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.

Incidence of pocket hematoma after electrophysiological device placement：dual antiplatelet therapy versus low-molecular-weight heparin regimen

Background Given the increasing number of patients who require dual antiplatelet （DAP） therapy and electrophysiological device （EPD） placement, perioperative antiplatelet management is a current challenge. In this study, we investigated the incidence of pocket hema-toma formation after EPD placement in patients undergoing DAP therapy or an alternative low-molecular-weight heparin （LMWH） regimen. Methods This clinical observational study was performed from July 2010 to July 2012. In total, 171 patients were enrolled in the analysis after meeting the inclusion criteria. These patients were divided into two groups： 86 patients were treated with DAP therapy at the time of device implantation, and the DAP therapy was discontinued for 5 to 7 days and replaced with enoxaparin before device implantation in the other 85 patients. Adenosine phosphate （ADP）-mediated platelet aggregation and arachidonic acid-induced platelet aggregation were tested preoperatively. We compared the incidence of pocket hematoma between the two groups and the association of pocket hematoma develop-ment with ADP-mediated platelet aggregation and arachidonic acid-induced platelet aggregation.Results The incidence of pocket hema-toma in the patients who continued DAP was lower than that in the patients who replaced the dual antiplatelet regimen with LMWH （3.49%vs. 16.47%, respectively;X2 = 6.66,P 〈 0.01）. Among the patients who continued DAP therapies, the rate of ADP-mediated platelet aggre-gation inhibition in patients with pocket hematomas was higher than that in patients without pocket hematomas. None of the patients under-going DAP or enoxaparin therapy developed pocket infection, thromboembolic events, or other serious complications. Multiple logistic re-gression analysis revealed that LMWH therapy was an independent risk factor for the development of pocket hematoma （RR = 0.054, 95%CI = 0.012-0.251）. Furthermore, patients undergoing LMWH therapy were 5.1-fold more likely to develop pocket hematomas than were DAP-treated individuals.Conclusion Continuance of DAP therapy does not increase the risk of pocket hematoma formation after EPD placement.

Comparison of low-molecular-weight-heparin and unfractionated heparin for acute PTE

Objective: Acute pulmonary thromboembolism (PTE) is a serious high mortality pulmonary vascular disease whose effective treatment decreases morbidity and mortality. To determine if low-molecular-weight-heparin (LMWH) is clinically as efficient and safe as unfractionated heparin (UH) in patients with diagnosis of acute non-massive PTE, our study compares the efficacy, adverse effects and costs of LMWH and UH. Methods: One hundred and fourteen patients with non-massive acute PTE were randomly divided into LMWH (nadroparin calcium) and UH groups. Oxygenation index, D-dimer, fibrinogen (FG), lung ventilation/perfusion (V/Q) scan and computed tomography pulmonary angiography (CTPA) were observed before anticoagula-tion and on day 14 after anticoagulation. Results: In both groups, the ABG (arterial blood gas) analysis showed PaO2 and PaCO2 were elevated, P(A-a)O2 was decreased and oxygenation index (PaO2/FIO2) was elevated, D-dimer and fibrinogen were decreased, lung V/Q and CTPA showed embolized segments reduced (P<0.05). Hemorrhage and thrombocytopenia occurred in 3.5% of the LMWH group. Hemorrhage occurred in 5.3% and thrombocytopenia occurred in 7.0% of the UH group. The average cost in the LMWH group was RMB 1218.60 Yuan and RMB 1541.40 Yuan in the UH group. Conclusion: LMWH and UH are equally effective for treatment of non-massive acute PTE, but LMWH may have a lower prevalence of complications and is less expen-sive.

