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

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

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.

Studies of Oral Preparation of Low Molecular Weight Heparin

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In vivo biodistribution of topical low molecular weight heparin-taurocholate in a neovascularized mouse cornea

AIM： To investigate the ocular biodistribution and clearance of topically administered 7-taurocholic acid conjugated low-molecular weight heparin（LHT7） in a neovascularized mouse cornea using an in vivo optical imaging system. METHODS： A total of 10 eyes of 6 to 8-week-old BALB/c mice were analyzed. Corneal neovascularization（CoNV） was induced in the inferior cornea（IC） of each animal by penetrating the stroma with two interrupted sutures. The development of CoNV was verified after one week and the area of each neovascularized region was measured. A near-infrared fluorescent probe of 20 μmol/L Cy5.5 labeled LHT7（LHT7-Cy5.5） in 0.02 mL solution was topically instilled onto the cornea in the experimental group（n=5）. Free-Cy5.5 of 20 μmol/L in 0.02 mL was instilled in the control group（n=5）. In vivo optical images were obtained before instillation and 5 min, 2, 4, and 6 h after instillation. The intensities were separately measured at the superior cornea（SC） and the IC. RESULTS： The mean CoNV areas were 1.97±0.17 mm^2 and 1.92±0.96 mm^2 in the experimental and control groups, respectively（P=0.832）. The SC remained normal in all 10 subject animals. The IC intensity of the LHT7-Cy5.5 was greater than the SC intensity at 5 min（P=0.038）, 2 h（P=0.041）, and 4 h（P=0.041） after application. The IC intensity fell to less than half of its initial value（42.9%±8.6%） at 6 h in the experimental group. In the control mice, here were no significant differences in the free-Cy5.5 intensity between the IC and SC. CONCLUSION： Topically administered LHT7 shows a high biodistribution in CoNV areas for 4 h and should be reapplied accordingly to maintain its effects. In vivo optical imaging can be a useful tool for evaluating the ocular biodistribution of a drug in an animal model.

Evaluation of the safety and effectiveness of direct oral anticoagulants and low molecular weight heparin in gastrointestinal cancer-associated venous thromboembolism

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.

Efficacy and Safety of Low Molecular Weight Heparin Prophylaxis for Venous Thromboembolism Following Lumbar Decompression Surgery

Objective To evaluate the efficacy and safety of low molecular weight heparin (LMWH) prophylaxis for venous thromboembolism (VTE) after lumbar decompression surgery. Methods Patients at high or the highest risk of VTE who underwent lumbar spine surgery in Peking Union Medical College Hospital from January 2004 to April 2011 were included in the present study. All the patients received a half dose of LMWH 6 hours after surgery followed by a full dose LMWH once per day until discharge. We recorded incidences of deep venous thrombosis (DVT), pulmonary embolism (PE), bleeding complications, and medication side effects. Results Seventy-eight consecutive patients were eligible and enrolled in this study. The mean hospital stat was 8.5±4.5 days. No symptomatic DVT, PE, or major bleeding events were observed. One patient developed wound ecchymosis, another developed wound bleeding, four had mild hepatic aminotransferase level elevation, and one developed a suspicious allergic reaction. Conclusion LMWH may be applied as an effective and safe prophylaxis for VTE in high-risk patients undergoing lumbar decompression 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.

Astrocytic effect of low molecular weight heparin-superoxide dismutase conjugate in interleukin-6 overexpressing mice following local cerebral ischemia

