Summary
A new abnormal plasminogen, Frankfurt I, has been identified in the plasma of a 42
year-old male patient who has recurrent deep vein thrombosis. Clinical laboratory
data showed normal hemostasis test results. Since plasma plasmin generation rates
gave low values, the fibrinolytic system was analyzed for a possible fibrinolytic
system defect. Functional and antigen plasminogen concentrations both in the plasma
and with the isolated, purified plasminogen showed that only 49% of the antigen concentration
had potential functional active sites. Also, a reduced antigen concentration was found
in both the propositus, and his mother (46% active sites).
Sodium dodecyl sulfate polyacrylamide gel electrophoresis of the purified Frankfurt
I plasminogen showed a normal native Glu-plasminogen band. Crossed-immunoelectrophoresis
revealed a peak with normal size and shape, but displaced with respect to normal Glu-plasminogen
toward the anode, i. e., was, as a whole, more negatively charged. Isoelectric focusing
followed by zymog-raphy on a agarose-fibrin plate proved this observation, but did
not indicate a separation of the normal from the abnormal plasminogen molecular species,
also, fewer bands were found in the abnormal plasminogen isozyme pattern.
Kinetic studies of Frankfurt I Glu-plasminogen and plasmin led to the conclusion that
most of the functional abnormality is related to absence of active sites in half of
the molecules. The plasmin generated was very unstable in the absence of stabilizing
ligands and/or substrates. After reduction, the plasmin was completely converted to
the typical two plasmin chains, A and B.
Keywords
Abnormal plasminogens - Variant plasminogen Frankfurt I - Deep vein thrombosis - Fibrinolysis
