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.

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.

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.

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.

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.

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.

Prevention of Deep Vein Thrombosis by Panax Notoginseng Saponins Combined with Low-Molecular-Weight Heparin in Surgical Patients

Objective:To evaluate the efficacy of deep vein thrombosis(DVT)prevention among realworld surgical inpatients who received panax notoginseng saponins(PNS)combined with low-molecularweight heparin(LMWH).Methods:A prospective cohort study was conducted among surgical patients between January 2016 and November 2018 in Xuanwu Hospital,Capital Medical University,Beijing,China.Participants received LMWH alone or PNS combined with LMWH for preventing DVT.The primary outcome was incidence of lower extremity DVT,which was screened once a week.Participants in the LMWH group were given LMWH(enoxaparin)via hypodermic injection,4000-8000 AxalU once daily.Participants in the exposure group received PNS(Xuesaitong oral tablets,100 mg,3 times daily)combined with LMWH given the same as LMWH group.Results:Of the 325 patients screened for the study,281 participants were included in the final analysis.The cohort was divided into PNS+LMWH group and LMWH group with 134 and 147 participants,respectively.There was a significant difference of DVT incidence between two groups(P=0.01),with 21(15.7%)incident DVT in the PNS+LMWH group,and 41(27.9%)incident DVT in the LMWH group.Compared with participants without DVT,the participants diagnosed with DVT were older and had higher D-dimer level.The multivariate logistic regression moclel showed a significant lower risk of incident DVT among participants in the PNS+LMWH group compared with the LMWH group(odds ratio 0.46,95%confidence interval,0.25-0.86).There were no significant differences in thromboelaslography values(including R,K,Angle,and MA)and differences in severe bleeding between two groups.No symptomatic pulmonary embolism occurred during the study.Conclusion:Combined application of PNS and LMWH can effectively reduce the incidence of DVT among surgical inpatients compared with LMWH monotherapy,without increased risk of bleeding.

Effect of low-molecular-weight heparin and urokinase on pulmonary arteries involved in pulmonary embolism

Background Recent studies have shown that T helper type-2 （Th2） cells can induce the apoptosis of CD4＋CD25＋ Treg cells or resist the immunosuppressive effect of Treg cells.We hypothesize that an imbalance of Th2/Treg is present in patients with allergic asthma.Methods Twenty-two patients with mild asthma,17 patients with moderate to severe asthma,and 20 healthy donors were enrolled.All patients were allergic to house dust mites.The proportion of peripheral blood CD4＋CD25＋ Treg cells and Th2 cells were determined by flow cytometry.The concentration of interleukin （IL）-10,transforming growth factor （TGF）-β and IL-4 in plasma was determined by enzyme linked immunosorbent assay.In these subjects,peripheral blood mononuclear cells from 17 mild asthmatic patients,13 moderate to severe asthmatic patients and 14 healthy donors were acquired and expression of forkhead box P3 （Foxp3） and GATA-3 mRNA was detected by reverse-transcriptase polymerase chain reaction.Results Compared with healthy donors and patients with mild asthma,the percent of CD4＋CD25＋ Treg cells and plasma IL-10 levels were decreased in patients with moderate to severe asthma.There were no significant differences in Foxp3 mRNA expression among three groups,but a downward trend seen among patients with asthma.However,the percent of Th2 cells,IL-4 levels and expression of GATA-3 mRNA was markedly higher in patients with mild and moderate to severe asthma than in the control group.The ratio of Th2/Treg and their cytokines was increased in allergic asthma,especially for moderate to severe asthma.The ratio of GATA-3/Foxp3 mRNA was also increased in allergic asthma.In patients with moderate to severe asthma,the percentage of peripheral blood Treg cells was negatively correlated to the percentage of Th2 cells and IL-4 levels.Conclusions The decline of CD4＋CD25＋ Treg cells in patients with moderate to severe asthma may play an important role in progress of the disease.Furthermore,the deficiency of CD4＋CD25＋ Treg cells was associated with the overexpression of Th2 response.

