Monoclonal antibodies to crosslinked fibrin degradation products (XL‐FDP) I. CHARACTERIZATION AND PRELIMINARY EVALUATION IN PLASMA

Abstract

Monoclonal antibodies (mabs) were raised against X-oligomers, the earliest soluble fragments released from crosslinked fibrin (XL-FN), by the action of plasmin. Two of the mabs (NIBn 52 and NIBn 123) were monospecific for X-oligomers in that they showed no binding to fibrinogen, the plasmic fragments of fibrinogen (D and E) and non-crosslinked fibrin (X, Y, D and E), or the terminal digestion product of XL-FN, fragment DD-E. One other mab (NIBn 178) was panspecific for X-oligomers in that it exhibited a weak affinity for fibrinogen. The mabs were used to develop a two-site immunoradiometric assay (IRMA) and an enzyme-linked immunospecific assay (ELISA) which permitted the specific measurement of X-oligomers directly in plasma, rather than in serum. This immunoassay is a true assay of fibrinolysis as distinct from fibrinogenolysis and may be a potential aid in the diagnosis and evaluation of thrombosis. In preliminary studies, the assay detected low levels of X-oligomers in normal plasma and elevated levels in patients with disseminated intravascular coagulation.

Monoclonal antibodies to crosslinked fibrin degradation products (XL‐FDP) II. EVALUATION IN A VARIETY OF CLINICAL CONDITIONS

“…Seifried et a1 (1987) have shown that normal healthy volunteers showed an increase in plasma crosslinked FDP following infusion with t-PA and suggested that the level of infusion was directly related to the FDP generated. Thus care must be exercised in drawing too optimistic a conclusion from the data in Fig 5. Further data are required and assays need to be conducted using monoclonal antibodies for the primary crosslinked fragments (Gaffney et al, 1988) and the terminal crosslinked fragments (e.g. D-dimer) of fibrin (Rylatt et al, 1983).…”

“…However, in plasmas with a high FDP level, most of the FDP fraction is crosslinked and of high molecular weight (Whitaker et al, 1980;Graeff et al, 19 79) and is known as X-oligomer. MAbs were raised to this fraction and have been characterized (Gaffney et al, 1988). We here report on the use of a two-site enzyme-linked immunospecific assay (ELSA) for the high molecular weight X-oligomer fraction in groups of patients whose plasma became available to us at the National Institute for Biological Standards and Control (NIBSC).…”

Avaliação do dímero D (D-Di) na doença hipertensiva específica da gravidez (DHEG)

“…A determinação de D-Di tem sido largamente empregada para exclusão de trombose venosa profunda (TVP) e de acidentes tromboembólicos. Os testes imunoenzimáticos deste marcador possuem aproximadamente 100% de sensibilidade e 60% de especificidade, o que confere um alto valor preditivo negativo para o diagnóstico de TVP (6,10). Além da TVP, um aumento de D-Di em pacientes com condições clínicas relacionadas à formação de fibrina, Em concordância com os resultados obtidos por Schjetlein et al (13), no presente estudo foi verificado um aumento de D-Di apenas na forma grave da DHEG.…”

Performance of Semiquantitative and Quantitative D-Dimer Assays in the ECAT External Quality Assessment Program

“…In patients with a variety of diseases, such as diffuse intravascular coagulation, deep vein thrombosis, and pulmonary embolism, the coagulation and fibrinolysis processes can be strongly activated, which results in elevated levels of coagulation and fibrinolysis activation products, collectively called fibrin degradation products (FDPs). [1][2][3][4] Fibrin degradation products can be the result of the plasmin digestion of fibrin (fibrinolysis), which proceeds with numerous intermediate products. Non-crosslinked desAA fibrin (fibrin I) will yield fragments X I , Y I , D, E I, and desAABB fibrin (fibrin II) will yield X II , Y II , D, E II .…”