Low molecular weight heparin for prevention of microvascular occlusion in digital replantation

  • Review
  • Intervention


  • Yi-Chieh Chen,

    1. Chang Gung University, College of Medicine, Taoyuan, Taiwan
    2. Chang Gung Memorial Hospital, Department of Plastic and Reconstructive Surgery, Taoyuan, Taiwan
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  • Ching-Chi Chi,

    1. Chang Gung University, College of Medicine, Taoyuan, Taiwan
    2. Chang Gung Memorial Hospital, Department of Dermatology and Centre for Evidence-Based Medicine, Chiayi, Taiwan
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  • Fuan Chiang Chan,

    Corresponding author
    1. Temple Street Children's University Hospital, Department of Plastic and Reconstructive Surgery, Dublin, Ireland
    • Fuan Chiang Chan, Department of Plastic and Reconstructive Surgery, Temple Street Children's University Hospital, Temple Street, Dublin, Ireland. fchan910@gmail.com. fchan@eircom.net.

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  • Yu-Wen Wen

    1. Chang Gung University, Clinical Informatics and Medical Statistics Research Centre, Taoyuan, Taiwan
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The success of digital replantation is highly dependent on the patency of the repaired vessels after microvascular anastomosis. Antithrombotic agents are frequently used for preventing vascular occlusion. Low molecular weight heparin (LMWH) has been reported to be as effective as unfractionated heparin (UFH) in peripheral vascular surgery, but with fewer adverse effects. Its benefit in microvascular surgery such as digital replantation is unclear.


To assess whether subcutaneous LMWH treatment improves the salvage rate of the digits in patients with digital replantation after traumatic amputation.

Search methods

The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (October 2012), CENTRAL (2012, Issue 10) and trials databases. In addition, the authors searched PubMed, CNKI (China National Knowledge Infrastructure) and CEPS (Chinese Electronic Periodical Services), and sought additional trials from reference lists of relevant publications.

Selection criteria

We selected randomised or quasi-randomised controlled trials of LMWH in patients who received digital replantation.

Data collection and analysis

Two review authors independently extracted data and assessed the risk of bias of the included trials. Disagreements were resolved by discussion.

Main results

Two randomised trials involving 114 patients with at least 122 replanted digits met the inclusion criteria and were included. Both trials compared the efficacy and safety of LMWH with UFH. We found no trials comparing LMWH with placebo or other anticoagulants. The data from the two included studies were insufficient for meta-analysis. The overall success rate of replantation did not differ between the LMWH and UFH groups, 92.3% versus 89.2% in one trial (risk ratio (RR) 1.03; 95% confidence interval (CI) 0.87 to 1.22) and 94.3% versus 94.15% in the other trial (RR 1.00; 95% CI 0.89 to 1.13). The incidence of both postoperative arterial and venous insufficiency were reported in one trial and did not significantly differ between the LMWH and UFH groups (RR 1.08; 95% CI 0.16 to 7.10 and RR 0.81; 95% CI 0.20 to 3.27, respectively). Direct and indirect causes of microvascular insufficiency were not reported in the trials. Different methods were used to monitor the adverse effects related to anticoagulation in the two trials. Bleeding tendency was monitored for the LMWH and UFH groups in one trial and was reported by the incidence of wound haemorrhage (11.5% versus 17.9%; RR 0.65; 95% CI 0.17 to 2.44), ecchymoses (3.8% versus 10.7%; RR 0.36; 95% CI 0.04 to 3.24), haematuria (3.8% versus 7.1%; RR 0.54; 95% CI 0.05 to 5.59), nasal bleeding (0% versus 7.1%; RR 0.21; 95% CI 0.01 to 4.28), gingival bleeding (0% versus 10.7%; RR 0.15, 95% CI 0.01 to 2.83) and faecal occult blood (0% versus 3.6%; RR 0.36; 95% CI 0.02 to 8.42). The bleeding tendency was increased in the UFH group but this was not statistically significant. This trial also monitored coagulability changes using parameters such as antithrombin activity, factor Xa activity, bleeding time, clotting time and activated partial thromboplastin time (aPTT). No comparison was made between the LMWH and UFH groups but all data consistently showed that coagulability was reduced more in the UFH group than in the LMWH group. The other trial reported a postoperative decrease in platelet count in the UFH group (preoperative 278.4 ± 18.7 x 109/L, postoperative 194.3 ± 26.5 x 109/L; P < 0.05) but not in the LMWH group (preoperative 260.8 ± 32.5 x 109/L, postoperative 252.4 ± 29.1 x 109/L; P > 0.05).

Authors' conclusions

Current limited evidence based on two small-scaled low-to-medium quality randomised trials found no differences in the success rate of replantation between LMWH and UFH, but a lower risk of postoperative bleeding and hypocoagulability after the use of LMWH. Further well-designed and adequately powered clinical trials are warranted.

Plain language summary

Low molecular weight heparin for preventing vascular occlusion in replanted fingers or toes after amputation injuries

Microvascular surgery refers to any surgery involving small sized blood vessels that is performed under the operating microscope, allowing the repair of arteries and veins of the digits. These are typically 1 mm to 2 mm in diameter. Replantation is the reattachment of a completely detached body part, with fingers and thumbs being the most commonly replanted body parts. This is often referred to as digital replantation. In principle, digital replantation involves not only restoring the blood flow through the arteries and veins but also restoring the bony skeleton of the toes, fingers or thumbs, along with repairing the tendons and nerves as indicated. Occlusion of one or more of the repaired vessels due to the formation of a clot (thrombus) within the blood vessel results in failure of the replantation. Anticoagulant medications are used to reduce clotting, and they could potentially prevent such a complication. Anticoagulants such as unfractionated heparin (UFH) have therefore been used to prevent clot formation after digital replantation. It is unclear if low molecular weight heparin (LMWH) has similar benefit. This systematic review identified only two randomised controlled trials comparing UFH with LMWH, with a total of 114 patients. No studies were identified that compared LMWH with placebo, no treatment or other anticoagulants. The limited data from the two trials showed no difference between LMWH and UFH in the success rate for digital replantation but there were less frequent anticoagulation-related adverse events (such as bleeding) with LMWH. The available evidence is insufficient to make a firm conclusion.