Adsorption/Desorption of Low-density Lipoprotein on a Heparinized Surface of Gold Sensors

Heparin has been considered to be a potentially useful ligand for low-density lipoprotein（LDL） detection and analysis in a clinical context.In order to construct an affinity surface for preferential adsorption of LDL,heparin-modified gold surface（GS-Hep） was fabricated by a self-assembling method and hydrophobic-modified gold surfaces（GS-Hydro） was used as a control.The morphologies of the modified gold surfaces were investigated by atomic force microscopy（AFM） and the quantity of heparin bound to gold surface was assayed by the toluidine blue（TB） colorimetric method.Water contact angles were determined to investigate wettability on GS-Hep and GS-Hydro.Surface plasmon resonance（SPR） technique was used subsequently to detect the selective binding of LDL with heparin.And the investigation on the effect of pH on LDL adsorption suggests that lower pH lead to higher quantities of LDL adsorption on GS-Hep.Compared with GS-Hydro,GS-Hep is selective for LDL from both single and binary protein solutions.Moreover,adsorbed LDL on GS-Hep could be washed off by injecting elution solution,such as NaCl solution,for the purpose of the regeneration of GS-Hep for further LDL adsorption.

In vitro Studies on Binding and Release of Vascular Endothelial Growth Factor in Heparinized Bovine Pericardiums

Objective： To investigate binding and release of vascular endothelial growth factor （VEGF） and its effect on adhesion and proliferation of endothelial cells （ECs） in acellular fresh specimens of bovine pericardiums, which were modified by heparinization. Methods： Cross-linked aeellular fresh specimens of bovine perieardiums were heparinized by three methods： （1） heparinizcd N-（3-diinethylaminopropyl）-N＇-ethylcarbodiimide hydrochloride （EDC） treated acellular tissue samples; （2） heparinized poly（ethyleneimine） （PEI） treated acellular tissue samples; （3） heparinized EDC-PEI treated aeellular tissue samples. Controlled release of VEGF and its effect on adhesion and proliferation of ECs was evaluated. Results： In the present study, binding and release of VEGF had better performance in heparinized EDC-PEI treated group, compared with heparinized EDC-alone treated group and heparinized PEI -alone group. We could observe enhanced ability to adhesion and proliferation via modest moisture and effective controlled binding and release of VEGF. Conclusion： Binding of VEGF in heparinized EDC treated group was stable, while reiease of VEGF in heparinized treated group was adjusted freely. Interestingly, controlled binding and release of VEGF could exert beneficial effect on adhesion and proliferation of ECs in heparinized EDC-PEI treated group.

Heparinized PGA host-guest hydrogel loaded with paracrine products from electrically stimulated adipose-derived mesenchymal stem cells for enhanced wound repair

The microenvironment of the wound bed is essential in the regulation of wound repair.In this regard,strategies that provide a repairing favorable microenvironment may effectively improve healing outcomes.Herein,we attempted to use electrical stimulation(ES)to boost the paracrine function of adipose-derived stem cells from rats(rASCs).By examining the concentrations of two important growth factors,VEGF and PDGF-AA,in the cell culture supernatant,we found that ES,especially 5𝜇A ES,stimulated rASCs to produce more paracrine factors(5𝜇A-PFs).Further studies showed that ES may modulate the paracrine properties of rASCs by upregulating the levels of TRPV2 and TRPV3,thereby inducing intracellular Ca^(2+) influx.To deliver the PFs to the wound to effectively improve the wound microenvironment,we prepared a heparinized PGA host-guest hydrogel(PGA-Hp hydrogel).Moreover,PGA-Hp hydrogel loaded with 5𝜇A-PFs effectively accelerated the repair process of the full-thickness wound model in rats.Our findings revealed the effects of ES on the paracrine properties of rASCs and highlighted the potential application of heparinized PGA host-guest hydrogels loaded with PFs derived from electrically stimulated rASCs in wound repair.

