Abstract
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
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Semeraro N, Colucci M . Tissue factor in health and disease Thromb Haemost 1997 78): 759 764
de Raucourt A, Dumont M, Tourani J et al. Acquired FVII deficiency associated with pleural liposarcoma Blood Coag Fibrinol 1994 5: 833 836
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
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
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
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
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
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
Vannuchi A, Rafanelli D, Longo G et al. Early hemostatic alterations following SCT: a prospective study Haematologica 1994 79: 519 525
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
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
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
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
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
Edson J, Vogt J, Hasegawa D . Abnormal prothrombin crossed immuno-electrophoresis in patients with lupus inhibitors Blood 1994 64: 807 816
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
Nicolaisen EM, Hansen LL, Poulsen F et al. Immunological aspects of recombinant factor VIIa (rFVIIa) in clinical use Thromb Haemost 1996 76: 200 204
Kasper CK, Aledort LM, Counts RB et al. A more uniform measurement of factor VIII inhibitors Thromb Diath Haemorrh 1975 34: 869 872
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
Galli M, Barbui T . Antiprothrombin antibodies: detection and clinical significance in the antiphospholipid syndrome Blood 1999 93: 49 57
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
Mammen EF . Coagulation defects in liver disease Med Clin N Am 1994 78: 545 554
Okajima K, Ishii M . Life-threatening bleeding in a case of autoantibody-induced factor VII deficiency Int J Hematol 1999 69: 129 132
Greeno EW, Haake R, McGlave P et al. Lupus inhibitors following bone marrow transplantation Bone Marrow Transplant 1995 15: 287 291
Biron C, Bengler C, Gris JC, Schved JF . Acquired isolated factor VII deficiency during sepsis Haemostasis 1997 27: 51 56
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
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
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
Ingerslev J, Kristensen HL . Clinical picture and treatment strategies in factor VII deficiency Haemophilia 1998 4: 689 696
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
Hedner U . Recombinant activated factor VII as a universal haemostatic agent Blood Coag Fibrinol 1998 9: (Suppl. 1) S147 S152
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
Acknowledgements
We would like to thank Luke Dandelet and Marie Johannessen for their technical contribution, and Carol Taubert for help in preparation of the manuscript.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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). https://doi.org/10.1038/sj.bmt.1703381
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1703381
Keywords
This article is cited by
-
Factor VII deficiency: a rare genetic bleeding disorder in a 7-year-old child: a case report
Journal of Medical Case Reports (2023)
-
Platelet Gene Therapy by Lentiviral Gene Delivery to Hematopoietic Stem Cells Restores Hemostasis and Induces Humoral Immune Tolerance in FIXnull Mice
Molecular Therapy (2014)
-
Acquired hemophilia-A in a patient with multiple sclerosis treated with autologous hematopoietic stem cell transplantation and interferon beta-1a
Bone Marrow Transplantation (2004)
-
Treatment of diffuse alveolar hemorrhage after allogeneic bone marrow transplant with recombinant factor VIIa
Bone Marrow Transplantation (2002)