What factor VIII activity level is seen in severe hemophilia A?

Factor VIII Levels in Severe Hemophilia A

Severe hemophilia A is defined by factor VIII activity levels less than 1 IU/dL (or <1% of normal plasma activity). 1, 2

Classification Threshold

• The International Society on Thrombosis and Haemostasis and American Society of Hematology both establish the diagnostic threshold for severe hemophilia A at factor VIII levels <1 IU/dL, which corresponds to less than 1% of normal factor VIII activity 1, 3, 2

• This classification distinguishes severe hemophilia from moderate disease (1-5 IU/dL) and mild disease (>5-40 IU/dL) 1, 2

Clinical Implications of This Threshold

• Patients with factor VIII levels <1 IU/dL experience spontaneous bleeding episodes, most frequently affecting joints and muscles, without requiring trauma or injury as a trigger 1, 2

• The severe category carries the highest risk for inhibitor development, with cumulative incidence of 20-35% in severe hemophilia A compared to only 4-9% in severe hemophilia B 1, 2

• Spontaneous bleeding typically manifests early in life, with clinically severe patients showing bleeding episodes before age 1 year or joint/muscular bleeding before age 3 years 1

Important Clinical Caveats

The <1 IU/dL threshold is somewhat arbitrary and does not fully capture clinical heterogeneity. Patients classified as severe based on this laboratory cutoff may exhibit variable bleeding phenotypes 1, 4

• Advanced testing such as clot waveform analysis can discriminate between different levels of factor VIII activity even within the severe category (<1 IU/dL), and these subtle differences may correlate better with actual bleeding severity 1

• Some patients with identical factor VIII levels below 1 IU/dL demonstrate markedly different bleeding patterns, suggesting that other factors (such as endogenous thrombin potential and factor VII levels) modulate clinical severity 4, 5

• The choice of assay method matters: chromogenic assays versus one-stage clotting assays may yield different results, particularly in the 0.2-1.0 IU/dL range, though both classify patients below 1 IU/dL as severe 6, 7