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 ...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.展开更多
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 u...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.展开更多
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 com...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.展开更多
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 ...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.展开更多
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...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.展开更多
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...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.展开更多
Exposure to heparin is associated with a high incidence of immunization against platelet factor 4(PF4)/heparin complexes. A subgroup of immunized patients is at risk of developing heparin-induced thrombocytopenia(HIT)...Exposure to heparin is associated with a high incidence of immunization against platelet factor 4(PF4)/heparin complexes. A subgroup of immunized patients is at risk of developing heparin-induced thrombocytopenia(HIT), an immune mediated prothrombotic adverse drug effect. Transplant recipients are frequently exposed to heparin either due to the underlying end-stage disease, which leads to listing and transplantation or during the transplant procedure and the perioperative period. To review the current scientific knowledge on antiheparin/PF4 antibodies and HIT in transplant recipients a systematic Pub Med literature search on articles in English language was performed. The definition of HIT is inconsistent amongst the publications. Overall, six studies and 15 case reports have been published on HIT before or after heart, liver, kidney, and lung transplantation, respectively. The frequency of seroconversion for anti-PF4/heparin antibodies ranged between 1.9% and 57.9%. However, different methods to detect anti-PF4/heparin antibodies were applied. In none of the studies HIT-associated thromboembolic events or fatalities were observed. More importantly, in patients with a history of HIT, reexposure to heparin during transplantation was not associated with thrombotic complications. Taken together, the overall incidence of HIT after solid organ transplantation seems to be very low. However, according to the current knowledge, cardiac transplant recipients may have the highest risk to develop HIT. Different alternative suggestions for heparin-free anticoagulation have been reported for recipients with suspected HIT albeit no official recommendations on management have been published for this special collective so far.展开更多
Aim: The objective of this study is to review all the reported outcomes of heparin application in amniotic fluid embolism (AFE) so far and to find out why, when and how heparin or other anticoagulants should be used i...Aim: The objective of this study is to review all the reported outcomes of heparin application in amniotic fluid embolism (AFE) so far and to find out why, when and how heparin or other anticoagulants should be used in AFE. Material and methods: We searched Medline (from 1969 to 2011), using two key words: 1) amniotic fluid embolism;2) amniotic fluid embolism and heparin. The search for the former produced 1127 replies, of which 208 were case reports of AFE. In response to the other key word, there were 94 articles. We looked through all the articles, selecting those relevant for our study. Results: In the years 1969-2011, 208 AFE cases were reported. Heparin (unfractionated heparin) or low molecular weight heparin (LMWH) was applied in 20 cases (9.6%), being the main drug in 11 cases (5.3%) and in 6 cases as a component of spectacular treatment of AFE (surgical treatment and extracorporal membrane oxygenation). In one of these cases anithrombin (AT) with LMWH was used. In one patient heparin therapy was considered to be unsuccessful and hence recombinant plasminogen activator (rt-PA) was instituted. All the patients survived. Conclusions: 1) The attempts to use heparin in AFE could be defined as promising, although the number of treated patients is too small for conclusion;2) The postulate to use heparin at the very onset of AFE (a bolus of 10,000 U followed by monitored intravenous infusion) has serious justification: one of the pathways of AFE is the target for heparin (coagulation pathway).展开更多
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-...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.展开更多
