Autologous 131I-Antithrombin III Turnover Studies in Man
A simple one-step heparin sepharose preparation of better than 95% pure human antithrombin III (AT3) has been developed along with a modification of the iodine monochloride method that allows consistent iodination of it. Iodination at a ratio of ~0.7 I atom/1.0 AT3 molecule results in loss of ca. 5% total thrombin neutralizing activity but negligible reduction in rate of reaction with thrombin. After iodination with 131I unreached 131I-products are removed by washing the 131I-AT3 on a second heparin sepharose column. Before injection the *I-AT3 is sterilized by millipore filtration. By this method autologous *I-AT3 can be prepared and reinjected into the patient in 36-48 titor less if desired. Serial measurements are made of plasma 131I-AT3, plasma TCA-soluble 131I, and whole body 131I, (using a whole body counter). Since human AT3 is ~ the same molecular weight as albumin if allowance is made for its increased catabolic rate its kinetic behavior should be predictable from results of our earlier studies with human autologous albumin. This is not found to be so and human *I-AT3 shows the same delay in catabolismos dog *I-AT3. Current studies indicate that this anomalous behavior is unlikely to invalidate estimates of AT3 catabolism but may result in considerable errors in estimates of total Interstitial AT3. As with our dog studies these suggest a protective role for AT3 in the interstitial fluids