Study designs of evaluations included in the review
Reviews were excluded; no other inclusion criteria for the study design were specified. All of the included studies were case studies.
Specific interventions included in the review
Studies that evaluated LMWH were eligible for inclusion. Studies of other antithrombotic drugs were excluded. The included studies mostly evaluated dalteparin or enoxaparin; the other drugs evaluated were tinzaparin, tedelparin, certoparin, nadroparin and LMW heparin-dihydroergotamine. Where reported, the daily dose of LMWH ranged from 2,000 IU anti-factor Xa to 5,000 IU (mean 4,300 IU) and treatment was by injection into the abdominal wall, thigh or arm.
Participants included in the review
Inclusion criteria were not defined in terms of the participants. In the included studies, the reasons for LMWH administration included prophylaxis (including post-operative) of thromboembolism, treatment of established venous thromboembolism, acute coronary syndrome and atrial fibrillation. About half of the participants were female and the mean age was 62 years (range: 34 to 87). Some of the included studies reported that the patients had been previously exposed to heparin, most commonly a few days prior to the administration of LMWH.
Outcomes assessed in the review
Studies that assessed LMWH-induced skin necrosis were eligible for inclusion. Studies that assessed skin necrosis caused by underlying immunological diseases were excluded. The review also assessed the size and location of skin necrosis, the time from first administration of LMWH until skin necrosis started, heparin-induced thrombocytopenia, thrombocytopenia, other measures of coagulation state, switch anticoagulant and outcome.
How were decisions on the relevance of primary studies made?
The authors did not state how the papers were selected for the review, or how many reviewers performed the selection.