BACKGROUND： Studies have shown that low molecular weight heparin-superoxide dismutase conjugate exhibits a remarkable neuroprotective effect. OBJECTIVE： To investigate the effect of low molecular weight heparin-superoxide dismutase conjugate on astrocytes in an interleukin-6 （IL-6） overexpressing mice following local cerebral ischemia. DESIGN, TIME AND SETTING： Randomized, cytological, controlled, animal study was performed in the Department of Physiology and Neuroscience, Neurology and Biochemistry and Molecular Biology, Medical University of South Carolina from January 2005 to March 2005. MATERIALS： Nine IL-6 transgenic mice, irrespective of gender, were randomly divided into three groups： sham-operated, model, and treatment, with three mice in each group. With exception of the sham-operated group, right middle cerebral artery occlusion was induced in the mice. Expression of glial fibrillary acidic protein, an astrocyte marker, was determined by immunohistochemistry. Low molecular weight heparin-superoxide dismutase conjugate was purchased from Biochemistry and Biotechnique Institute, Shandong University. METHODS： Two minutes prior to ischemia induction, 0.5 mL/kg saline or 20 000 U/kg low molecular weight heparin-superoxide dismutase conjugate were administrated via the femoral artery in the model group and treatment group, respectively. The sham-operated group underwent the same protocols, with the exception of occlusion and treatment. MAIN OUTCOME MEASURES： The number of glial fibrillary acidic protein-positive cells was quantified under light microscopy （x200）. RESULTS： In the sham-operated group, there were a large number of astrocytes in the IL-6 transgenic mice. However, the cell bodies were small, and the branches were few and thin. The number of astrocytes in the model group was remarkably less than the sham-operated group. Compared to the model and sham-operated groups, the number of astrocytes significantly increased, and the cell body became larger, following treatment with low molecular weight heparin-superoxide dismutase conjugate. Astrocytes exhibited hypertrophy and hyperplasia, and the processes became longer and thicker. CONCLUSION： The low molecular weight heparin-superoxide dismutase conjugate may provide neuroprotection through astrocytic activation at the super-early stage of cerebral ischemia and reperfusion.

Clinical and Experimental Study of Low Molecular Weight Heparin in Patients with Chronic Anemia

Objective: To preliminary study the significance of low molecular weight heparin (LMWH) in the treatment patients of with anemia of chronic diseases (ACD), and the changes in the serum levels of BMP6, hepcidin and IL-6. To preliminary study the significance of low molecular weight heparin (LMWH) in the treatment the patients with anemia of chronic diseases (ACD), and the changes in the serum levels of BMP6, hepcidin and IL-6. Methods: Used LMWH (4000 u/day, 7 - 15 days) to therapy 61 patients with ACD, and ELISA method was used to determine Hepcidin and BMP6 before and after treatment, and the determination of IL-6 by Electro-chemi-luminescence, and to analyze its clinical significance. Results: 1) In all 61 cases, the levels of Hepcidin in post-therapy were 0.82 ± 0.24 mg/L, which were lower than 1.05 ± 3.83 mg/L in pre-therapy (t = 2.5726, P < 0.05). The levels of IL-6 in post-therapy were 24.88 ± 12.58 mg/L, which were lower than 38.22 ± 31.23 mg/L in pre-therapy (t = 2.9650, P < 0.05), but there were no statistically significant both Hb and BMP6 between in pre-therapy and post-therapy (all P > 0.05). However, The levels of Hb in post-therapy were higher than in pre-therapy (t = 1.9832, P < 0.05). 2) The Hb level in the tumor anemia group after treatment was 91.18 ± 15.91 g/L, which was higher than that before treatment (85.45 ± 18.33 g/L), the difference was statistically significant (t = 1.9711, P < 0.05). 3) The levels of hepcidin and IL-6 in the tumor anemia group after treatment were 0.73 ± 0.45 mg/L and 30.33 ± 28.39 mg/ml, which were lower than those before treatment (1.09 ± 0.41 mg/L and 50.76 ± 42.10 mg/ml), respectively, the difference was statistically significant (t = 3.3941, P < 0.01 and t = 2.3597, P < 0.05). 4) There was no significant difference in all indexes in tumor anemia free group (all P > 0.05). 5) Although Hb level increased slightly in the non-tumor anemia group, there was no statistical significance (P > 0.05), and there was no statistical difference in other indexes (all P > 0.05). 6) After treatment, the level of Hb was negatively correlated with Hepcidin and IL-6 (respectively r = -0.2809, t = 2.2490, P < 0.05 and r = -0.2781, t = 2.2266, P < 0.05). Hepcidin was positively related to IL-6 (r = -0.2941, t = 2.3622, P < 0.05). There was no correlation between BMP6 and Hb, Hepcidin and IL-6 levels. Conclusion: LMWH could up-regulate the levels of Hb, and better for the degree of anemia in patients with ACD. The possible mechanism is to reduce the level of Hepcidin and IL-6.

