Hemophilia B Differential Diagnoses

  • Author: Robert A Zaiden, MD; Chief Editor: Steven C Dronen, MD, FAAEM   more...
 
Updated: Oct 18, 2011
 
 

Diagnostic Considerations

Problems to be considered include vitamin K and other factor deficiencies, as well as acquired hemophilia. Other congenital bleeding disorders must be excluded. These may include the following:

  • von Willebrand disease (autosomal dominant transmission)
  • Platelet disorders (eg, Glanzmann thrombasthenia)
  • Deficiency of other coagulation factors (ie, factor V [FV], FVII, FX, FXI, or fibrinogen)

Differentiating between severe hemophilia A and hemophilia B is almost clinically impossible, but specific laboratory factor assays can help with the distinction. Conditions that can increase FVIII levels (eg, age, ABO blood type, stress, exercise) can obscure the diagnosis of hemophilia A. The diagnosis of hemophilia B may be delayed by physiologically low levels of all vitamin K–dependent coagulation factors. FIX Leyden, in which FIX levels progressively increase after puberty to nearly normal values, must also be considered when hemophilia B is diagnosed.

For related information, see Hemophilia A, Acquired Hemophilia, and Hemophilia C.

Differential Diagnoses

Proceed to Workup
 
 
Contributor Information and Disclosures
Author

Robert A Zaiden, MD  Assistant Professor, Department of Hematology and Medical Oncology, University of Florida at Jacksonville College of Medicine

Robert A Zaiden, MD is a member of the following medical societies: American College of Physicians and American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Coauthor(s)

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.

Gary D Crouch, MD  Associate Professor, Program Director of Pediatric Hematology-Oncology Fellowship, Department of Pediatrics, Uniformed Services University of the Health Sciences

Gary D Crouch, MD is a member of the following medical societies: American Academy of Pediatrics and American Society of Hematology

Disclosure: Nothing to disclose.

Mary A Furlong, MD  Associate Professor and Program/Residency Director, Department of Pathology, Georgetown University School of Medicine

Mary A Furlong, MD is a member of the following medical societies: United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

Lawrence F Jardine, MD, FRCPC  Associate Professor, Department of Pediatrics, Schulich School of Medicine and Dentistry, University of Western Ontario; Head, Section of Pediatric Hematology and Oncology, Children's Hospital of Western Ontario; Associate Scientist, Child Health Research Institute

Lawrence F Jardine, MD, FRCPC is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, Canadian Medical Protective Association, Children's Oncology Group, College of Physicians and Surgeons of Ontario, Hemophilia and Thrombosis Research Society, Ontario Medical Association, and Royal College of Physicians and Surgeons of Canada

Disclosure: Baxter Honoraria Consulting; Bayer Honoraria Consulting; Novartis Honoraria Speaking and teaching

Adonis Lorenzana, MD  Consulting Staff, Department of Pediatric Oncology, St John Hospital and Medical Center

Adonis Lorenzana, MD is a member of the following medical societies: American Academy of Pediatrics and American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Saduman Ozturk, PA-C  Physician Assistant, Bone Marrow Transplant Center, Florida Hospital Cancer Institute

Disclosure: Nothing to disclose.

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

Hadi Sawaf, MD  Director, Pediatric Hematology Oncology, Van Elslander Cancer Center; Clinical Assistant Professor, Wayne State University School of Medicine

Hadi Sawaf, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Clinical Oncology, and American Society of Hematology

Disclosure: Nothing to disclose.

Karen Seiter, MD  Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, and American Society of Hematology

Disclosure: Novartis Honoraria Speaking and teaching; Novartis Consulting fee Speaking and teaching; Eisai Honoraria Speaking and teaching; Celgene Honoraria Speaking and teaching

Specialty Editor Board

William G Gossman, MD  Associate Clinical Professor of Emergency Medicine, Creighton University School of Medicine; Consulting Staff, Department of Emergency Medicine, Creighton University Medical Center

William G Gossman, MD is a member of the following medical societies: American Academy of Emergency Medicine

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

Jeffrey L Arnold, MD, FACEP  Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center

Jeffrey L Arnold, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physicians

Disclosure: Nothing to disclose.

Chief Editor

Steven C Dronen, MD, FAAEM  Chair, Department of Emergency Medicine, LeConte Medical Center

Steven C Dronen, MD, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Brendan R Furlong, MD, and Dimitrios P Agaliotis, MD, PhD, FACP,to the development and writing of the source articles.

