Anticoagulant Activities of Lung and Mucosal Heparin

Interaction with antithrombin III is thought to be the main mechanism whereby heparin exerts an anticoagulant effect, but measurements of this specific heparin activity by an anti-Xa assay do not always agree with measurements made by ‘multiple role’ assays, such as APTT or pharmacopoeial assays. Two batches of lung heparin had APTT activities in vitro about 1.4 times those found by anti-Xa, whereas in several batches of porcine mucosal heparin this ratio was about 0.8. All assays by both methods were carried out against the 3rd International Standard for heparin. After gel filtration, lung heparin maintained a high ratio of APTT to anti-Xa activity in all except the low molecular weight fractions, where the two activities were both about 60 i. u./mg. In contrast, low molecular weight mucosal fractions had negligible APTT activity, but high (120 i. u./mg) activity by anti-Xa assay. A nominal 1000 units of lung heparin injected I. V. into volunteers gave peak anti-Xa levels of about 0.2 i. u./ml; a comparable injection of mucosal heparin gave peak levels of about 0.3 i. u./ml. The resulting ratio agreed with the anti-Xa activities of these two batches in vitro. However, in vivo, APTT levels with both heparins were less than half the anti-Xa levels, and 50 mins. after injection there was virtually no effect on the APTT, while heparin levels by anti-Xa remained about 0.1 i. u./ml. Although their APTT activities were comparable, lung heparin had much less anti-Xa potentiating effect than mucosal heparin, both in vitro and in vivo; this has important implications for the assay and clinical use of heparin.