BACKGROUND: The incidence of pulmonary embolism (PE) in lung cancer patients who underwent surgery increased during the perioperative period, and prophylactic anticoagulation therapy was important part of enhanced recovery after surgery (ERAS). However, the timing of preventive anticoagulation in patients with lung cancer remained controversial. This study was designed to investigate the safety and efficacy of perioperative prophylactic anticoagulation therapy for lung cancer patients. METHODS: Retrospective research was conducted on 562 lung cancer patients who underwent video-assisted thoracoscopic (VATS) anatomic pulmonary resections in West China Hospital from June 2016 to December 2016. 56 patients were treated with low molecular weight heparin (LMWH) anticoagulation 12 hours before operation until discharge, while the other 506 patients were treated with LMWH 24 hours after operation until discharge. The postoperative chest drainage volume, postoperative bleeding, pulmonary embolism incidence, and respiratory complications were analyzed. RESULTS: (1) There were no significant differences in prothrombin time (PT), activated partial thromboplastin time (APTT) and international normalized ratio (INR) between the pre-operation prophylactic anticoagulation group (PRE group) [(11.5±3.9) s, (27.8±3.5) s, (0.96±0.06) s] and the post-operation prophylactic anticoagulation group (POST group) [(11.4±1.4) s, (28.3±4.0) s, (0.98±0.07) s] (P=0.796, P=0.250, P=0.137), and there was no significant difference in Caprini score between the PRE group (3.1±1.8) and the POST group (3.3±1.5) (P=0.104). (2) There were no significant differences in anesthesia time and intraoperative bleeding between PRE group [(130.2±53.9) min, (76.8±49.3) mL] and POST group [(142.2±56.5) min, (73.7±41.6) mL] (P=0.067, P=0.201). (3) The total drainage volume in 72 hours after operation in PRE group [(728.1±505.7) mL] was significantly higher than that of POST group [(596.4±373.5) mL] (P=0.005), while there were no significant differences between the two groups in total postoperative drainage volume [(1,066.8±1,314.6) mL vs (907.8±999.8) mL, P=0.203]. (4) There were no significant differences between the two groups in pulmonary embolism incidence (1.785% vs 0.019%, P=0.525) and postoperative bleeding rates (1.785% vs 0.039%, P=0.300). (5) There were no significant differences between PRE group and POST group in subcutaneous emphysema incidence (1.785% vs 1.581%, P=0.989) and pulmonary infection rates (14.285% vs 6.324%, P=0.085). CONCLUSIONS The clinical value of preoperative prophylactic anticoagulation is equal to postoperative prophylactic anticoagulation for lung cancer patients.
Adult ; Aged ; Anticoagulants ; pharmacology ; Female ; Heparin, Low-Molecular-Weight ; pharmacology ; Humans ; Lung Neoplasms ; surgery ; Male ; Middle Aged ; Perioperative Period ; Postoperative Complications ; etiology ; prevention & control ; Retrospective Studies ; Safety ; Young Adult

OBJECTIVETo evaluate the anticoagulant and antineoplastic activities of chemically modified low-molecular-weight heparin (LMWH).

METHODSLMWH obtained by splitting unfractionated heparin (UFH) with sodium periodate oxidation and sodium borohydride reduction was subjected to acetylation catalyzed by DCC and DMAP to produce acetylated LMWH (ALMWH). The anticoagulant activity of ALMWH was determined in mice, and its antiproliferative and anti-invasion activities was assessed in human breast cancer cells MDA-MB-231 and MFC-7.

RESULTSThe anticoagulant activity of LMWH was decreased significantly after acetylation. The concentrations of commercial LMWH* and ALMWH for doubling the coagulation time (CT) were 33.04 µmol/L and 223.56 µmol/L, respectively, and the IC(50) of ALMWH for doubling CT was 6 times of that of LMWH*. ALMWH and LMWH at 0.1, 0.3, 0.9, 2.7 and 8.1 mmol/L both significantly inhibited the proliferation of MDA-MB-231 and MCF-7 cells in a concentration-dependent manner, but ALMWH produced stronger inhibitory effects. The IC(50) of LMWH and ALMWH for inhibiting cell proliferation was 3168.4 µmol/L and 152.6 µmol/L in MCF-7 cells, and 12299.6 µmol/L and 22.2 µmol/L in MDA-MB-231 cells, respectively. ALMWH and LMWH all markedly suppressed the invasion of MDA-MB-231 cells with comparable effects.

