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Factor VII Deficiency Treatment & Management

  • Author: Muhammad A Mir, MD, FACP; Chief Editor: Perumal Thiagarajan, MD  more...
 
Updated: May 12, 2016
 

Medical Care

Replacement therapy for persons with factor VII deficiency depends on the site and severity of bleeding and the baseline factor VII activity.

Long-term prophylaxis with 10-50 U/kg 1-3 times per week has been successful in children with severe factor VII deficiency. Mild bleeding associated with bruising and skin lacerations may not require any replacement and can be controlled by applying local pressure at the bleeding site. Minimal mucosal bleeding episodes, such as occurs with epistaxis and during dental procedures, can be managed with antifibrinolytic agents or fibrin glue.

For spontaneous hemorrhage or mild trauma, therapeutic factor VII levels of 5-10% are sufficient to stop bleeding. This level may be achieved by administering plasma at a dose of 5-10 mL/kg of body weight and repeating the dose every 8-12 hours for 1-2 days.

For major hemorrhage or surgery, plasma may be administered in a loading dose of 15-20 mL/kg and followed by 3-6 mL/kg every 8-12 hours until the surgical wound heals. This may require 5-7 days of treatment. Plasma infusion may be associated with disadvantages such as volume overload, infectious complications, or an inability to achieve high levels of factor VII. Highly purified factor VII concentrates are useful in patients with severe bleeding or as prophylaxis for surgery. Unlike factor VIII and factor IX deficiencies, for which levels of 100% are required before surgery, factor VII deficiency requires levels in the range of 10-15% to produce efficient hemostasis. For major surgery, trough levels of factor VII must not fall to less than 20 U/dL.

Prothrombin complex concentrates are also a source of factor VII but carry the risk of infectious complications and thrombosis. When prothrombin concentrates are used, doses of 50 U/kg every 8 hours for 24 hours, followed by plasma infusions, have been shown to be effective for major orthopedic surgery.

Recombinant factor VIIa (rFVIIa) has proven effective in clinical trials as a treatment for bleeding in hemophilia A patients with inhibitors and in limited numbers of factor VII–deficient patients. rFVIIa is produced by recombinant technology and thus does not carry the risk of infectious complications. Note the following:

  • rFVIIa may be the treatment of choice for previously untreated patients with factor VII deficiency but is currently an expensive treatment. An online registry, the Seven Treatment Evaluation Registry (STER) has been set up, which helps in prospective study to evaluate the efficacy and safety of various therapies with which FVII-deficient patients may be treated. [19]
  • rFVIIa has been effective in the treatment of blood loss associated with various conditions, but reports from larger studies are not yet available to confirm these findings. [20] Off-labeled use of rFVII for 5 in-hospital indications including intracranial hemorrhage, cardiac surgery, trauma, liver transplantation, and prostatectomy were reviewed in a systematic literature review (16 RCTs and 6 observational studies) by Yank et al. [21] This analysis suggested no mortality reduction for any of the above indicated off-label conditions. In addition, there was an increased risk for thromboembolism. With the rapid increase over the past few years of the drug for off-label indications, [22] it is necessary to reconsider rFVII treatment given the limited efficacy without proven mortality benefit, costs involved, and the risks associated with thromboembolism.
  • rFVIIa is reportedly effective in controlling intracranial bleeding when administered within 3-4 hours of onset (from phase II studies, class IIb, level of evidence B), this is being confirmed in larger studies. [23] There is no proven efficacy for mortality reduction from systematic analysis of various studies.
  • In a comprehensive study of 35 randomized clinical trials of rFVIIa, patients, particularly elderly persons, who were treated with high doses of rFVIIa on an off-label basis experienced a substantially higher risk of arterial, but not venous, thromboembolic events. [24] Pooled data analysis reported by Levi et al showed an increased risk of arterial thrombosis when rFVIIa was administered in large doses for off-label indications to patients older than 65 years compared to younger patients. [24]
  • A single-center case series involving 15 patients who received rFVIIa for acute liver failure did not show any benefit in terms of length of hospital stay or mortality. [25]
  • A retrospective study of rVIIa use compared with standard therapy in warfarin-induced intracranial hemorrhage did not find any increased incidence of thrombotic complications when adjusted for preexisting thromboembolic risk factors in both groups. [26]
  • A retrospective review of 63 patients with warfarin-associated intracranial hemorrhage comparing fresh frozen plasma (FFP), prothrombin complex concentrate (PCC), and rVIIa (all in conjunction with vitamin K) found both PCC and rVIIa to be superior to FFP in speed of reversal and less INR rebound, but rVIIa was more expensive than the other two. [27]
  • A Cochrane systematic review of 2 clinical trials involving nearly 500 patients with upper gastrointestinal bleeding secondary to liver disease was inconclusive, and a benefit of rVIIa in this scenario could not be established. [28]
  • Off-label attempts to correct newer anticoagulants such as dabigatran (in conjunction with hemodialysis) with rVIIa have been reported but remain experimental. [29]
  • A large systematic review evaluated the studies involving off-label use of rVIIa for in-hospital indications, including intracranial hemorrhage, cardiac surgery, trauma, prostatectomy, and liver transplantation, failed to show any mortality benefit, although the risk of arterial thromboembolism increased with several indications. [30]
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Surgical Care

