Criteria

Disease severity of haemophilia A or B according to plasma procoagulation levels[1]

Mild:

  • Factor VIII or IX levels of >0.05 but <0.40 international units/mL (>5% and <40% of normal)

  • Typically presents with prolonged bleeding only after surgery or major trauma.

Moderate:

  • Factor VIII or IX levels of 0.01 to 0.05 international units/mL (between 1% and 5% of normal)

  • Frequently experience bleeding after minor trauma and occasional spontaneous bleeding.

Severe:

  • Factor VIII or IX levels <0.01 international units/mL (<1% of normal)

  • Frequently experience spontaneous bleeding into joints and muscles, soft-tissue bleeding, and life-threatening haemorrhage.

Presence of inhibitors[63]

The development of antibodies against factor VIII or factor IX, which is more likely during early factor concentrate treatment, results in major clinical difficulties in the management of haemophilia. The risk of inhibitor development is highest in previously untreated patients and tends to develop within the first few exposure days.[52]

The World Federation of Hemophilia guidelines state that indications for inhibitor screening include:[38]​ 

  • Initial factor exposure

  • Intensive factor exposure (e.g., daily exposure for more than 5 days)

  • Recurrent bleeds or target joint bleeds (despite adequate clotting factor concentrate replacement therapy)

  • Failure to respond to adequate clotting factor concentrate replacement therapy

  • Lower than expected factor recovery or half-­life after clotting factor concentrate replacement therapy

  • Suboptimal clinical or laboratory response to clotting factor concentrate replacement therapy

  • Before surgery

  • Suboptimal post-­operative response to clotting factor concentrate replacement therapy.

The inhibitor screen is either positive or negative. If positive, a Bethesda assay (or one of its modifications) is performed to measure the amount of inhibitory antibody present in the patient's sample. It is reported in Bethesda units (BU). The severity is based on the level of inhibitory antibody detected currently, as well as the potential for a secondary ('anamnestic') response to factor VIII or factor IX within a few days following exposure:

  • Low-responder inhibitors: persistently <5 BU/mL despite repeated challenge with exogenous factor concentrate[1]

  • High-responder inhibitors: inhibitor level ≥5 BU/mL at any given time.[1]

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