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Thromb Haemost 1997; 77(05): 0873-0878
DOI: 10.1055/s-0038-1656071
Coagulation
Schattauer GmbH Stuttgart

Fibrinogen Heterogeneity in Homozygous Plasminogen Deficiency Type I: Further Evidence that Plasmin Is not Involved in Formation of LMW- and LMW’-Fibrinogen

Carl-Erik Dempfle
1   The University of Heidelberg, Kiinikum Mannheim, First Department of Medicine, Germany
,
Susanne A Pfitzner
1   The University of Heidelberg, Kiinikum Mannheim, First Department of Medicine, Germany
,
Dorothee Schott
2   The University of Heidelberg, Kiinikum Mannheim, Department of Pediatrics, Mannheim, Germany
,
Karl-Heinz Niessen
2   The University of Heidelberg, Kiinikum Mannheim, Department of Pediatrics, Mannheim, Germany
,
Dieter L Heene
2   The University of Heidelberg, Kiinikum Mannheim, Department of Pediatrics, Mannheim, Germany
› Author Affiliations
Further Information

Publication History

Received 29 October 1996

Accepted after resubmission 13 January 1997

Publication Date:
11 July 2018 (online)

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Summary

Human plasma fibrinogen is heterogeneous in SDS-polyacrylamide gel electrophoresis and other methods for separation of proteins by molecular size. A high molecular weight fraction (HMW-fibrinogen, 340 kD) contributes approximately 50% of total fibrinogen antigen. Low molecular weight fibrinogen (LMW-fibrinogen, 300 kD) adds another 40%. The residual amount is LMW’-fibrinogen with a molecular weight of 280 kD, and a small amount of very high molecular weight fibrinogen (Fib420), the product of alternative splicing of the Aa-chain genetic information, resulting in an extended A?-chain C-terminus. Fibrinogen was detected by specific immunostaining of nonreduced SDS-PAGE gel immunoblots with antibodies against fibrinopeptide A. Using densitometric scans of the immunoblots we found a ratio of HMW-, LMW- and LMW’-fibrinogen in a patient with homozygous plasminogen deficiency that was similar to the ratio found in immunoblots of plasma from healthy blood donors. Treatment with plasminogen concentrate resulted in a slight decrease of the proportion of HMW-fibrinogen, followed by an increase to 78%. The LMW’- fibrinogen band gained intensity initially, increasing to 11.9% of fibrinogen antigen 6 h after starting plasminogen infusion, but then dropped to levels below detection limit of the immunoblotting assay. LMW-fibrinogen remained constant during the initial 72 h of plasminogen treatment, then dropping to values in the range of 22-25% afterwards. The proportion of HMW-, LMW-, and LMW’-fibrinogen.again reached the initial levels two weeks after starting treatment with plasminogen concentrate. We conclude that plasminogen is not involved in the limited proteolysis leading to formation of LMW-fibrinogen and LMW’-fibrinogen in the absence of a generalized fibrinolytic condition. Fibrinolytic activation may lead to the formation of fibrinogen degradation product X, which appears in a similar position as LMW’- fibrinogen in SDS-PAGE.

 

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