#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

A patient with AL amyloidosis and severe factor X deficiency has been in complete haematological remission with normal factor X activity for 7 years following high‑dose chemotherapy. A case study and literature review


Authors: Z. Adam 1;  M. Matýšková 2;  M. Krejčí 1;  L. Pour 1;  J. Kissová 2;  M. Šlechtová 2;  G. Chlupová 2;  Y. Stavařová 3;  J. Simonides 4;  M. Penka 2;  J. Mayer 1;  R. Hájek 1
Authors‘ workplace: Interní hematoonkologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Jiří Vorlíček, CSc. 1;  Oddělení klinické hematologie FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Miroslav Penka, CSc. 2;  Hematologicko transfuzní oddělení Baťovy krajské nemocnice, a. s., Zlín, přednostka prim. MUDr. Yveta Stavařová 3;  Hematologicko‑transfuzní oddělení Nemocnice Znojmo, přednosta prim. MUDr. Jan Simonides 4
Published in: Vnitř Lék 2010; 56(1): 67-78
Category: Case Reports

Overview

Disturbance of haemostasis and bleeding are rather frequent complications of AL amyloidosis. These are frequently caused by increased fragility of capillaries, thrombocyte function disorders and coagulation cascade defects. The most frequent coagulation disorder is decreased factor X activity. We describe a 34‑year old female after hysterectomy for myomatous uterus and metrorhagia. Before the surgery, the attending physicians did not identify any pathological changes suggesting a need for further investigations or presence of AL amyloidosis. Post‑surgery development was complicated by life-threatening diffuse haemorrhage. Extended investigations of coagulation cascade revealed reduction of factor X activity to 16%. Targeted histological examination of the resected uterus confirmed AL amyloid deposits consisting of κ chains. The patient’s bone marrow contained certain small level of multiplied κ chains-expressing plasma cells (< 10%); monoclonal immunoglobulins IgG κ and free κ chains were identified in serum. At that time, the patient did not satisfy the then valid Durie- Salmon criteria for multiple myeloma and thus the patient was diagnosed with primary systemic AL amyloidosis. The patient’s condition gradually improved following substitution therapy (Prothromplex, fresh frozen plasma and erythrocyte transfusion) and bleeding slowly ceased so that chemotherapy with VAD (vincristine, adriamycin and dexamethasone) was initiated 6 weeks after the surgery. A total of 8 chemotherapy cycles were administered and complete haematological remission was achieved after the 5th cycle. Administration of the 8 VAD chemotherapy cycles resulted in increased factor X activity; bleeding complications subsided completely, thereby decreasing the risk of life- threatening mucositis‑associated haemorrhage. Consequently, tandem high‑dose chemotherapy (melphalan 100 mg/ m2) with autologous haematopoietic stem cells transplantation was added to the treatment plan. Treatment was completed at the beginning of 2003 and, from that time, the patient is on continuous maintenance therapy with interferon α. Seven years from the diagnosis and 6 years from the completion of treatment the patient is in complete haematological remission, with no signs of organic damage caused by AL amyloid and with normal factor X activity. Factor X activity increased at the time when complete haematological remission was achieved after 8 cycles of VAD chemotherapy to 42%, it reached 68% the second year following high‑dose chemotherapy, 77% after 5 years and 85% after 7 years. We had considered administration of high‑dose chemotherapy in the standard regimen, i.e. following 4 cycles of VAD chemotherapy, as too high risk in the described young female patient. Therefore, we administered 8 cycles of conventional chemotherapy and only after complete haematological remission and partial organ response (factor X activity increased to 42%) were achieved, we added tandem high‑dose chemotherapy to the treatment. We thus achieved long‑term (7‑years so far) complete haematological and organ remission. Increase in factor X activity is explicit over the entire 7‑year observational period. We recommend starting treatment of high‑risk transplant patients with AL amyloidosis with traditional chemotherapy regimen and, in case of positive haematological and organ treatment response, we recommend re‑examination of potential benefits and risks of high‑dose chemotherapy with autologous transplantation.

