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.

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.

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.

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.

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.

Recurrent Implantation Failure and Low Molecular Weight Heparin

Implantation of the embryo into the endometrium is the first step in the establishment of pregnancy. This process is complex, and depends on many factors. Recurrent implantation failure is a source of distress to patients and specialists. It is defined as failure to achieve a viable pregnancy, following “>3 embryo transfers with high quality embryos or the transfer of ≥ 10 embryos in multiple transfers”. Thrombophilic conditions that contribute to recurrent implantation failure are the main concern in this review. The mechanism of implantation failure is believed to be due to decreased blood flow to the endometrium and placenta which can hinder normal endometrial receptivity leading to miscarriage. Defects in early placentation resulting in pregnancy failure, have focused attention on the therapeutic potential of low molecular weight heparin in the implantation process. Heparin has a role at all stages of implantation to improve pregnancy outcomes. There are controversies in literature regarding the association between thrombophilia and recurrent implantation failure and available literature regarding this issue is very heterogeneous. Various investigators, have shown that women with RIF are more likely to have a thrombophilia disorder, yet a clear cause cannot be acknowledged from these studies. Heparin treatment has been evaluated in several studies, showing conflicting evidence. However, several studies have pointed out that it may play a role in a subset of patients who presents a thrombophilia mutation, thus the group of patients that might benefit is needed to be identified. This review is dedicated to evaluate the published literature about the role of low molecular weight heparin in case of recurrent implantation failure with or without the presence of thrombophilia.

Heparin-induced thrombocytopenia in patients undergoing cardiac surgery

Objective Heparin-induced thrombocytopenia(HIT)is a complication characterized by thrombocytopenia,hemorrhage and/or thrombosis,which is caused by initial or repeated application of unfractionated heparin(UFH)and low-molecular-weight heparin(LMWH).This study aims to summarize the clinical features of HIT in patients undergoing cardiac surgery.

The Safety and Feasibility of Low-Molecular-Weight He-parin Prophylaxis in Major Abdominal Surgery Combined with Neuraxial Anesthesia

Background: Global guidelines for venous thromboembolism (VTE) prophylaxis of patients undergoing major surgery are well established. However, their applicability and safety in patients receiving neuraxial anesthesia is unproven. We sought to evaluate the safety and feasibility of chemical VTE prophylaxis in a prospective group of patients undergoing major foregut procedures under a combination of epidural and general anesthesia. Methods: A prospective database of all patients undergoing major foregut surgery from 2004-2009 was maintained and analyzed. Epidural catheters were placed pre-operatively and used for post-operative analgesia for three days in all patients. Factors evaluated included age, ethnicity, sex, length of stay, duration of epidural placement, complications of epidural placement and post-operative management, and VTE events. A uniform protocol was followed regarding the timing of low-molecular-weight heparin (LMWH) administration with epidural catheter insertion/removal. Results: A total of 237 patients formed the study group. The mean age was 57 years (range, 19 - 88) among 121 (51.1%) women and 65 years (range, 20 - 95) among 116 (48.9%) men. One hundred and sixty-six patients were Caucasian (70%), 37 Black (15.6%), 15 Hispanic (6.3%), 12 Asian/Pacific (5.1%), and 7 other (3%). All epidural catheters were removed on the third post-operative day. There were a total of five VTE (2.1%) events postoperatively. No peri-operative or post-operative epidural catheter associated complications occurred. Conclusions: Concomitant epidural catheterization and LMWH anticoagulation is safe and feasible in major abdominal surgery patients, including those undergoing major hepatic resection. Guidelines for VTE prophylaxis and LMWH administration in the setting of neuraxial anesthesia are well established and applicable to this unique patient population.

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.

