eMedicine Specialties > Pediatrics: General Medicine > Hematology

Hemophilia A and B: Differential Diagnoses & Workup

Author: Hadi Sawaf, MD, Director, Pediatric Hematology-Oncology, Department of Pediatrics, St John's Hospital of Detroit; Clinical Assistant Professor, Wayne State University
Coauthor(s): Adonis Lorenzana, MD, Consulting Staff, Department of Pediatrics, St John Hospital and Medical Center; 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
Contributor Information and Disclosures

Updated: Dec 2, 2008

Differential Diagnoses

Child Abuse & Neglect: Physical Abuse
Hemophilia C
Von Willebrand Disease

Workup

Laboratory Studies

The following laboratory findings may be observed in patients with hemophilia a or hemophilia b:

  • Usually, the activated partial thromboplastin time (aPTT) is prolonged; however, normal aPTT does not exclude mild or even moderate hemophilia because of the relative insensitivity of the test. Severe hemophilia is easily identified with a significantly prolonged aPTT.
  • Bleeding times, prothrombin times, and platelet counts are normal.
  • The diagnosis is based on functional assay results for factor VIII (FVIII) and factor IX (FIX). Usually, immunoassay of these factors is not required for diagnosis, but it assists in identifying dysfunctional coagulation problems in some patients with hemophilia.
  • Usually, von Willebrand factor (vWF) levels are also measured. The combination of low FVIII and low vWF may indicate vWF deficiency as the primary diagnosis.
  • Because FVIII and FIX are large molecules that do not cross the placenta, the diagnosis can be made at birth with quantitative assay of coagulation factors in the cord blood.
  • Early diagnosis of FIX deficiency is complicated by the physiologic reduction of vitamin K–dependent factors in young infants.
  • Other laboratory evaluations in the patient with hemophilia include periodic screening for the presence of FVIII or FIX inhibitor and screening for transfusion-related or transmissible diseases such as hepatitis and HIV. This may be less important in populations who receive only recombinant product.

Other Tests

  • Fetal testing
    • If the mutation is known, then restriction fragment length polymorphism (RFLP) can be performed on chorionic villous or amniocentesis samples.
    • Inversion of the factor VIII gene can be detected by Southern blot.
    • If the mutation is not known, gene sequencing can be performed.
  • Carrier testing
    • A reduced factor VIII C–to–vWF antigen ratio below 0.7 is suggestive of carrier status.
    • Direct genetic testing for known gene mutation is more accurate.
    • Linkage analysis by RFLP in multiple family members can be used.
    • FIX level is often normal in FIX carriers.
    • Direct mutation analysis is available in several laboratories for unknown FVIII or FIX mutations.

More on Hemophilia A and B

Overview: Hemophilia A and B
Differential Diagnoses & Workup: Hemophilia A and B
Treatment & Medication: Hemophilia A and B
Follow-up: Hemophilia A and B
Multimedia: Hemophilia A and B
References
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References

  1. Bogdanova N, Markoff A, Pollmann H, 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].

  2. Berntorp E, Astermark J, Bjorkman S, et al. Consensus perspectives on prophylactic therapy for haemophilia: summary statement. Haemophilia. May 2003;9 Suppl 1:1-4. [Medline].

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

  4. 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].

  5. [Best Evidence] Chapman WC, Singla N, Genyk Y, 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].

  6. O'Connell N, Mc Mahon C, Smith J, 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].

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

  8. Brettler DB, Levine PH. Clinical manifestations and therapy of inherited coagulation factor deficiencies. In: RW Colman, J Hirsh, VJ Marder, et al eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 3rd ed. Philadelphia, PA: JB Lippincott; 1994:169-83.

  9. Dunn AL, Busch MT, Wyly JB, Abshire TC. Radionuclide synovectomy for hemophilic arthropathy: a comprehensive review of safety and efficacy and recommendation for a standardized treatment protocol. Thromb Haemost. Mar 2002;87(3):383-93. [Medline].

  10. Fallaux FJ, Hoeben RC. Gene therapy for the hemophilias. Curr Opin Hematol. Sep 1996;3(5):385-9. [Medline].

  11. Gangadharan B, Parker ET, Ide LM, et al. High-level expression of porcine factor VIII from genetically modified bone marrow-derived stem cells. Blood. May 15 2006;107(10):3859-64. [Medline]. [Full Text].

  12. Lee C. Recombinant clotting factors in the treatment of hemophilia. Thromb Haemost. Aug 1999;82(2):516-24. [Medline].

  13. Lilleyman J, Hann I, Blanchette V. Hemophilia. In: Pediatric Hematology. 2nd ed. 1999:585-98.

  14. Manco-Johnson MJ, Abshire TC, Shapiro AD, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. Aug 9 2007;357(6):535-44. [Medline].

  15. Miller R. Counselling about diagnosis and inheritance of genetic bleeding disorders: haemophilia A and B. Haemophilia. Mar 1999;5(2):77-83. [Medline].

  16. Nathan DG, Oski FA. Hemophilia. In: Hematology of Infancy and Childhood. 5th ed. 1998:1631-45.

  17. Santagostino E, Mannucci PM, Bianchi Bonomi A. Guidelines on replacement therapy for haemophilia and inherited coagulation disorders in Italy. Haemophilia. Jan 2000;6(1):1-10. [Medline].

  18. Soucie JM, Nuss R, Evatt B, et al. Mortality among males with hemophilia: relations with source of medical care. The Hemophilia Surveillance System Project Investigators. Blood. Jul 15 2000;96(2):437-42. [Medline]. [Full Text].

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Further Reading

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Keywords

hemophilia a, hemophilia b, factor VIII deficiency, FVIII deficiency, factor VIII hemophilia, factor IX deficiency, FIX deficiency, factor IX hemophilia, Christmas disease, angiostaxis, coagulation disorder, coagulation deficiency, bleeding disorder, hepatitis A, hepatitis B, hepatitis C, human immunodeficiency virus infection, HIV, hemarthrosis, hematomas, petechiae, vasculitis

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Contributor Information and Disclosures

Author

Hadi Sawaf, MD, Director, Pediatric Hematology-Oncology, Department of Pediatrics, St John's Hospital of Detroit; Clinical Assistant Professor, Wayne State University
Hadi Sawaf, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Coauthor(s)

Adonis Lorenzana, MD, Consulting Staff, Department of Pediatrics, 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.

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

Medical Editor

Gary R Jones, MD, Associate Medical Director, Clinical Development, Berlex Laboratories
Gary R Jones, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, and Western Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Gary D Crouch, MD, Program Director of Pediatric Hematology-Oncology Fellowship, Department of Pediatrics, Associate Professor, 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.

CME Editor

Helen SL Chan, MBBS, FRCP(C), FAAP, Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Canada
Helen SL Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA, Executive Director, Center for Cancer and Blood Disorders, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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