Lauricella, A.M.; Sittinger, K.; Geisen, C.; Kordich, L.C. ""Dysfibrinogenemia Jujuy", associated to bleeding disorders " (2016) Acta Bioquimica Clinica Latinoamericana. 50(2):215-221
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The aim of this work was to study a young female with moderate bleeding symptoms, to characterize the plasma fibrin and to identify the possible molecular alteration in the fibrinogen of the patient and her family. A dysfibrinogenemia was diagnosed in the patient, the mother and the half-brother, both the latter asymptomatic. Kinetic parameters obtained from fibrin formation and lysis assays of the patient's plasma samples were significantly different compared to the ones obtained with control plasma. A prolonged lag phase indicated slow and defective fibrinopeptide releases, whereas a minor slope suggested an impaired fibrin assembly. A lower ODMax revealed a fibrin network composed of thinner fibers. Fibrinolysis induced by streptokinase resulted faster than control. DNA sequencing showed a homozygous deletion leading to AaGly14del (according to The mother and the half-brother resulted heterozygous for the same mutation. This previously undescribed alteration was named fibrinogen Jujuy. The mutate fibrinogen might not be correctly fixed to the active site of thrombin resulting in slow cleavage and release of fibrinopeptides, rendering thinner fibers, more susceptible to lysis than control. This mechanism may explain the moderate bleeding symptoms of the patient.


Documento: Artículo
Título:"Dysfibrinogenemia Jujuy", associated to bleeding disorders
Autor:Lauricella, A.M.; Sittinger, K.; Geisen, C.; Kordich, L.C.
Filiación:Laboratorio de Hemostasia y Trombosis, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Ciudad Autónoma de Buenos Aires, Pabellón II, piso 40, Güiraldes, Buenos Aires, 2160, Argentina
German Red Cross Blood Centre, Institute of Transfusion Medicine and Immunohematology, Goethe University, Frankfurt, Germany
Palabras clave:Coagulation tests; Dysfibrinogenemia; Fibrin formation; Fibrin lysability
Página de inicio:215
Página de fin:221
Título revista:Acta Bioquimica Clinica Latinoamericana
Título revista abreviado:Acta Bioquim. Clin. Latinoam.


