Coagulation factor inhibitors

Specimen:

4.5 mL blood added to 0.5 mL citrate.

Method:

Test based on the inability of normal plasma (in a 50:50 mixture) to correct prolonged APTT (or PT) of patient (test) plasma.

Further tests to identify and quantitate inhibitor are based on coagulation factor assays (see Bethesda assay) and should be requested in consultation with haematologist or pathologist.

Application:

Reduced clinical and/or assay response to coagulation factor replacement therapy in haemophilia A or B.

Unexplained prolongation of the APTT (or more rarely PT) in patients with recent onset of excessive bleeding; particularly in those with autoimmune disease, lymphoma or myeloma and in post-partum patients.

See also Lupus anticoagulant.

Interpretation:

Factor VIII inhibitors develop in < 10% of patients with haemophilia A; rarely in patients with autoimmune disease, lymphoproliferative disorders and other malignancies; in the post-partum period and in otherwise normal individuals.

Factor IX inhibitors develop in < 2% of patients with haemophilia B and are very rare in other disorders.

Factor XI inhibitors may develop in up to one third of Factor XI deficient patients exposed to plasma. 

Other specific coagulation factor inhibitors are extremely rare, but may develop (particularly in the elderly). Otherwise normal (non-haemophilic) patients who develop an inhibitor may present with acute bleeding.

Inhibitors may be low or high titre; low titre inhibitors do not cause major therapeutic problems and may become undetectable over time, even with continued coagulation factor replacement therapy. High titre inhibitors pose a major therapeutic problem; for factor VIII inhibitors the degree of cross reactivity with porcine factor VIII should be documented as a guide to whether this product, if available, can be used for replacement therapy.

Reference:

Brettler DB. Bailliere’s Clin Haematol 1996; 9: 319-329.

Cohen AJ and Kessler CM. Bailliere’s Clin Haematol 1996; 9: 331-354.

Salomon et al. Blood. 2003; 101:4783-8