Clinical effectiveness of a pneumatic compression device combined with low-molecular-weight heparin for the prevention of deep vein thrombosis in trauma patients:A single-center retrospective cohort study

BACKGROUND:To investigate the clinical effectiveness of a pneumatic compression device(PCD)combined with low-molecular-weight heparin(LMWH)for the prevention and treatment of deep vein thrombosis(DVT)in trauma patients.METHODS:This study retrospectively analyzed 286 patients with mild craniocerebral injury and clavicular fractures admitted to our department from January 2016 to February 2020.Patients treated with only LMWH served as the control group,and patients treated with a PCD combined with LMWH as the observation group.The incidence of DVT,postoperative changes in the visual analogue scale(VAS)score,and coagulation function were observed and compared between the two groups.Excluding the influence of other single factors,binary logistic regression analysis was used to evaluate the use of a PCD in the patient’s postoperative coagulation function.RESULTS:After excluding 34 patients who did not meet the inclusion criteria,252 patients were were included.The incidence of DVT in the observation group was significantly lower than that in the control group(5.6%vs.15.1%,χ^(2)=4.605,P<0.05).The postoperative VAS scores of the two groups were lower than those before surgery(P<0.05).The coagulation function of the observation group was significantly higher than that of the control group,with a better combined anticoagulant effect(P<0.05).There were no significant differences between the two groups in preoperative or postoperative Glasgow Coma Scale scores,intraoperative blood loss,postoperative infection rate,or length of hospital stay(P>0.05).According to logistic regression analysis,the postoperative risk of DVT in patients who received LMWH alone was 1.764 times that of patients who received LMWH+PCD(P<0.05).The area under the receiver operating characteristic(AUROC)curve of partial thromboplastin time(APTT)and platelet(PLT)were greater than 0.5,indicating that they were the influence indicators of adding PCD to prevent DVT.Excluding the influence of other variables,LMWH+PCD effectively improved the coagulation function of patients.CONCLUSIONS:Compared with LMWH alone,LMWH+PCD could improve blood rheology and coagulation function in patients with traumatic brain injury and clavicular fracture,reduce the incidence of DVT,shorten the length of hospital stay,and improve the clinical effectiveness of treatment.

Attenuation of corneal neovascularization by topical low-molecular-weight heparin-taurocholate 7 without bleeding complication

AIM：To investigate the antiangiogenic effects and safety of topically administered low-molecular-weight heparintaurocholate 7（LHT7） on corneal neovascularization（CoNV）.METHODS：Twenty-four Sprague-Dawley rats were randomly distributed into four groups of six rats each.The central corneas were cauterized using a silver/potassium nitrate solution.From 2d after cauterization,12.5 mg/mL（low LHT7 group） or 25 mg/mL（high LHT7group） LHT7 was topically administered three times daily;12.5 mg/mL bevacizumab was topically administered as positive control（bevacizumab） group,with normal saline（NS） administered as negative control（NS group）.The corneas were digitally photographed to calculate the CoNV percentage from the neovascularized corneal area at 1 and 2wk.RESULTS：The 4 study groups did not have different CoNV percentages at 1wk after injury（P〉0.05）.However,the low LHT,high LHT,and bevacizumab groups had significantly lower CoNV percentages than the NS group at 2wk（all P〈0.05）.No significant differences in CoNV percentage were found among the low LHT,high LHT,and bevacizumab groups（all P〉0.05）.All groups except the NS group had lower CoNV percentages at 2wk postinjury than the levels observed at 1wk（all P〈0.05）.CONCLUSION：Topically-administered LHT7 inhibited CoNV without complication after chemical cauterization in the rat.

The effect of subcutaneous injection duration on patients receiving low-molecular-weight heparin:Evidence from a systematic review

To assess the effect of the injection duration of subcutaneous low-molecular-weight heparin(LMWH)on pain and bruising in patients.Randomized controlled trials and quasiexperimental studies were searched for in four electronic databases.The pooled effect size was expressed as relative risk(RR)andmeandifference(MD)with95%confidence intervals(CI)for dichotomous and continuous data.Cochrane Q and p value were used to assess heterogeneity and the I2 statistic was adopted to quantify the level.Finally,eight studies involving a total of 532 participants met our inclusion criteria.The slow(30 second)injection was associated with a reduction in pain intensity and duration,and lower bruising occurrence at 48-72 hours and 48 hours post injection.The bruising area was also smaller at 48 hours and 60 hours post injection.Nodifferenceswere identified betweenthe slowand fast(10 second)injectionin bruising area and bruising occurrence at 24 hours and 60 hours post injection.With present evidences,slow injection of LMWH is beneficial to the patient's well being,but further studies to identify the feasibility and standardization of the technique is recommended.

