Serum versus lithium-heparin plasma for lipid testing: matrix-related bias and calculated LDL-C classification

Aims To assess whether serum and lithium-heparin plasma can be used interchangeably for routine lipid testing and whether matrix-related bias affects calculated low-density lipoprotein (LDL)-cholesterol (LDL-C) classification near clinical decision thresholds. Methods This prospective paired-sample method-comparison study included 104 fasting adult ambulatory patients referred for routine lipid testing. Serum and lithium-heparin plasma were collected during the same venipuncture and analysed on a Cobas 6000 c501 analyser. LDL-C was calculated using the Friedewald equation when triglycerides (TGs) were <4.5 mmol/L (n=103). Agreement was assessed using paired testing, Passing-Bablok regression, Bland-Altman analysis, intraclass correlation coefficients (ICCs), Cohen kappa and McNemar testing at selected decision thresholds. Interchangeability was interpreted using analytical bias, measurement uncertainty, limits of agreement and threshold discordance. Results Lithium-heparin plasma yielded lower total cholesterol and calculated LDL-C than serum, with mean biases (plasma - serum) of −0.15 mmol/L (−3.06%) and −0.14 mmol/L (−4.77%), respectively. TGs and HDL-cholesterol did not differ significantly. Serum-plasma correlations and ICCs were high. LDL-C classification was discordant in 3/103, 2/103 and 7/103 paired samples at thresholds of 1.4, 1.8 and 2.6 mmol/L, respectively; all discordances classified plasma below and serum above the threshold. Conclusions Under these local analytical and pre-analytical conditions, the mean bias was modest but directional and sufficient to alter calculated LDL-C classification in a minority of samples near decision thresholds. Laboratories using lithium-heparin plasma for lipid testing should verify matrix agreement locally, document the specimen matrix and avoid alternating serum and plasma during longitudinal monitoring unless equivalence has been demonstrated.