Hemophilia A Differential Diagnoses

Updated: Dec 12, 2017
  • Author: Douglass A Drelich, MD; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP  more...
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Diagnostic ConsiderationsCombined factor V and factor VIII deficiency

Problems to be considered include vitamin K deficiency and other factor deficiencies. 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 II, V, VII, X, or XI; or fibrinogen)

Clinical differentiation of severe hemophilia A from severe hemophilia B is almost impossible, but specific factor assays can help with the distinction. Conditions that can increase factor VIII levels (eg, age, ABO blood type, stress, exercise) can obscure the diagnosis of hemophilia A.

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In rare cases a true hemophilic factor VIII deficiency may be associated with hereditary factor V deficiency. Treatment of bleeding episodes in these patients requires use of fresh-frozen plasma (FFP) to replace factor V, and replacement of factor VIII by FFP and desmopressin or FVIII concentrates. [16]

Combined deficiency of factor VIII and factor V has been traced to mutations in the lectin mannose binding protein 1 (LMAN1) or multiple coagulation factor deficiency 2 (MCFD2) genes, which encode proteins involved in the intracellular transport of FV and FVIII. [16] A similarly reduced level of factor V and factor VIII clotting activities in plasma, and finding other members in the same family with combined factor V and factor VIII deficiency, are all clues to the disorder.

Most difficult to detect on the basis of the history alone is the presence or absence of consanguinity (a feature of recessive disorders requiring 2 doses of the gene for clinical manifestations). In families with known mutations, allele-specific hybridization studies show the difference between homozygotes and heterozygotes.

Acquired multiple-factor coagulopathies due to liver disease, diffuse intravascular coagulation (DIC), warfarin excess, or coagulopathy of dysproteinemias should also be considered.

Differential Diagnoses