References

  1. Venkateswaran L, Wilimas JA, Jones DJ, Nuss R. Mild hemophilia in children: prevalence, complications, and treatment. J Pediatr Hematol Oncol. Jan-Feb 1998;20(1):32-5. [Medline].

  2. Loveland KA, Stehbens J, Contant C, Bordeaux JD, Sirois P, Bell TS, et al. Hemophilia growth and development study: baseline neurodevelopmental findings. J Pediatr Psychol. Apr 1994;19(2):223-39. [Medline].

  3. Jones PK, Ratnoff OD. The changing prognosis of classic hemophilia (factor VIII "deficiency"). Ann Intern Med. Apr 15 1991;114(8):641-8. [Medline].

  4. Chorba TL, Holman RC, Strine TW, Clarke MJ, Evatt BL. Changes in longevity and causes of death among persons with hemophilia A. Am J Hematol. Feb 1994;45(2):112-21. [Medline].

  5. Ewenstein BM, Wong WY, Schoppmann A. Bypassing agent prophylaxis for preventing arthropathy in patients with inhibitors. Haemophilia. Jan 2010;16(1):179-80. [Medline].

  6. Berntorp E, Astermark J, Björkman S, Blanchette VS, Fischer K, Giangrande PL, et al. Consensus perspectives on prophylactic therapy for haemophilia: summary statement. Haemophilia. May 2003;9 Suppl 1:1-4. [Medline].

  7. Ljung RC. Prophylactic infusion regimens in the management of hemophilia. Thromb Haemost. Aug 1999;82(2):525-30. [Medline].

  8. Iorio A, Marchesini E, Marcucci M, Stobart K, Chan AK. Clotting factor concentrates given to prevent bleeding and bleeding-related complications in people with hemophilia A or B. Cochrane Database Syst Rev. Sep 7 2011;9:CD003429. [Medline].

  9. Miners AH, Sabin CA, Tolley KH, Lee CA. Assessing the effectiveness and cost-effectiveness of prophylaxis against bleeding in patients with severe haemophilia and severe von Willebrand's disease. J Intern Med. Dec 1998;244(6):515-22. [Medline].

  10. Chapman WC, Singla N, Genyk Y, McNeil JW, Renkens KL Jr, Reynolds TC, et al. A phase 3, randomized, double-blind comparative study of the efficacy and safety of topical recombinant human thrombin and bovine thrombin in surgical hemostasis. J Am Coll Surg. Aug 2007;205(2):256-65. [Medline].

  11. Siddiqui MA, Scott LJ. Recombinant factor VIIa (Eptacog Alfa): a review of its use in congenital or acquired haemophilia and other congenital bleeding disorders. Drugs. 2005;65(8):1161-77. [Medline].

  12. Coppola A, Margaglione M, Santagostino E, Rocino A, Grandone E, Mannucci PM, et al. Factor VIII gene (F8) mutations as predictors of outcome in immune tolerance induction of hemophilia A patients with high-responding inhibitors. J Thromb Haemost. Nov 2009;7(11):1809-15. [Medline].

  13. Carcao M, St Louis J, Poon MC, Grunebaum E, Lacroix S, Stain AM, et al. Rituximab for congenital haemophiliacs with inhibitors: a Canadian experience. Haemophilia. Jan 2006;12(1):7-18. [Medline].

  14. Aggarwal A, Grewal R, Green RJ, Boggio L, Green D, Weksler BB, et al. Rituximab for autoimmune haemophilia: a proposed treatment algorithm. Haemophilia. Jan 2005;11(1):13-9. [Medline].

  15. Stachnik JM. Rituximab in the treatment of acquired hemophilia. Ann Pharmacother. Jun 2006;40(6):1151-7. [Medline].

  16. Personal communication with Dr. Troy H. Guthrie, Jr. MD, Medical Director Baptist Cancer Institute, Jacksonville, Florida.

  17. Duncan N, Kronenberger W, Roberson C, Shapiro A. VERITAS-Pro: a new measure of adherence to prophylactic regimens in haemophilia. Haemophilia. Mar 2010;16(2):247-55. [Medline].