Heparin-induced thrombocytopenia (HIT) is a clinicopathologic syndrome because diagnosis is based on both clinical symptoms and laboratory data. We report a patient with multiple thromboembolic complications after dai...Heparin-induced thrombocytopenia (HIT) is a clinicopathologic syndrome because diagnosis is based on both clinical symptoms and laboratory data. We report a patient with multiple thromboembolic complications after daily flushing of intravenous line with small amounts of unfractionated heparin (UFH). At day 7 bilateral hemorrhagic infarction of the adrenal glands was misdiagnosed as adrenal adenoma. On day 10 thrombocytopenia was noted and the next day a myocardial infarction complicated by a left ventricular thrombus was diagnosed. On day 12, HIT was suspected. The pre-test probability for HIT according to the 4T-score was high (8/8 points) and detection of antibodies directed against the PF4/heparin-complex by particle gel immunoassay (Titer 1:1024) and ELISA (O.D. 2.784) was strongly positive. HIT can be induced by iv-line flushes with UFH. Arterial and venous thrombotic complications can be present before a clear platelet drop can be recognised.展开更多
Objective This study was designed to evaluate the efficacy and safety of aspirin-heparin treatment for un-explained recurrent spontaneous abortion(URSA). Methods Literatures reporting the studies on the aspirin-hepari...Objective This study was designed to evaluate the efficacy and safety of aspirin-heparin treatment for un-explained recurrent spontaneous abortion(URSA). Methods Literatures reporting the studies on the aspirin-heparin treatment of un-explained recurrent miscarriage with randomized controlled trials(RCTs) were collected from the major publication databases. The live birth rate was used as primary indicator, preterm delivery, preeclampsia, intrauterine growth restriction, and adverse reactions(thrombocytopenia) were used as the secondary indicators. The quality of the included studies was evaluated using RCT bias risk assessment tool in the Cochrane Handbook(v5.1.0). Meta-analysis was conducted using RevM an(v5.3) software. Subgroup analyses were conducted with an appropriately combined model according to the type of the treatments if heterogeneity among the selected studies was detected. Results Six publications of RCTs were included in this study. There were a total of 907 pregnant women with diagnosis of URSA, 367 of them were pooled in the study group with aspirin-heparin therapy and 540 women in the control group with placebo, aspirin or progesterone therapy. Meta-analysis showed that the live birth rate in the study group was significantly different from that in the control group [RR = 1.18, 95% CI(1.00-1.39), P=0.04]. Considering the clinical heterogeneity among the six studies, subgroup analysis were performed. Live birth rates in the aspirin-heparin treated groups and placebo groups were compared and no significant difference was found. There were no significant differences found between the two groups in the incidence of preterm delivery [RR=1.22, 95% CI(0.54-2.76), P=0.64], preeclampsia [RR=0.52, 95% CI(0.25-1.07), P=0.08], intrauterine growth restriction [RR=1.19, 95% CI(0.56-2.52), P=0.45] and thrombocytopenia [RR=1.17, 95% CI(0.09-14.42), P=0.90]. Conclusion This meta-analysis did not provide evidence that aspirin-heparin therapy had beneficial effect on un-explained recurrent miscarriage in terms of live birth rate, but it was relatively safe for it did not increase incidence of adverse pregnancy and adverse events. More well-designed and stratified double-blind RCT, individual-based meta-analysis regarding aspirin-heparin therapy are needed in future.展开更多
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 el...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.展开更多
AIM: To evaluate the effect of chronic thrombin inhibition by heparin on experimentally induced chronic liver injury (liver fibrosis) in rats. METHODS: Chronic liver injury (liver fibrosis) was induced in Wistar rats ...AIM: To evaluate the effect of chronic thrombin inhibition by heparin on experimentally induced chronic liver injury (liver fibrosis) in rats. METHODS: Chronic liver injury (liver fibrosis) was induced in Wistar rats by oral administration of carbon tetrachloride (CCl 4 ) for 7 wk, an animal model with persistent severe hepatic fibrosis. Intravenous administration of the thrombin antagonist (heparin) started 1 wk after the start of CCl 4 intoxication for 6 wk. After completion of treatment (7 wk), markers of hepatic dysfunction were measured and changes evaluated histopathologically. RESULTS: Higher serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), total, direct and indirect bilirubin levels, as well as lower fibrinogen levels, were found in CCl 4 intoxicated rats. Heparin, silymarin and combination of drug (heparin and silymarin) treatment for 6 wk prevented a rise in SGOT, SGPT, ALP, total, direct and indirect bilirubin levels and improved fibrinogen levels. Deterioration in hepatic function determined by the fibrosis area was retarded, as evident from hepatic histopathology. Total protein levels were not changed in all groups.CONCLUSION: Heparin, a thrombin antagonist, preserved hepatic function and reduced severity of hepatic dysfunction/fibrogenesis. Combination of heparin and silymarin produced additional benefits on liver fibrosis.展开更多
