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Post-Transplant Complications

Acquired factor VII deficiency in hematopoietic stem cell transplant recipients


Acquired factor VII (FVII) deficiency in the absence of vitamin K deficiency, oral anticoagulant therapy, synthetic liver dysfunction, or DIC is rare, with only a handful of cases thus far reported. In the period from 1990 to 1996 we identified eight patients with acquired FVII deficiency, all of whom presented with prolongation of the prothrombin time (PT) in the first 2 weeks following stem cell transplantation (SCT). The mean plasma FVII clotting activity (FVII:c) was 22% (range 8–35%) with an approximately equivalent reduction in FVII antigen (FVII:Ag) level. Mean plasma levels of fibrinogen and factors II, V, IX, and X were normal. Protein C activity was significantly depressed in only one of the three patients in whom it was measured. Several patients experienced bleeding complications, and hemorrhage directly accounted for death in two cases. Veno-occlusive disease of the liver developed in three patients. We conclude that FVII deficiency should be considered in the differential diagnosis of prolonged PT in patients who have recently undergone SCT. The mechanism of this acquired deficiency state remains to be defined.

Bone Marrow Transplantation (2002) 29, 403–408. doi:10.1038/sj.bmt.1703381

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Figure 1


  1. Semeraro N, Colucci M . Tissue factor in health and disease Thromb Haemost 1997 78): 759 764

    Google Scholar 

  2. de Raucourt A, Dumont M, Tourani J et al. Acquired FVII deficiency associated with pleural liposarcoma Blood Coag Fibrinol 1994 5: 833 836

    CAS  Article  Google Scholar 

  3. Fischer M, Lechner K, Hinterberger W et al. Deficiency of fibrinogen and FVII following treatment of severe aplastic anemia with antithymocyte globulin and high dose methyl prednisolone Scand J Haematol 1985 34: 312 316

    CAS  Article  PubMed  Google Scholar 

  4. Weisdorf D, Hasegawa D, Fair D . Acquired FVII deficiency associated with aplastic anemia: correction with bone marrow transplantation Br J Haematol 1989 71: 409 413

    CAS  Article  PubMed  Google Scholar 

  5. Kimka Ndimbie O, Raman K, Saeed S . Lupus anticoagulant associated with specific inhibition of FVII in a patient with AIDS Am J Clin Pathol 1989 91: 491 493

    Article  Google Scholar 

  6. Delmer A, Horellon M, Andreu G et al. Life threatening intra-cranial bleeding associated with presence of an anti-factor VII auto-antibody Blood 1989 74: 229 232

    CAS  PubMed  Google Scholar 

  7. Bazzarbachi A, Scrobohaci M, Gisselbrecht C et al. Changes in protein C, factor VII and endothelial markers after autologous SCT: possible implication in the pathogenesis of VOD Nouv Rev Fr Hematol 1993 35: 135 140

    Google Scholar 

  8. Collins P, Roderick A, O'Brien D et al. Factor VIIa and other haemostatic variables following bone marrow transplantation Thromb Haemost 1994 72: 28 32

    CAS  PubMed  Google Scholar 

  9. Vannuchi A, Rafanelli D, Longo G et al. Early hemostatic alterations following SCT: a prospective study Haematologica 1994 79: 519 525

    Google Scholar 

  10. Kaufman P, Jones R, Greenberg C, Peters W . Auto SCT and FXII, FVII and protein C deficiency. Report of a new association and its possible relationship to endothelial cell injury Cancer 1990 66: 515 21

    CAS  Article  PubMed  Google Scholar 

  11. Scrobohaci M, Drouet L, Monem-Mansi A et al. Liver VOD after bone marrow transplantation, changes in coagulation parameters and endothelial markers Thromb Res 1992 63: 509 519

    Article  Google Scholar 

  12. Nevo S, Enger C, Swan V et al. Acute bleeding after allogeneic bone marrow transplantation: association with graft versus host disease and effect on survival Transplantation 1999 67: 681 689

    CAS  Article  PubMed  Google Scholar 

  13. Price KJ, Thall PF, Kish SK et al. Prognostic indicators for blood and marrow transplant patients admitted to an intensive care unit Am J Resp Crit Care Med 1998 158: 876 884

    CAS  Article  PubMed  Google Scholar 

  14. Nevo S, Swan V, Enger C et al. Acute bleeding after bone marrow transplantation – incidence and effect on survival. A quantitative analysis in 1402 patients Blood 1998 91: 1469 1477

