Congenital plasminogen deficiency with an abnormal plasminogen: Frankfurt II, dysplasminogenaemia-hypoplasminogenaemia

Abstract

A five-member family (K) with a familial plasminogen (Plg) deficiency was studied; the propositus had a history of thromboembolic disease. There were varying degrees of hypoplasminogenaemia in all family members (Pig functional:antigen ratio of about 1:1), with the propositus having the most severe case, about 66%. All family members had low plasmin generation rates. Plg was isolated in a highly purified form from the plasma of each family member. The yields reflected the Plg deficiency but varied from the plasma antigen levels. The specific activity was about 50% of normal for the propositus, and averaged between 60 and 80% of normal for the other family members. The plasmin generation rates were variable with all family members using three different activators, about 2.5–14.2% of normal with streptokinase, 9.2–14.9% with urokinase, and 25.8–40% with the preformed plasmin-derived light (B) chain streptokinase complex. Active-site development in the equimolar plasminogen streptokinase (Plg SK) complexes was slow, reaching a maximum of 50–80% of the normal, native, Pig in 40–60 min at 37°C, normal Plg reaches a maximum in 15 min. In the formation of the equimolar complex, studied in PAGE and SDS-PAGE, a substantial amount of the mother's and the second brother's (KK) Pig did not react to form the complex. The father's and the first brother's (AK) Pig's formed two Pig SK complexes with different mobilities in PAGE, complex I (abnormal) with a slower mobility, and complex II (normal). The first brother's (AK) Pig SK complex I converts to complex II and then to plasmin streptokinase (Pln SK) complex I followed by Pin SK complex II. This Pig SK complex I also rapidly converts to a degraded Plg (plasmin) streptokinase complex, 78% in 60 min. The father's complex I slowly converts to the Pln SK complex, without forming the degraded complex. The propositus's, mother's, and second brother's (KK) Plg's form only complex II, which slowly converts to Pln SK. In reduced samples, in SDS-PAGE, the father's and first brother's (AK) complexes showed degraded A and B chains, and smaller streptokinase fragments were also found. These data show that in a family with a familial Plg deficiency, a hypoplasminogenaemia, dysfunctional Plg's are present in each family member. The K family (Frankfurt II) dysfunctional Plg can be classified as a dysplasminogenaemia-hypoplasminogenaemia, Type 2a.