CONCLUSIONChemical modification of structure can endow LMWH with a low anticoagulant and high antiproliferative activities.

Animals ; Anticoagulants ; chemistry ; pharmacology ; Antineoplastic Agents ; chemistry ; pharmacology ; Blood Coagulation ; Blood Coagulation Tests ; Cell Line, Tumor ; Heparin ; chemistry ; Heparin, Low-Molecular-Weight ; chemistry ; pharmacology ; Humans ; Mice

OBJECTIVETo establish the rat model of acute pulmonary embolism, and study the changes of vascular active substances in pulmonary embolism rats, and investigate the interventive effect of anticoagulant drugs on vascular active substances.

METHODSOne hundred and twenty-eight rats were randomly divided into four groups: control group, model group, low-molecular-weight heparin and warfarin treated group and rivaroxaban-treated group (n = 32 in each group). The method of autologous thrombosis was used to establish the animal model of acute pulmonary embolism. The animals were treated with saline or different anticoagulant drugs. The physiological and biochemical parameters were detected at different time points after embolization. The rats were killed after embolism of 24 h, 3 d, 5 d or 1 week respectively and the pathologic samples of lung tissues were collected to analyze the pulmonary pathological changes in different groups.

RESULTSRats in embolization group after blood clots injection showed shortness of breath, oral cyanosis; quicken heart rates and other symptoms. All embolization groups had pulmonary hypertension, the levels of type B natriuretic peptide (BNP) were increased significantly. The ratio of endothelin-1 (ET-1)/NO and thromboxane (TXB2) and prostacyclin (6-k-PGFla) were abnormal. After treated with effective anticoagulant drugs, the levels of BNP, ET-1, NO, TXB2 and 6-k-PGF1a were tended to the normal levels in the control group. The pulmonary hypertensions were gradually decreased. The efficacy of rivaroxaban on pulmonary embolism was the same as that of the low molecular weight heparin or warfarin.

CONCLUSIONAnticoagulation therapy can effectively improve endothelial function after pulmonary embolism, reduce pulmonary hypertension, and revise the increased BNP levels to normal levels. The efficacy of rivaroxaban is not inferior to that of low molecular weight heparin and warfarin.

Animals ; Anticoagulants ; pharmacology ; Disease Models, Animal ; Endothelin-1 ; metabolism ; Heparin, Low-Molecular-Weight ; pharmacology ; Hypertension, Pulmonary ; drug therapy ; metabolism ; Lung ; pathology ; Morpholines ; pharmacology ; Pulmonary Embolism ; drug therapy ; metabolism ; Rats ; Rivaroxaban ; Thiophenes ; pharmacology ; Warfarin ; pharmacology

OBJECTIVE: To explore the effects of low molecular weight heparin (LMWH) on cisplatin (DDP)- induced apoptosis in human hepatocellular carcinoma cell and the underlying mechanisms.
 METHODS: Hepatocellular carcinoma SMMC-7721 cells were divided into a control group, a LMWH group, a DDP group and a LMWH plus DDP group. The effect of the drugs on proliferation of hepatocellular carcinoma SMMC-7721 cells were evaluated by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay, and the apoptosis were detected by acridine orange/ethidium bromide (AO/EB) double fluorescence method and flow cytometry method. The expression levels of apoptosis-related protein Fas, Bcl-2 and Bax were detected by quantitative real-time PCR and Western blot.
 RESULTS: Compared with the control group, the proliferation of SMMC-7721 cells was inhibited in the DDP group and the LMWH plus DDP group (both P<0.05). The mRNA and protein levels of Fas, Bcl-2, Bax in the SMMC-7721 cells were not obviously changed in the LMWH group (all P>0.05). The Fas level was increased obviously (P<0.05), while the Bcl-2 level moderately reduced (P<0.05), Bax were not obviously changed in the DDP group (P>0.05). Compared with the control group and the DDP group, the Bcl-2 level was reduced significantly in the LMWH plus DDP group (both P<0.05), while the level of Bax was increased obviously (both P<0.05). Compared with control group, the Fas level was increased significantly in the LMWH plus DDP group (P<0.05), but the increase was not significant compared with the DDP group (P>0.05).
 CONCLUSION LMWH can enhance the cisplatin-induced apoptosis in SMMC-7721 cells, which might be related to activation of mitochondrial pathway.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; pathology ; Cell Line, Tumor ; drug effects ; Cisplatin ; pharmacology ; Flow Cytometry ; Heparin, Low-Molecular-Weight ; pharmacology ; Humans ; Liver Neoplasms ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Real-Time Polymerase Chain Reaction ; bcl-2-Associated X Protein ; metabolism ; fas Receptor ; metabolism

