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Congenital abnormal plasminogen, Frankfurt I, a cause for recurrent venous thrombosis
I Scharrer1, V Hach-Wunderle, R C Wohl
1Dept. of Internal Medicine, University Hospital, Frankfurt/Main, FRG.
Abstract:
A new abnormal plasminogen, Frankfurt I, has been identified in the plasma of a 42 year-old male patients who had recurring thromboses, thrombophlebitis and pulmonary embolism since his age of 29. Reduced functional and also slightly reduced antigen plasminogen concentrations were found in both the proposituts and his mother. Plasmin generation rates carried out by Streptokinase and Urokinase were also abnormal. The plasmin generated was very unstable in the absence of stabilizing ligands and/or substrates. Crossed immunoelectrophoresis of the purified Frankfurt I revealed a peak with normal size and shape, but displaced with respect to normal Glu-plasminogen toward the anode. Isoelectric focusing followed by zymography on an 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 showed that most of the functional abnormality is related to absence of active sites in half of the molecules.
Insights
A novel abnormal plasminogen, Frankfurt I, was identified in a patient with recurrent thrombosis. This variant exhibits reduced function and instability, linked to absent active sites in half its molecules.
Area of Science:
- Biochemistry
- Hematology
Background:
- Recurrent thrombotic events, including deep vein thrombosis and pulmonary embolism, can be associated with inherited thrombophilias.
- Plasminogen is a key protein in the fibrinolytic system, responsible for breaking down blood clots.
Observation:
- A new abnormal plasminogen variant, termed Frankfurt I, was identified in a 42-year-old male with a history of recurrent thromboses since age 29.
- Both the patient and his mother presented with reduced functional and slightly reduced antigen plasminogen levels.
- Plasmin generation rates using streptokinase and urokinase were abnormal, and the generated plasmin was unstable without stabilizing ligands or substrates.
Findings:
- Purified Frankfurt I plasminogen showed altered migration on crossed immunoelectrophoresis, shifting towards the anode compared to normal Glu-plasminogen.
- Isoelectric focusing and zymography revealed fewer bands in the abnormal plasminogen isozyme pattern, without clear separation of normal and abnormal species.
- Kinetic studies indicated that the functional abnormality in Frankfurt I plasminogen is primarily due to the absence of active sites in approximately 50% of the molecules.
Implications:
- The identification of plasminogen Frankfurt I contributes to understanding genetic factors influencing fibrinolysis and thrombophilia.
- This abnormal plasminogen variant may predispose individuals to thrombotic events due to impaired clot lysis.
- Further research into the structural and functional characteristics of plasminogen Frankfurt I could elucidate mechanisms of thrombotic disorders.