BACKGROUND Gastrointestinal cancer(GICA)is associated with a higher incidence of venous thromboembolism(VTE)compared to other solid tumors,moreover,recurrent VTE and major bleeding(MB)complications during anticoagulat...BACKGROUND Gastrointestinal cancer(GICA)is associated with a higher incidence of venous thromboembolism(VTE)compared to other solid tumors,moreover,recurrent VTE and major bleeding(MB)complications during anticoagulation treatment have an associated increase rate.GICA-VTE remains a challenging clinical scenario with MB concerns for utilization of direct oral anticoagulants(DOAC),especially with active cancer therapies.AIM To evaluate patient risk factors,effectiveness(VTE)and safety(MB)of DOACs and low molecular weight heparin(LMWH)in patients with active GICA-VTE.METHODS A retrospective chart review of patients receiving DOACs and LMWH with GICA and symptomatic or incidental VTE treated at comprehensive cancer center from November 2013 to February 2017 was performed.Inclusion criteria included active GI cancer diagnosed at any stage or treatment+/-6 mo of VTE diagnosis,whom were prescribed 6 mo or more of DOACs or LMWH.The Chi-squared test was used for overall and the Fisher exact test for pairwise comparisons of the proportions of patients experiencing recurrent VTE and MB events.Odds ratios were used to compare the relative odds of the occurrence of the outcome given exposure to the risk factor.RESULTS A total of 144 patients were prescribed anticoagulation,in which 106 fulfilled inclusion criteria apixaban(27.3%),rivaroxaban(34.9%)and enoxaparin(37.7%),and 38 were excluded.Patients median age was 66.5 years at GICA diagnosis and 67 years at CAVTE event,with 62%males,80%Caucasian,70%stage IV,pancreatic cancer(40.5%),30%Khorana Score(≥3 points),and 43.5%on active chemotherapy.Sixty-four percent of patients completed anticoagulation therapy(range 1 to 43 mo).Recurrent VTE at 6 mo was noted in 7.5%(n=3),6.8%(n=2)and 2.7%(n=1)of patients on enoxaparin,apixaban and rivaroxaban,respectively(all P=NS).MB at 6 mo were 5%(n=2)for enoxaparin,6.8%(n=2)for apixaban and 21.6%(n=8)for rivaroxaban(overall P=0.048;vs LMWH P=0.0423;all other P=NS).Significant predictors of a primary or secondary outcome for all anticoagulation therapies included:Active systemic treatment(OR=5.1,95%CI:1.3-19.3),high Khorana Score[≥3 points](OR=5.5,95%CI:1.7-17.1),active smoker(OR=6.7,95%CI:2.1-21.0),pancreatic cancer(OR=6.8,95%CI:1.9-23.2),and stage IV disease(OR=9.9,95%CI:1.2-79.1).CONCLUSION Rivaroxaban compared to apixaban and enoxaparin had a significantly higher risk of MB on GICA-VTE patients with equivocal efficacy.展开更多
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 patient...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.展开更多
Background The pathogenesis of diabetic nephropathy (DN) is a complex pathophysiological process.Its precise mechanism is not fully known. In recent years it has been recognized that synthesis of various extracelluar ...Background The pathogenesis of diabetic nephropathy (DN) is a complex pathophysiological process.Its precise mechanism is not fully known. In recent years it has been recognized that synthesis of various extracelluar matrix (ECM) components may increase, and that degradation of ECM may decrease in DN. It was reported heparin could inhibit mesangial cells proliferation in vitro. The main aim of this study is to explore whether heparin inhibits proliferation of mesangial cells grown in high glucose concentration and to measure the effect of heparin on matrix metalloproteinases (MMPs) expression in mesangial cells. Methods The medium contained either low glucose (5 mmol/L) or high glucose (25 mmol/L). The concentrations of heparin in the culture medium were 0, 25, 50,100, 200 or 400 μg/mL. A metabolic (WST-1) assay was used to measure mesangial cell proliferation and Western blot analysis was used to measure MMPs expression of mesangial cells. Results Normal human mesangial cell (NHMC) proliferation was higher in high glucose (HG) medium than in low glucose (LG) medium. They showed a 1.93 fold expansion after 72 h in high glucose in contrast to a 1.63 fold expansion in low glucose. In the presence of heparin, mesangial cells proliferation was inhibited, which was more obvious at high glucose concentrations than at low glucose concentrations. In high glucose, with heparin concentration of 50, 100, 200 and 400 μg/mL, the mesangial cells showed a 0. 61 fold, 0.52 fold, 0.52 fold and 0.41 fold reductions in cell number compared to cells grown without heparin. In low glucose, only concentrations of 200 μg/mL and 400 μg/mL showed reduction in cell number, namely 0.54 fold and 0.45 fold, when compared to cells grown without heparin. In Western blot analysis,MMP1, MMP2, MMP3 and MMP9 was expressed by mesangial cells expressed in both high and low glucose concentrations, which was more prominent in high glucose medium. Incubation of heparin further increased expression of MMP1, MMP2, MMP3 and MMP9. Conclusions This study suggests that glucose can accelerate mesangial cell proliferation while heparin can reduce proliferation, being more obvious at high glucose concentrations. Higher glucose concentrations led to increased MMP expression, which may take part in the regulation of mesangial matrix synthesis and degradation. Addition of heparin resulted in a corresponding increase in MMP expression, most notably at high glucose concentrations, indicating a potentially renoprotective role in DN.展开更多
