What is the role of lab studies in the workup of hemophilia A?

Updated: Apr 08, 2020
  • Author: Douglass A Drelich, MD; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP  more...
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Laboratory studies for suspected hemophilia include a complete blood cell count, coagulation studies, and a factor VIII (FVIII) assay. Never delay indicated coagulation correction pending diagnostic testing.

On the hemoglobin/hematocrit assay, expect normal or low values. Expect a normal platelet count. On coagulation studies, the bleeding time and prothrombin time (which assesses the extrinsic coagulation pathway) are normal.

Usually, the activated partial thromboplastin time (aPTT) is prolonged; however, a normal aPTT does not exclude mild or even moderate hemophilia because of the relative insensitivity of the test. The aPTT is significantly prolonged in severe hemophilia.

For FVIII assays, levels are compared with a normal pooled-plasma standard, which is designated as having 100% activity or the equivalent of FVIII U/mL. Normal values are 50-150%. Values in hemophilia are as follows:

  • Mild: > 5%
  • Moderate: 1-5%
  • Severe: < 1%

Aging, pregnancy, oral contraceptive use, and estrogen replacement therapy are associated with increased FVIII levels. Because FVIII is a large molecule that does not cross the placenta, the diagnosis can be made at birth with quantitative assay of cord blood.

Three main FVII assay methods are in use: one-stage and two-stage clotting assays and a two-stage chromogenic method. In approximately one-third of patients with mild hemophilia, FVIII levels on the automated one-stage FVIII assay are significantly higher than—typically, more than double—those of the two-stage coagulation assay. [25, 26]

Those discrepancies, which result from differences in the underlying FVIII mutations in these patients, can result in missed diagnoses or mismanagement due to underestimation of bleeding risk. [25, 27] Given the possibility of discrepant hemophilia A, as this condition is termed,  use of the chromogenic FVIII assay combined with FVIII gene mutation analysis has been recommended for diagnosis of mild hemophilia A. [25]

Differentiation of hemophilia A from von Willebrand disease is possible by observing normal or elevated levels of von Willebrand factor antigen and ristocetin cofactor activity. Bleeding time is prolonged in patients with von Willebrand disease but normal in patients with hemophilia.

In patients with an established diagnosis of hemophilia, periodic laboratory evaluations include screening for the presence of FVIII inhibitor and screening for transfusion-related or transmissible diseases such as hepatitis and HIV infection. Screening for infection may be less important in patients who receive only recombinant FVIII concentrate.

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