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Appropriate Use of Intravenous Unfractionated Heparin after Digital Replantation: A Randomized Controlled Trial Involving Three Groups

Nishijima, Akio M.D., Ph.D.; Yamamoto, Naoto M.D., Ph.D.; Gosho, Masahiko Ph.D.; Yanagibayashi, Satoshi M.D., Ph.D.; Yoshida, Ryuichi M.D.; Takikawa, Megumi M.D., Ph.D.; Hayasaka, Rie M.D.; Nagano, Hisato M.D.; Maruyama, Eri M.D.; Sekido, Mitsuru M.D., Ph.D.

Plastic and Reconstructive Surgery: June 2019 - Volume 143 - Issue 6 - p 1224e-1232e
doi: 10.1097/PRS.0000000000005665
Hand/Peripheral Nerve: Original Articles

Background: The purpose of this study was to clarify the appropriate use of unfractionated heparin as an anticoagulation agent after digital replantation.

Methods: This study was a prospective, randomized, single-blind, blinded-endpoint method, three-arm, parallel-group, controlled clinical trial conducted at a single institution. A total of 88 patients (101 fingers) following digital amputation and subsequent repair by anastomosis of both arteries and veins were randomly allocated into three groups: (1) control group (no heparin dose), (2) low-dose heparin group (10,000 IU/day), and (3) high-dose heparin group (start at 15,000 IU/day, then adjust the dose to achieve an activated partial thromboplastin time of 1.5 to 2.5 times the baseline). The outcomes were assessed regarding the proportion of success at 2 weeks after replantation of amputated digits, total or partial necrosis, and occurrence of complications.

Results: No significant differences were found among the three groups, except for complications of congestion. The odds ratio of the heparin group compared with the control group for a success proportion was 5.40 (95 percent CI, 0.85 to 34.20; p = 0.027) in subjects aged 50 years or older. Significant elevations of activated partial thromboplastin time, aspartate transaminase, and alanine aminotransferase occurred in high-dose heparin groups on day 7.

Conclusion: Unfractionated heparin administration is considered effective for patients aged 50 years or older, although the routine use of unfractionated heparin is not necessary after digital replantation.


Chiba, Ibaraki, Saitama, and Tsukuba, Japan

From the Department of Plastic and Reconstructive Surgery, New Tokyo Hospital; the Department of Plastic and Reconstructive Surgery, University of Tsukuba; the Department of Plastic and Reconstructive Surgery, Jichi Medical University Saitama Medical Center; and the Department of Biostatistics, Faculty of Medicine, University of Tsukuba.

Received for publication July 5, 2018; accepted November 2, 2018.

This trial is registered under the name “The Effect and Proper Dose of Unfractionated Heparin after Digital Replantation: A Prospective Study,” University Hospital Medical Information Network identification number UMIN 000021991 (

Disclosure:None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this article.

Akio Nishijima, M.D., Ph.D., Department of Plastic and Reconstructive Surgery, University of Tsukuba, 2-1-1 Amakubo, Tsukuba, Ibaraki 305-8576, Japan,

Copyright © 2019 by the American Society of Plastic Surgeons