Heparin is an effective treatment for preventing liver failure after hepatectomy

BACKGROUND Posthepatectomy liver failure(PHLF)is one of the most important causes of death following liver resection.Heparin,an established anticoagulant,can protect liver function through a number of mechanisms,and thus,prevent liver failure.AIM To look at the safety and efficacy of heparin in preventing hepatic dysfunction after hepatectomy.METHODS The data was extracted from Multiparameter Intelligent Monitoring in Intensive Care III(MIMIC-III)v1.4 pinpointed patients who had undergone hepatectomy for liver cancer,subdividing them into two cohorts:Those who were injected with heparin and those who were not.The statistical evaluations used were unpaired ttests,Mann-Whitney U tests,chi-square tests,and Fisher’s exact tests to assess the effect of heparin administration on PHLF,duration of intensive care unit(ICU)stay,need for mechanical ventilation,use of continuous renal replacement therapy(CRRT),incidence of hypoxemia,development of acute kidney injury,and ICU mortality.Logistic regression was utilized to analyze the factors related to PHLF,with propensity score matching(PSM)aiming to balance the preoperative disparities between the two groups.RESULTS In this study,1388 patients who underwent liver cancer hepatectomy were analyzed.PSM yielded 213 matched pairs from the heparin-treated and control groups.Initial univariate analyses indicated that heparin potentially reduces the risk of PHLF in both matched and unmatched samples.Further analysis in the matched cohorts confirmed a significant association,with heparin reducing the risk of PHLF(odds ratio:0.518;95%confidence interval:0.295-0.910;P=0.022).Additionally,heparin treatment correlated with improved short-term postoperative outcomes such as reduced ICU stay durations,diminished requirements for respiratory support and CRRT,and lower incidences of hypoxemia and ICU mortality.CONCLUSION Liver failure is an important hazard following hepatic surgery.During ICU care heparin administration has been proved to decrease the occurrence of hepatectomy induced liver failure.This indicates that heparin may provide a hopeful option for controlling PHLF.

Low-molecular-weight heparin and preeclampsia—does the sword cut both ways?Three case reports and review of literature

BACKGROUND Low-molecular-weight heparins(LMWH)are the most commonly used anticoagulants during pregnancy.It is considered to be the drug of choice due to its safety in not crossing placenta.Considering the beneficial effect in the improvement of microcirculation,prophylactic application of LMWH in patients with preeclampsia became a trend.However,the bleeding risk related with LMWH in preeclampsia patients has seldomly been evaluated.This current study aimed to identify the potential risks regarding LMWH application in patients with preeclampsia.CASE SUMMARY Herein we present a case series of three pregnant women diagnosed with preeclampsia on LMWH therapy during pregnancy.All the cases experienced catastrophic hemorrhagic events.After reviewing the twenty-one meta-analyses,the bleeding risk related with LMWH seems ignorable.Only one study analyzed the bleeding risk of LMWH and found a significantly higher risk of developing PPH in women receiving LMWH.Other studies reported minor bleeding risks,none of these were serious enough to stop LMWH treatment.Possibilities of bleeding either from uterus or from intrabdominal organs in preeclampsia patients on LMWH therapy should not be ignored.Intensive management of blood pressure even after delivery and homeostasis suture in surgery are crucial.CONCLUSION Consideration should be given to the balance between benefits and risks of LMWH in patients with preeclampsia.

Application of aspirin and low molecular weight heparin in major orthopedic surgery:Meta analysis of a randomized controlled trial