Cardiovascular disease is the leading causes of death.However,the complications can be treated with heparin and heparinoids,such as heparin pentasaccharide Fondaparinux,dermatan sulfate,and PSS made from alginate extr...Cardiovascular disease is the leading causes of death.However,the complications can be treated with heparin and heparinoids,such as heparin pentasaccharide Fondaparinux,dermatan sulfate,and PSS made from alginate extracted from brown seaweeds by chemical sulfation.Alginate is composed of a linear backbone of polymannuronate(PM),polyguluronate(PG),and alternate residues of mannuronic acid and guluronic acid.It is unknown if heparin and sulfated PG(PGS)/PM(PMS) have the same or different anticoagulant molecular targets.In the current study,the anticoagulant activities of PGS,PMS,and their oligosaccharides were directly compared to that of heparin,Fondaparinux,and dermatan sulfate by the activated partial thrombinplastin time(aP TT) assay using normal,antithrombin III(ATIII)-deficient,heparin co-factor II(HCII)-deficient,and ATIII-and HCII-double deficient human plasmas.Our results showed that PGS,PMS,and their oligosaccharides had better anticoagulant activity than that of Fondaparinux in all four human plasmas tested.As expected,heparin was the best anticoagulant in normal plasma.Moreover,PGS,PGS6,PGS12,PGS25,PMS6,PMS12,and PMS25 were better anticoagulants than dermatan sulfate in HCII-deficient plasma.Most strikingly,PGS,PGS12,PGS25,PMS6,PMS12,and PMS25 were better anticoagulants than that of heparin in ATIII-and HCII-double deficient human plasma.The results revealed for the first time that sulfated alginate had ATIII-and HCII-independent anticoagulant activities.Therefore,developing PGS and PMS-based anticoagulants might require to discover their major molecular targets and to develop target-specific anticoagulant assays.展开更多
基金Supported by National Natural Science Foundation of China,No.82301924.
文摘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.
文摘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.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (CAS) (XDB29010102)National Natural Science Foundation of China (NSFC) (91957124,82161148010,32041010)+4 种基金Self-supporting Program of Guangzhou Laboratory (SRPG22-001)National Science and Technology Infrastructure of China (National Pathogen Resource Center-NPRC-32)Management Strategy of the Tertiary Prevention and Treatment of Diabetes Based on DIP system (supported by China Health Promotion Foundation)supported by the Youth Innovation Promotion Association of CAS (Y2021034)Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202208)。
文摘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.
文摘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.
文摘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.
文摘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.
文摘Exposure to heparin is associated with a high incidence of immunization against platelet factor 4(PF4)/heparin complexes. A subgroup of immunized patients is at risk of developing heparin-induced thrombocytopenia(HIT), an immune mediated prothrombotic adverse drug effect. Transplant recipients are frequently exposed to heparin either due to the underlying end-stage disease, which leads to listing and transplantation or during the transplant procedure and the perioperative period. To review the current scientific knowledge on antiheparin/PF4 antibodies and HIT in transplant recipients a systematic Pub Med literature search on articles in English language was performed. The definition of HIT is inconsistent amongst the publications. Overall, six studies and 15 case reports have been published on HIT before or after heart, liver, kidney, and lung transplantation, respectively. The frequency of seroconversion for anti-PF4/heparin antibodies ranged between 1.9% and 57.9%. However, different methods to detect anti-PF4/heparin antibodies were applied. In none of the studies HIT-associated thromboembolic events or fatalities were observed. More importantly, in patients with a history of HIT, reexposure to heparin during transplantation was not associated with thrombotic complications. Taken together, the overall incidence of HIT after solid organ transplantation seems to be very low. However, according to the current knowledge, cardiac transplant recipients may have the highest risk to develop HIT. Different alternative suggestions for heparin-free anticoagulation have been reported for recipients with suspected HIT albeit no official recommendations on management have been published for this special collective so far.
