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Factor IX Deficiency Differential Diagnoses

  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP  more...
 
Updated: Jun 17, 2016
 
 

Diagnostic Considerations

Other problems to be considered in the differential diagnosis of hemophilia B include the following:

  • Hemophilia A and von Willebrand disease
  • Other inherited coagulation disorders - Multiple vitamin K–dependent factor deficiencies and FXI deficiency
  • Acquired antibodies against FIX in persons with known hemophilia (for more information, see Medication)
  • Acquired antibodies against FIX in patients without hemophilia
  • Common coagulation disorders secondary to liver disease, warfarin sodium or heparin overdose, disseminated intravascular coagulation, dysproteinemias causing coagulopathies, and vitamin K deficiency

Differential Diagnoses

 
 
Contributor Information and Disclosures
Author

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.

Coauthor(s)

Rajalaxmi McKenna, MD, FACP Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Pere Gascon, MD, PhD Professor and Director, Division of Medical Oncology, Institute of Hematology and Medical Oncology, IDIBAPS, University of Barcelona Faculty of Medicine, Spain

Pere Gascon, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, New York Academy of Medicine, New York Academy of Sciences, Sigma Xi

Disclosure: Nothing to disclose.

Elzbieta Klujszo, MD Head of Department of Dermatology, Wojewodzki Szpital Zespolony, Kielce

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.

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, SWOG

Disclosure: Partner received none from No financial interests for none.

Chief Editor

Srikanth Nagalla, MBBS, MS, FACP Director, Clinical Hematology, Cardeza Foundation for Hematologic Research; Assistant Professor of Medicine, Division of Hematology, Associate Program Director, Hematology/Medical Oncology Fellowship, Assistant Program Director, Internal Medicine Residency, Jefferson Medical College of Thomas Jefferson University

Srikanth Nagalla, MBBS, MS, FACP is a member of the following medical societies: American Society of Hematology, Association of Specialty Professors

Disclosure: Nothing to disclose.

Additional Contributors

David Aboulafia, MD Medical Director, Bailey-Boushay House, Clinical Professor, Department of Medicine, Division of Hematology, Attending Physician, Section of Hematology/Oncology, Virginia Mason Clinic; Investigator, Virginia Mason Community Clinic Oncology Program/SWOG

David Aboulafia, MD is a member of the following medical societies: American College of Physicians, American Medical Association, AMDA - The Society for Post-Acute and Long-Term Care Medicine, American Society of Hematology, Infectious Diseases Society of America, Phi Beta Kappa

Disclosure: Nothing to disclose.

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Obituary in the Salem Gazette (Massachusetts) of a 19-year-old man, March 22, 1796.
Major components of the factor IX structure.
Vitamin K–dependent carboxylation of precursor factor IX to procoagulant factor IX. Carboxylation of glutamate (Glu) to gamma-carboxyglutamate (Gla) residues in the precursor protein of the vitamin K–dependent factors occurs in the endoplasmic reticulum of the hepatocyte. Reduced vitamin K is oxidized in this process. Warfarin prevents the reduction and recycling of oxidized vitamin K.
The hemostatic pathway: role of factor IX.
Activation of factor IX and function of the intrinsic tenase complex. Activation of factor IX is followed by formation of the intrinsic tenase complex, which activates factor X to activated factor X, leading to a second and larger burst of thrombin production during activation of hemostasis.
Cell surfaced-directed hemostasis. Initially, a small amount of thrombin is generated on the surface of the tissue factor–bearing (TF-bearing) cell. Following amplification, the second burst generates a larger amount of thrombin, leading to fibrin (clot) formation. (Adapted from Hoffman and Monroe, Thromb Haemost 2001, 85(6): 958-65.)
Possible genetic outcomes in individuals carrying the hemophilic gene.
Teenage boy with bleeding into right thigh, both knees, and ankles.
Older adult man with chronic fused extended knee following open drainage of right knee bleed many years previously.
Severe bilateral hemophilic arthropathy and muscle wasting. Three puncture sites demonstrate attempts to aspirate a recent bleed into the knee joint.
Chronic severe arthritis, fusion, and loss of cartilage and joint space with deformities in the knees. Findings are of advanced hemophilic arthropathy.
Chronic severe arthritis, fusion, and loss of cartilage and joint space with deformities in the elbow. Findings are of advanced hemophilic arthropathy.
Hemophilic knee at surgery with synovial proliferation caused by repeated bleeding and requiring synovectomy.
Large amount of vascular synovium removed during knee surgery.
Microscopic appearance of synovial proliferation and high vascularity. If stained with iron, would show diffuse deposits. Iron-laden macrophages are present.
Male patient presenting with a slowly expanding abdominal and flank mass with increasing pain, inability to eat, weight loss, and weakness of the lower extremity.
Plain radiograph of the pelvis showing a large lytic area.
Intravenous pyelogram showing extreme displacement of the left kidney and ureter by the pseudocyst.
Dissection of a pseudocyst.
Transected pseudocyst with old chocolate brown–black blood.
Large pseudocyst involving left proximal femur.
Transected pseudocyst (following disarticulation of the lower left extremity because of vascular compromise, nerve damage, loss of bone, and nonfunctional lower left extremity) showing old black-brown blood, residual muscle, and bone.
Extensive spontaneous abdominal wall hematoma and thigh hemorrhage in a previously healthy older man with an acquired factor VIII inhibitor.
Extensive spontaneous abdominal wall hematoma and thigh hemorrhage in a previously healthy older man with an acquired factor VIII inhibitor.
Application of Velcro tourniquet followed by self-infusion of concentrate as part of home therapy.
Application of Velcro tourniquet followed by self-infusion of concentrate as part of home therapy.
Quality of life at summer camp.
Table 1. Correlation Between Severity of Bleeding and the Level of Basal FIX Activity
SeverityFunctional FIX Levels, %Bleeding and Hemarthroses
Severe≤ 1Lifelong spontaneous hemorrhages and hemarthroses starting in infancy
Moderate2-5Hemorrhage secondary to minor trauma or surgery; occasional spontaneous hemarthrosis
Mild6-25Hemorrhage secondary to trauma, surgery, or precipitated by the use of drugs such as nonsteroidal anti-inflammatory drugs
Table 2. Rough Guidelines for Treatment Using Factor IX Concentrates
Type of HemorrhageDesired FIX Activity, % of NormalDuration of Therapy, Days
Minor -



Uncomplicated



hemarthroses



superficial large



hematomas



20-301-2
Moderate -



Hematoma with dissection



Oral/mucosal hemorrhages and epistaxis hematuria*



25-503-7



(2-5 in oral hemorrhages)



Dental extraction(s)*50-1002-5
Major -



Pharyngeal/retropharyngeal,



retroperitoneal,



GI tract bleeding,



CNS bleeding surgery



~100 until bleeding is controlled; then taper to minimum required to prevent rebleed7-10



(5-10 in



oral hemorrhages)



*Concomitant administration of EACA or tranexamic acid (both fibrinolytic inhibitors) can help reduce the dose of clotting factor replacement required to treat such bleeds.
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