Key words:
factor X – AL amyloidosis – multiple myeloma – monoclonal gammopathy – high‑dose chemotherapy with autologous transplantation – coagulopath


Sources

1. Ščudla V, Pika T. Současné možnosti diagnostiky a léčby systémové AL‑amyloidózy. Vnitř Lék 2009; 55 (Suppl 1): S77–S87.

2. Tichý M. Primární amyloidóza. Lék Zpr. LF UK Hradec Králové 1999; 44: 5–6.

3. Abraham RS, Geyer SM, Price-Troska TL et al. Immunoglobulin light chain variable (V) region influence clinical presentation and outcome in light chain associated amyloidosis(AL). Blood 2003; 101: 3801–3808.

4. Kroupa R, Dastych M, Šenkyřík M et al. Systémové amyloidóza s dominující klinickou manifestací v trávicím traktu. Vnitř Lék 2005; 51: 588–592.

5. Linhartová K, Daum O. Srdeční amyloidóza. Cor Vasa 2005; 47: 328.

6. Ryšavá R. Amyloidóza ledvin. Postgrad Med 2006; 8: 207–212.

7. Ryšavá R. Léčba paraproteinemické nefropatie a primární amyloidózy ledvin. Aktual v Nefrol 2005; 11: 62–65.

8. Butler WM, Baldwin PE. Prolongation of thrombin and reptilase times in patients with amyloidosis and acquired factor X deficiency. South Med J 1984; 77: 648–651.

9. Dray X, Treton X, Joly F et al. Hemorrhagic bullous colitis as a primary manifestation of AL amyloidosis. Endoscopy 2006; 38 (Suppl 2): E15–E16.

10. James DG, Zuckerman GR, Sayuk GS et al. Clinical recognition of Al type amyloidosis of the luminal gastrointestinal tract. Clin Gastroenterol Hepatol 2007; 5: 582–588.

11. Stammler F. Haemorrhagic diathesis as an early symptom of systemic amyloidosis. Dtsch Med Wochenschr 2006; 131: 17–21.

12. Sucker C, Hetzel GR, Grabensee B et al. Amyloidosis and bleeding: pathophysiology, diagnosis, and therapy. Am J Kidney Dis 2006; 47: 947–955.

13. Takahashi T, Suzukawa M, Akiyama M et al. Systemic AL amyloidosis with disseminated intravascular coagulation associated with hyperfibrinolysis. Int J Hematol 2008; 87: 371–374.

14. Yamamoto T, Maeda N, Kawasaki H. Hepatic failure in a case of multiple myeloma‑associated amyloidosis (kappa-AL). J Gastroenterol 1995; 30: 393–397.

15. Higgins GT, Olujohungbe A, Kyle G. Recurrent subconjunctival and periorbital haemorrhage as the first presentation of systemic AL amyloidosis secondary to myeloma. Eye 2006; 20: 512–515.

16. 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: 879–881.

17. Korsan–Bengtsen K, Hjort PF, Ygge J. Acquired factor X deficiency in a patient with amyloidosis. Tromb Diath Haemorrh 1962; 7: 558–566.

18. Galbraith PA, Sharma N, Parker WL et al. Acquired factor X deficiency. Altered plasma antithrombin activity and association with amyloidosis. JAMA 1974; 230: 1658–1660.

19. Glenner GG. Factor X deficiency and systemic amyloidosis. N Engl J Med 1977; 297: 108–109.

20. Fogdall RP, Fischbach DP. Factor X deficiency in primary amyloidosis. N Engl J Med 1980; 302: 923.

21. Girmann G, Wilker D, Stadie H et al. Acquired isolated factor X deficiency associated with systemic amyloidosis. Case report and review of literature. Klin Wochenschr 1980; 58: 859–862.

22. Gloy J, Böhler J, Schollmeyer P et al. Primary amyloidosis with severe nephrotic syndrome and acquired factor X deficiency. Nephrol Dial Transplant 1997; 12: 588–590.