Objective:The perioperative period of major orthopedic surgery is associated with a high risk of thrombosis,but the best chemopreventive agent for thrombosis prophylaxis is still inconclusive.For this reason,this paper evaluated the efficacy and safety of aspirin versus low-molecular heparin using a Meta-analysis.Methods:Ten randomized controlled studies on the application of aspirin and low-molecular heparin for the prevention of deep vein thrombosis in orthopedic major surgery were retrieved by computer searches of PubMed,CochraneLibrary,WebofScience,China Knowledge Network,Wanfang,and Vipul databases according to inclusion and exclusion criteria,and the literature was managed using Endnote software,and the data were analyzed using Revman 5.3 software was used to perform Meta-analysis of the extracted data,focusing on the effects of these two drugs on pulmonary embolism,deep vein thrombosis,major bleeding events,minor bleeding events,wound complications,mortality and blood loss within 90 days after major orthopedic surgery.Results:(1)Ten randomized controlled trials of high quality were included,with a total of 12,974 patients,7,026 in the aspirin group and 5,948 in the low-molecular heparin group;(2)Meta-analysis showed that aspirin had a higher incidence of pulmonary embolism(OR=1.59,95%CI:1.02 to 2.49,P=0.04)and deep vein thrombosis(OR=1.60,95%CI:1.26 to 2.02,P=0.0001)than low molecular heparin;(3)The incidence of major bleeding events(OR=0.85,95%CI:0.47 to 1.55,P=0.60),minor bleeding events(OR=0.79,95%CI:0.55 to 1.12,P=0.18),adverse wound reactions(OR=0.79,95%CI:0.48 to 1.31,P=0.36),mortality within 90 days(OR=0.69,95%CI:0.20 to 2.31,P=0.55)and perioperative blood loss(MD=0.69,95%CI:0.20 to 2.31,P=0.55)in both drug groups,mortality within 90 days(OR=0.69,95%CI:0.20 to 2.31,P=0.55)and perioperative blood loss(MD=0.69,95%CI:0.20 to 2.31,P=0.55)were not statistically significant.Conclusion:Low-molecular heparin was superior to aspirin in the prevention of pulmonary embolism and lower extremity deep vein thrombosis after major orthopedic surgery,but the safety and adverse drug reactions of both groups were basically similar.Based on this,the authors recommend that low-molecular heparin should be preferred for the prevention of deep vein thrombosis in major orthopaedic surgery;however,the inclusion of randomized controlled trials remains limited,necessitating high-quality,large-sample,long-term follow-up clinical studies.

Effect of bivalirudin on myocardial microcirculation and adverse events after interventional therapy in older patients with acute coronary syndrome

BACKGROUND Bivalirudin,a direct thrombin inhibitor,is used in anticoagulation therapies as a substitute for heparin,especially during cardiovascular procedures such as percutaneous coronary intervention.AIM To explore the effect of bivalirudin on myocardial microcirculation following an intervention and its influence on adverse cardiac events in elderly patients with acute coronary syndrome(ACS).METHODS In total,165 patients diagnosed with acute myocardial at our hospital between June 2020 and June 2022 were enrolled in this study.From June 2020 to June 2022,elderly patients with ACS with complete data were selected and treated with interventional therapy.The study cohort was randomly divided into a study group(n=80,administered bivalirudin)and a control group(n=85,administered unfractionated heparin).Over a 6-mo follow-up period,differences in emergency processing times,including coronary intervention,cardiac function indicators,occurrence of cardiovascular events,and recurrence rates,were analyzed.RESULTS Significant differences were observed between the study cohorts,with the observation group showing shorter emergency process times across all stages:Emergency classification;diagnostic testing;implementation of coronary intervention;and conclusion of emergency treatment(P<0.05).Furthermore,the left ventricular ejection fraction in the observation group was significantly higher(P<0.05),and the creatine kinase-MB and New York Heart Association scores were CONCLUSION In elderly patients receiving interventional therapy for ACS,bivalirudin administration led to increased activated clotting time achievement rates,enhanced myocardial reperfusion,and reduced incidence of bleeding complications and adverse cardiac events.

