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Bleeding Disorders Associated with Cancer Dysproteinemias

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Coagulation in Cancer

Part of the book series: Cancer Treatment and Research ((CTAR,volume 148))

Acquired coagulation abnormalities are not infrequently detected in the laboratory evaluation of patients with paraproteinemias; however, clinically evident manifestations are observed in only 10% of such patients [1]. The hemorrhages observed with these abnormalities are rarely spontaneous, but often associated with surgical procedures. Hemostatic abnormalities have been reported in patients with primary AL amyloidosis, Waldenström macroglobulinemia, multiple myeloma and monoclonal gammopathy of undetermined significance (MGUS).

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References

  1. Liebman HA. Hemostatic defects associated with dysproteinemias. In: R. Hoffman et al., eds. Hematology: basic principles and practice, 3rd edn. New York: Churchill Livingstone, 2000;1996–1999

    Google Scholar 

  2. Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003;78(1):21–33

    Google Scholar 

  3. García-Sanz R, Montoto S, Torrequebrada A, et al. Waldenström macroglobulinaemia: presenting features and outcome in a series with 217 cases. Br J Haematol. 2001;115(3):575–82

    Article  PubMed  Google Scholar 

  4. Kyle RA, Gertz MA. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol 1995;32:45–59

    PubMed  CAS  Google Scholar 

  5. Perkins HA, MacKenzie MR, Fudenberg HH. Hemostatic defects in dysproteinemias. Blood 1970;35(5):695–707

    PubMed  CAS  Google Scholar 

  6. Gamba G, Montani N, Anesi E, et al. Clotting alterations in primary systemic amyloidosis. Haematologica 2000;85(3):289–92

    PubMed  CAS  Google Scholar 

  7. Mumford A, O’Donnell J, Gillmore J, et al. Bleeding symptoms and coagulation abnormalities in 337 patients with Al-amyloidosis. Br J Haematol 2000;110:454–460

    Article  PubMed  CAS  Google Scholar 

  8. Kyrtsonis M, Vassilakopoulos T, Angelopuolou M, et al. Waldenstrom’s macoglobulinemia: clinical course and prognostic factors in 60 patients. Ann Hematol 2001;80:722–727

    Article  PubMed  CAS  Google Scholar 

  9. Sucker C, Hetzel GR, Grabensee B, et al. Amyloidosis and bleeding: pathophysiology, diagnosis, and therapy. Am J Kidney Dis 2006;47(6):947–55

    Article  PubMed  CAS  Google Scholar 

  10. Hoshino Y, Hatake K, Muroi K, et al. Bleeding tendency caused by the deposit of amyloid substance in the perivascular region. Intern Med 1993;32(11):879–81

    Article  PubMed  CAS  Google Scholar 

  11. Choufani E, Sanchorawala V, Ernst T, et al. Acquired factor X deficiency in patients with amyloid light-chain amyloidosis: incidence, bleeding manifestations, and response to highdose chemotherapy. Blood 2001;97:1885–1887

    Article  PubMed  CAS  Google Scholar 

  12. Furie B, Voo L, McAdam KP, et al. Mechanism of factor X deficiency in systemic amyloidosis. N Engl J Med 1981;304(14):827–30

    Article  PubMed  CAS  Google Scholar 

  13. Furie B, Greene E, Furie BC. Syndrome of acquired factor X deficiency and systemic amyloidosis in vivo studies of the metabolic fate of factor X. N Engl J Med 1977;297(2):81–5

    Article  PubMed  CAS  Google Scholar 

  14. Galbraith PA, Sharma N, Parker WL, et al. Acquired factor X deficiency. Altered plasma antithrombin activity and association with amyloidosis. JAMA 1974;230(12):1658–60

    Article  PubMed  CAS  Google Scholar 

  15. Greipp PR, Kyle RA, Bowie EJ. Factor X deficiency in primary amyloidosis: resolution after splenectomy. N Engl J Med 1979;301(19):1050–1

