An acquired, calcium-dependent, factor X inhibitor

Area of Science:

• Hematology
• Immunology
• Coagulation Disorders

Background:

• Acquired factor X (FX) deficiency is a rare bleeding disorder.
• It is often associated with autoantibodies, but anti-FX antibodies are infrequently detected.
• This case describes a patient with severe bleeding due to a specific anti-FX antibody.

Observation:

• A patient presented with severe bleeding.
• The bleeding was attributed to a calcium ion-dependent anti-FX IgG antibody.
• The purified antibody bound the light chain of FX, requiring calcium ions for enhanced binding (>1000-fold).

Findings:

• The antibody demonstrated cross-reactivity with prothrombin (100-fold lower affinity) and factor VII (1000-fold lower affinity).
• In functional assays, increasing phospholipid concentrations reduced the antibody's inhibitory activity, similar to lupus anticoagulants.
• The antibody's binding was dependent on the γ-carboxyglutamic acid domain of FX.

Implications:

• Understanding the antibody's characteristics is crucial for accurate laboratory diagnosis of acquired FX deficiency.
• The calcium-dependency and phospholipid interactions offer insights into the antibody's mechanism of action.
• This case highlights the importance of considering specific autoantibodies in unexplained bleeding disorders.