Anti-infection effects of heparin on SARS-CoV-2 in a diabetic mouse model

Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity.However,the precise mechanisms responsible for the combined impact of coronavirus disease 2019(COVID-19)and diabetes have not yet been elucidated,and effective treatment options for SARS-Co V-2-infected diabetic patients remain limited.To investigate the disease pathogenesis,K18-h ACE2 transgenic(h ACE2^(Tg))mice with a leptin receptor deficiency(h ACE2-Lepr^(-/-))and high-fat diet(h ACE2-HFD)background were generated.The two mouse models were intranasally infected with a 5×10^(5) median tissue culture infectious dose(TCID_(50))of SARSCo V-2,with serum and lung tissue samples collected at 3days post-infection.The h ACE2-Lepr^(-/-)mice were then administered a combination of low-molecular-weight heparin(LMWH)(1 mg/kg or 5 mg/kg)and insulin via subcutaneous injection prior to intranasal infection with1×10^(4) TCID_(50)of SARS-Co V-2.Daily drug administration continued until the euthanasia of the mice.Analyses of viral RNA loads,histopathological changes in lung tissue,and inflammation factors were conducted.Results demonstrated similar SARS-Co V-2 susceptibility in h ACE2^(Tg)mice under both lean(chow diet)and obese(HFD)conditions.However,compared to the h ACE2-Lepr^(+/+)mice,h ACE2-Lepr^(-/-)mice exhibited more severe lung injury,enhanced expression of inflammatory cytokines and hypoxia-inducible factor-1α(HIF-1α),and increased apoptosis.Moreover,combined LMWH and insulin treatment effectively reduced disease progression and severity,attenuated lung pathological changes,and mitigated inflammatory responses.In conclusion,preexisting diabetes can lead to more severe lung damage upon SARS-Co V-2 infection,and LMWH may be a valuable therapeutic approach for managing COVID-19patients with diabetes.

Effect of heparin on recurrent IVF-ET failure patients

Objective:To elucidate the possible role of unfractionated heparin in patients with failed repeated in in vitro fertilization and embryo transfer(IVF-ET)and thrombophilia.Methods:This case control study evaluated the efficacy of the unfractionated heparin in increasing the pregnancy and implantation ratio in women with recurrent IVF-ET failures.Eighty-six women received in vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)with a record of three or more previous IVF-ET failures.Participants were randomly distributed into two groups.Group A(n=43)received unfractionated heparin 5000 IU twice daily,and group B(n=43)did not take any antithrombotic drugs.Coagulation abnormalities such as factor桋Leiden(FVL)mutation,methylene tetra hydro folate reductase(MTHFR)mutation and prothrombin mutation(F栻)were evaluated.Age,body mass index,basal follicular stimulating hormone,basal estradiol,duration of infertility,and number of IVF-ET failures were compared between two groups.Results:45.0%and 17.4%of women were pregnant with and without MTHFR and prothrombin mutation,respectively,when they received unfractionated heparin treatment.The implantation rate was more in group A(12.5%)than group B(4.3%)and differences in the fertilization rate of the two groups were observed(27.7%vs.35.9%).The clinical pregnancy rate per cycle was remarkably more in group A(30.2%)than group B(14.0%).Conclusions:Heparin is a safe and valuable treatment for patients with repeated IVF-ET failures.The clinical pregnancy and implantation rates are higher in the heparin-treated group in contrast with the control group.

Rivaroxaban for the treatment of heparin-induced thrombocytopenia with thrombosis in a patient undergoing artificial hip arthroplasty:A case report

BACKGROUND Anticoagulation treatment after lower limb surgery is one of the key methods to avoid thrombosis,and low-molecular-weight heparin is the treatment that is most frequently used in clinical practice.But one uncommon side effect of lowmolecular-weight heparin is heparin-induced thrombocytopenia(HIT),which can develop into thrombosis if not caught early or managed incorrectly.CASE SUMMARY We present a case of a patient who underwent hip arthroplasty and experienced thrombocytopenia due to HIT on the 9th d following the application of lowmolecular-weight heparin anticoagulation.We did not diagnose HIT in time and applied 1 unit of platelets to the patient,which led to thrombosis.Luckily,the patient recovered following effective and timely surgery and treatment with rivaroxaban.CONCLUSION Patients using low-molecular-weight heparin after lower limb surgery need to have their platelet counts regularly checked.If HIT develops,platelet treatment should be given with caution.

Delayed Onset Low Molecular Weight Heparin Induced Skin Necrosis on a Hemodialysis Patient

Delayed onset low molecular weight heparin induced skin necrosis is a rare adverse event. It usually occurs at the site of injection, and typically develops within 2 weeks of starting therapy. However, in our case, we presented a 62-year-old woman who is on Hemodialysis twice a week. Her hemodialysis prescription included Enoxaparine 0.2 cc IV as anticoagulant. On her third month of regular hemodialysis, she developed skin necrosis on her right leg and left hand. The diagnosis was made clinically and by exclusion of other possible causes of skin necrosis in a chronic kidney disease patient, such as calciphylaxis. The most important aspect of management, in this case, is early recognition and withdrawal of its use, which were done in our patient.

