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A novel use of serum bilirubin measurement investigated
Summarized from Nevler A, Berger Y, Rabinovitz A et al. Diagnostic value of serum bilirubin and liver enzyme levels in acute appendicitis. IMAJ 2018; 20: 176-81.
Measurement of serum bilirubin has established clinical utility in diagnosis of diseases that result in increased rate of red-cell destruction (in vivo hemolysis) and in diagnosis of liver/biliary tract diseases that are associated with decreased rate of bilirubin elimination from blood. In both cases, bilirubin accumulates in blood; serum concentration increases.
The notion that measurement of serum bilirubin might also be useful in diagnosis of acute appendicitis has been investigated in a number of studies over the past 5 years, including this, the most recent, published earlier this year.
In the preamble to their study report, the authors justify the ongoing search for reliable blood markers of acute appendicitis. Diagnosis of acute appendicitis, currently based principally on clinical examination, remains a challenge. Ultrasound/CT scan imaging and the use of conventional blood markers of infection/inflammation such as white blood cell count and CRP are helpful, but not entirely reliable. It is still quite common for patients presumed to be suffering acute appendicitis and submitted for appendectomy surgery to be found to have had a non-inflamed (normal) appendix when examined postoperatively.
The study focused on 100 consecutive emergency room patients whose presenting symptom (right abdominal and/or right iliac fossa pain) suggested they might have acute appendicitis. All were submitted for further assessment/ investigation by the hospital surgical team. The blood investigations ordered for each study patient at this time included: total white blood count (WBC), absolute neutrophil count (ANC), C-reactive protein (CRP), serum total bilirubin and serum alanine transferase (ALT); all potential blood markers of acute appendicitis.
On the basis of imaging study and surgical assessment, 57 of the 100 study patients were judged to be suffering acute appendicitis and submitted for appendectomy; postoperative histological examination of appendixes from four of these patients revealed no evidence of inflammation. So, in total 53 study patients had acute appendicitis and the remaining 47 did not.
Mean serum bilirubin of those with acute appendicitis (0.97 ±0.68 mg/dL, 16.6 ±11.6 µmol/L) was significantly (p=0.001) higher than the mean serum bilirubin of those without acute appendicitis (0.53 ±0.3 mg/dL, 9.0±5.1 µmol/L). Receiver operating characteristic (ROC) analysis of the data revealed that the serum bilirubin cut-off value to diagnose acute appendicitis with greatest sensitivity/specificity would be 0.73 mg/dL, (12.5 µmol/L). Using this cut-off value, serum bilirubin had a positive predictive value (PPV) of 81.8 %, negative predictive value (NPV) of 62.9 % and an overall accuracy rate of 70 %.
When compared with other blood markers of acute appendicitis measured in this study (WBC, ANC, CRP and ALT), serum bilirubin proved to be of comparable or slightly superior diagnostic accuracy. Diagnostic accuracy of serum bilirubin was shown to improve if it was combined with ANC and ALT values.
In discussion of their study findings, the authors highlight the results of previous studies examining the value of serum bilirubin in the diagnosis of acute appendicitis and speculate on the mechanism(s) that could account for the evident association between increased bilirubin and inflamed/infected appendix.
They conclude that ”combining serum bilirubin with ALT and ANC results in a marker that highly correlates with the diagnosis and prognosis of patients with acute appendicitis” but caution that more study is required to validate their findings.
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