Standardization of Lp(a) measurements.

The standardization of immunoassays for Lp(a) is a major challenge to clinical chemists. In order to establish a reference material acknowledged by the International Federation of Clinical Chemistry, the Center of Disease Control and possibly the World Health Organization, a working group with participants from four continents was put together. With the aid of 34 companies, eight proposed reference materials have been tested in the last 3 years and two of them have been selected for value assignment. A reference method based on dissociation-enhanced lanthanide fluorescence immunoassays was therefore developed which gives linear and parallel response curves by assaying freshly prepared primary reference standards, fresh plasma or serum as well as lyophilized or frozen proposed reference material. For value assignment, four laboratories simultaneously prepare primary reference standards with known isoforms and molecular weights. By assaying the amino acid composition of these primary reference standards, the molar concentration which is the basis of value transfer to the lyophilized proposed reference material can be calculated. In a final step, harmonization of all commercially available Lp(a) kits is to be tested by assaying 50 Lp(a) samples with increasing Lp(a) concentrations and varying isoforms. We hope to be able in the near future to create a basis for comparable results in epidemiological studies in different laboratories and also to help to improve future long-term precision in clinical chemical laboratories.