BACKGROUND: The intense ischemic pain of acute compartment syndrome can be difficult to discriminate from the pain related to an associated fracture. Lacking objective measures, the decision to perform fasciotomy is often only based on clinical findings and performed at a low threshold. Biomarkers of muscle cell damage might help to identify and monitor patients at risk. In patients with fractures, however, markers of muscle cell damage could be elevated because of other reasons associated with the trauma, which would make interpretation difficult. In a review of all patients who underwent emergency fasciotomy in our health care district we aimed to investigate the decision-making process and specifically the use of biomarkers in patients with and without fractures.

METHODS: In the southeast health care region of Sweden 79 patients (60 men) with fractures (median age 26 years) and 42 patients (34 men) without associated fractures (median age 44 years) were treated with emergency fasciotomy of the lower leg between 2007 and 2016. Differences in clinical findings, p-myoglobin and p-creatine phosphokinase as well as pressure measurements were investigated.

RESULTS: P-myoglobin was analyzed preoperatively in 20% of all cases and p-creatine phosphokinase in 8%. Preoperative levels of p-myoglobin were lower in patients with fractures (median 1065 μg/L, range 200-3700 μg/L) compared with those without fractures (median 7450 μg/L, range 29-31,000 μg/L), p < 0.05. Preoperative intracompartmental pressure was lower in the fracture group (median 45 mmHg, range 25-90 mmHg) compared with those without fractures (median 83 mmHg, range 18-130 mmHg), p < 0.05.

CONCLUSIONS: Biomarkers are seldom used in the context of acute fasciotomy of the lower leg. Contrary to our expectations, preoperative levels of p-myoglobin and intracompartmental pressures were lower in fracture patients. These findings support differences in the underlying pathomechanism between the groups and indicate that biomarkers of muscle cell necrosis might play a more important role in the diagnosis of acute compartment syndrome than previously thought.

Circulating microRNAs (miRNAs) have become increasingly popular biomarker candidates in various diseases. However, heparin-based anticoagulants might affect the detection of target miRNAs in blood samples during quantitative polymerase chain reaction (qPCR)-based analysis of miRNAs involving RNA extraction, cDNA synthesis and the polymerase catalyzed reaction. Because low-molecular-weight heparins (LMWH) are widely used in routine healthcare, we aimed to investigate whether a prophylactic dose of the LMWH tinzaparin influences qPCR-based quantification of circulating miRNAs. A total of 30 subjects were included: 16 fracture patients with tinzaparin treatment and 14 non-fracture controls without anticoagulation therapy. To control for the effect of tinzaparin on miRNA analysis an identical concentration of synthetic miRNAs was added to plasma, isolated RNA and prepared complementary DNA (cDNA) from all samples in both groups. No significant difference was observed for cDNA synthesis or qPCR when comparing tinzaparin-treated patients with untreated controls. Among the tinzaparin-treated patients, plasma levels of six endogenous miRNAs (hsa-let-7i-5p, hsa-miR-30e-5p, hsa-miR-222-3p, hsa-miR-1-3p, hsa-miR-133a-3p, hsa-miR-133b) were measured before and one to six hours after a subcutaneous injection of tinzaparin 4500IU. No significant effect was observed for any of the investigated miRNAs. A prophylactic dose of 4500IU tinzaparin does not seem to affect cDNA synthesis or qRT-PCR-based quantification of circulating miRNAs.

Introduction The ischaemic pain of acute compartment syndrome (ACS) can be difficult to discriminate from the pain linked to an associated fracture. Lacking objective measures, the decision to perform fasciotomy is based on clinical findings and performed at a low level of suspicion. Biomarkers of muscle cell damage may help to identify and monitor patients at risk, similar to current routines for patients with acute myocardial infarction. This study will test the hypothesis that biomarkers of muscle cell damage can predict ACS in patients with tibial fractures. Methods and analysis Patients aged 15-65 years who have suffered a tibial fracture will be included. Plasma (P)-myoglobin and P-creatine phosphokinase will be analysed at 6-hourly intervals after admission to the hospital (for 48 hours) and-if applicable-after surgical fixation or fasciotomy (for 24 hours). In addition, if ACS is suspected at any other point in time, blood samples will be collected at 6-hourly intervals. An independent expert panel will assess the study data and will classify those patients who had undergone fasciotomy into those with ACS and those without ACS. All primary comparisons will be perforated between fracture patients with and without ACS. The area under the receiver operator characteristics curves will be used to identify the success of the biomarkers in discriminating between fracture patients who develop ACS and those who do not. Logistic regression analyses will be used to assess the discriminative abilities of the biomarkers to predict ACS corrected for prespecified covariates. Ethics and dissemination The study has been approved by the Regional Ethical Review Boards in Linkoping (2017/514-31) and Helsinki/Uusimaa (HUS/2500/2000). The BioFACTS study will be reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology recommendations.