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. 1971 Sep;50(9):1874–1884. doi: 10.1172/JCI106680

Functional evaluation of an inherited abnormal fibrinogen: fibrinogen “Baltimore”

Eugene A Beck 1,2,3,4, John R Shainoff 1,2,3,4, Alfred Vogel 1,2,3,4, Dudley P Jackson 1,2,3,4
PMCID: PMC292114  PMID: 5564395

Abstract

The rate of clotting and the rate of development and degree of turbidity after addition of thrombin to plasma or purified fibrinogen from a patient with fibrinogen Baltimore was delayed when compared with normal, especially in the presence of low concentrations of thrombin. Optimal coagulation and development of translucent, rather than opaque, clots occurred at a lower pH with the abnormal fibrinogen than with normal. Development of turbidity during clotting of the abnormal plasma or fibrinogen was less than normal at each pH tested, but was maximal in both at approximately pH 6.4. The physical quality of clots formed from fibrinogen Baltimore was abnormal, as demonstrated by a decreased amplitude on thromboelastography. The morphologic appearance of fibrin strands formed from fibrinogen Baltimore by thrombin at pH 7.4 was abnormal when examined by phase contrast or electron microscopy, but those formed by thrombin at pH 6.4 or by thrombin and calcium chloride were similar to, though less compact, than normal fibrin. The periodicity of fibrin formed from fibrinogen Baltimore was similar to normal and was 231-233 Å.

