undergo PCI directly and no UFH is necessary before or during PCI.

Heparin resistance in severe thermal injury:a prospective cohort study

Background:Low molecular-weight heparin(LMWH)is routinely administered to burn patients for thromboprophylaxis.Some studies have reported heparin resistance,yet the mechanism(s)and prevalence have not been systematically studied.We hypothesized that nucleosomes,composed of histone structures with associated DNA released from injured tissue and activated immune cells in the form of neutrophil extracellular traps(NETs or NETosis),neutralize LMWH resulting in suboptimal anticoagulation,assessed by reduction in anti-factor Xa activity.Methods:Blood was sampled from>15%total body surface area(TBSA)burn patients receiving LMWH on days 5,10 and 14.Peak anti-factor Xa(AFXa)activity,anti-thrombin(ATIII)activity,cellfree DNA(cfDNA)levels and nucleosome levels were measured.Mixed effects regression was adjusted for multiple confounders,including injury severity and ATIII activity,and was used to test the association between nucleosomes and AFXa.Results:A total of 30 patients with severe burns were included.Mean TBSA 43%(SD 17).Twentythree(77%)patients were affected by heparin resistance(defined by AFXa activity<0.2 IU/mL).Mean peak AFXa activity across samples was 0.18 IU/mL(SD 0.11).Mean ATIII was 81.9%activity(SD 20.4).Samples taken at higher LWMH doses were found to have significantly increased AFXa activity,though the effect was not observed at all doses,at 8000 IU no samples were heparin resistant.Nucleosome levels were negatively correlated with AFXa(r=−0.29,p=0.050)consistent with the hypothesis.The final model,with peak AFXa as the response variable,was adjusted for nucleosome levels(p=0.0453),ATIII activity(p=0.0053),LMWH dose pre-sample(p=0.0049),drug given(enoxaparin or tinzaparin)(p=0.03),and other confounders including severity of injury,age,gender,time point of sample.Conclusions:Heparin resistance is a prevalent issue in severe burns.Nucleosome levels were increased post-burn,and showed an inverse association with AFXa consistent with the hypothesis that they may interfere with the anticoagulant effect of heparin in vivo and contribute to heparin resistance.Accurate monitoring of AFXa activity with appropriate therapy escalation plans are recommended with dose adjustment following severe burn injury.

Unfractionated Heparin with Sequential Enoxaparin in Patients with Complex Coronary Artery Lesions during Percutaneous Coronary Intervention

Background： 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. Methods： 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 l-year major adverse cardio-cerebrovascular events （MACCE）. Results： 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 PC1 between groups as well as in the subgroup analysis of transfemoral approach. Conclusions： UFH with sequential enoxaparin has similar anticoagulant effect and safety as UFH in PCI of complex coronary artery disease.

Low-Dose Unfractionated Heparin with Sequential Enoxaparin in Patients with Diabetes Mellitus and Complex Coronary Artery Disease during Elective Percutaneous Coronary Intervention

Background： Despite its limitations, unfractionated heparin （UFH） has been the standard anticoagulant used during percutaneous coronary intervention （PCl）. 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 PCl. Methods： 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 PCl 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. Results： 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^2= 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^2 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 difl＇erence between the two groups （χ^2 = 0.37, P= 0.57）. Conclusion： In elective PCI, low-dose UFH with sequential enoxaparin has similar effects and safety to the UFH-only method.