OBJECTIVETo investigate the anti-cancer effect of low-molecular-weight heparin (LMWH) combined with doxorubicin and explore the mechanism.

METHODSHepatocellular cancer HepG2 cells exposed to LMWH, doxorubicin, or both were evaluated for cell viability with MTT assay and for changes in their migration ability using wound healing assay and Transwell migration assay. The changes in cellular expressions of matrix metalloproteinase-9 (MMP-9) and MMP-2 mRNA and proteins were analyzed with quantitative real-time PCR (qRT-PCR) and Western blotting, and ELISA was used to determine heparanase (HPA) concentration in the cell culture medium.

RESULTSHepG2 cells exhibited suppressed proliferation in response to LMWH and doxorubicin treatments. The combined treatment caused a significantly higher inhibition rate of cell migration than LMWH and doxorubicin alone. LMWH enhanced doxorubicin-induced down-regulation of MMP-9, MMP-2 and HPA in the cells.

CONCLUSIONSLMWH can enhance the inhibitory effect of doxorubicin on the migration of HepG2 cells, the mechanism of which may involve the down-regulation of MMP-9, MMP-2 and HPA expressions.

Cell Movement ; drug effects ; Cell Survival ; Down-Regulation ; Doxorubicin ; pharmacology ; Glucuronidase ; chemistry ; Hep G2 Cells ; Heparin, Low-Molecular-Weight ; pharmacology ; Humans ; Liver Neoplasms ; pathology ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Neoplasm Invasiveness ; RNA, Messenger ; Real-Time Polymerase Chain Reaction

BACKGROUNDDue to lack of point-of-care testing, the use of low-molecular-weight heparin (LMWH) therapy in some special patients is restricted. This study was designed to explore the effects of LMWH on clot rate (CR) and activated clotting time (ACT), and to search for an appropriate method for bedside monitoring of anticoagulant activity of LMWH.

METHODSThirty-two healthy volunteers were selected from the staff of Beijing Tongren Hospital. CR and ACT were measured with different reagents (glass beads, diatomite, kaolin and magnetic bar) on blood samples spiked with increasing concentrations of LMWH (dalteparin, 0.2-1.8 IU/ml). Correlations between concentrations of LMWH and values of CR and ACT were analysed based on the data obtained and regression analysis was performed to establish a regression equation.

RESULTSWith the increase in doses of dalteparin, CR values reduced gradually. The values of CR of four reagents (glass beads, diatomite, kaolin and magnetic bar) were 20.4-4.5 IU/min, 27.4-6.9 IU/min, 27.5-7.9 IU/min and 7.8-0.1 IU/min respectively and an linear relationship was observed between the CR values and dalteparin concentrations (P < 0.05). The values of ACT were 173-615 seconds, 130-270 seconds, 123-226 seconds, 337-1411 seconds respectively, which showed a linear regression between the ACT values and dalteparin concentrations (P < 0.01). Differences in slope of the regression curves of ACT were observed with all the reagents tested (glass beads 248.2 s/IU, diatomite 74.8 s/IU, kaolin 58.2 s/IU and magnetic bar 1112.2 s/IU, P < 0.01). While the minimum concentration of dalteparin was 0.2 IU/ml, 0.4 IU/ml, 1.4 IU/ml and 0.2 IU/ml separately, the ACT values of the four coagulants (glass beads, diatomite, kaolin and magnetic bar) were beyond the normal limit and showed a noticeable increase respectively (P < 0.01).

