Factor VII Clinical Presentation

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

History

Bleeding history is a crucial element in the evaluation of any patient with a hemorrhagic disorder. Of all factors evaluated, clinical history appears to be the best predictor of bleeding risk after hemostatic challenges in inherited FVII deficiencies.[15] A bleeding disorder is considered likely when a bleeding tendency is discovered in one or more family members or when an abnormal coagulation assay result is obtained as a part of a routine examination or before surgery.

Knowing the mode of inheritance of hereditary disorders is important when eliciting the family history. Factor VII deficiency is an autosomal recessive disease, unlike hemophilia, which is an X-linked recessive disease.

Only homozygote or compound heterozygote patients with factor VII deficiency are symptomatic. Heterozygotes who have partial factor VII deficiency may not exhibit hemorrhagic manifestations, even following trauma. In symptomatic patients, clinical phenotypes vary from mild to severe and do not necessarily correlate with factor VII levels. A multicenter European study of patients who are congenitally factor VII deficient showed that clinical symptoms did not vary with the frequency of functional polymorphisms and that homozygotes with the same mutation presented with striking differences in severity of bleeding.[16]

Patients with factor VII levels of less than 1% frequently present with bleeding symptoms indistinguishable from those of persons with severe hemophilia A or hemophilia B. They may present with life-threatening intracerebral hemorrhage manifesting as headaches, seizures, or focal deficits or with recurrent hemarthrosis leading to severe arthropathy. Intracranial hemorrhage has been reported, especially in neonates after vaginal delivery.

Unlike in hemophilia, hemarthrosis rarely occurs but may be precipitated by trauma. Patients should be asked about recurrent joint pain, swelling, and motion limitation. Hemarthrosis is sometimes heralded by an aura of mild discomfort that becomes progressively painful over a period of minutes to hours. In children, hemarthrosis usually occurs when the affected child begins to walk.

Patients with factor VII levels of 5% or more have much milder disease characterized by epistaxis, gingival bleeding, menorrhagia, and easy bruising. In patients with mild disease, dental extractions, tonsillectomy, and procedures involving the urogenital tract are frequently associated with bleeding (due to local fibrinolysis), while surgical procedures such as laparotomy, herniorrhaphy, appendectomy, and hysterectomy are not. Postpartum hemorrhage is noted in patients with levels less than 10-20% of the reference range.

Bleeding isolated to a single organ or system (eg, hematuria, hematemesis, hemoptysis) is less likely to be due to a hemostatic abnormality than to a local cause such as neoplasm or ulcer.

A family history is particularly important when a hereditary factor deficiency is considered likely. A specific inquiry should be made about consanguinity. Population genetics information may be helpful; for example, a higher frequency of factor VII deficiency is observed in Iranian and Moroccan Jews.

Drug history is important; drugs of concern may include hepatotoxic drugs, oral anticoagulants (eg, warfarin), and agents such as aspirin. Nutritional history is important to assess the likelihood of vitamin K deficiency. Rarely, drugs such as penicillins and cephalosporins have been associated with selective factor VII deficiency, but other antibiotics can cause vitamin K deficiency and consequently inhibit the synthesis of functional vitamin K-dependent factors, including factor VII.

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Physical

Physical findings depend on the site and severity of bleeding.

Hemarthrosis may lead to findings of joint swelling, motion limitation, and mild fever. If significant fever develops, infection should be considered. Repeated hemarthrosis leads to joint deformity complicated by muscle atrophy and contractures.

Focal neurological deficits depend on the location of bleeding into the nervous system. Symptoms and signs of subdural hematoma may be delayed for weeks.

Bruising and soft tissue bleeding may be observed with or without trauma. Large hematomas may expand locally and cause compression of adjacent organs, blood vessels, and nerves. Pharyngeal and retropharyngeal hematomas may enlarge and obstruct the airway.

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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].

 
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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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