OBJECTIVE: To review current status of clinical application and research progress of different anticoagulants in perioperative period of free flap transplantation. METHODS: A comprehensive review of recent relevant literature was conducted, focusing on clinical research concerning the application of anticoagulants in the perioperative period of free flap transplantation. The administration route, timing, dosage selection, effectiveness, and safety of commonly used and novel anticoagulants were summarized. RESULTS: At present, the anticoagulants mainly used in the perioperative period of free flap transplantation include drugs for venous thrombosis prophylaxis, drugs for arterial thrombosis prophylaxis, and physical/colloidal anticoagulants, etc. The administration strategies can be classified into two major categories: single-agent anticoagulation and combined anticoagulation. Single-agent anticoagulation mainly includes unfractionated heparin, low-molecular-weight heparin, aspirin, and novel anticoagulants. Combined anticoagulation is commonly a synergistic anticoagulation regimen dominated by heparin drugs, combined with aspirin, different antiplatelet drugs, and expansion agents. Studies indicate that perioperative anticoagulant administration can effectively reduce the risk of thrombosis in free flaps and improve the overall flap survival rate. However, significant differences exist in the impact of drug types, administration routes, initiation timing, and dosage intensity on efficacy and bleeding risk. A unified, standardized application protocol has not yet been established. In addition, there has been a growing number of studies on novel anticoagulant drugs. However, their superiority and optimal application strategies in the field of free flap transplantation still necessitate more high-quality evidence. CONCLUSION Perioperative anticoagulation therapy represents one of the key strategies for improving the survival rate of free flaps. However, there is still a lack of high-level evidence to establish a standard protocol. Future research should focus on the optimization of individualized anticoagulation strategies, the validation of the effectiveness of new anticoagulants, and the exploration of the advantages of different anticoagulation strategies. At the same time, attention should be paid to balancing anticoagulation and bleeding risks to promote the standardization of clinical practice and the improvement of treatment safety.
Humans ; Anticoagulants/therapeutic use* ; Free Tissue Flaps/blood supply* ; Thrombosis/prevention & control* ; Perioperative Care/methods* ; Heparin/therapeutic use* ; Heparin, Low-Molecular-Weight/administration & dosage* ; Perioperative Period ; Aspirin/therapeutic use*

PURPOSE: To investigate the incidence of venous thromboembolism (VTE) after total knee arthroplasty (TKA) with chemoprophylaxis using acetylsalicylic acid (AA) or rivaroxaban in Korean patients. MATERIALS AND METHODS: Between May 2011 and November 2013, 268 TKA patients (330 cases) were randomly allocated to 3 groups (group A: subcutaneous injection of 5,000 IU low-molecular-weight heparin for 2 days followed by oral administration of 100 mg AA for 5 days; group X7: oral administration of 10mg rivaroxaban for 7 days; and group X10: oral administration of 10 mg rivaroxaban for 10 days). Multidetector-row computed tomography (MDCT) was performed at 10 days and 3 months postoperatively to evaluate VTE changes. RESULTS: The VTE incidence was 38.2%, 20.0%, and 10.0% in groups A, X7, and X10, respectively (p < 0.001). Pulmonary embolism (PE) was identified in 19.1%, 10.0%, and 2.7% in groups A, X7, and X10, respectively (p < 0.001). Proximal or symptomatic deep vein thrombosis (DVT) occurred primarily in group A, but the incidence was not significantly different among groups. On follow-up MDCT, PE was resolved completely with treatment in 29/30 (96.7%), and so was asymptomatic distal DVT in 24/27 (88.8%) without treatment. CONCLUSIONS: Rivaroxaban had a lower incidence of overall VTE than AA, but no difference was observed in symptomatic VTE. The 10-day course of rivaroxaban had a lower incidence of overall VTE than the 7-day course.
Administration, Oral ; Arthroplasty ; Arthroplasty, Replacement, Knee ; Aspirin ; Chemoprevention ; Follow-Up Studies ; Heparin, Low-Molecular-Weight ; Humans ; Incidence ; Injections, Subcutaneous ; Knee ; Multidetector Computed Tomography ; Pulmonary Embolism ; Rivaroxaban ; Venous Thromboembolism ; Venous Thrombosis

OBJECTIVETo observe the effects of low molecular weight heparin (LMWH) on the inflammatory response and vascular injury in rat after electric burn.