CONCLUSIONSThis study showed that there was an excellent linear relationship between the CR and ACT values and dalteparin concentrations for all the four reagents (glass beads, diatomite, kaolin and magnetic bar) in vitro. The sensitivity of different coagulation reagents to LMWH different. Choosing a suitable reagent, both CR and ACT were possible to be used as a convenient bedside test for LMWH.

Adult ; Anticoagulants ; pharmacology ; Blood Coagulation ; drug effects ; Blood Coagulation Tests ; Female ; Heparin, Low-Molecular-Weight ; pharmacology ; Humans ; Male ; Middle Aged

PURPOSE: Postoperative adhesion is the most frequent complication of abdominal surgery. Therefore, we investigated the individual effects of synthetic barrier [hyaluronic acid/carboxymethylcellulose (HA/CMC)] and pharmacologic agents [low molecular weight heparin (LMWH) cyclo-oxygenase-2 inhibitor (COX-2 inhibitor)] using animal model of intra-abdominal adhesion. MATERIALS AND METHODS: The cecum was rubbed with sterile alcohol wet gauze until subserosal haemorrhage and punctate bleeding developed under the general anesthesia. Five animal groups were prepared using the film HA/CMC, gel HA/CMC, LMWH and COX-2 inhibitor. RESULTS: The grade of adhesion by modified Leach method for group I (control), II (film type HA/CMC), III (gel type HA/CMC), IV (LMWH) and V (COX-2 inhibitor) were 5.35+/-1.8, 6.15+/-1.3, 4.23+/-2.6, 5.05+/-0.7 and 5.50+/-0.9, respectively. Group III showed the least grade of adhesion and it is statistically significant in adhesion formation (p=0.028). The numbers of lymphocytes were significantly low in group III and group V compared to the control group (lymphocyte: p=0.004). The mast cell counts were generally low except for the control group (I: 1.05, II: 0.35, III: 0.38, IV: 0.20, V: 0.37), however, it was not statistically significant (p=0.066). CONCLUSION: The gel barriers were shown to be partly efficient in inhibiting the formation of postoperative adhesions and might provide an option for abdominal surgery to reduce postoperative adhesions. The LMWH and COX-2 inhibitor had been known for their inhibitor effect of fibrin formation and anti-angiogenic/anti-fibroblastic activity, respectively. However, their preventive effects of adhesion and fibrosis were found to be obscure.
Animals ; Carboxymethylcellulose Sodium/metabolism ; Cyclooxygenase 2 Inhibitors/*pharmacology ; Heparin, Low-Molecular-Weight/*pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Tissue Adhesions/*prevention & control

OBJECTIVETo investigate the effect of low-molecular-weight heparin (LMWH) combined with paclitaxel (PTX) on the invasiveness and migration of nasopharyngeal carcinoma cells and explore the molecular mechanisms.

METHODSMTT assay was used to detect the growth inhibition induced by LMWH and PTX in CNE1 and CNE2 cells. Wound healing assay and Transwell migration assay were employed to assess the effects of the drugs on the cell migration, and Transwell invasion assay was used to evaluate the cell invasiveness. The cellular expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were analyzed by Western blotting. ELISA was used to determine the expression of heparanase (HPA) in the culture medium of the cells.

RESULTSMTT assay showed an obvious suppression of CNE1 and CNE2 cell proliferation in response to LMWH and PTX treatments. Treatment with 200 U·ml LMWH combined with 0.1 µmol·L PTX for 24 h resulted in the inhibition rates of migration of 66.70% and 70.53% in CNE1 and CNE2 cells, respectively significantly higher than the rates in cells with PTX treatment alone. The combined treatment with LMWH and PTX for 24 h also caused a significantly higher inhibition rate of cell invasion than LMWH and PTX alone. LMWH enhanced the down-regulation of MMP-9 and HPA induced by PTX.