23. Van Dam FE, de Pauw BE, Schutjes CP et al. Isolated factor X deficiency in amyloidosis. Case report and review of the literature. Neth J Med 1975; 18: 129–134.

24. Wick A, Sulser H, Pflugshaupt R. Acquired isolated factor X deficiency in generalized amyloidosis. Schweiz Med Wochenschr 1972; 102: 1799–1803.

25. Krause JR. Acquired factor X deficiency and amyloidosis. Am J Clin Pathol 1977; 67: 170–173.

26. Lucas FV, Fishleder AJ, Becker RC et al. Acquired factor X deficiency in systemic amyloidosis. Cleve Clin J Med 1987; 54: 399–406.

27. Rapoport M, Yona R, Kaufman S et al. Unusual bleeding manifestations of amyloidosis in patients with multiple myeloma. Clin Lab Haematol 1994; 16: 349–353.

28. Yood RA, Skinner M, Rubinow A et al. Bleeding manifestations in 100 patients with amyloidosis. JAMA 1983; 249: 1322–1324.

29. Zeitler KD, Blatt PM. Amyloidosis and factor X deficiency. South Med J 1982; 75: 306–308.

30. McPherson RA, Onstad JW, Ugoretz RJ et al. Coagulopathy in amyloidosis: combined deficiency of factors IX and X. Am J Hematol 1977; 3: 225–235.

31. Greipp PR, Kyle RA, Bowie EJ. Factor-X deficiency in amyloidosis: a critical review. Am J Hematol 1981; 11: 443–450.

32. Gatel A, Cacoub P, Piette JC. AL amyloidosis combined with acquired factor V deficiency. Ann Intern Med 1998; 128: 604–605.

33. 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: 555–559.

34. Wiest R, Klouche M, Härle P et al. Acquired combined factor X and XII deficiency with isolated bleeding complications in a patient with AL amyloidosis. Ann Hematol 2005; 84: 196–199.

35. Kos CA, Ward JE, Malek K et al. Association of acquired von Willebrand syndrome with AL amyloidosis. Am J Hematol 2007; 82: 363–367.

36. Quitt M, Aghai E, David M et al. Acquired factor X and antithrombin III deficiency in a patient with primary amyloidosis and nephrotic syndrome. Scand J Haematol 1985; 35: 155–157.

37. Perlin E, Brankman P, Berg HS et al. Enhanced blood coagulation and fibrinolysis in a patient with primary amylidos. Tromb Diath Haemorrh 1971; 26: 9–14.

38. Liebman H, Chinowsky M, Valdin J et al. Increased fibrinolysis and amyloidosis. Arch Intern Med 1983: 143: 678–682.

39. Gastineau DA, Gertz MA, Daniels TM et al. Inhibitor of thrombin in the systemic amyloidosis. A common coagulation abnormality. Blood 1991; 77: 2637–2640.

40. Gamba G, Montani N, Anesi E et al. Abnormalities in thrombin‑antithrombin pathway in AL amyloidosis. Amyloid 1999; 6: 273–277.

41. 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: 81–85.

42. Furie B, Voo L, McAdam KP et al. Mechanism of factor X deficiency in systemic amyloidosis. N Engl J Med 1981; 304: 827–830.

43. Greipp PR, Kyle RA, Bowie EJ. Factor X deficiency in primary amyloidosis: resolution after splenectomy. N Engl J Med 1979; 301: 1050–1051.

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

45. Ménmaché D, Boivin P. Deficit acquis en facteur X chez un malade atteint d’amyloisoe primitive. Nouv Rev Fr Hematol 1962; 71: 764–667.

46. Rosenstein ED, Itzkowitz SH, Penziner AS et al. Resolution of factor X deficiency in primary amyloidosis following splenectomy. Arch Intern Med 1983; 143: 597–599.

47. Bohler A, Lämmle B. Decreased Quick percentage, acquired factor X deficiency, hemarthrosis and ecchymosis: amyloidosis. Ther Umsch 1999; 56: 523–525.