  • Blombäck, B., Fibrinogen and fibrin-proteins with complex roles in haemostasis and thrombosis (1996) Thromb Res, 83 (1), pp. 1-75
  • Moen, J.L., Lord, S.T., Afibrinogenemias and dysfibrinogenemias (2006) Haemostasis and Thrombosis. Basic Principles and Clinical Practice, pp. 939-952. , Colman RW, Marder VJ, Clowes AW, George JN, Goldhaber SZ, editors. 5th ed, Philadelphia: Lippincott Williams & Wilkins
  • Moerloose, P., Neerman-Arbez, M., Congenital fibrinogen disorders (2009) Semin Throm Hemost, 35 (4), pp. 356-366
  • Asselta, R., Duga, S., Tenchini, M.L., The molecular basis of quantitative fibrinogen disorders (2006) J Thromb Haemost, 4 (10), pp. 2115-2129
  • Peyvandi, F., Epidemiology and treatment of congenital fibrinogen deficiency (2012) Thromb Res, 130, pp. 7-11
  • Hanss, M., Biot, F., A database for human fibrinogen variants (2001) Ann N y Acad Sci, 936, pp. 89-90
  • Hill, M., Dolan, G., Diagnosis, clinical features and molecular assessment of the dysfibrinogenaemias (2008) Haemophilia, 14, pp. 889-897
  • Krammer, B., Anders, O., Nagel, H.R., Burstein, C., Steiner, M., Screening of dysfibrinogenaemia using the fibrinogen function versus antigen concentration ratio (1994) Thromb Res, 76 (6), pp. 577-579
  • Moerloose, P., Casini, A., Neerman-Arbez, M., Congenital fibrinogen disorders: An update (2013) Semin Thromb Hemost, 39, pp. 585-595
  • Casini, A., Blondon, M., Lebreton, A., Koegel, J., Tintillier, V., De Maistre, E., Natural history of patients with congenital dysfibrinogenemia (2015) Blood, 125 (3), pp. 553-561
  • Haverkate, F., Samama, M., Familial dysfibrinogenemia and thrombophilia. Report on a study of the SSC Subcommittee on Fibrinogen (1995) Thromb Haemost, 73 (1), pp. 151-161
  • Shapiro, S.E., Phillips, E., Manning, R.A., Morse, C.V., Murden, S.L., Laffan, M.A., Clinical phenotype, laboratory features and genotype of 35 patients with heritable dysfibrinogenaemia (2013) Br J Haematol, 160 (2), pp. 220-227
  • Casini, A., De Moerloose, P., Neerman-Arbez, M., Clinical features and management of congenital fibrinogen deficiencies (2016) Semin Thromb Hemost
  • Lauricella, A.M., Castañon, M.M., Kordich, L.C., Quintana, I.L., Alterations of fibrin network structure mediated by dermatan sulfate (2013) J Thromb Thrombolysis, 35 (2), pp. 257-263
  • Lauricella, A.M., Quintana, I., Castañon, M.M., Sassetti, B., Kordich, L., Influence of homocysteine on fibrin network lysis (2006) Blood Coagul Fibrinolysis, 17, pp. 181-186
  • Lahiri, D.K., Nurnberger, J.I., A rapid non-enzimatic method for the preparation of HMW DNA from blood for RFLP studies (1991) Nucleic Acids Research, 19, p. 5444
  • Ivaskevicius, V., Jusciute, E., Steffens, M., Geisen, C., Hanfland, P., Wienker, T., Gamma Ala82Gly represents a common fibrinogen gamma-chain variant in Caucasians (2005) Blood Coagul Fibrinolysis, 16 (3), pp. 205-208
  • Weisel, J.W., Litvinov, R.I., Mechanisms of fibrin polymerization and clinical implications (2013) Blood, 121 (10), pp. 1712-1719
  • Wolberg, A.S., Gabriel, D.A., Hoffman, M., Analysing fibrin clot structure using a microplate reader (2002) Blood Coagul Fibrinol, 13 (6), pp. 533-539
  • Weisel, J.W., Litvinov, R.I., The biochemical and physical process of fibrinolysis and effects of clots structure and stability on the lysis rate (2008) Cardiovasc Hematol Agents Med Chem, 6 (3), pp. 161-180
  • Rose, T., Di Cera, E., Three-dimensional modeling of thrombin-fibrinogen interaction (2002) J Biol Chem, 277 (21), pp. 18875-18880
  • Stubbs, M.T., Oschkinat, H., Mayr, I., Huber, R., Angliker, H., Stone, S.T., The interaction of thrombin with fibrinogen (1992) Eur J Biochem, 206 (1), pp. 187-195
  • Kaczmarck, E., McDonagh, J., Thrombin binding to the Aα-, Bβ-, and γ-chains of fibrinogen and to their remnants contained in fragment e (1988) J Biolog Chemist, 263 (27), pp. 13896-13900
  • Niwa, B.Z., Yaginuma, A., Nakanishi, M., Wada, Y., Sugo, T., Fibrinogen Mitaka II: A heredaty dysfibrinogen with defective thrombin binding caused by an Aα Glu-11 to Gly substitution (1993) Blood, 82 (12), pp. 3658-3663
  • Ni, F., Konishi, Y., Bullock, L.D., Rivetna, M.N., Scheraga, H.A., High-resolution NMR studies of fibrinogen-like peptides in solution: Structural basis for the bleeding disorder caused by a single mutation of Gly(12) to Val(12) in the A alpha chain of human fibrinogen Rouen (1989) Biochemistry, 28 (7), pp. 3106-3119
  • Kotlín, R., Zichová, K., Suttnar, J., Reicheltová, Z., Salaj, P., Hrachovinová, I., Congenital dysfibrinogenemia Aα Gly13Glu associated with bleeding during pregnancy (2011) Thromb Res, 127 (3), pp. 277-278


---------- APA ----------
Lauricella, A.M., Sittinger, K., Geisen, C. & Kordich, L.C. (2016) . "Dysfibrinogenemia Jujuy", associated to bleeding disorders . Acta Bioquimica Clinica Latinoamericana, 50(2), 215-221.
Recuperado de [ ]
---------- CHICAGO ----------
Lauricella, A.M., Sittinger, K., Geisen, C., Kordich, L.C. ""Dysfibrinogenemia Jujuy", associated to bleeding disorders " . Acta Bioquimica Clinica Latinoamericana 50, no. 2 (2016) : 215-221.
Recuperado de [ ]
---------- MLA ----------
Lauricella, A.M., Sittinger, K., Geisen, C., Kordich, L.C. ""Dysfibrinogenemia Jujuy", associated to bleeding disorders " . Acta Bioquimica Clinica Latinoamericana, vol. 50, no. 2, 2016, pp. 215-221.
Recuperado de [ ]
---------- VANCOUVER ----------
Lauricella, A.M., Sittinger, K., Geisen, C., Kordich, L.C. "Dysfibrinogenemia Jujuy", associated to bleeding disorders . Acta Bioquim. Clin. Latinoam. 2016;50(2):215-221.
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