CONCLUSIONLMWH can enhance the inhibitory effect of PTX on the migration and invasion of nasopharyngeal carcinoma cells, the mechanism of which may involve the down-regulation of MMP-9 and HPA expressions.

Carcinoma ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Glucuronidase ; metabolism ; Heparin Lyase ; metabolism ; Heparin, Low-Molecular-Weight ; administration & dosage ; pharmacology ; Humans ; Matrix Metalloproteinase 9 ; metabolism ; Nasopharyngeal Neoplasms ; pathology ; Paclitaxel ; administration & dosage ; pharmacology ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism

OBJECTIVETo investigate the anti-apoptotic effect of low molecular weight heparin (LMWH) in the placenta of rats with preeclampsia-like symptoms.

METHODSThirty pregnant Wistar rats were randomized equally into 3 groups and received subcutaneous saline injection (control group), 200 mg/kg L-NAME injection to induce preeclampsia symptoms (PE group), or L-NAME with 40 µl/kg LMWH injections (LMWH group). The blood pressure, urine protein, the number of pups and the weight of the fetuses and placenta were measured, and the placental apoptotic index was measured by TUNEL assay. The expression of cleaved caspase-3, Bcl-2 and Bax in the placenta were examined by Western blotting.

RESULTSCompared with the control group, L-NAME injections caused significantly increased blood pressure and urine protein (P<0.05), which were significantly lowered by LWMH (P<0.05). The number and weight of normal pups were significantly lower in PE group than in the control group (P<0.05) and LMWH group (P<0.05); in LMWH group, the weight of pups was still lower than that of the control group (P<0.05) but the number of normal pups was comparable (P>0.05). The LMWH group showed a significantly lower placental apoptosis index than the PE group (P<0.05) with also significantly lower cleaved caspase-3 and Bax and higher Bcl-2 expressions (P<0.05). The apoptosis index and expressions of cleaved caspase-3, Bcl-2 and Bax protein were similar between LMWH group and normal pregnant group (P>0.05).

CONCLUSIONLMWH can alleviate preeclampsia-like symptoms and decrease the apoptosis in the placenta of rats possibly by enhancing Bcl-2 and suppressing Bax expressions.

Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Female ; Heparin, Low-Molecular-Weight ; pharmacology ; Placenta ; cytology ; Pre-Eclampsia ; pathology ; Pregnancy ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Wistar ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo observe the clinical curative effects of lower extremity deep venous thrombosis (DVT) postoperative fracture treated by maixuekang capsule and low molecular heparin calcium (Subilin).

METHODFrom Feb 2008 to Apr 2010, 214 cases of lower extremity DVT postoperative fracture were randomly divided into experimental group and control group. The 107 cases of them were treated by maixuekang capsule based on the comprehensive treatment.

RESULTThe 89 cases were cured and improved in the observation group, but 18 cases were ineffectiveness. The 66 cases were cured and improved in the control group, but 41 cases were ineffectiveness. Maixuekang capsule group had 83. 18% (89/107) total effective rate and 61.68% (66/107) total effective rate in the control group. There was significant difference between the two groups (P < 0.05). After the treatment, the perimeter between the suffered limb and the healthy one was significantly reduced, the blood rheology examination had been improved significantly. There was also significant difference between the two groups (P < 0.05).

CONCLUSIONMaixuekang capsule for lower extremity deep vein thrombasis has good effect It has both thrombolytic and anticoagulant effects for lower extremity DVT postoperative fracture treated by maixuekang capsule and low molecular heparin calcium (Subilin). It's a recommended treatment.

Adolescent ; Adult ; Aged ; Capsules ; Female ; Fractures, Bone ; surgery ; Hemodynamics ; drug effects ; Heparin, Low-Molecular-Weight ; adverse effects ; pharmacology ; therapeutic use ; Humans ; Lower Extremity ; injuries ; surgery ; Male ; Middle Aged ; Postoperative Complications ; drug therapy ; pathology ; physiopathology ; Treatment Outcome ; Venous Thrombosis ; drug therapy ; pathology ; physiopathology ; Young Adult