文摘Aim: The objective of this study is to review all the reported outcomes of heparin application in amniotic fluid embolism (AFE) so far and to find out why, when and how heparin or other anticoagulants should be used in AFE. Material and methods: We searched Medline (from 1969 to 2011), using two key words: 1) amniotic fluid embolism;2) amniotic fluid embolism and heparin. The search for the former produced 1127 replies, of which 208 were case reports of AFE. In response to the other key word, there were 94 articles. We looked through all the articles, selecting those relevant for our study. Results: In the years 1969-2011, 208 AFE cases were reported. Heparin (unfractionated heparin) or low molecular weight heparin (LMWH) was applied in 20 cases (9.6%), being the main drug in 11 cases (5.3%) and in 6 cases as a component of spectacular treatment of AFE (surgical treatment and extracorporal membrane oxygenation). In one of these cases anithrombin (AT) with LMWH was used. In one patient heparin therapy was considered to be unsuccessful and hence recombinant plasminogen activator (rt-PA) was instituted. All the patients survived. Conclusions: 1) The attempts to use heparin in AFE could be defined as promising, although the number of treated patients is too small for conclusion;2) The postulate to use heparin at the very onset of AFE (a bolus of 10,000 U followed by monitored intravenous infusion) has serious justification: one of the pathways of AFE is the target for heparin (coagulation pathway).
文摘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.
文摘Heparin-induced thrombocytopenia (HIT) is a clinicopathologic syndrome because diagnosis is based on both clinical symptoms and laboratory data. We report a patient with multiple thromboembolic complications after daily flushing of intravenous line with small amounts of unfractionated heparin (UFH). At day 7 bilateral hemorrhagic infarction of the adrenal glands was misdiagnosed as adrenal adenoma. On day 10 thrombocytopenia was noted and the next day a myocardial infarction complicated by a left ventricular thrombus was diagnosed. On day 12, HIT was suspected. The pre-test probability for HIT according to the 4T-score was high (8/8 points) and detection of antibodies directed against the PF4/heparin-complex by particle gel immunoassay (Titer 1:1024) and ELISA (O.D. 2.784) was strongly positive. HIT can be induced by iv-line flushes with UFH. Arterial and venous thrombotic complications can be present before a clear platelet drop can be recognised.
文摘Objective This study was designed to evaluate the efficacy and safety of aspirin-heparin treatment for un-explained recurrent spontaneous abortion(URSA). Methods Literatures reporting the studies on the aspirin-heparin treatment of un-explained recurrent miscarriage with randomized controlled trials(RCTs) were collected from the major publication databases. The live birth rate was used as primary indicator, preterm delivery, preeclampsia, intrauterine growth restriction, and adverse reactions(thrombocytopenia) were used as the secondary indicators. The quality of the included studies was evaluated using RCT bias risk assessment tool in the Cochrane Handbook(v5.1.0). Meta-analysis was conducted using RevM an(v5.3) software. Subgroup analyses were conducted with an appropriately combined model according to the type of the treatments if heterogeneity among the selected studies was detected. Results Six publications of RCTs were included in this study. There were a total of 907 pregnant women with diagnosis of URSA, 367 of them were pooled in the study group with aspirin-heparin therapy and 540 women in the control group with placebo, aspirin or progesterone therapy. Meta-analysis showed that the live birth rate in the study group was significantly different from that in the control group [RR = 1.18, 95% CI(1.00-1.39), P=0.04]. Considering the clinical heterogeneity among the six studies, subgroup analysis were performed. Live birth rates in the aspirin-heparin treated groups and placebo groups were compared and no significant difference was found. There were no significant differences found between the two groups in the incidence of preterm delivery [RR=1.22, 95% CI(0.54-2.76), P=0.64], preeclampsia [RR=0.52, 95% CI(0.25-1.07), P=0.08], intrauterine growth restriction [RR=1.19, 95% CI(0.56-2.52), P=0.45] and thrombocytopenia [RR=1.17, 95% CI(0.09-14.42), P=0.90]. Conclusion This meta-analysis did not provide evidence that aspirin-heparin therapy had beneficial effect on un-explained recurrent miscarriage in terms of live birth rate, but it was relatively safe for it did not increase incidence of adverse pregnancy and adverse events. More well-designed and stratified double-blind RCT, individual-based meta-analysis regarding aspirin-heparin therapy are needed in future.
