Factor VII Treatment & Management

  • Author: Jeyanthi Ramanarayanan, MD; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: May 19, 2011
 

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.[17]
  • 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.[18] 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.[19] 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,[20] 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.[21] 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.[22] 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.[22]
Next

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.

Previous
Next

Consultations

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

Previous
Next

Diet

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

Previous
Next

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.

Previous
Proceed to Medication
 
 
Contributor Information and Disclosures
Author

Jeyanthi Ramanarayanan, MD  Assistant Professor, Department of Medicine, Division of Medical Oncology, Roswell Park Cancer Institute

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.

Coauthor(s)

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.

Francisco J Hernandez-Ilizaliturri, MD  Assistant Professor, Departments of Medicine and 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.

Specialty Editor Board

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 Heart Association, American Society of Hematology, International Society on Thrombosis and Haemostasis, and New York Academy of Sciences

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

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

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

Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

Rebecca J Schmidt, DO, FACP, FASN  Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine

Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association

Disclosure: Renal Ventures Ownership interest Other

Chief Editor

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

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. Jun 1951;30(6):596-608. [Medline].

  2. Roberts HR, Monroe DM, Hoffman M. Molecular biology and biochemistry of the coagulation factors and pathways of hemostasis. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn U, eds. William's Hematology. 2001. 6th ed. New York, NY: McGraw-Hill; 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. May 1992;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. Jun 1 2000;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. 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].

  7. 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. Nov 1993;92(5):446-50. [Medline].

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

  9. 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. Oct 30 1993;342(8879):1076-9. [Medline].

  10. 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. May 1995;15(5):655-64. [Medline].

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

  12. 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. Apr 1997;28(4):816-21. [Medline].

  13. 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. Jan 18 2003;361(9353):201-5. [Medline].

  14. 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. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn U, eds. William's Hematology. 6th ed. New York, NY: McGraw-Hill; 2001:1617-38.

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

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

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

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

  19. 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. Apr 19 2011;154(8):529-40. [Medline].

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

  21. 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. Jun 2007;38(6):2001-23. [Medline].

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

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

  24. 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. Mar 1 2003;101(5):1864-70. [Medline].

  25. 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. Mar 2003;120(5):808-13. [Medline].

  26. 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].

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

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

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

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

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

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

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

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

  35. 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. Jan 8 1998;338(2):79-85. [Medline].

  36. 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. Apr 2006;95(4):600-5. [Medline].

  37. 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. Jul 1 2000;96(1):374. [Medline].

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

 
Previous
Next
 
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.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.