Impact of Pharmaceutical Care on Self-Administration of Outpatient Low-Molecular-Weight Heparin Therapy

Outpatient subcutaneous (s.c.) therapies are becoming more and more common in the treatment of different diseases. The effectiveness of community-pharmacy-based interventions in preventing problems that arise during s.c. self-injections of low-molecular-weight heparins (LMWH) is unknown. Our objective was to provide a standard operating procedure (SOP) for community pharmacists and to compare pharmaceutical vs. standard care in both clinical and daily life settings. We hypothesized that: pharmaceutical care results in improved adherence, safety, and satisfaction, and in fewer complications;the interventions used are feasible in daily life;and the results achieved in clinical and daily life settings are comparable. In the clinical setting (randomized controlled trial), patients were recruited sequentially in hospital wards;in the daily life setting (quasi-experimental design with a comparison group), recruitment took place in community pharmacies by pharmacists and trained master students during their internship. Interventions were offered according to patient needs. Data were collected by means of a monitored self-injection at home and structured questionnaire-based telephone interviews at the beginning and the end of the LMWH treatment. The main outcome measures were: scores to assess patient’s skills;syringe count to assess adherence;and frequency, effectiveness, and patient’s assessment of received interventions. The results show a median age of the 139 patients of 54 years. Interventions resulted in improved application quality (p p = 0.03). Oral instructions were pivotal for improving patients’ application quality. We found no significant score differences between the intervention groups in the clinical and daily life settings. Patients’ baseline skills were high, with the lowest score being 0.86 (score range ?2.00 to +2.00). Adherence rate was high (95.8%). In conclusion, our SOP for pharmacist interventions was of good quality, adequate, appreciated, and feasible in daily life. Patients are capable of managing s.c. injection therapies if adequate assistance is provided.

Evaluation of a Dose-Monitoring Method for Prophylactic Anticoagulant Therapy with Low-Molecular-Weight Heparin

Objective: In the present study, we report on the results of our investigation of optimum dose monitoring using coagulation and fibrinolytic system indicators during obstetric prophylactic anticoagulant therapy with enoxaparin. Study Design: Of 103 cases of cesarean section performed at our hospital, 37 cases were selected for this study after obtain ing their consent for blood collection. Variables of the coagulation and fibrinolytic systems [anti-factor Xa activity, endogenous thrombin potential (ETP), prothrombin time (PT) or international normalized ratio (INR), activated partial thromboplastin time (APTT) and D-dimer levels] were determined. Results: In the 5-day administration group, the anti-factor Xa activitywas 0.0 U/ml on the postoperative day 1, increased to 0.05 U/ml ± 0.04 U/ml on the postoperative day 3, and mildly increased to 0.06 U/ml ± 0.05 U/ml on the postoperative day 5. On the other hand, the anti-factor Xa activity in the 3-day administration group was 0.0 U/ml on the postoperative day 1 (before enoxaparin administration), increased to 0.06 U/ml ± 0.05 U/ml on the postoperative day 3, and significantly decreased to 0.02 U/ml ± 0.03 U/ml on the postoperative day 5 (p = 0.003);thus, the pattern of change was significantly different from that in the 5-day administration group (p = 0.004). Enoxaparin administration did not result in any significant fluctuation of the ETP, and no significant difference was observed between the 5-day and 3-day administration groups. Conclusion: Enoxaparin administration was associated with increase of the anti-factor Xa activity, and prolonged administration led to more sustained increase of the activity.