    CAS  PubMed  Google Scholar 

  15. Edson J, Vogt J, Hasegawa D . Abnormal prothrombin crossed immuno-electrophoresis in patients with lupus inhibitors Blood 1994 64: 807 816

    Google Scholar 

  16. Triplett DA, Brandt JT, Kaczor D, Schaeffer J . Laboratory diagnosis of lupus inhibitors: a comparison of the tissue thromboplastin inhibition procedure with a new platelet neutralization test Am J Clin Pathol 1983 79: 678 82

    CAS  Article  PubMed  Google Scholar 

  17. Nicolaisen EM, Hansen LL, Poulsen F et al. Immunological aspects of recombinant factor VIIa (rFVIIa) in clinical use Thromb Haemost 1996 76: 200 204

    CAS  Article  PubMed  Google Scholar 

  18. Kasper CK, Aledort LM, Counts RB et al. A more uniform measurement of factor VIII inhibitors Thromb Diath Haemorrh 1975 34: 869 872

    Google Scholar 

  19. Verbruggen B, Novakova I, Wessels H et al. The Nijmegen modification of the Bethesda assay for factor VIII:c inhibitors: improved specificity and reliability Thromb Haemost 1995 73: 247 251

    CAS  Article  PubMed  Google Scholar 

  20. Galli M, Barbui T . Antiprothrombin antibodies: detection and clinical significance in the antiphospholipid syndrome Blood 1999 93: 49 57

    Google Scholar 

  21. Park YD, Yasui M, Yoshimoto T et al. Changes in hemostatic parameters in hepatic veno-occlusive disease following bone marrow transplantation Bone Marrow Transplant 1997 19: 915 920

    CAS  Article  PubMed  Google Scholar 

  22. Mammen EF . Coagulation defects in liver disease Med Clin N Am 1994 78: 545 554

    CAS  Article  PubMed  Google Scholar 

  23. Okajima K, Ishii M . Life-threatening bleeding in a case of autoantibody-induced factor VII deficiency Int J Hematol 1999 69: 129 132

    CAS  PubMed  Google Scholar 

  24. Greeno EW, Haake R, McGlave P et al. Lupus inhibitors following bone marrow transplantation Bone Marrow Transplant 1995 15: 287 291

    CAS  PubMed  Google Scholar 

  25. Biron C, Bengler C, Gris JC, Schved JF . Acquired isolated factor VII deficiency during sepsis Haemostasis 1997 27: 51 56

    CAS  PubMed  Google Scholar 

  26. Li A, Morrissey J, Chang AKC et al. Factors VIIc and VIIa plasma concentration are depressed following bolus injection of endotoxin into normal human subjects Blood 1996 88: (Suppl. 1) 443a

    Google Scholar 

  27. Drake TA, Morrissey JH, Edgington TS . Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosis Am J Pathol 1989 134: 1087 1097

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Key NS, Slungaard A, Dandelet L et al. Whole blood tissue factor procoagulant activity in patients with sickle cell disease Blood 1998 11: 4216 4223

    Google Scholar 

  29. Ingerslev J, Kristensen HL . Clinical picture and treatment strategies in factor VII deficiency Haemophilia 1998 4: 689 696

    CAS  Article  PubMed  Google Scholar 

  30. Kristensen J, Killander A, Hippe E et al. Clinical experience with recombinant factor VIIa in patients with thrombocytopenia Haemostasis 1996 26: (Suppl. 1) 159 164

    CAS  PubMed  Google Scholar 

  31. Hedner U . Recombinant activated factor VII as a universal haemostatic agent Blood Coag Fibrinol 1998 9: (Suppl. 1) S147 S152

    CAS  Google Scholar 

  32. White B, Martin M, Kelleher S et al. Successful use of recombinant FVIIa (Novoseven) in the management of pulmonary haemorrhage secondary to Aspergillus infection in a patient with leukaemia and acquired factor VII deficiency Br J Haematol 1999 106: 254 255

    CAS  Article  PubMed  Google Scholar 

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We would like to thank Luke Dandelet and Marie Johannessen for their technical contribution, and Carol Taubert for help in preparation of the manuscript.

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Toor, A., Slungaard, A., Hedner, U. et al. Acquired factor VII deficiency in hematopoietic stem cell transplant recipients. Bone Marrow Transplant 29, 403–408 (2002).

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  • factor VII
  • stem cell transplantation
  • hemorrhage
  • acquired deficiency
  • acute myelogenous leukemia

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