Journal Mobile Options
Table of Contents
Vol. 120, No. 2, 2008
Issue release date: December 2008
Acta Haematol 2008;120:75–81

Acquired Dysfibrinogenemia Secondary to Multiple Myeloma

Kotlín R. · Sobotková A. · Riedel T. · Salaj P. · Suttnar J. · Reicheltová Z. · Májek P. · Khaznadar T. · Dyr J.E.
Institute of Hematology and Blood Transfusion, Praha, Czech Republic

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Abnormal coagulation properties indicative of a dysfibrinogen were found in the plasma of a 72-year-old male with multiple myeloma (IgGĸ, stage IIIA). The patient had high paraprotein concentration (85.75 g/l) and prolonged thrombin time (76.8 s), activated partial thromboplastin time (39.5 s), prothrombin time (23.5 s) and reptilase time (72.0 s). The fibrinogen level was increased. The fibrin polymerization induced by both thrombin and reptilase was impaired. Scanning electron microscopy revealed abnormal clot morphology. After six months of treatment, the paraprotein level decreased (19.48 g/l) and coagulation normalized as well as fibrin polymerization and fibrin clot morphology. It was found that the paraprotein interacts with the γ-chain of fibrinogen. Acquired dysfibrinogenemia associated with multiple myeloma was diagnosed in the 72-year-old patient.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Maniatis A: Pathophysiology of paraprotein production. Ren Fail 1998;20:821–828.
  2. DiMinno G, Coraggio F, Cerbone AM, Capitanio AM, Manzo C, Spina M, Scarpato P, Dattoli GM, Mattioli PL, Mancini M: A myeloma paraprotein with specifity for platelet glycoprotein IIIa in a patient with a fatal bleeding disorder. J Clin Invest 1986;77:157–164.
  3. Hoots WK, Carrell NA, Wagner RH, Cooper HA, McDonagh J: A naturally occurring antibody that inhibits fibrin polymerization. N Engl J Med 1981;304:857–861.
  4. Ruiz-Arguelles A: Spontaneous reversal of acquired autoimmune dysfibrinogenemia probably due to an anti-idiotypic antibody directed to an interspecies cross-reactive idiotype expressed on antifibrinogen antibodies. J Clin Invest 1988;82:958–963.
  5. Rosenberg RD, Colman RW, Lorand L: A new haemorrhagic disorder with defective fibrin stabilization and cryofibrinogenaemia. Br J Haematol 1974;26:269–284.
  6. Marciniak R, Greenwood MF: Acquired coagulation inhibitor delaying fibrinopeptide release. Blood 1979;53:81–92.
  7. Levy J, Pettei MJ, Weitz JI: Dysfibrinogenemia in obstructive liver disease. J Pediatr Gastroenterol Nutr 1987;6:967–970.
  8. Martinez J, MacDonald KA, Palascak JE: The role of sialic acid in the dysfibrinogenemia associated with liver disease: distribution of sialic acid on the constituent chains. Blood 1983;61:1196–1202.
  9. Maak B, Meyer M, Dietze H: Acquired dysfibrinogenemia in a child in the course of a liver disease. Monatsschr Kinderheilkd 1990;138:446–450.
  10. Reganon E, Vila V, Aznar J, Garrido G, Estelles A, Berenguer J: Study of the formation of fibrin clot in cirrhotic patients. An approach to study of acquired dysfibrinogenemia, Thromb Res 1987;46:705–714.
  11. Narviaza MJ, Fernandez J, Cuesta B, Paramo JA, Rocha E: Role of sialic acid in acquired dysfibrinogenemia associated with liver cirrhosis. Ric Clin Lab 1986;16:563–568.