A study of the release of the fibrinopeptides from the patient's fibrinogen and its chromatographic subfractions verified the existence of both a normally behaving and a defective form of fibrinogen in the patient's plasma. The defective form differed from normal in three functionally different ways: (a) the rate of release of fibrinopeptides A and AP was slower than normal; (b) no visible clot formation accompanied either partial or complete release of the fibrinopeptides from the defective form in 0.3 M NaCl at pH 7.4; and (c) the defective component possessed a high proportion of phosphorylated, relative to nonphosphorylated, fibrinopeptide A, while the coagulable component contained very little of the phosphorylated peptide (AP). The high phosphate content of the defective component did not appear to be the cause of the abnormality, but may be the result of an associated metabolic or genetic phenomenon.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ABILDGAARD U. ACCELERATION OF FIBRIN POLYMERIZATION BY ACETATE AND OTHER LOW MOLECULAR IONS. Scand J Clin Lab Invest. 1964;16:521–530. doi: 10.3109/00365516409060550. [DOI] [PubMed] [Google Scholar]
  2. BLOMBAECK B., BLOMBAECK M., DOOLITTLE R. F., HESSEL B., EDMAN P. ON THE PROPERTIES OF A NEW HUMAN FIBRINOPEPTIDE. Biochim Biophys Acta. 1963 Nov 15;78:563–566. doi: 10.1016/0006-3002(63)90929-6. [DOI] [PubMed] [Google Scholar]
  3. Beck E. A., Charache P., Jackson D. P. A new inherited coagulation disorder caused by an abnormal fibrinogen ('fibrinogen Baltimore'). Nature. 1965 Oct 9;208(5006):143–145. doi: 10.1038/208143a0. [DOI] [PubMed] [Google Scholar]
  4. Beck E. A., Jackson D. P. Studies on the degradation of human fibrinogen by plasmin and trypsin. Thromb Diath Haemorrh. 1966 Dec 1;16(3):526–540. [PubMed] [Google Scholar]
  5. Blombäck B., Blombäck M., Henschen A., Hessel B., Iwanaga S., Woods K. R. N-terminal disulphide knot of human fibrinogen. Nature. 1968 Apr 13;218(5137):130–134. doi: 10.1038/218130a0. [DOI] [PubMed] [Google Scholar]
  6. Blombäck M., Blombäck B., Mammen E. F., Prasad A. S. Fibrinogen Detroit--a molecular defect in the N-terminal disulphide knot of human fibrinogen? Nature. 1968 Apr 13;218(5137):134–137. doi: 10.1038/218134a0. [DOI] [PubMed] [Google Scholar]
  7. EDSALL J. T., LEVER W. F. Effects of ions and neutral molecules on fibrin clotting. J Biol Chem. 1951 Aug;191(2):735–756. [PubMed] [Google Scholar]
  8. Egeberg O. Inherited fibrinogen abnormality causing thrombophilia. Thromb Diath Haemorrh. 1967 Feb 28;17(1-2):176–187. [PubMed] [Google Scholar]
  9. Forman W. B., Ratnoff O. D., Boyer M. H. An inherited qualitative abnormality in plasma fibrinogen: fibrinogen Cleveland. J Lab Clin Med. 1968 Sep;72(3):455–472. [PubMed] [Google Scholar]
  10. HASSELBACK R., MARION R. B., THOMAS J. W. Congenital hypofibrinogenemia in five members of a family. Can Med Assoc J. 1963 Jan 5;88:19–22. [PMC free article] [PubMed] [Google Scholar]
  11. Hampton J. W., Cunningham G. R., Bird R. M. The pattern of inheritance of defective fibrinase (Factor 13). J Lab Clin Med. 1966 Jun;67(6):914–921. [PubMed] [Google Scholar]
  12. Herzig R. H., Ratnoff O. D., Shainoff J. R. Studies on a procoagulant fraction of southern copperhead snake venom: the preferential release of fibrinopeptide B. J Lab Clin Med. 1970 Sep;76(3):451–465. [PubMed] [Google Scholar]
  13. IMPERATO C., DETTORI A. G. Ipofibrinogenemia congenita con fibrinoastenia. Helv Paediatr Acta. 1958 Oct;13(4):380–399. [PubMed] [Google Scholar]
  14. Jackson D. P., Beck E. A., Charache P. Congenital disorders of fibrinogen. Fed Proc. 1965 Jul-Aug;24(4):816–821. [PubMed] [Google Scholar]
  15. Kay D., Cuddigan B. J. The fine structure of fibrin. Br J Haematol. 1967 May;13(3):341–347. doi: 10.1111/j.1365-2141.1967.tb08749.x. [DOI] [PubMed] [Google Scholar]
  16. LAKI K. The polymerization of proteins; the action of thrombin on fibrinogen. Arch Biochem Biophys. 1951 Jul;32(2):317–324. doi: 10.1016/0003-9861(51)90277-9. [DOI] [PubMed] [Google Scholar]
  17. Mammen E. F., Prasad A. S., Barnhart M. I., Au C. C. Congenital dysfibrinogenemia: fibrinogen Detroit. J Clin Invest. 1969 Feb;48(2):235–249. doi: 10.1172/JCI105980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mosesson M. W., Beck E. A. Chromatographic, ultracentrifugal, and related studies of fibrinogen "Baltimore". J Clin Invest. 1969 Sep;48(9):1656–1662. doi: 10.1172/JCI106130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. RATNOFF O. D., MENZIE C. A new method for the determination of fibrinogen in small samples of plasma. J Lab Clin Med. 1951 Feb;37(2):316–320. [PubMed] [Google Scholar]
  20. SHAINOFF J. R., PAGE I. H. Significance of cryoprofibrin in fibrinogen-fibrin conversion. J Exp Med. 1962 Nov 1;116:687–707. doi: 10.1084/jem.116.5.687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sasaki T., Page I. H., Shainoff J. R. Stable complex of fibrinogen and fibrin. Science. 1966 May 20;152(3725):1069–1071. doi: 10.1126/science.152.3725.1069. [DOI] [PubMed] [Google Scholar]
  22. Vogel A., Beck E. A. Qualitative elektronenmikroskopische Untersuchung der aus Fibrinogen Baltimore entstehenden Fibrinstruktur. Schweiz Med Wochenschr. 1968 Oct 19;98(42):1651–1653. [PubMed] [Google Scholar]
  23. Von Felten A., Duckert F., Frick P. G. Familial disturbance of fibrin monomer aggregation. Br J Haematol. 1966 Nov;12(6):667–677. doi: 10.1111/j.1365-2141.1966.tb00152.x. [DOI] [PubMed] [Google Scholar]

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