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Homogeneous assays for LDL-C and HDL-C are widely used and accepted because of their rapid and precise analytical performance. However, disturbance of such assays has been described for some conditions that involve atypical lipoprotein metabolism,
such as hypertriglyceridaemia. There is little information on the analytical and clinical performance of these tests in patients with other pathologies.
We could not identify any interference in the LDL-C assay by triglycerides up to 4.52 mmol/L, bilirubinaemia up to 0.66 mmol/L or moderate haemolysis. Furthermore, the bias of the LDL-C assay was not associated with triglyceride or bile salt concentrations, but showed a strong correlation with the Lp X concentration and a weak correlation with the total bilirubin concentration. However, bilirubin alone did not disturb the LDL-C assay in the present and other interference studies, so that the double association may be explained by the coexistence of bilirubin and Lp X as interfering factors in cholestatic samples.
The atypical lipoprotein Lp X is present in samples from patients with cholestasis, presumably as a result of bile lipoprotein transfer into the bloodstream due to obstruction. Although its density is similar tothat of LDL, the composition of the particle is fairly different from that of LDL cholesterol.
This peculiar composition is likely to affect sample reactivity with the detergents of some homogeneous assays that take advantage of the selective micellary solubilisation of LDL-C.
It has been reported that the cholesterol content in Lp X particles varies with the pathogenesis of the background cholestasis. The different degrees of interference we observed in patients could, at least partly, be explained on this basis.
We conclude that the LDL-C, but not the LDLD assay, seems to be subject to interference by Lp X and is, despite acceptable overall analytical performance, of limited use in cholestatic conditions.