维生素D辅助低分子肝素钙对子痫前期患者机体凝血功能、脂质代谢及妊娠结局的影响

目的探讨分析维生素D辅助低分子肝素钙对子痫前期患者机体凝血功能、脂质代谢及妊娠结局的影响。方法选取52例子痫前期患者为研究对象,采用抛硬币法随机分为对照组和研究组,每组26例。对照组给予低分子肝素钙治疗,研究组在对照组基础上辅助应用维生素D,比较两组凝血功能、血脂指标以及妊娠结局。结果治疗前,两组纤维蛋白原(FIB)、活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、血清凝血酶时间(TT)水平比较,差异均无统计学意义(P>0.05);治疗后,两组FIB、APTT、PT、TT水平均优于治疗前,且研究组优于对照组(P<0.05);治疗前,两组总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平比较,差异均无统计学意义(P>0.05);治疗后,研究组TC、TG、HDL-C、LDL-C水平均优于治疗前,且研究组优于对照组(P<0.05);两组HELLP综合征、肾功能不全发生率比较差异无统计学意义(P>0.05);研究组胎盘早剥发生率低于对照组,孕妇自觉症状改善率高于对照组(P<0.05)。结论子痫前期采用维生素D辅助低分子肝素钙治疗效果较好,可有效改善患者凝血功能与脂质代谢水平,减少不良妊娠结局发生率,值得临床推广与应用。

小剂量肝素钠与低分子肝素钙对脓毒症治疗作用的对比研究

目的:对比小剂量肝素钠与低分子肝素钙治疗脓毒症的效果。方法:选取2021年10月—2022年10月脓毒症患者100例,随机分为观察组和对照组,每组50例。对比两组患者的治疗效果。结果:对照组弥散性血管内凝血8例(16.0%),观察组弥散性血管内凝血1例(2.0%),观察组临床疗效高于对照组(P<0.05)。随访1个月,观察组病死率低于对照组(P<0.05)。观察组各项凝血指标显著优于对照组(P<0.05)。观察组各项炎性因子水平低于对照组(P<0.05)。两组治疗后急性生理与健康评分(APACHEⅡ)优于治疗前,且观察组优于对照组,差异有统计学意义(P<0.05)。结论:低分子肝素钙相比小剂量肝素钠治疗脓毒症更加可行,可降低并发症发生率,改善短期预后。

低分子肝素钙联合逐级加压弹力袜预防妇科恶性肿瘤患者术后下肢深静脉血栓的临床研究

目的探讨低分子肝素钙联合逐级加压弹力袜预防妇科恶性肿瘤患者术后下肢深静脉血栓(DVT)的临床效果。方法选取2022年1—12月于赣南医学院第一附属医院经外科手术治疗的180例妇科肿瘤患者作为研究对象,按照随机数字表法分为对照组与研究组,每组90例。对照组予低分子肝素钙进行常规治疗,研究组在对照组基础上联合逐级加压弹力袜治疗。比较两组血清学指标、凝血功能指标、血流速度、下肢周径及术后DVT发生情况。结果干预后,研究组血小板计数、纤维蛋白原、D-二聚体水平均低于对照组,差异有统计学意义(P<0.05)。干预后,研究组活化部分凝血活酶时间、凝血酶原时间、凝血酶时间均长于对照组,下肢血流峰速、血流平均速度均快于对照组,差异有统计学意义(P<0.05)。干预后,研究组下肢周径短于对照组,术后下肢DVT发生率低于对照组,差异有统计学意义(P<0.05)。结论低分子肝素钙联合逐级加压弹力袜治疗经外科手术的妇科肿瘤患者,有助于预防术后DVT形成,改善机体血流状态,值得临床推广应用。

低分子量肝素钙联合寿胎丸加减方治疗早期先兆流产合并绒毛膜下血肿的临床研究

目的:探讨低分子量肝素钙联合寿胎丸加减方治疗早期先兆流产合并绒毛膜下血肿(SCH)的临床疗效及其作用机制。方法:将早期先兆流产合并SCH患者60例随机分为对照组和治疗组,各30例。对照组采用寿胎丸加减方治疗,治疗组在对照组的基础上加用低分子量肝素钙治疗。比较两组治疗效果、症状缓解时间、血清指标以及药物安全性。结果:治疗组总有效率高于对照组,各项症状缓解时间短于对照组;血清指标改善情况优于对照组(P<0.05)。两组均未出现明显不良反应。结论:联合疗法效果确切,能够快速缓解患者症状,改善血清指标水平,且安全性较高。