Role of Early Low-Molecular-Weight Heparin Prophylaxis in the Surgical Treatment of Degenerative Spinal Diseases in the Elderly Patients

Study Design: Retrospective review. Summary of Background Data: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are potential complications following major orthopaedic surgical procedures. Venous thromboembolism (VTE) is the disease process underlying DVT and PE. Pharmacological options can be use low-molecular-weight heparin (LMWH). Objective: The purpose of this study is to evaluate the hemorrhage risk when LMWH is started after 24 hours from surgery and to assess venous thromboembolism and pulmonary embolism risk in patients undergoing early prophylaxis after spine surgery. Methods: A consecutive cohort of 100 patients undergoing spinal surgery. Diagnosis was multilevel lumbar spinal stenosis in 46 cases and, degenerative thoracolumbar kypho-scoliosis in 54 cases. Starting on the first postoperative day, patients were routinely administered daily prophylactic enoxaparin at 8 pm (40 mg). Analysis was performed to identify risk factors of VTE among five independent variables (age, sex, obesity defined as body mass index > 30 kg/m2, smoking, duration of surgery), with statistical significance defined as P < 0.05. Results: No deaths in this 100 patient cohort;2 patients developed symptomatic pulmonary embolism during the first three postoperative days and 1 patient had thromboembolic complications, with acute deep venous thrombosis. Only one statistically significant predictor of acute VTE (duration of surgery, P < 0.05). Conclusion: LMWH prophylaxis seems to carry a very low hemorrhage risk and low rate of PE and DVT when started 24 hours after spine surgery. Prophylaxis with LMWH should be considered in all patients underwent major spinal surgery particularly when VTE risk factors are present.

Effect of adjuvant low-molecular-weight heparin therapy on placental hypoxia and cell apoptosis in puerperae with severe preeclampsia

Objective:To study the effect of adjuvant low-molecular-weight heparin therapy on placental hypoxia and cell apoptosis in puerperae with severe preeclampsia.Methods:A total of 94 puerperae with severe preeclampsia who received treatment and safely gave birth in our hospital between May 2014 and May 2016 were selected as the research subjects and randomly divided into the LMWH group who received low-molecular-weight heparin combined with conventional symptomatic treatment and the control group who received conventional symptomatic treatment. Before and after treatment, serum was collected respectively to determine the levels of placental hypoxia-related cytokines, and after delivery, the placentas were collected to detect oxidative stress indexes and cell apoptosis indexes.Results: After treatment, serum PLGF and PAPP-A levels of both groups were significantly higher than those before treatment while sFlt-1 and sEng levels were significantly lower than those before treatment, and after treatment, serum PLGF and PAPP-A levels of LMWH group were significantly higher than those of control group while sFlt-1 and sEng levels were significantly lower than those of control group;ROS and RNS levels as well as Fas, FasL, caspase-3 and caspase-8 protein expression in placenta tissue of LMWH group were significantly lower than those of control group while GPx-1, SOD-1 and Trx levels as well as Survivin, XIAP and Bcl-2 protein expression were significantly higher than those of control group.Conclusion:Adjuvant low-molecular-weight heparin therapy can relieve the placental hypoxia, improve oxidative stress reaction and inhibit cell apoptosis in puerperae with severe preeclampsia.

Combined effect of Traditional Chinese Medicine decoction and low-molecular-weight heparin calcium on the postoperative deep venous thrombosis in patients with lower limb fracture