Influence of Heparin on Fibrinogen Assay by Clauss Method

Objective:To investigate the effect of heparin on fibrinogen detection by Clauss method.Methods:A normal plasma pool(NPP)of 20 healthy people was prepared with 3.2%sodium citrate anticoagulant.For experimental group 1,samples containing different concentrations of heparin were prepared.For experimental group 2,samples of experimental group 1 were diluted twice.For experimental group 3,samples of experimental group 1 were diluted 4 times.For the control group,samples of normal saline with the same volume as heparin in experimental group 1 were prepared.The fibrinogen contents of experimental group 1,experimental group 2,experimental group 3,and control group were detected by Clauss method and prothrombin time(PT)-derived method,and the fibrinogen detection results of different groups were analyzed.Results:The trend of fibrinogen detected by Clauss method and PT-derived method in experimental group 1 was different;there was significant difference between the results of experimental group 1 and the control group(P<0.05);there was no significant difference between the results of experimental group 2 and the control group(P>0.05);there was no significant difference between the results of experimental group 3 and the control group(P>0.05);there was no significant difference between the results of experimental group 2 and experimental group 3(P>0.05);the relative deviation between experimental group 1 and the control group was higher in high-concentration heparin sample.Conclusion:Heparin affects fibrinogen detection by Clauss method,and the effect can be reduced by sample dilution.

Venous thromboembolism prophylaxis of a patient with MYH-9 related disease and COVID-19 infection:A case report

BACKGROUND The May-Hegglin anomaly is among a group of genetic disorders known as MYH9-related disease.Patients with inherited platelet disorders such as May-Hegglin anomaly are at a variably increased risk for bleeding due to a combination of platelet dysfunction and thrombocytopenia.Patients admitted to the hospital with coronavirus disease 2019(COVID-19)infection are at an increased risk for a venous thromboembolism event(VTE).The National Institutes of Health COVID-19 treatment guidelines recommend using a prophylactic dose of heparin as VTE prophylaxis for adults who are receiving high-flow oxygen.We describe a patient admitted for COVID-19 infection with pneumonia and a history of May-Hegglin anomaly.The patient presented a challenge to determine prophylactic anticoagulation as there are no clear guidelines for this patient population.CASE SUMMARY Herein,we describe the case of a 39-year-old woman admitted with acute hypoxic respiratory failure secondary to COVID-19 pneumonia.She had a history of May-Hegglin anomaly and demonstrated risk for bleeding since childhood,including a life-threatening bleeding event at the age of 9 years requiring blood and platelet transfusions.Her baseline platelet count was 40-50×109/L throughout her adult life.Her family history was also notable for May-Hegglin disorder in her mother,maternal uncle,maternal grandfather and her son.Computed tomography/pulmonary angiography revealed bilateral consolidative opacities consistent with multifocal pneumonia.Complete blood count was notable for platelet count of 54×109/L.She was admitted for inpatient respiratory support with high-flow oxygen per nasal cannula and was managed with guideline-directed therapy for COVID-19,including baricitinib and dexamethasone.The Hematology/Oncology consultation team was requested to assist with management of VTE prophylaxis in the setting of active COVID-19 infection and an inherited bleeding disorder.After review of the literature and careful consideration of risks and benefits,it was decided to treat the patient with prophylactic enoxaparin.She was closely monitored in the hospital for bleeding and worsening thrombocytopenia.She had no bleeding or signs of VTE.Her respiratory status improved,and she was discharged home after 5 d of hospitalization with supplemental oxygen by nasal cannula and dexamethasone.At the 6-month follow-up,the patient successfully discontinued her home oxygen use after only a few weeks following discharge.CONCLUSION The patient presented a challenge to determine prophylactic anticoagulation as anticoagulation guidelines exist for patients with COVID-19,but there are no clear guidelines for management of patients with COVID-19 and inherited bleeding disorders,particularly those with MYH9-related disease.She was discharged after recovery from the COVID-19 infection without bleeding or thrombosis.As there are no published guidelines for this situation,we present a pragmatic,informed approach to a patient with MYH9-related disease who had an indication for anticoagulation.