48. Mumford AD, O‘Donnell J, Gillmore JD et al. Bleeding symptoms and coagulation abnormalities in 337 patients with AL‑amyloidosis. Br J Haematol 2000; 110: 454–460.

49. Sinha U, Wolf DL. Carbohydrate residues modulate the activation of coagulation factor X. J Biol Chem 1993; 268: 3048–3051.

50. Mulhare PE, Tracy PB, Golden EA et al. A case of acquired factor X deficiency with in vivo and in vitro evidence of inhibitor activity directed against factor X. Am J Clin Pathol 1991; 96: 196–200.

51. Wissløff F, Michaelsen TE, Godal HC. Inhibition or acceleration of fibrin polymerisation by monoclonal immunoglobulin fragments. Tromb Res 1984; 35: 81–90.

52. le Quellec A, Sotto A, Ciurana AJ. Spontaneous resolution of acquired factor X deficiency in amyloidosis. J Intern Med 1993; 234: 329–330.

53. Duncan EM, Cole J, Clarkson AR et al. Poor recovery and short survival of infused factor X in a case of acquired factor X deficiency and amyloidosis. Thromb Haemost 1999; 82: 1375–1376.

54. Takabe K, Holman PR, Herbst KD et al. Successful perioperative management of factor X deficiency associated with primary amyloidosis. J Gastrointest Surg 2004; 8: 358–362.

55. Smith SV, Liles DK, White GC 2nd et al. Successful treatment of transient acquired factor X deficiency by plasmapheresis with concomitant intravenous immunoglobulin and steroid therapy. Am J Hematol 1998; 57: 245–252.

56. Spero JA, Lewis JH, Hasiba U et al. Treatment of amyloidosis associated factor X deficiency. Thromb Haemost 1976; 35: 377–381.

57. Gertz MA, Comenzo R, Falk RA. Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis. A consensus opinion from the 10th international symposium on amyloid and amyloidosis. Am J Hematol 2005; 79: 319–328.

58. Camoriano JK, Greipp PR, Bayer GK et al. Resolution of acquired factor X deficiency and amyloidosis with melphalan and prednisone therapy. N Engl J Med 1987; 316: 1133–1135.

59. Levin M, Chokas W. Acquired factor X deficiency and amyloidosis treated with melphalan and prednisone. N Engl J Med 1987; 317: 1155–1156.

60. Mohri H. Resolution of acquired factor X deficiency with amyloidosis secondary to plasma cell dyscrasia. Am J Hematol 2004; 77: 421–422.

61. Schwarzinger I, Stain‑Kos M, Bettelheim P et al. Recurrent, isolated factor X deficiency in myeloma: repeated normalization of factor X levels after cytostatic chemotherapy followed by late treatment failure associated with the development of systemic amyloidosis. Thromb Haemost 1992; 68: 648–651.

62. Breems DA, Sonneveld P, de Man RA et al. Successful treatment of systemic amyloidosis with hepatic involvement and factor X deficiency by high dose melphalan chemotherapy and autologous stem cell reinfusion. Eur J Haematol 2004; 72: 181–185.

63. Choufani EB, Sanchorawala V, Ernst T et al. Acquired factor X deficiency in patients with amyloid light‑chain amyloidosis: incidence, bleeding manifestations, and response to high‑dose chemotherapy. Blood 2001; 97: 1885–1887.

64. Dispenzieri A, Kyle RA, Lacy MQ et al. Superior survival in primary systemic amyloidosis patients udergoing peripheral blood stem cell transplantation. A case control study. Blood 2004; 103: 3960–3963.

65. Jaccard A, Moreau P, Leblond V et al. High dose melphalan versus melphalan plus dexamethasone for AL‑amyloidosis. N Engl J Med 2007; 357: 1083–1093.

66. Sanchorawala V, Seldin DC, Magnani B et al. Serum free light‑chain responses after high‑dose intravenous melphalan and autologous stem cell transplantation for AL (primary) amyloidosis. Bone Marrow Transplant 2005; 36: 597–600.

