BACKGROUNDTo systematically evaluate the prophylaxis efficacy of low-molecular-weight heparin (LMWH) in the prevention of deep venous thrombosis (DVT) after total knee arthroplasty (TKA).METHODPubMed, Cochrane, Embase, Wanfang, CNKI, and VIP databases were searched by index words to identify the eligible RCTs; relevant literature sources were also searched. The latest research was conducted in March 2017. Relative risks (RR), mean difference (MD), and their corresponding 95% confidence intervals (95% CIs) were used to analyze the main outcomes.RESULTA total of 22 articles were included in the meta-analysis with a total number of 11,320 patients (5543 in the LMWH group and 5777 in the control group). The results indicated that in the LMWH group, the incidence of DVT (OR: 0.57, 95% CI: 0.41-0.77) and wound complications (SMD: 0.96, 95% CI: 0.75-1.22) was significantly lower than that in the control group. Furthermore, LMWH also increased the occurrence of bleeding event (OR: 1.57, 95% CI: 1.31-1.88) and the total blood transfused (SMD: 0.12, 95% CI: 0.04-0.19). However, no statistical difference was found in blood loss (SMD: -0.26, 95% CI: -0.65-0.14) between the two group. In the subgroup analysis, the incidence of DVT was significantly decreased in the ardeparin sodium group (OR: 0.70, 95%CI: 0.53-0.94) and the dalteparin group (OR:0.40, 95%CI:0.32-0.50).CONCLUSIONOur meta-analysis demonstrated that LMWH is obviously efficacious in the prophylaxis of DVT after TKA. However, it has some negative effects, such as the increase in the number of bleeding events and the total blood transfused.

01 Jan 2017·Cellular Physiology and Biochemistry

Effectiveness and Tolerability of Anticoagulants for Thromboprophylaxis after Major Joint Surgery: a Network Meta-Analysis

Article

Author: Xiang, Yungai ; Zhao, Yongqiang ; Wang, Zhen ; Chen, Xiao ; Jin, Yi ; Zheng, Jia

Background/Aims: Venous thromboembolism (VTE) is the most common complication after major joint surgery. VTE can easily develop into pulmonary embolism (PE), leading to cardiopulmonary dysfunction or sudden death. We aimed to comprehensively analyse the thromboprophylactic drugs that are used to prevent thrombosis and reduce bleeding risk. Methods: We searched the PubMed, EMBASE, and Cochrane databases for randomized controlled trials that evaluated the use of thromboprophylaxis after major joint surgery. The major outcomes were the numbers of all-cause VTE and bleeding events, and the secondary outcomes were major VTE and major bleeding/clinically relevant non-major bleeding events. A random-effects network meta-analysis was used to assess the effectiveness and tolerability of each anticoagulant after major joint surgery. Results: We included 104 trials that assessed 110,643 patients in our meta-analysis. The cluster ranking of major outcomes indicated that FXI-ASO, ardeparin, aspirin, and apixaban were ideal for preventing all-cause VTE and avoiding all bleeding events. Nadroparin, recombinant hirudin, and rivaroxaban effectively inhibited VTE but were associated with a high risk of bleeding. For secondary outcomes, we found that betrixaban, dalteparin, warfarin, and eribaxaban were ideal for preventing major VTE and reducing major bleeding, while rivaroxaban effectively inhibited major VTE but was associated with a high risk of major/clinically relevant non-major bleeding. A sensitivity analysis showed that the effect of apixaban was more robust for major outcomes, while aspirin was more robust for preventing all-cause bleeding events. In secondary outcomes, the effect of warfarin was more robust, while apixaban was still considered an ideal treatment to inhibit major VTE and bleeding events. Conclusion: Our study indicates that FXI-ASO, ardeparin, aspirin, and apixaban are ideal for preventing all-cause VTE and reducing all bleeding events, among which apixaban is the most reliable. Betrixaban, dalteparin, warfarin, and eribaxaban are ideal for preventing major VTE and reducing major/clinically relevant non-major bleeding events, among which warfarin is the most reliable.

01 May 2006·Journal of Pharmacy and PharmacologyQ3 · MEDICINE

Modulation of gastrointestinal permeability of low-molecular-weight heparin by L-arginine: in-vivo and in-vitro evaluation

Q3 · MEDICINE

Article

Author: Motlekar, Nusrat Abbas ; Youan, Bi-Botti Celestin ; Srivenugopal, Kalkunte Srirangachar ; Wachtel, Mitchell S

AbstractL-Arginine is the principal physiological precursor of nitric oxide (NO, a key neurotransmitter) that plays a versatile role in the physiology of the gastrointestinal tract. In this study, the efficacy of L-arginine in enhancing intestinal absorption of ardeparin, a low-molecular-weight heparin (LMWH) was investigated in Caco-2 cell monolayers and a rat model. Regional permeability studies using rat intestine were performed using a modified Ussing chamber. Cell viability in the presence of various concentrations of enhancer was determined by MTT assay. Furthermore, the eventual mucosal epithelial damage was histologically evaluated. LMWH formulated with L-arginine was administered orally to male Sprague-Dawley rats and the absorption of LMWH was determined by measuring plasma anti-factor Xa activity. Higher ardeparin in-vitro permeability (∼3 fold) compared with control was observed in the presence of 2% L-arginine. Regional permeability studies indicated predominant absorption in the colon region. Cell viability studies showed no significant cytotoxicity below 0.8% L-arginine. The oral bioavailability of ardeparin formulated with L-arginine (250 mg kg−1) was increased by ∼2 fold compared with control. The formulation was well tolerated by the rats and no abnormal histopathological findings were observed in intestinal tissues of rats exposed to L-arginine. These results suggest that L-arginine may be useful in enhancing the intestinal absorption of LMWHs.

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