What tests would be abnormal in Hemophilia A (Hemophilia A, also known as Classic Hemophilia or Factor VIII deficiency)?

From the Guidelines

In hemophilia A, the most significant abnormality is a prolonged activated partial thromboplastin time (aPTT), which measures the intrinsic and common pathways of coagulation, as evidenced by a study published in the Journal of Clinical Oncology in 2018 1. The aPTT is prolonged due to the deficiency of Factor VIII, a crucial component of the intrinsic pathway.

• Factor VIII activity levels will be decreased, with severity classified based on the percentage of normal activity: severe (<1%), moderate (1-5%), or mild (5-40%) 1.
• The prothrombin time (PT) and bleeding time typically remain normal because they don't depend on Factor VIII function.
• Thrombin time is also usually normal.
• Specific Factor VIII assays will confirm the diagnosis by directly measuring the reduced or absent Factor VIII levels.
• Mixing studies, where patient plasma is mixed with normal plasma, will show correction of the aPTT, indicating a factor deficiency rather than an inhibitor.
• Genetic testing may reveal mutations in the Factor VIII gene located on the X chromosome. These abnormalities reflect the fundamental pathophysiology of hemophilia A, which is characterized by impaired thrombin generation due to Factor VIII deficiency, resulting in inadequate fibrin clot formation at sites of vascular injury. A study published in the Journal of Thrombosis and Haemostasis in 2013 1 also highlights the importance of assessing clotting function in patients with hemophilia A, using techniques such as clot waveform analysis (CWA) to illustrate severely impaired patterns in these cases. However, the most recent and highest quality study, published in 2018 1, provides a more comprehensive overview of the diagnostic work-up for hemophilia A, including the typical findings of a prolonged activated PTT with a normal PT.

From the FDA Drug Label

Prior to treatment with desmopressin acetate injection, verify that factor VIII coagulant activity levels are >5% and exclude the presence of factor VIII autoantibodies. Also assess serum sodium and aPTT prior to treatment The tests that would be abnormal in Hemophilia A are:

• Factor VIII coagulant activity levels (less than 5% or presence of factor VIII autoantibodies)
• aPTT (activated partial thromboplastin time) 2

From the Research

Abnormal Tests in Hemophilia A

The following tests may be abnormal in Hemophilia A:

• Activated Partial Thromboplastin Time (aPTT) 3, 4, 5, 6
• Factor VIII activity assay 4, 5, 7
• Prothrombin Time (PT) may be normal, but aPTT is typically prolonged 4
• Platelet count and complete blood cell count may be normal, but bleeding time may be prolonged 4

Specific Test Abnormalities

• Isolated prolongation of aPTT may result from low levels of factors VIII, IX, or XI 4
• A slightly prolonged aPTT and a moderate decrease in factor VIII may reflect von Willebrand disease or the "carrier" state for hemophilia A 4
• A greatly prolonged aPTT and very low levels of factor VIII (< 3%) most often result from an acquired factor VIII inhibitor or from severe von Willebrand disease 4

Diagnostic Challenges

• Coexistence of factor VIII inhibitor and lupus anticoagulant can make diagnosis difficult due to conflicting clinical presentations and laboratory results 3
• Assay discrepancies have been described when measuring the activity of extended half-life factor VIII and IX concentrates 5
• Emicizumab, a bispecific antibody, can artificially shorten aPTT-based clotting times, making standard assays inapplicable for analysis of samples from patients treated with this drug 5