    Article  PubMed  CAS  Google Scholar 

  16. Rosenstein ED, Itzkowitz SH, Penziner AS, et al. Resolution of factor X deficiency in primary amyloidosis following splenectomy. Arch Intern Med 1983;143(3):597–9

    Article  PubMed  CAS  Google Scholar 

  17. Gabriel DA, Smith LA, Folds JD, et al. The influence of immunoglobulin (IgG) on the assembly of fibrin gels. J Lab Clin Med 1983;101(4):545–52

    PubMed  CAS  Google Scholar 

  18. Korsan-Bengsten K, Hjort PF, Ygge J. Acquired factor X deficiency in a patient with amyloidosis. Thromb Diath Haemorrh 1962;7:558–66

    Google Scholar 

  19. Greipp PR, Kyle RA, Bowie EJ. Factor-X deficiency in amyloidosis: a critical review. Am J Hematol 1981;11(4):443–50

    Article  PubMed  CAS  Google Scholar 

  20. McPherson RA, Onstad JW, Ugoretz RJ, et al. Coagulopathy in amyloidosis: combined deficiency of factors IX and X. Am J Hematol 1977;3:225–35

    PubMed  CAS  Google Scholar 

  21. Liebman H, Chinowsky M, Valdin J, et al. Increased fibrinolysis and amyloidosis. Arch Intern Med 1983;143(4):678–82

    Article  PubMed  CAS  Google Scholar 

  22. Emori Y, Sakugawa M, Niiya K, et al. Life-threatening bleeding and acquired factor V deficiency associated with primary systemic amyloidosis. Blood Coagul Fibrinolysis 2002;13(6):555–9

    Article  PubMed  CAS  Google Scholar 

  23. Gertz MA, Fonseca R, Rajkumar SV. Waldenstrom's macroglobulinemia. Oncologist 2000;5(1):63–7

    Article  PubMed  CAS  Google Scholar 

  24. Penny R, Castaldi PA, Whitsed HM. Inflammation and haemostasis in paraproteinaemias. Br J Haematol 1971;20(1):35–44

    Article  PubMed  CAS  Google Scholar 

  25. Cohen I, Amir J, Ben-Shaul Y, et al. Plasma cell myeloma associated with an unusual myeloma protein causing impairment of fibrin aggregation and platelet function in a patient with multiple malignancy. Am J Med 1970;48(6):766–76

    Article  PubMed  CAS  Google Scholar 

  26. DiMinno G, Coraggio F, Cerbone AM, et al. A myeloma paraprotein with specificity for platelet glycoprotein IIIa in a patient with a fatal bleeding disorder. J Clin Invest 1986;77(1):157–64

    Article  PubMed  CAS  Google Scholar 

  27. Zima T, Spicka I, Stípek S, et al. Antioxidant enzymes and lipid peroxidation in patients with multiple myeloma. Neoplasma 1996;43(2):69–73

    PubMed  CAS  Google Scholar 

  28. Cieslar P, Masova L, Scheiner T, et al. Oxidative stress and platelet function in multiple myeloma and renal insufficiency: clinical relations of different tests. Thromb Res 2002;105(4):277–83

    Article  PubMed  CAS  Google Scholar 

  29. Taher A, Abiad R, Uthman I. Coexistence of lupus anticoagulant and acquired haemophilia in a patient with monoclonal gammopathy of unknown significance. Lupus 2003;12(11):854–6

    Article  PubMed  CAS  Google Scholar 

  30. Mohri H, Noguchi T, Kodama F, et al. Acquired von Willebrand disease due to inhibitor of human myeloma protein specific for von Willebrand factor. Am J Clin Pathol 1987;87(5):663–8

    PubMed  CAS  Google Scholar 

  31. Loftus LS, Arnold WN. Acquired hemophilia in a patient with myeloma. West J Med 1994;160(2):173–6

    PubMed  CAS  Google Scholar 

  32. Eby CS. Bleeding and thrombosis risks in plasma cell dyscrasias. Hematology Am Soc Hematol Educ Program 2007;2007:158–64

