With an estimated 32.7 million lower-leg fractures occurring annually, tibial fractures represent a considerable cause of morbidity worldwide. Acute compartment syndrome (ACS) is a potentially devastating complication requiring urgent fasciotomy to prevent irreversible neuromuscular damage. However, diagnosis remains challenging because clinical signs have low sensitivity,intracompartmental pressure (ICP) measurements have limited diagnostic specificity, and no universally accepted diagnostic reference standard exists. In the clinical situation, this uncertainty often leads to fasciotomy to prevent progressive muscle and nerve injury.

Biomarkers reflecting skeletal muscle injury could potentially provide more objective diagnostic information to guide such a decision. Myoglobin and creatine kinase (CK) are established markers of muscle injury, while microRNAs (miRNAs) have emerged as potential biomarkers of tissue damage. However, the accuracy of miRNA analysis may be affected by heparins commonly administered as thromboprophylaxis.

The overall aim of this thesis was to investigate whether biomarkers could assist in diagnosing ACS. We investigated which clinical parameters had historically been used in the decision to perform fasciotomy in our healthcare setting, whether thromboprophylactic doses of tinzaparin affected PCR-based miRNA analysis, and whether plasma myoglobin and CK could contribute to the diagnosis of ACS in patients with tibial fractures.

Clinical signs and ICP measurements were the most common clinical parameters underlying the decision to perform fasciotomy, whereas biomarkers contributed in only a few cases (Study I). ICP and myoglobin concentrations were substantially higher in patients with non-fracture-related suspected ACS than in those with tibial fractures.

Tinzaparin had a small effect on one step of the PCR-based miRNA analysis, which is unlikely to be clinically relevant (Study II).

In the prospective multicentre study described in Study III and reported in Study IV, 398 patients with traumatic tibial fractures were included, of whom 18 (4.5%) underwent fasciotomy for suspected ACS. Plasma myoglobin and CK concentrations did not differ significantly between patients who underwent fasciotomy and those who did not. Instead, biomarker concentrations appeared to reflect the severity of traumatic muscle damage during injury. Also, patients undergoing fasciotomy had worse functional outcomes at 1 year. However, in the absence of an objective reference standard, it could not be determined whether all patients undergoing fasciotomy actually had ACS.

In conclusion, ACS remains a diagnostic challenge. Neither plasma myoglobin nor CK could distinguish patients who subsequently underwent fasciotomy from those who did not, and both appeared to reflect the extent of muscle damage rather than ACS specifically. Thromboprophylactic doses of tinzaparin are unlikely to have a clinically relevant effect on miRNA analysis. More reliable objective diagnostic methods are needed to identify patients who truly require fasciotomy.