Prophylactic administration of factor VII concentrates or plasma may help minimize bleeding during surgery. For surgery, factor VII concentrates have been used in doses ranging from 8-40 U/kg every 4-6 hours.

Fibrin glue or fibrin tissue adhesives have been used as adjunctive therapy to achieve hemostasis. Fibrin glue contains fibrinogen, thrombin, and factor XIII.

Antifibrinolytic agents such as epsilon-aminocaproic acid and tranexamic acid have been used to enhance hemostasis during dental procedures as an adjunct to replacement therapy.

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Consultations

Obtain consultations with orthopedists, physical therapists, general surgeons, dental surgeons, and genetic counselors as needed.

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Diet

Instruct patients to maintain a regular, healthy diet without restrictions.

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Activity

Recommend that patients limit activity of the involved joints or muscles during acute bleeding episodes. Early physical therapy is recommended once bleeding is resolved to prevent contractures or deformity.

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Contributor Information and Disclosures
Author

Muhammad A Mir, MD, FACP Assistant Professor of Medicine (Hematology, Blood/Marrow Transplant) Milton S Hershey Medical Center, Pennsylvania State University College of Medicine

Muhammad A Mir, MD, FACP is a member of the following medical societies: American College of Physicians, American Society of Hematology, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ronald A Sacher, MB, BCh, FRCPC, DTM&H Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MB, BCh, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada, American Clinical and Climatological Association, International Society of Blood Transfusion

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: GSK Pharmaceuticals,Alexion,Johnson & Johnson Talecris,,Grifols<br/>Received honoraria from all the above companies for speaking and teaching.

Chief Editor

Perumal Thiagarajan, MD Professor, Department of Pathology and Medicine, Baylor College of Medicine; Director, Transfusion Medicine and Hematology Laboratory, Michael E DeBakey Veterans Affairs Medical Center

Perumal Thiagarajan, MD is a member of the following medical societies: American College of Physicians, American Society for Clinical Investigation, Association of American Physicians, American Society for Biochemistry and Molecular Biology, American Heart Association, American Society of Hematology, Royal College of Physicians

Disclosure: Nothing to disclose.

Additional Contributors

Paul Schick, MD Emeritus Professor, Department of Internal Medicine, Jefferson Medical College of Thomas Jefferson University; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital

Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology

Disclosure: Nothing to disclose.

Acknowledgements

Francisco J Hernandez-Ilizaliturri, MD Associate Professor of Medicine, Department of Medicine, Assistant Professor of Immunology, Department of Immunology, Roswell Park Cancer Institute, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

Francisco J Hernandez-Ilizaliturri, MD is a member of the following medical societies: American Association for Cancer Research and American Society of Hematology

Disclosure: Nothing to disclose.

Ganapathy S Krishnan, MBBS Fellow, Department of Hematology and Oncology, Michigan State University

Ganapathy S Krishnan, MBBS is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

Jeyanthi Ramanarayanan, MD Assistant Professor, Medical Oncology, Veterans Affairs Medical Center of Buffalo

Jeyanthi Ramanarayanan, MD is a member of the following medical societies: American Association of Physicians of Indian Origin and American Society of Hematology

Disclosure: Nothing to disclose.