Histopathologic effects of a low molecular weight heparin on bone healing in rats:a promising adjuvant in dacryocystorhinostomy

AIM： To investigate the effect of short -term prophylactic dose of a low molecular weight heparin （LMWH） drug on the bone healing process in an animal model simulating the osteotomy obtained in dacryocystorhinostomy. METHODS： Forty male Wistar albino rats were divided into 2 groups. Subcutaneous injections of enoxaparin 1 mg/kg （enoxaparin-treated group） and saline solution （control group） were performed once daily for 4d, beginning on the first preoperative day. The osteotomy was created at the femoral diaphysis in all animals by using a Kirschner wire. Each group was further divided into 2 subgroups depending on the timing of the second operation, 14 or 21d following initial osteotomy. Patent osteotomy area on the second and the third weeks in each group were calculated by using a computer software on digital micrographs. RESULTS： The patent osteotomy areas at the second and the third weeks were significantly larger in the enoxaparin-treated group than those of the control group （P〈0.001 for each time-period）. In the control group, the patent osteotomy area at the third week of healing was significantly smaller than that of the second week （P=0.003）, whereas there was no significant difference between these two measurements in the enoxaparin-treated group （P=0.185）. CONCLUSION： Short -term administration of enoxaparin resultes in a significant alteration in bone healing at 14 and 21d after injury. LMWHs can be regarded as promising alternative adjuvants in dacryocystorhinostomy after being evaluated with further clinical and animal studies,

Effect of low molecular weight heparin therapy on maternal endothelial injury and placental pathological injury after hypertensive disorder complicating pregnancy

Objective: To study the effect of low molecular weight heparin therapy on maternal endothelial injury and placental pathological injury after hypertensive disorder complicating pregnancy. Methods: A total of 70 patients with hypertensive disorder complicating pregnancy who were treated in the hospital between September 2014 and May 2016 were divided into control group and observation group according to the random number table method, 35 cases in each group. Control group received conventional therapy, the observation group received low molecular weight heparin combined with conventional therapy, and both therapies lasted until delivery. The differences in the levels of endothelial injury indexes in serum as well as the expression of oxidative stress indexes and apoptosis molecules in the placental grinding fluid were compared between the two groups of patients. Results: After treatment, serum ET and VCAM-1 levels of both groups of patients were lower than those before treatment while NO and PGE levels were higher than those before treatment, and serum ET and VCAM-1 levels of observation group were lower than those of control group while NO and PGE levels were higher than those of control group;after delivery, AOPP and MDA levels in placental grinding fluid were significantly lower than those of control group while SOD and GSH-Px levels were higher than those of control group;Fas, p53 and caspase-3 mRNA expression in placental grinding fluid were lower than those of control group while Bcl-2 and bax mRNA expression were higher than those of control group. Conclusion: Adjuvant low molecular weight heparin therapy can help to reduce the maternal endothelial injury, reduce the systemic oxidative stress and suppress the placental cell apoptosis in patients with hypertensive disorder complicating pregnancy.

Effects of low molecular weight heparin-superoxide dismutase conjugate on serum levels of nitric oxide,glutathione peroxidase,and myeloperoxidase in a gerbil model of cerebral ischemia/reperfusion injury

