Inhibitors of coagulation factors

Circulating inhibitors of blood coagulation may be found in:

• hereditary coagulation disorders in response to replacement therapy - e.g. 5 to 10% of Haemophilia A patients have no circulating Factor VIII and produce antibodies against therapeutic Factor VIII
• autoimmune disorders - e.g. rheumatoid arthritis
• in women during the postpartum period
• in elderly patients without underlying disease

The inhibitors are immunoglobulins, usually IgG or IgM, or rarely, IgA, and are targeted against specific coagulation factors. Inhibitors to Factor VIII:C are most common; but Factors V, IX and XI, and Factor VII:von Willebrand's Factor can also be affected. Severe bleeding may result.

Characteristically, the APTT is increased and is not corrected by 1:1 mixture of pooled and normal plasma.

Additionally:

• PT is prolonged in Factor V inhibition
• bleeding time is increased and ristocetin co-factor activity is abnormal in von Willebrands Factor inhibition

Refs: 1) Chesterman (1992). Haemostatic Failure. Med. Int. 97. 2) Schroeder (1991). Current: med. diag. and tr. Lange.