References
  1. Alexander B, R Goldstein and G Landwehr, CooK CD. Congenital SPCA deficiency: a hitherto unrecognized coagulation defect with hemorrhage rectified by serum and serum fractions. J Clin Invest. 1951 Jun. 30(6):596-608. [Medline].

  2. Roberts HR, Monroe DM, Hoffman M. Molecular biology and biochemistry of the coagulation factors and pathways of hemostasis. Beutler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn U, eds. William's Hematology. 6th ed. New York, NY: McGraw-Hill; 2001. 2001: 1409-34.

  3. Lane A, Cruickshank JK, Mitchell J, et al. Genetic and environmental determinants of factor VII coagulant activity in ethnic groups at differing risk of coronary heart disease. Atherosclerosis. 1992 May. 94(1):43-50. [Medline].

  4. Pinotti M, Toso R, Girelli D, et al. Modulation of factor VII levels by intron 7 polymorphisms: population and in vitro studies. Blood. 2000 Jun 1. 95(11):3423-8. [Medline].

  5. Laurian Y. Treatment of bleeding in patients with platelet disorders: is there a place for recombinant factor VIIa?. Pathophysiol Haemost Thromb. 2002. 32 Suppl 1:37-40. [Medline].

  6. Geng Y, Verhamme IM, Sun MF, Paul Bajaj S, Emsley J, Gailani D. Analysis of the factor XI variant Arg184Gly suggests a structural basis for factor IX binding to factor XIa. J Thromb Haemost. 2013 Apr 26. [Medline].

  7. Herrmann FH, Wulff K, Auberger K, et al. Molecular biology and clinical manifestation of hereditary factor VIIdeficiency. Semin Thromb Hemost. 2000. 26(4):393-400. [Medline].

  8. Bernardi F, Patracchini P, Gemmati D, et al. Molecular analysis of factor VII deficiency in Italy: a frequent mutation(FVII Lazio) in a repeated intronic region. Hum Genet. 1993 Nov. 92(5):446-50. [Medline].

  9. Cutler JA, Patel R, Mitchell MJ, Savidge GF. The significance of published polymorphisms in 14 cases of mild factor VII deficiency. Blood Coagul Fibrinolysis. 2005 Mar. 16(2):91-5. [Medline].

  10. Meade TW, Ruddock V, Stirling Y, et al. Fibrinolytic activity, clotting factors, and long-term incidence ofischaemic heart disease in the Northwick Park Heart Study. Lancet. 1993 Oct 30. 342(8879):1076-9. [Medline].

  11. Moor E, Silveira A, van't Hooft F, Suontaka AM, Eriksson P, Blombäck M, et al. Coagulation factor VII mass and activity in young men with myocardial infarction at a young age. Role of plasma lipoproteins and factor VII genotype. Arterioscler Thromb Vasc Biol. 1995 May. 15(5):655-64. [Medline].

  12. Rodgers GM, Greenberg CS. Inherited coagulation disorders. Lee GR, Foerster J, Lukens J, Paraskevas F, Greer JP, Rodgers GM, eds. Wintrobe's Clinical Hematology. 10th ed. Baltimore, Md: Williams & Wilkins; 1999. Vol 2: 1682-732.

  13. Heywood DM, Carter AM, Catto AJ, et al. Polymorphisms of the factor VII gene and circulating FVII:C levels in relation to acute cerebrovascular disease and poststroke mortality. Stroke. 1997 Apr. 28(4):816-21. [Medline].

  14. Friederich PW, Henny CP, Messelink EJ, et al. Effect of recombinant activated factor VII on perioperative blood loss in patients undergoing retropubic prostatectomy: a double-blind placebo-controlled randomised trial. Lancet. 2003 Jan 18. 361(9353):201-5. [Medline].

  15. Seligsohn U, White GC. Inherited deficiencies of coagulation factors II, V, VII, XI and XIII and the combined deficiencies of factors V and VII and of the vitamin K-dependent factors. Beutler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn U, eds. William's Hematology. 6th ed. New York, NY: McGraw-Hill; 2001. 1617-38.

