The Poor Reliability of Factor X Chromogenic Assays in Coumarin Treated Patients

We have read with interest the paper by Han et al. (1) on factor X and protein C chromogenic assays in coumarin plasmas. Since we have been the first ones to demonstrate discrepancies between clotting and amidolytic assays, we take the liberty of making a few comments. In fact it has been shown by us in 1980 that an abnormal prothrombin (prothrombin Padua) (2) resulted to have normal activity if assayed by a chromogenic method, whereas it had an activity of about 50% of normal using several one-stage or twostage clotting methods. Discrepancies have also been seen for other congenital disorders, namely prothrombin Molise (2), protein C Rouen (3), AT III Padua (4), factor X Friuli (5). Overestimation of factor X in coumarin treated patients has also already been described by at least two groups in 1980 and 1981 (6, 7). At page 612 (legend to Fig.Z) of one of these papers it is stated "the distribution of values indicates that chromogenic substrate overestimates factor X" (7). Therefore, the data presented by Han et al. for factor X (1) are not new and the previous studies on the subject should have been properly quoted in the references In view of the above, the results on protein C are not surprisirg. Unpublished data by us confirm those presented by the authors. It is worth remembering also that the overestimation seen by us in 1981 (7) and now by Han et al. (1) is even more significant if one takes into due account that chromogenic assays were compared in both studies with Rw-Cephalin assays. It is known in fact that Rw-Cephalin methods slightly overestimate factor X in coumarin treated patients as compared with tissue thromboplastin methods (8). Some practical considerations seem also indicated. In light of overestimation of the factor X seen in coumarin treated patients, the proposal of the use of single factor chromogenic assays instead of global tests in the follow-up of coumarin treated patients does not seem justified (9). The entire story of chromogenic substrates, once again, suggests that a careful evaluation of new tests should be undertaken before proposing them as a substitute for existing ones.