晚期肺癌患者血栓预防的临床分析

目的探讨晚期肺癌患者血栓预防的临床价值。方法选取晚期肺癌患者80例,随机均分为观察组(n=41)和对照组(n=39),对照组给予常规治疗,观察组在常规治疗的基础上加用低分子肝素钙治疗,检测2组治疗前后血小板计数(PLT)、D-二聚体(D-D)、纤维蛋白原(FIB)、凝血酶原时间(PT)和部分活化凝血活酶时间(APTT),同时观察深静脉血栓、肺栓塞的发生情况。结果治疗后,观察组PLT、D-D和FIB水平分别为(301.10±22.30)×10^(9)/L、(271.10±71.02)mg/L和(3.60±0.32)g/L,均低于对照组的(388.18±26.61)×10^(9)/L、(410.02±77.40)mg/L、(4.01±0.40)g/L(t=15.894,P<0.001;t=8.371,P<0.001;t=5.075,P<0.001);观察组PT和APTT水平分别为(11.28±1.01)、(25.03±1.01)s,均高于对照组的(10.28±1.05)、(24.17±0.92)s(t=4.341,P<0.001;t=3.975,P<0.001);观察组深静脉血栓发生率为4.88%,低于对照组的23.08%(χ^(2)=5.582,P=0.018)。结论低分子肝素钙能有效预防晚期肺癌患者血栓的发生,值得临床使用。

急性缺血性脑卒中伴发下肢深静脉血栓应用低分子肝素钙治疗的效果评估

目的 讨论在急性缺血性脑卒中伴发下肢深静脉血栓患者中使用低分子肝素钙治疗的效果,并评估其安全性。方法 选取50例急性缺血性脑卒中伴发下肢深静脉血栓患者,按随机数字表法分为对照组与治疗组,每组25例。对照组给予脑卒中常规治疗,治疗组给予脑卒中常规治疗联合低分子肝素钙治疗。比较两组临床疗效、临床预后[美国国立卫生研究院卒中量表(NIHSS)评分]、静脉血栓栓塞(VTE)风险[无手术患者静脉血栓栓塞风险评分表(Padua)评分]、不良反应(血小板减少、注射部位皮肤变化、肝肾功能异常、出血)发生率。结果 治疗组总有效率为80%,对照组总有效率为52%,治疗组高于对照组,差异有统计学意义(P<0.05)。治疗后,治疗组NIHSS评分(7.08±1.29)分低于对照组的(11.24±1.20)分,差异具有统计学意义(P<0.05)。治疗后,治疗组Padua评分(2.28±1.02)分低于对照组的(4.40±1.35)分,差异具有统计学意义(P<0.05)。治疗组不良反应发生率为28%(7/25),对照组不良反应发生率为32%(8/25),两组比较无统计学意义(P>0.05)。结论 低分子肝素钙可以促进急性缺血性脑卒中伴发下肢深静脉血栓患者肢体功能恢复,减少不良反应发生,在急性缺血性脑卒中伴发下肢深静脉血栓的治疗中取得理想效果。

低分子肝素钙联合前列地尔在甲状腺术后甲状旁腺功能减退治疗中的应用

目的 探讨低分子肝素钙联合前列地尔在甲状腺术后甲状旁腺功能减退(hypoparathyroidism,HP)治疗中的应用价值。方法 将甲状腺术后出现HP患者60例采用随机数字表法分为研究组30例和对照组30例,研究组采用术后连续3d使用低分子肝素钙和前列地尔+口服补充钙剂及骨化三醇或静脉滴注葡萄糖酸钙治疗,对照组采用口服补充钙剂及骨化三醇或静脉滴注葡萄糖酸钙治疗。比较两组患者术后甲状旁腺激素(parathyroid hormone,PTH)值及变化值、术后引流量及术后并发症情况等指标。结果 两组患者术后3d,术后1周,术后1个月,术后6个月的PTH值比较,差异均无统计学意义(P>0.05);术后3d与术后1dPTH差值研究组为(6.77±2.61)ng/L,对照组为(1.29±1.12)ng/L,两组比较差异有统计学意义(P<0.05);术后1周与术后1d PTH差值研究组为(10.51±3.66)ng/L,对照组为(2.65±2.17)ng/L,两组比较差异有统计学意义(P<0.05);术后1个月PTH值、术后6个月PTH值与术后1d PTH差值比较,差异无统计学意义(P>0.05)。研究组术后引流量为(90.07±22.24)ml,对照组术后引流量为(88.20±24.09)ml,两组比较差异无统计学意义(P>0.05)。两组术后并发症比较,差异无统计学意义(P>0.05)。结论 甲状腺全切术后出现HP,及时使用低分子肝素钙及前列地尔药物,可加快PTH的恢复,减少患者麻木不适感,安全有效。

