PMID- 32302004
OWN - NLM
STAT- MEDLINE
DCOM- 20200831
LR  - 20210417
IS  - 1469-493X (Electronic)
IS  - 1361-6137 (Linking)
VI  - 4
IP  - 4
DP  - 2020 Apr 17
TI  - Low molecular weight heparin for prevention of microvascular occlusion in digital 
      replantation.
PG  - CD009894
LID - 10.1002/14651858.CD009894.pub3 [doi]
LID - CD009894
AB  - BACKGROUND: 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. This is 
      an update of the review first published in 2013. OBJECTIVES: To assess if 
      treatment with subcutaneous LMWH improves the salvage rate of the digits in 
      patients with digital replantation after traumatic amputation. SEARCH METHODS: 
      The Cochrane Vascular Information Specialist searched the Cochrane Vascular 
      Specialised Register, CENTRAL, MEDLINE, Embase, AMED and CINAHL databases, and 
      the World Health Organization International Clinical Trials Registry Platform and 
      ClinicalTrials.gov trials registers, to 17 March 2020. The authors searched 
      PubMed, China National Knowledge Infrastructure (CNKI) and Chinese Electronic 
      Periodical Services (CEPS) on 17 March 2020 and sought additional trials from 
      reference lists of relevant publications. SELECTION CRITERIA: We included 
      randomised or quasi-randomised controlled trials comparing treatment with LMWH 
      versus any other treatment in participants who received digital replantation 
      following traumatic digital amputation. DATA COLLECTION AND ANALYSIS: Two review 
      authors (PL, CC) independently extracted data and assessed the risk of bias of 
      the included trials using Cochrane's 'Risk of bias' tool. Disagreements were 
      resolved by discussion. We assessed the certainty of evidence using the GRADE 
      approach. MAIN RESULTS: We included two new randomised trials in this update, 
      bringing the total number of included trials to four. They included a total of 
      258 participants, with at least 273 digits, from hospitals in China. Three 
      studies compared LMWH versus UFH, and one compared LMWH versus no LMWH. The mean 
      age of participants ranged from 24.5 to 37.6 years. In the studies reporting the 
      sex of participants, there were a total of 145 men and 59 women. The certainty of 
      the evidence was downgraded to low or very low because all studies were at high 
      risk of performance or reporting bias (or both) and there was imprecision in the 
      results due to the small numbers of participants. The three studies comparing 
      LMWH versus UFH reported the success rate of replantation using different units 
      of analysis (participant or digit), so we were unable to combine data from all 
      three studies (one study reported results for both participants and digits). No 
      evidence of a benefit in success of replantation was seen in the LMWH group when 
      compared with UFH, regardless of whether the outcomes were reported by number of 
      participants (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.87 to 1.10; 
      130 participants, 2 studies; very low-certainty evidence); or by number of digits 
      (RR 0.97, 95% CI 0.90 to 1.04; 200 digits, 2 studies; low-certainty evidence). No 
      studies reported the incidence of compromised microcirculation requiring surgical 
      or non-surgical therapy, or any systemic/other causes of microvascular 
      insufficiency. There was no evidence of a clear difference between the LMWH and 
      UFH groups in occurrence of arterial occlusion (RR 1.08, 95% CI 0.16 to 7.10; 54 
      participants, 1 study; very low-certainty evidence) or venous occlusion (RR 0.81, 
      95% CI 0.20 to 3.27; 54 participants, 1 study; very low-certainty evidence). Two 
      studies reported adverse effects. The LMWH and UFH groups showed no evidence of a 
      difference in wound bleeding (RR 0.53, 95% CI 0.23 to 1.23; 130 participants, 2 
      studies; low-certainty evidence), haematuria (RR 0.43, 95% CI 0.09 to 2.11; 130 
      participants, 2 studies; very low-certainty evidence), ecchymoses (RR 0.82, 95% 
      CI 0.21 to 3.19; 130 participants, 2 studies; very low-certainty evidence), 
      epistaxis (RR 0.27, 95% CI 0.03 to 2.32; 130 participants, 2 studies; very 
      low-certainty evidence), gingival bleeding (RR 0.18, 95% CI 0.02 to 1.43; 130 
      participants, 2 studies; very low-certainty evidence), and faecal occult blood 
      (RR 0.27, 95% CI 0.03 to 2.31; 130 participants, 2 studies; very low-certainty 
      evidence). We could not pool data on coagulation abnormalities as varying 
      definitions and tests were used in the three studies. One study compared LMWH 
      versus no LMWH. The success rate of replantation, when analysed by digits, was 
      reported as 91.2% success in the LMWH group and 82.1% in the control group (RR 
      1.11, 95% CI 0.93 to 1.33; 73 digits, 1 study; very low-certainty evidence). 
