Background and objectives. Recent evidence has demonstrated that mildly elevated bilirubin concentrations are protective against various oxidative stress-mediated diseases, including autoimmune disorders. Based on this, the present study aimed to investigate the association between serum bilirubin levels, albumin-based inflammatory ratios, and the presence of primary antiphospholipid syndrome (APS) in women with a history of spontaneous miscarriages.
Materials and methods. This cross-sectional observational study included 72 women aged 21–40 years (median age 27) with a history of spontaneous miscarriages in the first trimester. Based on clinical and laboratory findings, 47 women were diagnosed with APS, and 25 were classified as non-APS. All participants underwent a complete evaluation, including blood count, coagulation tests, glucose and lipid profiles, CRP, vitamin D, and assessments of thyroid, liver, and kidney function.
Results. A total bilirubin level below 8 μmol/L was observed in 53% of APS patients, significantly higher than in non-APS women (24%, p = 0.024). Total, direct, and indirect bilirubin concentrations were significantly lower, while inflammatory markers such as fibrinogen, CRP, and CRP/albumin ratio were significantly higher in APS patients (p < 0.05). Logistic regression and ROC analysis confirmed the diagnostic value of these markers. The AUC values for total bilirubin, bilirubin/albumin ratio, fibrinogen, albumin/fibrinogen ratio, CRP, and CRP/albumin ratio demonstrated moderate diagnostic
accuracy (AUC = 0.723, 0.793, 0.693, 0.828, 0.761, and 0.699, respectively).
Conclusions. Serum bilirubin levels and the bilirubin/albumin ratio were negatively associated with APS in women with a history of spontaneous miscarriage. These findings suggest impaired antioxidant and anti-inflammatory defenses in APS patients. Serum bilirubin combined with albumin-based inflammatory ratios may serve as additional screening tools for APS in this population.

Keywords: antiphospholipid syndrome, total bilirubin, total bilirubin to albumin ratio, oxidative stress

The aim: To investigate the relationship between serum bilirubin level and the presence of the APS in women with a history of spontaneous miscarriages.
Materials and methods: Fifty six women aged 22-38 (median 27) years with a history of spontaneous miscarriages were divided into two groups: 33 women with the APS and 23 without. Patients were tested for the presence of lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein 1, antiphospholipid antibodies and genetic thrombophilic defects.
Results: Groups were comparable by age, blood pressure, BMI, co-morbidity (anemia, heart abnormality, thyroid disease, overweight). Median serum total bilirubin levels were 7,2 μmol/L (interquartile range [5,8-9,7]) in women with the APS and 10,5 μmol/L (interquartile range [7,5-15,1]) in control group, p=0.005. The chance of detecting a total bilirubin level of less than 8 μmol/L is 4.1 times higher in the APS patients than in the control group (OR 4,1; 95% CI 1,274-13,213). Logistic regression analysis found a statistically significant association between total bilirubin and the presence of the APS (odds ratio, 0.856; 95% CI, 0.734-0.997, p =0.046). Patients with the APS had elevated serum C-reactive protein (medians 2,3 vs 1,1 mg/L, p=0.01) and fibrinogen (medians 2,8 vs 2,5 g/L, p=0.006) levels compared with controls. Correlation analysis revealed a significant correlation between all types of bilirubin and inflammatory markers.
Conclusions: All types of serum bilirubin (total, direct and indirect) are significantly reduced in women with APS, associated with higher inflammatory markers and lower levels of 25-hydroxyvitamin D, which may be the result of oxidative stress.