低分子肝素钙/磺达肝癸钠序贯联合双嘧达莫预防性抗凝在肾病综合征中的应用效果及安全性

目的探讨低分子肝素钙/磺达肝癸钠序贯联合双嘧达莫预防性抗凝在原发性肾病综合征(PNS)中的应用效果及安全性。方法回顾性选取2020年3月至2022年12月期间四川省凉山彝族自治州第一人民医院收治的188例PNS患者,根据肾穿刺活检病理结果及磷脂酶A2受体抗体分为膜性肾病组(n=73)与非膜性肾病组(n=115)。两组患者均根据血清白蛋白水平,采用低分子肝素钙或磺达肝癸钠序贯联合双嘧达莫抗凝。比较两组患者治疗前及治疗后4周、治疗后6个月的肾功能指标[白蛋白、尿素氮、血肌酐、肾小球滤过率(eGFR)和24 h尿蛋白定量(24 h PRO)],治疗前及治疗后4周的血栓弹力图指标[反应指数(R时间)、凝血时间(K时间)、血栓最大弹力度(MA)、凝血指数(CI)和α角],以及随访6个月记录血栓事件、出血事件。结果治疗后4周、6个月,两组的白蛋白、eGFR均较治疗前明显升高,尿素氮、血肌酐、24 h PRO均较治疗前明显降低,差异均有统计学意义(P<0.05),但两组治疗后各肾功能指标比较,差异均无统计学意义(P>0.05)。治疗后4周,两组患者的R时间、K时间均较治疗前明显延长,MA、CI值和α角均较治疗前明显降低,差异均有统计学意义(P<0.05),但两组患者治疗后4周的R时间、K时间、MA、CI值和α角比较,差异均无统计学意义(P>0.05)。膜性肾病组患者的血栓、出血事件发生率分别为6.85%、10.96%,均高于非膜性肾病组(0.87%、3.48%),但两组间血栓事件总发生率、出血事件发生率比较,差异均无统计学意义(P>0.05)。结论低分子肝素钙/磺达肝癸钠序贯联合双嘧达莫预防性抗凝有利于改善PNS患者的肾功能,缓解高凝状态,降低血栓栓塞事件发生率,且非膜性肾病患者获益较膜性肾病患者更明显,安全性更高。

低分子肝素钙配合美罗培南对重症肺炎患者凝血功能及外周血Toll样受体2 Toll样受体4水平的影响

目的 研究低分子肝素钙配合美罗培南对重症肺炎(severe pneumonia,SP)患者凝血功能及外周血Toll样受体(TLR2)、TLR4水平的影响。方法以随机对照法将我院(2020年3月至2022年3月)确诊的SP患者96例分为研究组(48例)、对照组(48例)。对照组采用美罗培南治疗,研究组采用低分子肝素钙配合美罗培南治疗。比较2组临床疗效、治疗前后肺功能指标[第1秒用力呼气容积(FEV_(1))、用力肺活量(FVC)、FEV1/FVC]、凝血功能指标[凝血酶时间(TT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)]、外周血降钙素原(PCT)、C反应蛋白(CRP)、Toll样受体2(TLR2)、Toll样受体4(TLR4)水平、不良反应发生率。结果研究组总有效率(96%)高于对照组(83%)(P<0.05);治疗后研究组FEV_(1)、FVC、FEV_(1)/FVC指标高于对照组(P<0.05);治疗后研究组TT、APTT时间长于对照组,FIB水平低于对照组(P<0.05);治疗后研究组外周血PCT、CRP、TLR2、TLR4水平均低于对照组(P<0.05);治疗后研究组不良反应总发生率(12%)与对照组(8%)相比,差异无统计学意义(P>0.05)。结论低分子肝素钙配合美罗培南治疗SP患者,可进一步提高临床疗效,改善患者凝血功能,调节机体炎性反应,降低外周血TLR2、TLR4水平,且安全性较高,值得临床借鉴推广。