METHODSA homemade regulator and transformer apparatus was used to reproduce the model of electric burn (0.5 cm×0.5 cm in size) with depth from full-thickness to full-thickness skin plus muscle and bone on the middle of the inside of right hind limb in 60 Wistar rats. The open wounds were covered with 20 g/L sulfadiazine silver paste immediately after injury. The wound condition was observed every day. The injured rats were divided into group LMWH and control group (C) according to the random number table, with 30 rats in each group. Rats in group LMWH were given subcutaneous injection of LMWH (1 U/g) in abdominal wall, 2 times a day. No other treatment was given in rats in group C. On post burn day (PBD) 3, 5, and 10, 10 rats respectively of two groups were sacrificed. The damaged tissue of wound and that around the wound (1.0 cm×0.5 cm in size) were excised, and heart blood was obtained. The pathological changes and thrombosis in damaged tissue were observed with HE, Masson, and aldehyde fuchsin staining, and the thrombosis rate was calculated. Serum contents of TNF-α and endothelin-1 were determined with ELISA. The mRNA expression of TNF-α in damaged tissue was detected with RT-PCR. Data were processed with Levene homogeneity test, analysis of variance of factorial design, LSD- t test, SNK- q test, and Friedman M nonparametric test.

RESULTS(1) The injured limb of rats was obviously swollen after electric burn, which reached deeply to the muscle and bone. Compared with those of group C, the swelling of rats subsided slightly faster and the inflammatory response was lighter in group LMWH at each time point. (2) The necrosis of damaged tissue and profuse infiltration of inflammatory cells were observed. Dilatation of blood vessels, congestion and thrombosis, and swelling, necrosis, and desquamation of vascular endothelial cells were observed in the damaged tissue. Damaged blood vessel wall, ruptured elastic fiber, loss of internal elastic membrane, and other pathological changes were observed in the damaged tissue of rats in the two groups. Above lesions were improved gradually along with the passage of time, and the improvement was more obvious in rats of group LMWH compared with that of group C on PBD 5 and 10. (3) The thrombosis rates of rats in group LMWH were obviously lower than those of rats in group C (F = 4.921, P < 0.05). The thrombosis rates of rats in group LMWH on PBD 3 and 10 were respectively (0.07 ± 0.11)% and (0.03 ± 0.05)%, which were significantly lower than those of rats in group C [(0.16 ± 0.15)% and (0.13 ± 0.18)%, with t values respectively 2.17 and 2.07, P values below 0.05]. In group LMWH, the thrombosis rate of rats on PBD 10 was obviously lower than that on PBD 3 (t = 3.61, P < 0.05). (4) The serum contents of TNF-α and endothelin-1 of rats in group LMWH were significantly lower than those of rats in group C (F = 47.161, χ(2) = 81.46, P values below 0.01). In group LMWH, TNF-α contents were respectively (71 ± 24), (74 ± 14), (72 ± 20) pg/mL, and endothelin-1 contents were respectively (20.9 ± 3.2), (19.8 ± 5.2), (18.6 ± 1.1) ng/mL on PBD 3, 5, and 10, and they were significantly lower than those of rats in group C [(195 ± 148), (96 ± 20), (159 ± 46) pg/mL and (38.8 ± 15.4), (27.9 ± 3.6), (25.6 ± 7.6) ng/mL, with t values from 3.81 to 8.05, q values from 4.41 to 7.85, P < 0.05 or P < 0.01]. (5) The mRNA expression levels of TNF-α in damaged tissue of rats in group LMWH were significantly lower than those of rats in group C (F = 199.113, P < 0.01). The mRNA expression levels of TNF-α of rats in group LMWH were respectively 0.93 ± 0.10, 1.15 ± 0.12, 1.21 ± 0.11 on PBD 3, 5, and 10, and they were significantly lower than those of group C (1.68 ± 0.15, 1.43 ± 0.12, 1.50 ± 0.13, with t values from 3.75 to 6.12, P < 0.05 or P < 0.01). In group LMWH, the mRNA expression level of TNF-α of rats on PBD 10 was obviously higher than that on PBD 3 (t = 3.61, P < 0.05).

CONCLUSIONSLMWH intervention can ameliorate vascular injury and inflammatory response of electrically burned wounds in rats, and it decreases thrombosis rate in the vessels of injured limb.

Animals ; Anticoagulants ; administration & dosage ; Burns, Electric ; blood ; complications ; therapy ; Endothelin-1 ; Heparin, Low-Molecular-Weight ; administration & dosage ; Male ; Rats ; Rats, Wistar ; Serum ; metabolism ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; blood ; Vascular System Injuries ; therapy

INTRODUCTIONThere is considerable controversy regarding the best method to prevent venous thromboembolism. In 2008, the American College of Chest Physicians (ACCP) published specific guidelines recommending the use of ow-molecular-weight heparin or warfarin, and a target international normalised ratio of 2.0-3.0 for a duration of at least 7-10 days, after elective knee arthroplasties. Many orthopaedic surgeons believe that these recommendations are biased toward reducing deep venous thrombosis (DVT), but neglect the implicated possibility of a higher incidence of wound complications. In order to enable an objective evaluation of the fit of the ACCP recommendations to the needs of our local cohort of patients, we aimed to look at the incidence of DVT in our local population.

