Standardization of APTT Reagents for Heparin Therapy Monitoring: Urgent Or Fading Priority?(Editorial‪)‬

Tremendous improvements have been made in the outcomes of patients with acute venous thromboembolic events (VTE) since Murray et al. successfully administered heparin to postsurgery patients in 1937 [1]. Advances include accurate methods for diagnosis of deep vein thromboses (DVT) and pulmonary emboli (PE); effective regimens for initial and long-term anticoagulation; and wide acceptance of a system for standardization of thromboplastin sensitivities to the anticoagulant effects of warfarin (International Normalized Ratio; INR). In this issue of Clinical Chemistry, van den Besselaar et al. [2] address an unresolved aspect of anticoagulation therapy: standardization of activated partial thromboplastin time (APTT) reagents for monitoring heparin therapy. Heparin is a glycosaminoglycan extracted from mast cells of porcine intestinal mucosa or bovine lung. It is composed of long chains of alternating D-glucuronic acid and N-acetyl-D-glucosamine sugar residues, which undergo a series of chemical modifications, primarily sulfation, leading to unique pentasaccharide sequences that serve as a binding site for antithrombin III (AT III) [3]. The anticoagulant effect of heparin is mediated through this interaction, which markedly accelerates the rate of AT III inhibition of thrombin (factor IIa) and factor Xa. Heparin polysaccharides are heterogeneous in length and anticoagulation activity and range in mass from 5000 to 30 000 kDa. Commercial preparations are calibrated in USP units, 1 unit being defined as the quantity that prevents 1.0 mL of citrated sheep plasma from clotting for 1 h after the addition of 0.2 mL of 10 g/L Ca[Cl.sub.2] [3].