文摘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.
文摘AIM: To evaluate the effect of chronic thrombin inhibition by heparin on experimentally induced chronic liver injury (liver fibrosis) in rats. METHODS: Chronic liver injury (liver fibrosis) was induced in Wistar rats by oral administration of carbon tetrachloride (CCl 4 ) for 7 wk, an animal model with persistent severe hepatic fibrosis. Intravenous administration of the thrombin antagonist (heparin) started 1 wk after the start of CCl 4 intoxication for 6 wk. After completion of treatment (7 wk), markers of hepatic dysfunction were measured and changes evaluated histopathologically. RESULTS: Higher serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), total, direct and indirect bilirubin levels, as well as lower fibrinogen levels, were found in CCl 4 intoxicated rats. Heparin, silymarin and combination of drug (heparin and silymarin) treatment for 6 wk prevented a rise in SGOT, SGPT, ALP, total, direct and indirect bilirubin levels and improved fibrinogen levels. Deterioration in hepatic function determined by the fibrosis area was retarded, as evident from hepatic histopathology. Total protein levels were not changed in all groups.CONCLUSION: Heparin, a thrombin antagonist, preserved hepatic function and reduced severity of hepatic dysfunction/fibrogenesis. Combination of heparin and silymarin produced additional benefits on liver fibrosis.
基金The University of Arizona Hematology and Medical Oncology Fellowship program
文摘BACKGROUND Gastrointestinal cancer(GICA)is associated with a higher incidence of venous thromboembolism(VTE)compared to other solid tumors,moreover,recurrent VTE and major bleeding(MB)complications during anticoagulation treatment have an associated increase rate.GICA-VTE remains a challenging clinical scenario with MB concerns for utilization of direct oral anticoagulants(DOAC),especially with active cancer therapies.AIM To evaluate patient risk factors,effectiveness(VTE)and safety(MB)of DOACs and low molecular weight heparin(LMWH)in patients with active GICA-VTE.METHODS A retrospective chart review of patients receiving DOACs and LMWH with GICA and symptomatic or incidental VTE treated at comprehensive cancer center from November 2013 to February 2017 was performed.Inclusion criteria included active GI cancer diagnosed at any stage or treatment+/-6 mo of VTE diagnosis,whom were prescribed 6 mo or more of DOACs or LMWH.The Chi-squared test was used for overall and the Fisher exact test for pairwise comparisons of the proportions of patients experiencing recurrent VTE and MB events.Odds ratios were used to compare the relative odds of the occurrence of the outcome given exposure to the risk factor.RESULTS A total of 144 patients were prescribed anticoagulation,in which 106 fulfilled inclusion criteria apixaban(27.3%),rivaroxaban(34.9%)and enoxaparin(37.7%),and 38 were excluded.Patients median age was 66.5 years at GICA diagnosis and 67 years at CAVTE event,with 62%males,80%Caucasian,70%stage IV,pancreatic cancer(40.5%),30%Khorana Score(≥3 points),and 43.5%on active chemotherapy.Sixty-four percent of patients completed anticoagulation therapy(range 1 to 43 mo).Recurrent VTE at 6 mo was noted in 7.5%(n=3),6.8%(n=2)and 2.7%(n=1)of patients on enoxaparin,apixaban and rivaroxaban,respectively(all P=NS).MB at 6 mo were 5%(n=2)for enoxaparin,6.8%(n=2)for apixaban and 21.6%(n=8)for rivaroxaban(overall P=0.048;vs LMWH P=0.0423;all other P=NS).Significant predictors of a primary or secondary outcome for all anticoagulation therapies included:Active systemic treatment(OR=5.1,95%CI:1.3-19.3),high Khorana Score[≥3 points](OR=5.5,95%CI:1.7-17.1),active smoker(OR=6.7,95%CI:2.1-21.0),pancreatic cancer(OR=6.8,95%CI:1.9-23.2),and stage IV disease(OR=9.9,95%CI:1.2-79.1).CONCLUSION Rivaroxaban compared to apixaban and enoxaparin had a significantly higher risk of MB on GICA-VTE patients with equivocal efficacy.