FIRRE在脂多糖诱导急性肺损伤中的作用及机制研究

目的探讨FIRRE在脂多糖(LPS)诱导急性肺损伤(ALI)中的作用及机制。方法研究时间为2020年6月至2022年5月,地点为滨州医学院附属医院。第一部分:FIRRE在LPS诱导A549细胞损伤中的作用研究。A549细胞分为4组,对照组采用生理盐水,低分子肝素钙组采用5 IU/ml低分子肝素钙,LPS组采用10 mg/L LPS,LPS+低分子肝素钙组采用10 mg/L LPS+5 IU/ml低分子肝素钙;处理24 h。采用CCK-8检测各组细胞活性;采用酶联免疫吸附试验(ELISA)检测白细胞介素(IL)-6、IL-10和肿瘤坏死因子(TNF-α)的表达;采用实时定量PCR检测FIRRE基因的相对表达量。第二部分:FIRRE在LPS诱导C57BL/6J小鼠ALI中的作用研究。将24只健康清洁SPF级雄性C57BL/6J小鼠(体质量25~30 g,6~8周)随机分为3组,对照组腹腔注射等体积生理盐水,ALI组注射5 mg/kg LPS诱发ALI,低分子肝素钙组腹腔注射5 mg/kg LPS诱发ALI+低分子肝素钙5 AXa IU/kg。分别于6 h、12 h评估各组小鼠毛色、反应能力、对抗外界阻力等变化;肺组织切片HE染色观察肺组织损伤程度,并进行肺损伤评分;腹主静脉取血,采用ELISA检测血清IL-6、IL-10的表达情况;采用ELISA检测肺泡灌洗液IL-6、IL-10含量;采用RT-PCR检测FIRRE基因的相对表达量。采用单因素方差分析、LSD-t检验、Dunnett-t检验。结果第一部分:LPS组A549细胞活性低于对照组,LPS+低分子肝素钙组A549细胞活力高于LPS组,多组间比较差异有统计学意义(F=44.25,P<0.05)。LPS组、LPS+低分子肝素钙组IL-6、IL-10、TNF-α水平均高于对照组、低分子肝素钙组,LPS+低分子肝素钙组IL-6、IL-10、TNF-α水平均低于LPS组(均P<0.05)。LPS组、LPS+低分子肝素钙组A549细胞FIRRE表达水平均高于对照组,LPS+低分子肝素钙组低于LPS组,多组间比较差异有统计学意义(F=242.23,P<0.001)。第二部分:ALI组及低分子肝素钙组小鼠反应能力、对抗外界阻力能力均低于对照组。LPS注射后6 h、12 h,ALI组HE染色肺组织切片显示,肺泡腔内大量炎症细胞浸润,肺泡塌陷肺损伤评分为4分;低分子肝素钙组HE染色肺组织切片炎性损伤低于ALI组;ALI组血清及肺泡灌洗液中IL-6、IL-10水平均高于对照组(均P<0.05);低分子肝素钙组血清及肺泡灌洗液中IL-6、IL-10水平均低于ALI组(均P<0.05);ALI组、低分子肝素钙组FIRRE表达量均高于对照组,低分子肝素钙组低于ALI组,多组间比较差异均有统计学意义(F=7.23、6.51,均P<0.05)。结论第一部分:低分子肝素钙可能通过抑制FIRRE基因的表达,下调炎症因子水平,减轻LPS诱导A549细胞损伤。第二部分:低分子肝素钙可能通过抑制FIRRE基因的表达,下调炎症因子水平,减轻LPS诱导C57BL/6J小鼠ALI。