Low molecular weight heparin-induced skin necrosis-a systematic review.
BACKGROUND
Low molecular weight heparins (LMWHs) are currently used as a standard for anti-thrombotic therapy. Skin necrosis caused by LMWH is a rare and probably under-reported complication. The aim of our systematic review is to analyse the present literature for cases of LMWH-induced skin necrosis, emphasising the pathogenesis, clinical pattern, and management of this rare side effect.


METHODS
We performed a Medline literature search (PubMed database) and manual cross-referencing to identify all articles related to LMWH-induced skin necrosis. Data were analysed for type of LMWH used, time until skin necrosis occurred, localisation, size, laboratory findings, switch anticoagulant, complications, and outcome. Additionally, the case of a patient from our hospital is presented.


RESULTS
We included a total of 20 articles (21 cases) reporting on LMWH-induced skin necrosis. Skin necrosis occurred locally and distant from the injection site. Heparin-induced antibodies were frequently observed (positive 9/11 articles, negative 2/11). However, severe thrombocytopenia (platelet count <100,000 cells/ml) occurred in only four cases, while platelet count remained normal in 50% of the cases. After patients had been switched to other anti-thrombotic drugs, the clinical course was usually benign; however, reconstructive surgery was necessary in two cases.


CONCLUSIONS
LMWH-induced skin necrosis may occur as part of the heparin-induced thrombocytopenia (HIT) syndrome, but other pathomechanisms, including allergic reactions and local trauma, may also be involved. When HIT is excluded, unfractionated heparin is a safe switch anticoagulant. Otherwise, non-heparin preparations such as hirudin or fondaparinux should be preferred.
Handschin
A E
AE
Division of Trauma Surgery, University Hospital of Zürich, Raemistrasse 100, 8091, Zürich, Switzerland. alexander.handschin@usz.ch
Trentz
O
O
Kock
H J
HJ
Wanner
G A
GA
D000925:Anticoagulants / Q000009:adverse effects*; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects*; D006801:Humans; D007267:Injections; D008297:Male; D008875:Middle Aged; D009104:Multiple Trauma / Q000601:surgery; D009336:Necrosis; D012867:Skin / Q000473:pathology*; D016103:Spinal Fractures / Q000601:surgery; D013923:Thromboembolism / Q000517:prevention & control; D013997:Time Factors
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight