Protamine Titration

Protamine titration is the gold standard method for the measurement of unfractionated heparin (UFH) concentration in plasma. Protamine titration produces reliable and reproducible results; however it is �generally not considered a convenient assay for current clinical management of UFH as it is not readily automated (Olson et al. Arch Pathol Lab Med 122(9):782–798, 1998). Early clinical trials of UFH therapy determined that a heparin concentration of 0.2–0.4 U/ml by protamine titration correlated to an APTT of 1.5–2.5 times higher compared to baseline values produced desirable UFH safety and efficacy outcomes (Hull et al. N Engl J Med 315(18):1109–1114, 1986; Hull et al. N Engl J Med 322:1260–1264, 1990; Turpie et al. N Engl J Med 320:352–357, 1989; Brill-Edwards et al. Ann Intern Med 119(2):104–109, 1993; Hull Int Angiol 14(1):32–34, 1995). Such studies paved the way to the current view that it is no longer ideal to manage UFH based solely upon a 1.5–2.5 times prolongation of the “normal” APTT. Most advisory bodies recommend therapeutic APTTs be determined by correlating APTT results with therapeutic UFH levels as measured by anti-Xa assay (0.35–0.7 U/ml) or protamine titration (0.2–0.4 U/ml) (Hirsh and Raschke. Chest 126(3):188S-203S, 2004) (see Note 1 ).