67. Sanchorawala V, Skinner M, Quillen K et al. Long‑term outcome of patients with AL amyloidosis treated with melphalan and stem cell transplantation. Blood 2007; 110: 3561–3563.

68. Gertz MA, Lacy MQ, Bjornsson J et al. Fatal pulmonary toxicity related to the administration of granulocyte colony stimulation factor in amyloidosis. A report and review of growth factor pulmonary toxicity. J Hematother Stem Cell Res 2000; 9: 635–643.

69. Hayes–Lattin BM, Curtin PT, Fleming WH et al. Toxic megacolon: a life threatening complication of high dose therapy and autologous transplantation among patients with AL‑amyloidosis. Bone Marrow Transplant 2002; 30: 279–285.

70. Kumar S, Dispenzieri A, Lacy MQ et al. High incidence of gastrointestinal tract bleeding after autologous stem cell transplant for primary systemic amyloidosis. Bone Marrow Transplant 2001; 28: 381–385.

71. Kyle RA, Gertz MA, Lacy MQ et al. Localized AL amyloidosis of the colon: an unrecognized entity. Amyloid 2003; 10: 36–41.

72. Gertz MA, Lacy MQ, Dispenzieri A et al. Amyloidosis. Best Pract Res Clin Haematol 2005; 18: 709–727.

73. Leung N, Slezak JM, Bergstralh EJ. Acute renal insufficiency after high dose melphalan in patients with primary systemic amyloidosis during stem cell transplantation. Am J Kidney Dis 2005; 45: 102–111.

74. Fadia A, Casserly LF, Sanchorawala V et al. Incidence and outcome of acute renal failure complicating autologous stem cell transplantation for AL‑amyloidosis. Kidney Int 2003; 63: 1868–1873.

75. Vesole DH, Akasheh M, Peréz WS et al. High dose therapy and autologous hematopoietic stem cell transplantation for patients with primary systemic amyloidosis. A center for International blood and marrow transplant research study. Mayo Clin Proc 2006; 81: 880–888.

76. Spier BJ, Einstein M, Johnson EA et al. Amyloidosis presenting as lower gastrointestinal hemorrhage. WMJ 2008; 107: 40–43.

77. Röcken C, Ernst J, Hund E et al. Interdisciplinary guidelines on the diagnosis and therapy of extracerebral amyloidosis: issued by the German Society of Amyloid Disease e.V. (www.amyloid.de). Med Klin (Munich) 2006; 101: 825–829.

78. United kingdom myeloma forum: Guidelines on the diagnosis and management of AL‑amyloidosis. Brit J Hematology 2004; 125: 681–700.

79. Perfetti V, Siena S, Palladini G et al. Long term results of a risk adapted approach to melphalan conditioning in autologous peripheral blood stem cell transplantation for primary AL amyloidosis. Haematologica 2006; 91: 1635–1643.

80. Böhrer H, Waldherr R, Martin E et al. Splenectomy in an uraemic patient with acquired factor X deficiency due to AL amyloidosis. Nephrol Dial Transplant 1998; 13: 190–193.

81. Enjeti AK, Walsh M, Seldon M. Spontaneous major bleeding in acquired factor X deficiency secondary to AL‑amyloidosis. Haemophilia 2005; 11: 535–538.

82. Adam Z, Ščudla V, Tomíška M. Léčba AL‑amyloidózy a ně­kte­rých dalších typů amyloidóz. Vnitř Lék 2001; 47: 46–52.

83. Adam Z, Ščudla V. Klinické projevy a diagnostika AL‑amyloidózy a ně­kte­rých dalších typů amyloidóz. Vnitř Lék 2001; 47: 36–45.

84. Ščudla V, Minařík J, Schneiderka P et al. Význam sérových hladin volných lehkých řetězců imunoglobulinu v diagnostice a hodnocení aktivity mnohočetného myelomu a vybraných monoklonálních gamapatií. Vnitř Lék 2005; 51: 1249–1259.

Labels
Diabetology Endocrinology Internal medicine

Article was published in

Internal Medicine

Issue 1

2010 Issue 1

Most read in this issue
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#