      Compromised microcirculation requiring surgical re-exploration, analysed by 
      digits, was 11.8% in the LMWH group and 17.9% in the control group (RR 0.86, 95% 
      CI 0.21 to 3.58; 73 digits, 1 study; very low-certainty evidence). Compromised 
      microcirculation requiring incision occurred in five out of 34 digits (14.7%) in 
      the LMWH group and eight out of 39 digits (20.5%) in the control group (RR 0.72, 
      95% CI 0.26 to 1.98; 73 digits; very low-certainty evidence). Microvascular 
      insufficiency due to arterial occlusion, analysed by digits, was 11.8% in the 
      LMWH group and 17.9% in the control group (RR 0.66, 95% CI 0.21 to 2.05; 73 
      digits, 1 study; very low-certainty evidence), and venous occlusion was 14.7% in 
      the LMWH group and 20.5% in the control (RR 0.72, 95% CI 0.26 to 1.98; 73 digits, 
      1 study; very low-certainty evidence). The study did not report complications or 
      adverse effects. AUTHORS' CONCLUSIONS: There is currently low to very 
      low-certainty evidence, based on four RCTs, suggesting no evidence of a benefit 
      from LMWH when compared to UFH on the success rates of replantation or affect 
      microvascular insufficiency due to vessel occlusion (analysed by digit or 
      participant). LMWH had similar success rates of replantation; and the incidence 
      rate of venous and arterial microvascular insufficiency showed no evidence of a 
      difference between groups when LMWH was compared to no LMWH (analysed by digit). 
      Similar rates of complications and adverse effects were seen between UFH and 
      LMWH. There was insufficient evidence to draw conclusions on any effect on 
      coagulation when comparing LMWH to UFH or no LMWH. The certainty of the evidence 
      was downgraded due to performance and reporting bias, as well as imprecision in 
      the results. Further adequately powered studies are warranted to provide 
      high-certainty evidence.
CI  - Copyright (c) 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
FAU - Lin, Pei-Tzu
AU  - Lin PT
AD  - Chang Gung Memorial Hospital, Chiayi, Department of Pharmacy, 6, Sec West, 
      Chia-Pu Rd, Puzih, Chiayi, Taiwan, 61363.
AD  - Chang Gung University of Science and Technology, Department of Nursing, 2, Sec 
      West, Chia-Pu Rd, Puzih, Chiayi, Taiwan, 61363.
FAU - Wang, Shu-Hui
AU  - Wang SH
AD  - Far Eastern Memorial Hospital, Department of Dermatology, 21, Sec 2, Nanya S Rd, 
      Banciao District, New Taipei, Taiwan, 22060.
AD  - Fu Jen Catholic University, Graduate Institute of Applied Science and 
      Engineering, College of Science and Engineering, 510, Zhongzheng Rd, Xinzhuang 
      Dist, New Taipei, Taiwan, 24205.
FAU - Chi, Ching-Chi
AU  - Chi CC
AD  - Chang Gung University, College of Medicine, Taoyuan, Taiwan.
AD  - Chang Gung Memorial Hospital, Linkou, Department of Dermatology, 5, Fuxing St, 
      Guishan Dist, Taoyuan, Taiwan, 33305.
LA  - eng
GR  - CSO_/Chief Scientist Office/United Kingdom
GR  - Scottish Government Health Directorates/International
GR  - Scottish Government, UK./International
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Systematic Review
DEP - 20200417
PL  - England
TA  - Cochrane Database Syst Rev
JT  - The Cochrane database of systematic reviews
JID - 100909747
RN  - 0 (Anticoagulants)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 9005-49-6 (Heparin)
SB  - IM
UOF - Cochrane Database Syst Rev. 2013 Jul 08;(7):CD009894. PMID: 23836382
MH  - Adult
MH  - Anticoagulants/adverse effects/*therapeutic use
MH  - Blood Coagulation Disorders/chemically induced
MH  - Female
MH  - Fingers/blood supply/*transplantation
MH  - Heparin/therapeutic use
MH  - Heparin, Low-Molecular-Weight/adverse effects/*therapeutic use
MH  - Humans
MH  - Male
MH  - Microvessels/*surgery
MH  - Peripheral Arterial Disease/epidemiology
MH  - Postoperative Hemorrhage/chemically induced
MH  - Randomized Controlled Trials as Topic
MH  - Replantation/*adverse effects
MH  - Venous Insufficiency/epidemiology
PMC - PMC7164413
COIS- PTL: none known
 SHW: none known
 CCC: none known
EDAT- 2020/04/18 06:00
MHDA- 2020/09/01 06:00
PMCR- 2021/04/17
CRDT- 2020/04/18 06:00
PHST- 2020/04/18 06:00 [entrez]
PHST- 2020/04/18 06:00 [pubmed]
PHST- 2020/09/01 06:00 [medline]
PHST- 2021/04/17 00:00 [pmc-release]
AID - CD009894.pub3 [pii]
AID - 10.1002/14651858.CD009894.pub3 [doi]
PST - epublish
SO  - Cochrane Database Syst Rev. 2020 Apr 17;4(4):CD009894. doi: 
      10.1002/14651858.CD009894.pub3.