Introduction

Abstract

Since the earliest developments of quantitative precipitation and single radial immunodiffusion techniques,^44,73 clinical immunology has played a significant role in the study of infectious disease,^33,88,100 blood group antigens,^1,98,117,122 serum immunoglobulins,^3,9,16,51,99 detection of hormones,^{4,21,27,30,49} drugs,^17,65,83 and histocompatibility mechanisms.^12,15,111 However, quantitative immunoassays were not effectively utilized in testing coagulation disorders until recently. The probable cause for such delay has been the late discoveries of coagulation factors and subsequent elucidation of biochemical mechanisms of coagulation.^{23,55,69,77,93,96} In recent years, the precise role of various serine proteases and their inhibitors in the regulation of hemostatic functions has been determined^43,45,75,80 and amino acid sequences of thrombin, prothrombin, fibrinogen, and antithrombin-III discovered.^60,70,87 The physiology of hemostasis is now explained in relation to the coagulation factors, activators, and inhibitors that are present in plasma. Among the serine protease inhibitors, antithrombin-III (AT-III) modulates the biologic functions of thrombin, factor Xa, plasmin, and kallikrein, thereby regulating the formation of a blood clot. A genetic deficiency of AT-III has been shown to cause thrombotic episodes.^{10,61,97,101,106} In addition, molecular abnormalities of AT-III in patients have also been recognized, and in such patients, functional activity of AT-III did not correlate to its immunologic concentration.