文摘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.
文摘Background The pathogenesis of diabetic nephropathy (DN) is a complex pathophysiological process.Its precise mechanism is not fully known. In recent years it has been recognized that synthesis of various extracelluar matrix (ECM) components may increase, and that degradation of ECM may decrease in DN. It was reported heparin could inhibit mesangial cells proliferation in vitro. The main aim of this study is to explore whether heparin inhibits proliferation of mesangial cells grown in high glucose concentration and to measure the effect of heparin on matrix metalloproteinases (MMPs) expression in mesangial cells. Methods The medium contained either low glucose (5 mmol/L) or high glucose (25 mmol/L). The concentrations of heparin in the culture medium were 0, 25, 50,100, 200 or 400 μg/mL. A metabolic (WST-1) assay was used to measure mesangial cell proliferation and Western blot analysis was used to measure MMPs expression of mesangial cells. Results Normal human mesangial cell (NHMC) proliferation was higher in high glucose (HG) medium than in low glucose (LG) medium. They showed a 1.93 fold expansion after 72 h in high glucose in contrast to a 1.63 fold expansion in low glucose. In the presence of heparin, mesangial cells proliferation was inhibited, which was more obvious at high glucose concentrations than at low glucose concentrations. In high glucose, with heparin concentration of 50, 100, 200 and 400 μg/mL, the mesangial cells showed a 0. 61 fold, 0.52 fold, 0.52 fold and 0.41 fold reductions in cell number compared to cells grown without heparin. In low glucose, only concentrations of 200 μg/mL and 400 μg/mL showed reduction in cell number, namely 0.54 fold and 0.45 fold, when compared to cells grown without heparin. In Western blot analysis,MMP1, MMP2, MMP3 and MMP9 was expressed by mesangial cells expressed in both high and low glucose concentrations, which was more prominent in high glucose medium. Incubation of heparin further increased expression of MMP1, MMP2, MMP3 and MMP9. Conclusions This study suggests that glucose can accelerate mesangial cell proliferation while heparin can reduce proliferation, being more obvious at high glucose concentrations. Higher glucose concentrations led to increased MMP expression, which may take part in the regulation of mesangial matrix synthesis and degradation. Addition of heparin resulted in a corresponding increase in MMP expression, most notably at high glucose concentrations, indicating a potentially renoprotective role in DN.
基金supported by the National Natural Science Foundation of China(No.91129706)NSFCShandong Joint Fund(No.U1406402)Taishan Scholar Special Fund of Shandong Province in China(L.Z.)
文摘Cardiovascular disease is the leading causes of death.However,the complications can be treated with heparin and heparinoids,such as heparin pentasaccharide Fondaparinux,dermatan sulfate,and PSS made from alginate extracted from brown seaweeds by chemical sulfation.Alginate is composed of a linear backbone of polymannuronate(PM),polyguluronate(PG),and alternate residues of mannuronic acid and guluronic acid.It is unknown if heparin and sulfated PG(PGS)/PM(PMS) have the same or different anticoagulant molecular targets.In the current study,the anticoagulant activities of PGS,PMS,and their oligosaccharides were directly compared to that of heparin,Fondaparinux,and dermatan sulfate by the activated partial thrombinplastin time(aP TT) assay using normal,antithrombin III(ATIII)-deficient,heparin co-factor II(HCII)-deficient,and ATIII-and HCII-double deficient human plasmas.Our results showed that PGS,PMS,and their oligosaccharides had better anticoagulant activity than that of Fondaparinux in all four human plasmas tested.As expected,heparin was the best anticoagulant in normal plasma.Moreover,PGS,PGS6,PGS12,PGS25,PMS6,PMS12,and PMS25 were better anticoagulants than dermatan sulfate in HCII-deficient plasma.Most strikingly,PGS,PGS12,PGS25,PMS6,PMS12,and PMS25 were better anticoagulants than that of heparin in ATIII-and HCII-double deficient human plasma.The results revealed for the first time that sulfated alginate had ATIII-and HCII-independent anticoagulant activities.Therefore,developing PGS and PMS-based anticoagulants might require to discover their major molecular targets and to develop target-specific anticoagulant assays.