In vitro anticoagulation monitoring of low-molecular-weight heparin

Background Although low-molecular-weight heparin has replaced unfractionated heparin to become the primary anticoagulation drug for treatment of acute coronary syndrome, there is no convenient bedside monitoring method. We explored the best laboratory monitoring method of low-molecular-weight heparins （enoxaparin, dalteparin, and nadroparin） by use of the Sonoclot coagulation analyzer to monitor the activated clotting time. Methods A total of 20 healthy volunteers were selected and 15 ml of fasting venous blood samples were collected and incubated. Four coagulants, kaolin, diatomite, glass bead, and magnetic stick, were used to determine the activated clotting time of the low-molecular-weight heparins at different in vitro anti-Xa factor concentrations. A correlation analysis was made to obtain the regression equation. The activated clotting time of the different low-molecular-weight heparins with the same anti-Xa factor concentration was monitored when the coagulant glass beads were applied. Results The activated clotting time measured using the glass beads, diatomite, kaolin, and magnetic stick showed a linear correlation with the concentration of nadroparin （r = 0.964, 0.966, 0.970, and 0.947, respectively）. The regression equation showed that the linear slopes of different coagulants were significantly different （glass beads 230.03 s/IU, diatomite 89.91 s/IU, kaolin 50.87 s/IU, magnetic stick could not be calculated）. When the concentration of the anti-Xa factor was the same for different low-molecular-weight heparins, the measured activated clotting time was different after the application of the glass bead coagulant. Conclusions The glass bead coagulant is most feasible for monitoring the in vitro anticoagulation activity of nadroparin The different effects of different low-molecular-weight heparins on the activated clotting time may be related to the different anti-11a activities.

Inhibiting effects of low-molecular weight heparin and adrenocortical hormone on hemolysis of red cells in patients with paroxysmal nocturnal hemoglobinuria in vitro

OBJECTIVE: To study the effects of low-molecular weight heparin (LMWH) and adrenocortical hormone (dexamethasone) on the hemolysis of red cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) in vitro. METHODS: Using Ham's test and micro-complement lysis sensitive test (mCLST), the changes in hemolysis of red cells from 6 typical PNH cases were examined after adding LMWH and dexamethasone in different concentrations into the test solution in vitro. The effects of LMWH and dexamethasone on the coagulation of the tested blood samples were also studied using the activated partial thromboplastin time (APTT) test. RESULTS: Both LMWH and dexamethasone inhibited the hemolysis of PNH red cells, and they also showed a synergistic effect. The inhibiting effects were dose-dependent. Moreover, a tolerable dose of LMWH induced a limited prolongation of APTT. Dexamethasone showed two possible mechanisms in the inhibition of PNH red cells hemolysis through Ham's test and mCLST, respectively: (1) inhibiting both antibodies binding to red cells and (2) the initiation of the activation of complement 3 (C3). LMWH could inhibit hemolysis as determined by both Ham's test and mCLST, which indicated that LMWH could block the activation of complement cascade. CONCLUSIONS: Both LMWH and dexamethasone could inhibit hemolysis in PNH, and they showed a synergistic effect. Their mechanisms of inhibiting hemolysis differed from each other. Furthermore, a tolerable dose of LMWH induced a limited prolongation of APTT. LMWH might be useful for controlling acute hemolysis in patients with PNH and reducing the dose of adrenocortical hormone.

Comparison of fondaparinux sodium and low molecular weight heparin in the treatment of hypercoagulability secondary to traumatic infection

