A Reference System Approach to Future Standardization of Laboratory Tests for Hemostasis, ,

Abstract

A description of the development of a strategy for improving the standardization of coagulation tests and the rationale behind the recommendations that follow are the subject of this position paper. Such an endeavor has been occasioned by the advances in the technology for the diagnosis and therapeutic treatment of hemorrhagic and thromboembolic diseases. These and anticipated further advances make it imperative that the standardization of laboratory tests used in diagnosis and in monitoring therapeutic treatments be the 'state-of-the-art' so that the accuracy, comparability and clinical utility is of the highest order. The complexity of the hemostatic system makes achieving accuracy and comparability among these tests a substantial challenge. Another impetus for improving the comparability of the results from different laboratories throughout the world arises as a consequence of the globalization of the pharmaceutical and medical diagnostic companies that began in the 1990's and is continuing into this, the 21 st century.The assay of a component of the coagulation system presently employs a "substrate plasma" deficient in the component of interest and the measurement of the elapsed time between initiation of the clotting process and clot formation (gelation). Quantitative assessment of the activity of this component is achieved through a dose-response relationship between a dilution of a reference plasma that contains all coagulation components in their "normal concentrations and the elapsed time (clotting time) for each dilution. Many variations and modifications of this approach that have improved the specificity of these tests are in routine use today. These methods have been key to many of the biochemical advances made in the past and have been invaluable to local laboratories with expertise and understanding of hemostasis. However, coagulation tests are now being passed to contract laboratories where those responsible for performing these assays do not have the necessary background in coagulation.Independent of the need for advancing the art of coagulation testing; the completion of the human genome project will mandate a change in the perspective that must be taken to standardize the protein products that the genome encodes. Phenotypic expression of impaired 1 Hemostasis is intended to be interpreted broadly and to include proteins components of coagulation, fibrinolysis and platelets. 2 Designated C-SCT, Committee on Standardization of Coagulation Tests in the IFCC Scientific Division 3 A decision was made by the C-SCT to exclude the two common or "global" screening tests, the PT and the aPTT and variations of these tests such as the aPTT used for heparin monitoring and in APC resistance detection from this effort. The proposals made here are not intended to apply to these tests, nor have tests related to platelet function been considered.