[Notes on laboratory coagulation testing for acquired hemophilia A].
Acquired hemophilia A (AHA) is a bleeding disorder characterized by autoantibodies directed against coagulation factor VIII (FVIII). Patients with the disorder show a mortality rate of 7.9-25%; therefore, rapid and accurate diagnosis is critical. Isolated prolonged APTT in patients showing spontaneous bleeding with no previous history of a bleeding disorder suggests a diagnosis of AHA. AHA is confirmed by a markedly reduced FVIII activity without a reduction of von Willebrand factor and measurement of the inhibitor titer to FVIII. APTT cross-mixing tests are useful for the rapid distinction between factor deficiency and the presence of an inhibitor. FVIII inhibitor is time and temperature-dependent; therefore, mixing tests performed immediately and after 2 hours of incubation should be compared. In some cases, all intrinsic factors are decreased, which may represent an in vitro artifact due to the depletion of FVIII in the substrate plasma by the inhibitor. A lupus anticoagulant (LA) can also cause the artifactual lowering of factor levels due to the inhibition of phospholipids in the assay. Factor assays should be repeated at higher serial dilutions of the test plasma, which will attenuate the effect of the inhibitor or LA on the factor measurement and may also distinguish between AHA and LA. Acquired inhibitors to FVIII often display non-linear type 2 kinetics; therefore, the inhibitor titer measured by the Bethesda assay corresponding to the dilution that is closest to 50% inhibition should be reported. Moreover, plasma samples with some FVIII activity should be preincubated for 30 minutes at 56 degrees C in order to inactivate residual FVIII in the test samples.
Amano
Kagehiro
K
Department of Laboratory Medicine, Tokyo Medical University Hospital, Shinjuku-ku, Tokyo 160-0023, Japan. kamano@tokyo-med.ac.jp
D001780:Blood Coagulation Tests / Q000379:methods*; D006467:Hemophilia A / Q000175:diagnosis*; D006801:Humans