Purpose： To compare the effects and side-effects of fondaparinux sodium and low molecular weight heparin in patients with hypercoagulability accompanied with traumatic infection. Methods： Thirty-six patients with post-traumatic infections in our hospital intensive care center were diagnosed with hypercoagulability from February 2012 to February 2013. These patients were randomly divided into 2 groups. In group F （18 patients）, the patients were treated with fondaparinux sodium, 2.5 rag, 1/d for 11 d. In group L （18 patients）, the patients were treated with low molecular weight heparin, 4100 U, 1/12 h for 11 d. The incidence of deep vein thrombosis, bleeding events and multiple organ dysfunction syndrome （MODS） and mortality of two groups after anticoagulation therapy were analyzed. Fibrinogen, D-dimer level and activity of antithrombin Ⅲ were measured by the coagulation analyzer. Results： The incidence of deep vein thrombosis, MODS incidence and mortality were not significantly different between the two groups. The rate of bleeding evens in group F was lower than group L （p 〈 0.05）. Antithrombin Ⅲ got an upward trend after anticoagulant therapy, in which it was higher in group F than in group L on the 5th d and llth d （p 〈 0.05）. Fibrinogen levels were gradually increased, and there was no significant difference between two groups （p 〉 0.05）. D-dimer was significantly decreased after anticoagulant therapy for 5 d （p 〈 0.01 ）, and there were significant differences between two groups on the 5th d and 7th d （p 〈 0.05）. It showed no significant difference on the llth d （p 〉 0.05）. Conclusion： Fondaparinux sodium and low molecular weight heparin can effectively improve coagulopathy in patients with traumatic infection. Compared with low molecular weight heparin, fondaparinux sodium may reduce the risk of bleeding events in patients with hypercoagulability accompanied by traumatic infection.

低分子肝素联合前列地尔治疗高脂血症性SAP患者的临床疗效

【目的】探讨低分子肝素联合前列地尔治疗高脂血症性重症急性胰腺炎(SAP)患者的临床疗效。【方法】选择2020年7月至2022年7月本院收治的92例高脂血症性SAP患者,采用随机数字表法将其分为观察组和对照组,每组46例。对照组在常规治疗的基础上给予前列地尔治疗,观察组在对照组治疗的基础上联合低分子肝素治疗。比较两组病情恢复情况、Ranson评分、序贯器官衰竭量表(SOFA)评分、血液流变学指标[D-二聚体(D-D)、血浆黏度、纤维蛋白原(FIB)、血小板聚集率]、血脂[低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)]、炎症因子[白细胞计数(WBC)、肿瘤坏死因子-α(TNF-α)、降钙素原(PCT)]水平及预后情况。【结果】治疗后,观察组机械通气时间、腹痛消退时间、ICU住院时间、肠道功能恢复时间短于对照组(P<0.05);两组Ranson评分、SOFA评分均低于治疗前,观察组低于对照组,差异有统计学意义(P<0.05);观察组D-D、血浆黏度、FIB、血小板聚集率低于治疗前,观察组低于对照组,差异有统计学意义(P<0.05);两组LDL-C、TG低于治疗前,HDL-C高于治疗前,观察组LDL-C、TG低于对照组,HDL-C高于对照组,差异有统计学意义(P<0.05);两组PCT、TNF-α、WBC均低于治疗前,观察组低于对照组(P<0.05)。观察组并发症总发生率、复发率低于对照组,差异有统计学意义(P<0.05)。【结论】低分子肝素联合前列地尔治疗高脂血症性SAP临床效果较好,可促进患者病情恢复,改善微循环,还可降脂、抗炎,有助于改善患者预后。

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.

血管生成相关生物标志物与非小细胞肺癌PD-1免疫治疗疗效的相关性分析

目的:探讨血管生成相关生物标志物与非小细胞肺癌(NSCLC)PD-1免疫治疗疗效的相关性。方法:选取2018年1月-2019年9月在我院肿瘤科行PD-1免疫治疗的56例NSCLC患者作为研究对象,所有患者均接受至少2个周期免疫治疗。利用Luminex平台检测17种血管生成相关生物标志物,分析标志物基线水平与免疫治疗疗效的相关性。结果:按首次疗效评价结果,患者被分为疾病控制组(DCR,n=34)和疾病进展组(PD,n=22)。其中DCR组含9例部分缓解(PR)和25例疾病稳定(SD)。DCR组患者的基线血清肝素结合表皮生长因子(HB-EGF)、白介素-8(IL-8)显著低于PD组(P=0.023,P=0.012),血管内皮生长因子(VEGF-D)显著高于PD组(P=0.032)。Logistic回归分析显示,低水平IL-8为NSCLC患者免疫治疗达到疾病控制的独立影响因素(OR=14.882,P=0.038)。结论:IL-8、HB-EGF、VEGF-D的水平可能与NSCLC的PD-1免疫治疗疗效相关。