    External Resources

  12. Bohler A, Redondo M, Lämmle B: Verlängerte Thrombinzeit bei einem Patienten mit multiplem Myelom. Ther Umsch 1999;56:491–494.
  13. Carr ME, Zekert SL: Abnormal clot retraction, altered fibrin structure, and normal platelet function in multiple myeloma. Am J Physiol 1994;266:H1195–H1201.
  14. Saif MW, Allegra CJ, Greenberg B: Bleeding diathesis in multiple myeloma. J Hematother Stem Cell Res 2001;10:657–660.
  15. Lackner H, Hunt V, Zucker MB, Pearson J: Abnormal fibrin ultrastructure, polymerization, and clot retraction in multiple myeloma. Br J Haematol 1970;18:625–636.
  16. Gralnick HR, Givelber H, Abrams E: Dysfibrinogenemia associated with hepatoma. N Engl J Med 1978;299:221–226.
  17. Ballard JO, Kelly GA, Kukrika MD, Sanders JC, Eyster ME: Acquired dysfibrinogenemia in a hemophiliac with hepatoma: resolution of fibrinogen dysfunction following chemotherapy. Cancer 1981;48:686–690.
  18. Dawson NA, Barr CF, Alving BM: Acquired dysfibrinogenemia. Paraneoplastic syndrome in renal cell carcinoma. Am J Med 1985;78:682–686.
  19. Kwaan HC, Levin M, Sakurai S, Kucuk O, Rooney MW, Lis LJ, Kauffman JW: Digital ischemia and gangrene due to red blood cell aggregation induced by acquired dysfibrinogenemia. J Vasc Surg 1997;26:1061–1068.
  20. Aurousseau MH, Levacher S, Bénéton C, Blaise M, Pourrait JL: Dysfibrinogénémie et thrombocytopénie transitoires associées à une pancréatite aiguë récidivante lors d’un traitement par l’isotrétinoïne. Rev Méd Interne 1995;16:622–625.
  21. Ashby MA, Lazarchick J: Case report: acquired dysfibrinogenemia secondary to mithramycin toxicity. Am J Med Sci 1986;292:53–55.
  22. Mori T, Murata M, Wakui M, Muto A, Ishida A, Tanosaki R, Okamoto S, Ikeda Y: Acquired dysfibrinogenemia following allogenic bone marrow transplantation. Am J Hematol 1997;56:294–295.
  23. Shigekiyo T, Kosaka M, Shintani Y, Azuma H, Iishi Y, Saito S: Inhibition of fibrin monomer polymerization by Bence Jones protein in a patient with primary amyloidosis. Acta Haematol 1989;81:160–165.
  24. Dear A, Brennan SO, Sheat MJ, Faed JM, George PM: Acquired dysfibrinogenemia caused by monoclonal production of immunoglobulin λ light chain. Haematologica 2007;92:e111–e117.
  25. Sugai S: IgA pyroglobulin, hyperviscosity syndrome and coagulation abnormality in a patient with multiple myeloma. Blood 1972;39:224–237.
  26. Gabriel DA, Smith LA, Folds JD, Davis L, Cancelosi SE: The influence of immunoglobulin (IgG) on the assembly of fibrin gels. J Lab Clin Med 1983;101:545–552.
  27. O’Kane MJ, Wisdom GB, Desai ZR, Archbold GPR: Inhibition of fibrin monomer polymerization by myeloma immunoglobulin. J Clin Pathol 1994;47:266–268.
  28. Panzer S, Thaler E: An acquired cryoglobulinemia which inhibits fibrin polymerization in a patient with IgG kappa myeloma. Haemostasis 1993;23:69–76.
  29. Brennan SO, Hammonds B, George PM: Aberrant hepatic processing causes removal of activation peptide and primary polymerization site from fibrinogen Canterbury (Aα Val → Asp). J Clin Invest 1995;96:2854–2858.
  30. Kotlín R, Chytilová M, Suttnar J, Salaj P, Riedel T, Šantrůček J, Klener P, Dyr JE: A novel fibrinogen variant – Praha I: hypofibrinogenemia associated with γ 351 Gly → Ser substitution. Eur J Haematol 2007;78:410–416.
  31. Suttnar J, Dyr JE, Fořtová H, Pristach J: Determination of fibrinopeptides by high performance liquid chromatography. Biochem Clin Bohemoslov 1989;18:17–25.
  32. Kotlín R, Chytilová M, Suttnar J, Riedel T, Salaj P, Blatný J, Šantrůček J, Klener P, Dyr JE: Fibrinogen Nový Jičín and Praha II: cases of hereditary Aalpha 16 Arg → Cys and Aalpha 16 Arg → His dysfibrinogenemia. Thromb Res 2007;121:75–84.
  33. Laemmli UK: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970;227:680–685.
  34. Scheiner T, Jiroušková M, Nagaswami C, Coller BS, Weisel JW: A monoclonal antibody to the fibrinogen gamma-chain alters fibrin clot structure and its properties by producing short, thin fibers arranged in bundles. J Thromb Haemost 2003;1:2594–2602.
  35. Yang Z, Mochalkin I, Doolittle RF: A model of fibrin formation based on crystal structures of fibrinogen and fibrin fragments complexed with synthetic peptides. Proc Natl Acad Sci USA 2000;97:14156–14161.
  36. Smith E, Kochwa S, Wasserman LR: Aggregation of IgG globulin in vivo. The hyperviscosity syndrome in multiple myeloma. Am J Med 165;39:35–48.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50