ABNORMALITIES OF COAGULATION IN EXPERIMENTAL NEPHROTIC SYNDROME

The human nephrotic syndrome is accompanied by important alterations o f the coagulation system related proteins. The purpose of the present study was to examine the activity of coagulation- and fibrinolysis-rel ated proteins in plasma and urine of control and puromycin aminonucleo side injected rats on days 2 (prenephrotic stage) and 10 (nephrotic st age). We measured the prothrombin time (PT), the activated partial thr omboplastin time (aPTT), and the activities of (I) the coagulation fac tors (CFs) I, II, V, and VII-XII; (2) the inhibitor of coagulation ant ithrombin III (ATIII), and (3) the component of the fibrinolytic syste m alpha(2)-antiplasmin (alpha(2)-APL). PT and aPTT and the activities of CE ATIII, and alpha(2)-APL were not measurable in the urine of cont rol and puromycin aminonucleoside injected rats on day 2. On this same day, plasma ATIII and CF VIII decreased. On day 10 (1) PT and aPTT de creased in plasma and were not measurable in urine; (2), plasma CFs I, II, V, VII, VIII, X, and XI increased; (3), plasma ATIII decreased; ( 4), plasma CFs IX and XII and alpha(2)-APL did not change, and (5) ATI II and CFs II, VII, VIII, IX, X, XI, and XII, but not CFs I and V and alpha(2)-APL, appeared in urine on day 10. ATIII deficiency was second ary probably to the urinary losses; however, the plasma activity of CF s LI, VII, Vm, X, and XI increased and that of CFs IX and XII remained unchanged in spite of their urinary losses which suggests that other mechanisms such as deranged catabolism and altered hepatic synthesis m ay be involved. This model may be useful to study the pathophysiology of the abnormalities of coagulation in humans with nephrotic syndrome.