  16. Giansily-Blaizot M, Schved JF. Potential predictors of bleeding risk in inherited factorVII deficiency. Clinical, biological and molecular criteria. Thromb Haemost. 2005 Nov. 94(5):901-6. [Medline].

  17. Zantek ND, Hsu P, Refaai MA, Ledford-Kraemer M, Meijer P, Van Cott EM. Factor VII assay performance: an analysis of the North American Specialized Coagulation Laboratory Association proficiency testing results. Int J Lab Hematol. 2013 Jun. 35(3):314-21. [Medline].

  18. Mariani G, Herrmann FH, Dolce A, et al. Clinical phenotypes and factor VII genotype in congenital factor VII deficiency. Thromb Haemost. 2005 Mar. 93(3):481-7. [Medline].

  19. Mariani G, Lapecorella M, Dolce A. Steps towards an effective treatment strategy in congenital factor VII deficiency. Semin Hematol. 2006 Jan. 43(1 Suppl 1):S42-7. [Medline].

  20. Mannucci PM, Levi M. Prevention and treatment of major blood loss. N Engl J Med. 2007 May 31. 356(22):2301-11. [Medline].

  21. Yank V, Tuohy CV, Logan AC, Bravata DM, Staudenmayer K, Eisenhut R, et al. Systematic Review: Benefits and Harms of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications. Ann Intern Med. 2011 Apr 19. 154(8):529-40. [Medline].

  22. Logan AC, Yank V, Stafford RS. Off-Label Use of Recombinant Factor VIIa in U.S. Hospitals: Analysis of Hospital Records. Ann Intern Med. 2011 Apr 19. 154(8):516-22. [Medline].

  23. Broderick J, Connolly S, Feldmann E, Hanley D, Kase C, Krieger D, et al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Stroke. 2007 Jun. 38(6):2001-23. [Medline].

  24. Levi M, Levy JH, Andersen HF, Truloff D. Safety of recombinant activated factor VII in randomized clinical trials. N Engl J Med. 2010 Nov 4. 363(19):1791-800. [Medline].

  25. Pham HP, Hsu SX, Parker-Jones S, Samstein B, Diuguid D, Schwartz J. Recombinant activated factor VII in patients with acute liver failure with UNOS Status 1A: a single tertiary academic centre experience. Vox Sang. 2013 Jul 1. [Medline].

  26. H-Y CS, Xuemei C, G KR, M BL, V HG, A SF, et al. Thromboembolic risks of recombinant factor VIIa Use in warfarin-associated intracranial hemorrhage: a case-control study. BMC Neurol. 2012 Dec 15. 12:158. [Medline]. [Full Text].

  27. Woo CH, Patel N, Conell C, Rao VA, Faigeles BS, Patel MC, et al. Rapid Warfarin Reversal in the Setting of Intracranial Hemorrhage: A Comparison of Plasma, Recombinant Activated Factor VII, and Prothrombin Complex Concentrate. World Neurosurg. 2012 Dec 5. [Medline].

  28. Martí-Carvajal AJ, Karakitsiou DE, Salanti G. Human recombinant activated factor VII for upper gastrointestinal bleeding in patients with liver diseases. Cochrane Database Syst Rev. 2012 Mar 14. 3:CD004887. [Medline].

  29. Warkentin TE, Margetts P, Connolly SJ, Lamy A, Ricci C, Eikelboom JW. Recombinant factor VIIa (rFVIIa) and hemodialysis to manage massive dabigatran-associated postcardiac surgery bleeding. Blood. 2012 Mar 1. 119(9):2172-4. [Medline].

  30. Yank V, Tuohy CV, Logan AC, Bravata DM, Staudenmayer K, Eisenhut R. Systematic review: benefits and harms of in-hospital use of recombinant factor VIIa for off-label indications. Ann Intern Med. 2011 Apr 19. 154(8):529-40. [Medline].

  31. Gruppo RA, Kessler CM, Neufeld EJ, Cooper DL. Assessment of individual dose utilization vs. physician prescribing recommendations for recombinant activated factor VII (rFVIIa) in paediatric and adult patients with congenital haemophilia and alloantibody inhibitors (CHwI): the Dosing Observational Study in Hemophilia (DOSE). Haemophilia. 2013 Apr 1. [Medline].