METHODSThis study was a prospective observational study involving existing local patients in Singapore General Hospital, Singapore, who underwent total knee arthroplasty (TKA) and were on a short course of chemothromboprophylaxis (< 7 days) after the operation. The incidence of DVT in patients was evaluated using DVT imaging 4-6 days after the operation and at one month after the operation.

RESULTSIn our study cohort, the prevalence of DVT during the period between postoperative Days 4 and 6 was 12% (11% were distal DVT and 1% was proximal DVT). Only 9% of the patients had DVT one month after the operation. Using chi-square analysis, we found that there was no significant increase in the number of DVT and pulmonary embolism cases 4-6 days and 1 month after the operation (p > 0.05).

CONCLUSIONContrary to the ACCP guidelines, a short course of chemothromboprophylaxis post TKA, lasting no more than 7 days, is safe and adequate in the low-risk Asian population.

Adult ; Aged ; Aged, 80 and over ; Anticoagulants ; therapeutic use ; Arthroplasty, Replacement, Knee ; adverse effects ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Heparin, Low-Molecular-Weight ; therapeutic use ; Humans ; Incidence ; Male ; Middle Aged ; Osteoarthritis, Knee ; surgery ; Postoperative Complications ; Prognosis ; Prospective Studies ; Singapore ; epidemiology ; Treatment Outcome ; Venous Thrombosis ; epidemiology ; etiology ; prevention & control ; Warfarin ; therapeutic use

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

The difference between absorption of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) after oral and oral cavity administration were studied respectively, and the compatible enhancer for oral cavity delivery system of both drugs was found. The LMWH and UFH films were prepared with two bioadhesive materials Carbopol and alginate sodium for oral cavity delivery. The activated partial thromboplastin time (APTT) was used to determine LMWH and UFH in plasma after oral, oral cavity and sc administration in rats. The results show that the enhancer (Labrasol) can increase the absorption of LMWH and UFH through oral cavity in rats but not obviously. The oral cavity iontophoretic delivery system is a useful method to improve the absorption of LMWH and UFH through oral cavity mucosa.
Absorption ; Acrylic Resins ; Administration, Oral ; Alginates ; chemistry ; Animals ; Anticoagulants ; administration & dosage ; pharmacokinetics ; Drug Carriers ; Drug Delivery Systems ; Glucuronic Acid ; chemistry ; Glycerides ; Heparin ; administration & dosage ; pharmacokinetics ; Heparin, Low-Molecular-Weight ; administration & dosage ; pharmacokinetics ; Hexuronic Acids ; chemistry ; Injections, Intradermal ; Iontophoresis ; Male ; Mouth ; Organic Chemicals ; pharmacology ; Partial Thromboplastin Time ; Polyvinyls ; chemistry ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the efficacy and feasibility of the Chinese drugs for supplementing Qi and activating blood circulation in preventing DVT after big operations in orthopaedics and traumatology and observe the change of D-dimer before and after treatment.

METHODSeventy patients ranging in age from 39 to 94 years who were treated by big operations in orthopaedics and traumatology were divided into two groups randomly. Traditional Chinese medinine (TCM) group (group A) and western medicine group (group B). On the 2rd day after operation d-dimer was tested from both groups and the patients in group A were given one dose of TCM every day and the patients in group B were subcutaneously injected low-molecular-weight heparins calcium (LMWH). On the 8th after operation d-dimer was tested again from both groups. The parameters, such as the incidence of DVT and pulmonary thromboembolism, bleeding condition, were evaluated respectively.

RESULTThe D-dimer decreased in group A and had significant difference (P < 0.05), group B had no significant difference, there was also no significant difference between two groups. DVT was found in 1 patient in group B (1/35). Petechiae were found in 10 patients in group A (10/35) and in 26 patients in group A (26/35), which had significant difference (P < 0.05).

CONCLUSIONBoth the Chinese drugs and anti-coagulation drug can prevent the incidence of DVT effectively, and Chinese herbs are feasible in the prevention of DVT.

Adult ; Aged ; Aged, 80 and over ; Anticoagulants ; administration & dosage ; Blood Circulation ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Heparin, Low-Molecular-Weight ; administration & dosage ; Humans ; Male ; Middle Aged ; Orthopedic Procedures ; Orthopedics ; Postoperative Complications ; drug therapy ; prevention & control ; Qi ; Traumatology ; Venous Thrombosis ; drug therapy ; prevention & control