A review of the technical, diagnostic, and epidemiologic considerations for protein S assays.

OBJECTIVES: To review the state of the art relating to protein S deficiency as a risk factor for thrombosis and to make recommendations regarding the use of protein S measurements in the assessment of thrombotic risk in individual patients and families.

DATA SOURCES, EXTRACTION, AND SYNTHESIS: Selection criteria were developed for the inclusion of publications from 1985 to 2001 based on the relevant literature concerned with the systematic review of diagnostic tests. Minimal selection criteria were agreed on and the articles stratified into level 1 if they met these criteria and level 2 if they did not meet these criteria. The included articles were reviewed by the authors and abstracted onto predetermined data collection forms. These forms were then scored and recommendations based on level 1 studies. As described elsewhere, results of discussions at the College of American Pathologists Conference XXXVI on Diagnostic Issues in Thrombophilia were used to revise the manuscript into its final form.

CONCLUSIONS: Consensus was reached on 16 recommendations for the use of protein S assays in the assessment of thrombotic risk in individuals and families. Two themes run through the conclusions. First, protein S assays are the most technically problematic of the assays reviewed at this conference. Second, only 2 papers evaluating the diagnostic use of protein S assays met our level 1 inclusion criteria. These 2 problems point out the need for better standardized assays and rigorous studies of the diagnostic utility of these assays.