    Article  Google Scholar 

  33. Federici AB, Mannucci PM. Diagnosis and management of acquired von Willebrand syndrome. Clin Adv Hematol Oncol 2003;1(3):169–75

    PubMed  Google Scholar 

  34. Mant MJ, Hirsh J, Gauldie J, et al. Von Willebrand's syndrome presenting as an acquired bleeding disorder in association with a monoclonal gammopathy. Blood 1973;42(3):429–36

    PubMed  CAS  Google Scholar 

  35. Tiede A, Priesack J, Werwitzke S, et al. Diagnostic workup of patients with acquired von Willebrand syndrome: a retrospective single-centre cohort study. J Thromb Haemost 2008;6:569–76

    Article  PubMed  CAS  Google Scholar 

  36. Kumar S, Pruthi RK, Nichols WL. Acquired von Willebrand disease. Mayo Clin Proc 2002;77(2):181–7

    Google Scholar 

  37. Shinagawa A, Kojima H, Berndt MC, et al. Characterization of a myeloma patient with a life-threatening hemorrhagic diathesis: presence of a lambda dimer protein inhibiting shear-induced platelet aggregation by binding to the A1 domain of von Willebrand factor. Thromb Haemost 2005;93(5):889–96

    PubMed  CAS  Google Scholar 

  38. van Genderen PJ, Vink T, Michiels JJ, et al. Acquired von Willebrand disease caused by an autoantibody selectively inhibiting the binding of von Willebrand factor to collagen. Blood 1994;84(10):3378–84

    PubMed  Google Scholar 

  39. Brody JI, Haidar ME, Rossman RE. A hemorrhagic syndrome in Waldenstrom's macroglobulinemia secondary to immunoadsorption of factor VIII. Recovery after splenectomy. N Engl J Med 1979;300(8):408–10

    Article  PubMed  CAS  Google Scholar 

  40. Saif MW, Allegra CJ, Greenberg B. Bleeding diathesis in multiple myeloma. J Hematother Stem Cell Res 2001;10(5):657–60

    Article  PubMed  CAS  Google Scholar 

  41. Colwell NS, Tollefsen DM, Blinder MA. Identification of a monoclonal thrombin inhibitor associated with multiple myeloma and a severe bleeding disorder. Br J Haematol 1997;97(1):219–26

    Article  PubMed  CAS  Google Scholar 

  42. Wisløff F, Michaelsen TE, Godal HC. Inhibition or acceleration of fibrin polymerization by monoclonal immunoglobulins and immunoglobulin fragments. Thromb Res 1984;35(1):81–90

    Article  PubMed  Google Scholar 

  43. Lackner H, Hunt V, Zucker MB, et al. Abnormal fibrin ultrastructure, polymerization, and clot retraction in multiple myeloma. Br J Haematol 1970;18(6):625–36

    Article  PubMed  CAS  Google Scholar 

  44. Wisløff F, Michaelsen TE, Kierulf P, et al. The molecular localization of the ability of certain monoclonal immunoglobulins to interfere with fibrin polymerization. Thromb Res 1985;40(4):473–82

    Article  PubMed  Google Scholar 

  45. Beardell FV, Varma M, Martinez J. Normalization of plasma factor X levels in amyloidosis after plasma exchange. Am J Hematol 1997;54(1):68–71

    Article  PubMed  CAS  Google Scholar 

  46. Gertz MA, Kyle RA. Hyperviscosity syndrome. J Intensive Care Med 1995;10:128–141

    PubMed  CAS  Google Scholar 

  47. Torjemane L, Guermazi S, Ladeb S, et al. Heparin-like anticoagulant associated with multiple myeloma and neutralized with protamine sulfate. Blood Coagul Fibrinolysis 2007;18(3):279–81

    Article  PubMed  Google Scholar 

  48. Llamas P, Outeiriño J, Espinoza J, et al. Report of three cases of circulating heparin-like anticoagulants. Am J Hematol 2001;67(4):256–8

