Factor IX Deficiency (Hemophilia B) Workup

Updated: Nov 29, 2022
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Srikanth Nagalla, MD, MS, FACP  more...
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Workup

Laboratory Studies

Tests for preliminary identification of the coagulation disorder are as follows:

  • Activated partial thromboplastin time (aPTT)
  • Prothrombin time (PT)
  • Platelet count
  • Bleeding time

A prolonged aPTT with a normal PT indicate an abnormality in the early part of the intrinsic coagulation pathway. However, a normal aPTT does not exclude hemophilia B, since aPTT may not be sufficiently sensitive to detect slightly reduced levels of factor IX (FIX) in the 20-30% range, as occurs in mild hemophilia and in carriers. [18] If the clinical history warrants, a specific FIX level should be obtained.

Prolongation of PT alone, or both the PT and aPTT, is not consistent with hemophilia B alone. This kind of coagulopathy may result from superimposition of other causes, such as liver disease, overdose of heparin or warfarin sodium, or disseminated intravascular coagulation (DIC).

Thrombocytopenia and platelet dysfunction are not consistent with hemophilia B alone.

Assessment of the nature and severity of bleeding involves the following studies:

  • Complete blood cell count (CBC)
  • Testing of stools for blood
  • Urinalysis to test for hematuria

Confirmatory tests include specific coagulation factor assays. In addition, a mixing test is performed in which the patient's plasma is mixed with normal pooled plasma, incubated at 37°C, and then tested for aPTT. Correction of the aPTT in this test implies a deficiency, whereas persistence of an abnormally prolonged aPTT suggests the presence of an inhibitor.

If the mixing test is positive, the next step is determination of the specific titer of an inhibitor to FIX  Ideally, this is done using a special method termed the Nijmegen modification of the Bethesda inhibitor assay. Specific antibodies to FIX usually are IgG subclass 4 or a mixture of IgG subclasses 1 and 4. An experienced laboratory must perform these tests.

Identification of carriers

When coagulation assays for the plasma level of FIX are used, only two thirds of carriers can be identified by a reduced FIX level. Carriers can be detected by linkage studies using restriction fragment length polymorphism analysis, but only if the precise genetic defect is known.

Prenatal diagnosis

Use of several diagnostic procedures has been well established in the treatment of patients with FVIII and FIX deficiencies. Prior to the availability of molecular diagnostic techniques, cord blood sampling by fetoscopy at approximately 20 weeks of gestation was used to identify a male fetus with hemophilia with reduced in utero FIX levels.

Currently, many reports exist of antenatal diagnosis using molecular diagnostic techniques. Chorionic villus sampling at approximately 10-12 weeks of gestation or amniocentesis at 16-20 weeks of gestation can be performed to obtain fetal cells for DNA analysis when the mutation in the family is known or for linkage studies. In general, these procedures carry a risk ranging from a low of approximately 0.5% for maternal-fetal complications to a high of approximately 1-6% for fetal death for fetoscopy. These procedures should be undertaken only after intense genetic and obstetric counseling of the parents.

Other laboratory tests

Other tests that may be indicated include the following:

  • Liver function tests
  • Kidney function testing
  • HIV type 1 and HIV type 2 antigen/antibody tests
  • Hepatitis A, B, C, D, and E antigen/antibody tests.
  • Alpha-fetoprotein levels for evidence of hepatocellular carcinoma, in patients with chronic longstanding hepatitis.
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Imaging Studies

 

Magnetic resonance imaging, computed tomography, and ultrasound have been used to localize and size bleeds and to follow response to therapy.

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