A comparative study of latex d-dimer reagents

Abstract

D-dimers are terminal fragments resulting from plasmin digestion of cross-linked fibrin. They are assayed in citrated plasma by agglutination of latex particles coated with monoclonal antibodies directed against D-dimer epitopes. In the following study we have compared six latex D-dimer reagents in several experiments: reactivity with freshly drawn and frozen plasma samples, with so-called “D-dimer standards”, with increasing fibrinogen concentration, with fibrinogen and fibrin split products prepared in fresh normal samples and with “purified” D and E fragments. We have also tested the influence of several diluting fluids and the effect of freezing and thawing. We have found remarkable titre differences of D-dimers between the six reagents in fresh and frozen samples. The reagents do not recognize, or in a titre different from the labelled value, ELISA standards from Ortho and Stago. They do not react with fibrinogen and fibrinogen split products. Self prepared fibrin split products are recognized by all latex reagents but with amazing titre differences, also depending on the plasmin digestion time. According to our experiments the titre is dependent on the diluting fluid used. None of the tested latex reagents react with pure E fragments but all react, in a rather strong way, with pure D fragments except one. We have tested six commonly available D-dimer latex reagents showing quite different titre reading of fresh and frozen plasma samples and of self prepared fibrin split products. Perhaps these results can be explained by differences in specificity and/or affinity of the coating monoclonal antibodies for the D-dimer cross-link. Perhaps some of the used monoclonal antibodies are also sensitive to the presence of early and intermediate fibrinolysis products and not only to terminal fragments (D-dimers). The reaction of all but one of the reagents with purified D fragments is in favour of a lack of specificity of the monoclonal antibodies for the D-dimer cross-link. We conclude that D-dimer titres of plasma samples assayed by latex reagents have no absolute value making interlaboratory comparison of D-dimer results impossible especially when different reagents are used. The only meaningful application of such reagents is the follow up of the D-dimer titre in a same patient for example during therapy.