At a Glance

Hemophilia A is a deficiency of factor VIII, and a deficiency of this factor results in a prolongation of the partial thromboplastin time (PTT). It is an inherited bleeding disorder that is sex linked and affects males with rare exceptions. The female carriers do not typically have bleeding disorders. A family history of bleeding that primarily affects males should prompt a consideration of hemophilia A. A family history of bleeding is not absolutely required, as there are many new mutations in the factor VIII gene that can produce mild hemophilia A.

Individuals with mild hemophilia A and factor VIII levels greater than 5% have a fairly normal life and suffer severe bleeding only after major surgery or trauma. Individuals with moderate hemophilia A and a factor VIII percentage between 1 and 5% experienced bleeding with minor trauma. Those with severe disease have factor VIII levels less than 1% and experience spontaneous bleeding, especially in the joints. Hemophilia A, a deficiency of factor VIII, is clinically indistinguishable from hemophilia B, which is a deficiency of factor IX.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

The screening test for hemophilia A is the PTT. With a significant deficiency of factor VIII, the PTT is prolonged. For very mild deficiencies, the PTT may be in the upper end of the reference range. The next test after the PTT for consideration is an assay for factor VIII to determine the percentage of normal factor VIII that is present. If a low factor VIII level is obtained, PTT mixing studies should be performed to determine if a low factor VIII is a result of a simple deficiency of the factor or the presence of a neutralizing factor VIII inhibitor.

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It may be necessary, if the mixing study is equivocal, to perform a Bethesda United quantitation study for a factor VIII inhibitor to determine if a mild inhibitor is present. If factor VIII levels of approximately 20% or more are obtained, tests for von Willebrand factor antigen and ristocetin cofactor should be performed to be certain that the low level of factor VIII is consistent with hemophilia A and not with von Willebrand disease, which can show factor VIII levels similar to those found in patients with mild hemophilia A.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

It is important to determine the baseline factor VIII level to determine the severity of the patient’s hemophilia A. If the patient has been treated with factor VIII concentrate, or any product that contains factor VIII, including fresh frozen plasma, the factor VIII level will be misleading and will reflect the amount produced by the patient plus the amount of factor VIII received by infusion.

The presence of a lupus anticoagulant can result in a low factor VIII level that is not a true factor deficiency. The lupus anticoagulant is an in vitro inhibitor of the clotting reaction required to measure the factor VIII level. Patients can usually be identified as having a lupus anticoagulant instead of a truly low factor VIII by demonstrating the presence of a positive lupus anticoagulant test. In addition, in patients with a lupus anticoagulant, a low factor VIII is often accompanied by low values for factor IX, factor XI, and/or factor XII. Low factor VIII levels in patients with a lupus anticoagulant are not associated with an increased risk for bleeding.

Hemarthrosis is a common indication for addition to the hospital for patients with hemophilia A or B. The hemarthrosis most commonly affects the knee. An indication that an inhibitor to factor VIII has arisen is a poor hemostatic response to infusion of factor VIII that was previously effective in controlling a bleeding episode.

What Lab Results Are Absolutely Confirmatory?

A low factor VIII level with a negative test for the lupus anticoagulant and normal values for von Willebrand factor antigen and ristocetin cofactor confirm a diagnosis of hemophilia A. A PTT mixing study and, if equivocal, a Bethesda unit assay determines whether the low factor VIII is a simple deficiency or the result of a factor VIII inhibitor.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

A rare form of von Willebrand disease, known as type 2N, results in impaired binding of factor VIII by von Willebrand factor. Patients with type 2N von Willebrand disease present with low factor VIII levels and normal values for von Willebrand factor and ristocetin cofactor. A special assay to assess the ability of the patient’s von Willebrand factor to bind factor VIII is required to establish a diagnosis of type 2N von Willebrand disease.

Von Willebrand disease occurs in males and females, and, therefore, families in which there is bleeding affecting both males and females should suggest type 2N von Willebrand disease rather than hemophilia A. Rare carriers of hemophilia A can have factor VIII levels low enough to permit excessive bleeding with trauma. Typically, carriers have values in the 50% range and do not bleed. However, values in the low 20% range, on rare occasions, are found in carriers, and such women can have a bleeding predisposition.