Haemocompatibility of Ti-3Zr-2Sn-3Mo-25Nb biomedical alloy with surface heparinization using electrostatic self assembly technology

The haemocompatibility of Ti-3Zr-2Sn-3Mo-25Nb biomedical alloy was studied after surface heparinization. A layer of sol-gel TiO2 films was applied on the alloy samples followed by active treatment in the bio-functionalized solution for introducing the OH- and groups, and then the heparin was immobilized on the active TiO2 films through the electrostatic self assembly technology. It is shown that the heparinized films are mainly composed of anatase and rutile with smooth and dense surface. In vitro blood compatibility was evaluated by haemolysis test, clotting time and platelet adhesion behavior tests. The results show that the haemocompatibility of the alloy could be significantly improved by surface heparinization.

肝素诱导的血小板减少症--识别与处理

随着肝素和低分子肝素被广泛应用于临床,一种严重的肝素相关性并发症——肝素诱导的血小板减少症（heparin-induced thrombocytopenia,HIT）悄然危害着患者健康。HIT是在应用肝素（包括普通肝素、低分子肝素）过程中出现的以血小板计数降低及栓塞并发症为主要表现的临床疾病,可引起致命性的血栓栓塞并发症,包括肺栓塞、坏疽、急性心肌梗死及脑卒中等。

低分子肝素生物活性测定方法的比较研究

目的:对低分子肝素(low molecular weight heparin,LMWH)生物活性即抗活化10因子(抗-FXa)和抗活化2因子(抗-FⅡa)测定的不同方法进行比较与研究,建立国家标准。方法:(1)比较量反应平行线与标准曲线2种分析方法在发色底物的分光光度法即利用发色底物对 FXa 或 FⅡa特异的405 nm 显色反应测定抗-FXa 或抗-FⅡa效价的差异。(2)比较发色底物的分光光度法与血液凝固法(观察兔全血或兔血浆的凝结时间)测定 LMWH 的抗凝血酶(抗-FⅡa)效价的异同。结果:量反应平行线法比标准曲线法测定结果可靠、准确、精确;发色底物分光光度法与血液凝固法的实验结果相似,其差异无统计学意义(P>0.05),并且具有良好相关性(r=0.997 P<0.01和 r=0.976 P<0.01)。结论:对 LMWH 的抗-FXa 和抗-FⅡa效价测定采用发色底物的分光光度法;并以量反应平行线法进行分析。

一种快速大量纯化骨骼肌Ryanodine受体的方法

Ryanodine受体1(RyR1)在骨骼肌细胞的兴奋收缩偶联过程中扮演重要角色,是肌质网快速释放Ca2+的通道.RyR1的结构研究需要大量的且纯度很高的蛋白.目前,文献中的方法不能一次性得到大量的纯化蛋白,因而不能满足结构研究的需要.通过运用肝素(heparin,HP)层析与羟基磷灰石(hydroxyapatite,HA)层析,可以在1d内纯化获得毫克级RyR1.SDSPAGE显示,RyR1纯度达95%以上.在透射电子显微镜下观察到RyR1是一个正方形的结构,形态类似儿童玩具风车.这些结果表明,该纯化方法获得的RyR1不仅纯度高而且结构完整.

肝素诱导血小板减少症的诊治进展

肝素诱导的血小板减少症(heparin induced thrombocytopenia, HIT)是在应用肝素类药物过程中出现的不良反应,以普通肝素(unfractionated heparin,UFH)诱发的HIT为主,低分子肝素( low molecular weight heparin,LMWH)引起HIT的机率要低于普通肝素[1]。HIT临床上以血小板计数降低为主要表现,可引发静脉或动脉血栓形成,严重者甚至导致死亡。成人HIT发病率0.5%~5%,其中30%~60%的患者出现血栓事件[2]。近年回顾性分析儿童HIT总体发病率仅0.058%,伴血栓的发生率为0.047%,远低于成人[3],且多见于心脏手术体外循环或体外膜肺等重症患儿。另有系统性综述显示非新生儿心脏术后的HIT发生率0.33%,而新生儿未见HIT报道[4]。鉴于成人和儿童的差别,本文将简单阐述HIT的相关诊治进展。