OBJECTIVE: To investigate the combined effect of Traditional Chinese Medicine(TCM) decoction and low-molecular-weight heparin calcium on deep vein thrombosis(DVT) induced by surgery in patients with lower limb fracture.METHODS: Totally 86 hospitalized patients with DVT after surgery of lower limb fracture between September 2012 and January 2015 were recruited and randomly divided into control group and observation group, 43 cases in each group. The patients in the control group were treated with subcutaneous injection of low-molecular-weight heparin calcium, and those in the observation group were additionally given Danshen Injection and TCM decoction. The differences between two groups in occurrence rate, medication time, therapeutic effects,recurrence rate of thrombosis, activated partial thromboplastin time(APTT), and prothrombin time(PT) were compared.RESULTS: The occurrence rate of DVT in observation group(4.65%, 2/43) was lower than that in control group(27.91%,12/43)(P<0.05). The medication time of observation group was(6.15±2.94) d, shorter than(9.76±3.12) d in the control group(P<0.05). In observation group, 2 cases of DVT were cured(2/2); in the control group, 9 cases presented therapeutic effects and the total effective rate was 75.00%(9/12). The improvement of APTT and PT in the observation group was better than that in the control group(P<0.05).CONCLUSION: Integrative TCM decoction plus low-molecularweight heparin calcium is superior to applicaton of low-molecularweight heparin calcium alone in reducing and treating DVT in the postoperative patients with lower limb fracture.

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.

Observational study:efficacy of aspirin and low-molecular-weight heparin in the management of recurrent miscarriage

In the present study,we aimed to assess the comparative efficacy of low-molecular-weight heparin(LMWH)in combination with low-dose aspirin for the management of recurrent miscarriage and scrutinize alterations in coagulation function following such treatment.A retrospective analysis was conducted on clinical data obtained from 97 patients with recurrent miscarriage treated at our institution from January 2019 to June 2020.Patients were categorized into either the study or control groups based on the administration of LMWH.The control group comprised 48 patients treated solely with aspirin,while the study group included 49 patients treated with both LMWH and aspirin.Comparative evaluations between the two groups encompassed pregnancy outcomes,coagulation function,adverse reactions,and blood loss during delivery.Results revealed a higher term birth rate in the study group(83.67%)compared to the control group(50%).Post-treatment,the study group exhibited lower prothrombin time,plasminogen activator inhibitor,and D-dimer levels than the control group.Moreover,the study group experienced fewer adverse reactions and reduced blood loss during delivery in comparison to the control group,demonstrating statistical significance(P<0.05).The combination of LMWH and low-dose aspirin exhibited noteworthy application in the management of recurrent miscarriage.This therapeutic approach not only fostered the enhancement of coagulation function conducive to pregnancy but also diminished the incidence of adverse reactions observed with aspirin alone.

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.

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.

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.

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.

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.

Low-Molecular-Weight Heparin and Protamine-Based Polyelectrolyte Nano Complexes for Protein Delivery (A Review Articles)

We produced low-molecular-weight heparin/protamine micro (nano) particles (LMW-H/P MPs·NPs) as a carrier for heparin-binding growth factors (GFs), such as fibroblast growth factor (FGF)-2 and various GFs in platelet-rich plasma (PRP). A mixture of LMW-H (MW: approximately 5000 Da, 6.4 mg/ml) and protamine (MW: approximately 3000 Da, 10 mg/ml) at a ratio of 7:3 (vol:vol) yields a dispersion of micro (nano) particles (200 nm - 3 μm in diameter). The diluted LMW-H solution in saline (0.32 mg/ml) mixed with diluted protamine (0.5 mg/ml) at a ratio at 7:3 (vol:vol) resulted in soluble nanoparticles (approximately 100 nm in diameter). The generated NPs could be then stabilized by adding 2 mg/ml dextran (MW: 178-217 kDa) and remained soluble after lyophilization of dialyzed LMW-H /P NPs solution. The LMW-H/P MPs·NPs adsorb GFs, control their release, protect GFs and activate their biological activities. Furthermore, administration of GFs-containing F/P MPs·NPs exhibited significantly higher inductions of vascularization and fibrous tissue formation in vivo than GFs alone. LMW-H/P MPs·NPs can also efficiently bind to tissue culture plates and retain the binding of GFs. The LMW-H/P MPs·NP-coated matrix with various GFs or cytokines provided novel biomaterials that could control cellular activity such as proliferation and differentiation. Thus, LMW-H/P MPs·NPs are an excellent carrier for GFs and are a functional coating matrix for various kinds of cell cultures.

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.