Factors predisposing to thrombosis after major joint arthroplasty

BACKGROUND Total joint arthroplasty is one of the most common options for end stage osteoarthritis of major joints.However,we must take into account that thrombosis after hip/knee arthroplasty may be related to mutations in genes encoding for blood coagulation factors and immune reactions to anticoagulants[heparininduced thrombocytopenia(HIT)/thrombosis].Identifying and characterizing genetic risk should help to develop diagnostic strategies or modify anticoagulant options in the search for etiological mechanisms that cause thrombophilia following major orthopedic surgery.AIM To evaluate the impact of patients’coagulation profiles and to study specific pharmacologic factors in the development of post-arthroplasty thrombosis.METHODS In 212(51 male and 161 female)patients that underwent primary total hip arthroplasty(100)or total knee arthroplasty(112)due to osteoarthritis during a period of 1 year,platelet counts and anti-platelet factor 4(PF4)/heparin antibodies were evaluated pre/postoperatively,and antithrombin III,methylenetetrahydrofolate reductase,factor V and prothrombin gene mutations were evaluated preoperatively.In a minimum follow-up of 3 years,196 patients receiving either low-molecular-weight heparins(173)or fondaparinux(23)were monitored for the development of thrombocytopenia,anti-PF4/heparin antibodies,HIT,and thrombosis.RESULTS Of 196 patients,32 developed thrombocytopenia(nonsignificant correlation between anticoagulant type and thrombocytopenia,P=0134.)and 18 developed anti-PF4/heparin antibodies(12/173 for low-molecular-weight heparins and 6/23 for fondaparinux;significant correlation between anticoagulant type and appearance of antibodies,P=0.005).Odds of antibody emergence:8.2%greater in patients receiving fondaparinux than low-molecular-weight heparins.Gene mutations in factor II or V(two heterozygotes for both factor V and II)were identified in 15 of 196 patients.Abnormal low protein C and/or S levels were found in 3 of 196(1.5%)patients,while all patients had normal levels of von Willebrand factor,lupus anticoagulant,and antithrombin III.Four patients developed HIT(insignificant correlation between thrombocytopenia and antibodies)and five developed thrombosis(two had positive antibodies and two were heterozygotes for both factor II&V mutations).Thrombosis was not significantly correlated to platelet counts or HIT.The correlation of thrombosis to antibodies,factor II,factor V was P=0.076,P=0.043,P=0.013,respectively.CONCLUSION Screening of coagulation profile,instead of platelet monitoring,is probably the safest way to minimize the risk of post-arthroplasty thrombosis.In addition,fondaparinux can lead to the formation of anti-PF4/heparin antibodies or HIT.

川崎病患儿血液流变学改变及低分子肝素干预的研究

【目的】探讨川崎病（KD）患儿高黏状态血液流变学改变与病情严重程度的关系以及用低分子肝素干预对病情变化的影响。【方法】149例川崎病儿随机分成对照组与治疗组，两组均监测血液流变学指标，对照组予常规治疗，治疗组加用低分子肝素静滴一周，对比治疗前后血液流变学指标变化。【结果】川崎病患儿易发生高凝状态及血液流变学指标改变。且血液流变学指标改变的程度与冠脉损害的发生存在相关性，治疗组予以低分子肝素静滴可明显改善川崎病患儿高凝状态且与对照组比较差异有统计学意义（P〈0．05）。【结论】川崎病高黏状态为川崎病常出现的症状，并与冠脉损害存在相关性。血液流变学改变可帮助川崎病高黏状态的判断，早期低分子肝素干预可有效改善川崎病高黏高凝状态，从而起到缓解症状的作用。