BACKGROUND： Several studies have demonstrated that low molecular weight heparin-superoxide dismutase （LMWH-SOD） conjugate may exhibit good neuroprotective effects on cerebral ischemia/reperfusion injury though anticoagulation, decreasing blood viscosity, having anti-inflammatory activity, and scavenging oxygen free radicals. OBJECTIVE： To investigate the intervention effects of LMWH-SOD conjugate on serum levels of nitric oxide （NO）, glutathione peroxidase （GSH-Px）, and myeloperoxidase （MPO） following cerebral ischemia/reperfusion injury. DESIGN, TIME AND SETTING： A randomized, controlled, and neurobiochemical experiment was performed at the Institute of Biochemical Pharmacy, School of Pharmaceutical Sciences, Shandong University between April and July 2004. MATERIALS： A total of 60 Mongolian gerbils of either gender were included in this study. Total cerebral ischemia/reperfusion injury was induced in 50 gerbils by occluding bilateral common carotid arteries. The remaining 10 gerbils received a sham-operation （sham-operated group）. Kits of SOD, NO, and MPO were sourced from Nanjing Jiancheng Bioengineering Institute, China. LMWH, SOD, and LMWH-SOD conjugates were provided by Institute of Biochemistry and Biotechnique, Shandong University, China. METHODS： Fifty successful gerbil models of total cerebral ischemia/reperfusion injury were evenly randomized to five groups： physiological saline, LMWH-SOD, SOD, LMWH ＋ SOD, and LMWH. At 2 minutes prior to ischemia, 0.5 mL/65 g physiological saline, 20 000 U/kg LMWH-SOD conjugate, 20 000 U/kg SOD, a mixture of SOD （20 000 U/kg） and LMWH （LMWH dose calculated according to weight ratio, LMWH： SOD = 23.6：51）, and LMWH （dose as in the LMWH ＋ SOD group） were administered through the femoral artery in each above-mentioned group, respectively. MAIN OUTCOME MEASURES： Serum levels of NO, MPO, and GSH-Px. RESULTS： Compared with 10 sham-operated gerbils, the cerebral ischemia/reperfusion injury gerbils exhibited decreased serum levels of GSH-Px and increased serum levels of NO and MPO （P 〈 0.01）. The serum level of GSH-Px was significantly upregulated in all groups, in particular in the LMWH-SOD group （P 〈 0.01）, compared with the physiological saline group （P 〈 0.05-0.01）. Following medical treatment, serum levels of NO and MPO were significantly downregulated in all groups, in particular in the LMWH-SOD group （P 〈 0.01）. Serum levels of GSH-Px, NO, and MPO in the LMWH-SOD group were close to those in the sham-operated group （P 〉 0.05）. CONCLUSION： In cerebral ischemia/reperfusion injury, LMWH-SOD conjugate exhibits stronger neuroprotective effects on free radical scavenging, inflammation inhibition, and cytotoxicity inhibition than simple or combined application of LMWH and SOD by downregulating NO and MPO levels and upregulating the GSH-Px level.

Effect of glutamine enteral nutrition + low molecular weight heparin on systemic inflammatory response in patients with severe pneumonia

Objective: To investigate the effect of glutamine enteral nutrition + low molecular weight heparin on systemic inflammatory response in patients with severe pneumonia. Methods:A total of 52 patients with severe pneumonia who were hospitalized in this hospital between January 2017 and October 2017 were divided into glutamine group (n=26) and control group (n=26) by random number table method. Control group received conventional enteral nutrition+ low molecular weight heparin treatment, glutamine group were treated with glutamine nutrient solution on the basis of the therapy for control group, and both therapies lasted for 7 d. The differences in serum levels of inflammatory factors, oxidative stress indexes and myocardial injury indexes were compared between the two groups before and after treatment. Results: Before treatment, serum levels of inflammatory factors, oxidative stress indexes and myocardial injury indexes were not significantly different between the two groups. After 7 d of treatment, serum inflammatory factors IL-10 and IL-18 levels of glutamine group were higher than those of control group whereas IL-17, sTREM-1 and PCT levels were lower than those of control group;serum oxidative stress indexes MDA and LHP levels were lower than those of control group whereas GSH-Px and CAT levels were higher than those of control group;serum myocardial injury indexes α-HBDH, cTnⅠ, NT-ProBNP and LDH levels were lower than those of control group. Conclusion: glutamine enteral nutrition + low molecular weight heparin can effectively relieve systemic inflammatory response and oxidative stress response, and reduce the myocardial injury in patients with severe pneumonia.

LOW MOLECULAR WEIGHT HEPARIN ENHANCES THE EFFECT OF aFGF IN ACCELERATING NEOVASCULA-RIZATION

Objective To explore the potential of low molecular weight heparin (LMWH) in combination cooperated with aFGF in accelerating neovascularization in vivo. Methods Ischemic model was set up in the right hindlimbs of 28 New Zealand white rabbits. Four groups of animals treated with saline, LMWH, aFGF and aFGF plus LMWH were allocated equally in group Ⅰ, group Ⅱ, group Ⅲ and group Ⅳ respectively. Vascular neovascularization and smooth muscular thickness of the ischemic hindlimb vessels of each animal in different groups were compared with each other on the 28th day postoperatively by angiography with DSA and the standard immunoperoxidase technique. Results No significant neovascularization was seen when aFGF adiministered in low dosage by venous infusion. But when the same dosage of aFGF plus LMWH were administered by venous infusion, a significant neovascularization was observed. Conclusion LMWH can potentiate aFGF in accelerating neovascularization.