    Article  PubMed  CAS  Google Scholar 

  49. Chapman GS, George CB, Danley DL. Heparinlike anticoagulant associated with plasma cell myeloma. AJCP 1985; 83:764–766

    PubMed  CAS  Google Scholar 

  50. Kaufman PA, Gockerman JP, Greenberg CS. Production of a novel anticoagulant by neoplastic plasma cells: report of a case and review of the literature. Am J Med 1989;86(5):612–6

    Article  PubMed  CAS  Google Scholar 

  51. Endo T, Yatomi Y, Amemiya N, et al. Antibody studies of factor VIII inhibitor in a case with Waldenström's macroglobulinemia. Am J Hematol 2000;63(3):145–8

    Article  PubMed  CAS  Google Scholar 

  52. Gawryl MS, Hoyer LW. Inactivation of factor VIII coagulant activity by two different types of human antibodies. Blood 1982;60(5):1103–9

    PubMed  CAS  Google Scholar 

  53. Takahashi H, Koike T, Yoshida N, et al. Excessive fibrinolysis in suspected amyloidosis: demonstration of plasmin-alpha 2-plasmin inhibitor complex and von Willebrand factor fragment in plasma. Am J Hematol 1986;23(2):153–66

    Article  PubMed  CAS  Google Scholar 

  54. Liebman HA, Carfagno MK, Weitz IC, et al. Excessive fibrinolysis in amyloidosis associated with elevated plasma single-chain urokinase. Am J Clin Pathol 1992;98(5):534–41

    PubMed  CAS  Google Scholar 

  55. Sane DC, Pizzo SV, Greenberg CS. Elevated urokinase-type plasminogen activator level and bleeding in amyloidosis: case report and literature review. Am J Hematol 1989;31(1):53–7

    Article  PubMed  CAS  Google Scholar 

  56. Ostrowska JD, Wojtukiewicz MZ, Chabielska E, et al. Proteasome inhibitor prevents experimental arterial thrombosis in renovascular hypertensive rats. Thromb Haemost 2004;92(1):171–177

    PubMed  CAS  Google Scholar 

  57. Wang M, Giralt S, Delasalle K, et al. Bortezomib in combination with thalildomide-dexamethasone for previously untreated multiple myeloma. Hematology 2007;12:235–239

    Article  PubMed  CAS  Google Scholar 

  58. Avcu F, Ural AU, Cetin T, et al. Effects of bortezomib on platelet aggregation and ATP release in human platelets, in vitro. Thromb Res 2008;121(4):567–71

    Article  PubMed  CAS  Google Scholar 

  59. Zangari M, Guerrero J, Cavallo F, et al. Coagulation-related effect of bortezomib treatment in patients with relapsed or refractory multiple myeloma. Blood (ASH Annual Meeting Abstracts) 2007; 110: Abstract 2733

    Google Scholar 

  60. Federici AB, Stabile F, Castaman G, et al. Treatment of acquired von Willebrand syndrome in patients with monoclonal gammopathy of uncertain significance: comparison of three different therapeutic approaches. Blood 1998;92(8):2707–11

    PubMed  CAS  Google Scholar 

  61. Hayashi T, Yagi H, Suzuki H, et al. Low-dosage intravenous immunoglobulin in the management of a patient with acquired von Willebrand syndrome associated with monoclonal gammopathy of undetermined significance. Pathophysiol Haemost Thromb 2002;32(1):33–9

    Article  PubMed  CAS  Google Scholar 

  62. Friederich PW, Wever PC, Briët E, et al. Successful treatment with recombinant factor VIIa of therapy-resistant severe bleeding in a patient with acquired von Willebrand disease. Am J Hematol 2001;66(4):292–4

    Article  PubMed  CAS  Google Scholar 

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Zangari, M., Elice, F., Tricot, G., Fink, L. (2009). Bleeding Disorders Associated with Cancer Dysproteinemias. In: Kwaan, H., Green, D. (eds) Coagulation in Cancer. Cancer Treatment and Research, vol 148. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-79962-9_17

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  • DOI: https://doi.org/10.1007/978-0-387-79962-9_17

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