  18. Den Uijl I, Mauser-Bunschoten EP, Roosendaal G, Schutgens R, Fischer K. Efficacy assessment of a new clotting factor concentrate in haemophilia A patients, including prophylactic treatment. Haemophilia. Nov 2009;15(6):1215-8. [Medline].

  19. Ingerslev HJ, Hindkjaer J, Jespersgaard C, Lind MP, Kølvraa S. [Preimplantation genetic diagnosis. The first experiences in Denmark]. Ugeskr Laeger. Oct 1 2001;163(40):5525-8. [Medline].

  20. Lissens W, Sermon K. Preimplantation genetic diagnosis: current status and new developments. Hum Reprod. Aug 1997;12(8):1756-61. [Medline].

  21. Wells D, Delhanty JD. Preimplantation genetic diagnosis: applications for molecular medicine. Trends Mol Med. Jan 2001;7(1):23-30. [Medline].

  22. Chuah MK, Collen D, VandenDriessche T. Gene therapy for hemophilia. J Gene Med. Jan-Feb 2001;3(1):3-20. [Medline].

  23. Castaman G, Mancuso ME, Giacomelli SH, Tosetto A, Santagostino E, Mannucci PM, et al. Molecular and phenotypic determinants of the response to desmopressin in adult patients with mild hemophilia A. J Thromb Haemost. Nov 2009;7(11):1824-31. [Medline].

  24. Adamson S, Charlebois T, O'Connell B, Foster W. Viral safety of recombinant factor IX. Semin Hematol. Apr 1998;35(2 Suppl 2):22-7. [Medline].

  25. Aronson DL. Cause of death in hemophilia A patients in the United States from 1968 to 1979. Am J Hematol. Jan 1988;27(1):7-12. [Medline].

  26. Bitting RL, Bent S, Li Y, Kohlwes J. The prognosis and treatment of acquired hemophilia: a systematic review and meta-analysis. Blood Coagul Fibrinolysis. Oct 2009;20(7):517-23. [Medline].

  27. Bogdanova N, Markoff A, Pollmann H, Nowak-Göttl U, Eisert R, Wermes C, et al. Spectrum of molecular defects and mutation detection rate in patients with severe hemophilia A. Hum Mutat. Sep 2005;26(3):249-54. [Medline].

  28. Coagulation Factor VII a (Recombinant) [package insert]. Denmark: Novo Nordisk; 2006. [Full Text].

  29. Konkle BA, Kessler C, Aledort L, Andersen J, Fogarty P, Kouides P, et al. Emerging clinical concerns in the ageing haemophilia patient. Haemophilia. Nov 2009;15(6):1197-209. [Medline].

  30. O'Connell N, Mc Mahon C, Smith J, Khair K, Hann I, Liesner R, et al. Recombinant factor VIIa in the management of surgery and acute bleeding episodes in children with haemophilia and high responding inhibitors. Br J Haematol. Mar 2002;116(3):632-5. [Medline].

 
Previous
Next
 
Coagulation system
Table 1. Severity, Factor Activity, and Hemorrhage Type
ClassificationFactor Activity, %Cause of Hemorrhage
Mild>5-40Major trauma or surgery
Moderate1-5Mild-to-moderate trauma
Severe< 1Spontaneous, hemarthrosis
Table 2. General Guidelines for Factor Replacement for the Treatment of Bleeding in Hemophilia B
Indication or Site of BleedingFactor level Desired, %FIX Dose, IU/kg*Comment
Severe epistaxis; mouth, lip, tongue, or dental work20-5020-50Consider aminocaproic acid (Amicar), 1-2 d
Joint (hip or groin)4040Repeat transfusion in 24-48 h
Soft tissue or muscle20-4040No therapy if site small and not enlarging (transfuse if enlarging)
Muscle (calf and forearm)30-4040None
Muscle deep (thigh, hip, iliopsoas)40-6040-60Transfuse, repeat at 24 h, then as needed
Neck or throat50-8050-80None
Hematuria4040Transfuse to 40% then rest and hydration
Laceration4040Transfuse until wound healed
GI or retroperitoneal bleeding60-8060-80None
Head trauma (no evidence of CNS bleeding)5050None
Head trauma (probable or definite CNS bleeding, eg, headache, vomiting, neurologic signs)100100Maintain peak and trough factor levels at 100% and 50% for 14 d if CNS bleeding documented†
Trauma with bleeding, surgery†80-10010010-14 d
Previous
Next
 
 
 
 
 
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.