Effects of low molecular weight heparin on the function of blood coagulation and serum levels of TNF-α, CK-MB, CRP of patients with acute exacerbations of chronic obstructive pulmonary diseases and respiratory failur

Objective:To study the effects of low molecular weight heparin on the function of blood coagulation and serum levels of tumor necrosis factor-α(TNF-α), creatine kinase isoenzyme (CK-MB), C-reactive protein (CRP) of patients with acute exacerbations of chronic obstructive pulmonary diseases and respiratory failure.Methods:A total of 80 patients with acute exacerbations of chronic obstructive pulmonary diseases and respiratory failure in our hospital from June 2014 to October 2016 were enrolled in this study. The subjects were divided into the control group (n=40) and the treatment group (n=40) randomly. The control group were treated with conventional treatment, the treatment group were treated with the conventional treatment combined with low molecular weight heparin. The two groups were treated for 7 d. The D-dimer (D-D), fibrinogen (FBG), pro thrombin time (PT), thrombin time (TT), TNF-α, CK-MB and CRP of the two groups before and after treatment were compared.Results:There were no significantly differences of the blood levels of D-D, FBG, PT and TT of the two groups before treatment. After treatment, the blood levels of D-D and FBG of the two groups were significantly lower than before treatment, and that of the treatment group were significantly lower than the control group, the PT and TT of the two groups were significantly higher than before treatment, and that of the treatment group were significantly higher than the control group. There were no significantly differences of the serum levels of the TNF-α, CK-MB and CRP of the two groups before treatment. After treatment, the serum levels of the TNF-α, CK-MB and CRP of the two groups were significantly lower than before treatment, and that of the treatment group were significantly lower than the control group.Conclusion:Low molecular weight heparin can significantly reduce the inflammatory factors of the patients with acute exacerbations of chronic obstructive pulmonary diseases and respiratory failure, can alleviath the patients conditions and reduce the myocardial damage.

Thrombin Generation Increasing with Age and Decreasing with Use of Heparin Indicated by Calibrated Automated Thrombogram Conducted in Chinese

Objective Calibrated Automated Thrombogram（CAT） is a test to monitor the generation of thrombin. It can be described by four parameters： lag time, peak thrombin, endogenous thrombin potential （ETP） and time to peak （ttPeak）. This study aims to determine the normal ranges of CAT parameters in Chinese, and evaluate whether thrombin generation is correlated with the concentration of heparin/Iow molecular weight heparin. Methods Plasma from 120 healthy subjects were collected to determine the normal rangea of CAT parameters in Chinese. Normal plasma pool （NPP, n=25） spiked with different concentrations of heparin or enoxaparin were used to detecte CAT parameters. The overall and age specific normal ranges of CAT parameters were calculated using descriptive statistics method with mean＋-2SD. The correlation between CAT parameters and age or concentrations of heparin, enoxaparin were analyzed with linear regression model. Results The normal ranges for lag time, peak thrombin, ETP, ttPeak in the subjects were 3.648＋2.465 min, 367.39＋151.93 nmol/L, 2277＋_1030 nmol/L.min and 6.372＋_4.280 min respectively. Age was linearly correlated with lag time （r=-0.6583, P〈0.0002）, peak thrombin （r=0.4863, P〈0.0002）, ETP （r=0.3608, P〈0.0014） and ttPeak （r=-0.6323, P〈0.0002）. The values of ETP/peak ratio were linearly correlated with concentrations of heparin. Conclusion The normal ranges of four CAT parameters for Chinese were determined. CAT parameters are associated with age. ETP/peak ratio could be used to monitor the process of anticoagulation therapy.

Heparin and other anticoagulants in amniotic fluid embolism(AFE):Literature review and concept of the therapy

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).

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.

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.