  32. Ludlam CA. The evidence behind inhibitor treatment with recombinant factor VIIa. Pathophysiol Haemost Thromb. 2002. 32 Suppl 1:13-8. [Medline].

  33. Lisman T, Moschatsis S, Adelmeijer J, et al. Recombinant factor VIIa enhances deposition of platelets with congenital or acquired alpha IIb beta 3 deficiency to endothelial cell matrix and collagen under conditions of flow via tissue factor-independent thrombin generation. Blood. 2003 Mar 1. 101(5):1864-70. [Medline].

  34. Ludlam CA, Smith MP, Morfini M, et al. A prospective study of recombinant activated factor VII administered by continuous infusion to inhibitor patients undergoing elective major orthopaedic surgery: a pharmacokinetic and efficacy evaluation. Br J Haematol. 2003 Mar. 120(5):808-13. [Medline].

  35. Logan AC, Goodnough LT. Recombinant factor VIIa: an assessment of evidence regarding its efficacy and safety in the off-label setting. Hematology Am Soc Hematol Educ Program. 2010. 2010:153-9. [Medline].

  36. Butenas S, Brummel KE, Branda RF, et al. Mechanism of factor VIIa-dependent coagulation in hemophilia blood. Blood. 2002 Feb 1. 99(3):923-30. [Medline].

  37. Monroe DM, Hoffman M, Oliver JA, Roberts HR. A possible mechanism of action of activated factor VII independent of tissue factor. Blood Coagul Fibrinolysis. 1998 Mar. 9 Suppl 1:S15-20. [Medline].

  38. Mayer SA, Brun NC, Begtrup K, et al. Recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2005 Feb 24. 352(8):777-85. [Medline].

  39. Barletta JF, Ahrens CL, Tyburski JG, Wilson RF. A review of recombinant factor VII for refractory bleeding in nonhemophilic trauma patients. J Trauma. 2005 Mar. 58(3):646-51. [Medline].

  40. Bidot CJ, Jy W, Horstman LL, et al. Factor VII/VIIa: a new antigen in the anti-phospholipid antibody syndrome. Br J Haematol. 2003 Feb. 120(4):618-26. [Medline].

  41. Butenas S, van''t Veer C, Mann KG. "Normal" thrombin generation. Blood. 1999 Oct 1. 94(7):2169-78. [Medline].

  42. Deveras RA, Kessler CM. Reversal of warfarin-induced excessive anticoagulation with recombinanthuman factor VIIa concentrate. Ann Intern Med. 2002 Dec 3. 137(11):884-8. [Medline].

  43. Hoffman M, Monroe DM 3rd. A cell-based model of hemostasis. Thromb Haemost. 2001 Jun. 85(6):958-65. [Medline].

  44. Iacoviello L, Di Castelnuovo A, De Knijff P, et al. Polymorphisms in the coagulation factor VII gene and the risk of myocardial infarction. N Engl J Med. 1998 Jan 8. 338(2):79-85. [Medline].

  45. Kavakli K, Makris M, Zulfikar B, Erhardtsen E, Abrams ZS, Kenet G. Home treatment of haemarthroses using a single dose regimen of recombinant activated factor VII in patients with haemophilia and inhibitors. A multi-centre, randomised, double-blind, cross-over trial. Thromb Haemost. 2006 Apr. 95(4):600-5. [Medline].

  46. Mariani G, Herrmann FH, Bernardi F, et al. Clinical manifestations, management, and molecular genetics in congenitalfactor VII deficiency: the International Registry on Congenital Factor VII Deficiency (IRF7). Blood. 2000 Jul 1. 96(1):374. [Medline].

  47. Roberts HR, Monroe DM, White GC. The use of recombinant factor VIIa in the treatment of bleeding disorders. Blood. 2004 Dec 15. 104(13):3858-64. [Medline].

 
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Factor VII. Intrinsic and extrinsic pathways of coagulation. Factor VII/tissue factor complex activates factor IX and factor X. Factor IXa along with factor VIIIa results in formation of more factor Xa. Factor Xa along with factor Va converts prothrombin to thrombin.
 
 
 
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