Critical aspects in routine coagulation testing

The major improvements obtained in the quality of commercial reagents and in the accuracy of coagulometers has rendered comparabilty of the results among different laboratories a major task of the bodies devoted to standardization of coagulation testing. Commutability of results is of major importance especially in the monitoring of anticoagulant therapy. Critical aspects relate to the preanalytical phase, the anaytical phase and to the expression of results with the adoption of proper correction factors like the international sensitivity index (IS9 for thromboplastin reagents. Problems with the APTT in the monitoring of heparin treatment include the variable sensitivity of commercially available A€" reagents to clinically insignificant deficiencies of factors involved in the contact phase of coagulation and to the presence of lupus anticoagulants, which in addition to the different sensitivity of the reagents to the anticoagulant effect of heparin render commutability of results unworkable in practice. The tasks of the routine coagulation laboratory should include the following: a) the identification of patients with congenital or acquired defects potentially leading to bleeding; b) the monitoring of anticoagulant therapy; c) the monitoring of the course of disseminated intravascular coagulation PIC). The assays required to these purposes comprehend the prothrombin time (PT), the activated partial thromboplastin time (APT"), the thrombin time 0, and the measurements of fibrinogen (Fib) and of fibrin specific degradation products At variance with most of the analyses of clinical chemistry the PT and the A€" do not measure a single analyte but are screening tests sensitive to single or multiple clotting factor deficiencies of the clotting cascade. These peculiar characteristic coupled with the low cost of the tests have suggested a wide range of applications. However, the very same properties are also responsible for the hard work required in the standardization of these assays. As pointed out in recent NCCLS documents (2,3), the PT and APTT tests have their original scope in the detection of clinically relevant coagulation defects, that is congenital deficiencies of the intrinsic or extrinsic coagulation pathways which may be responsible for a bleeding diathesis. The two tests are also commonly employed to detect acquired clotting factor deficiencies or inhibitors the most common of which is the broad spectrum of lupus anticoagulants. In screening for congenital clotting factor deficiencies, the characteristics of the reagents are of the utmost importance as they differ in the degree of sensitivity to moderate deficiencies of single factors. Ideally, neither test should be sensitive to a 50% deficiency in any single factor, because such a deficiency cannot be responsible for a clinically significant bleeding diathesis. Insensitivity to single factor deficiencies close to 50% also permits correction of clotting time prolongations in mixing experiments aimed to rule out the presence of inhibitors.