Acquired hemophilia with inhibitors presenting as an emergency: misinterpretation of clotting results during direct oral anticoagulation

Abstract

Background: Direct oral anticoagulants (DOACs) were recently introduced and are being increasingly prescribed. Most DOACs alter the values of traditional coagulation tests, such as the international normalized ratio (INR) or the activated partial thromboplastin time (aPTT). Although vitamin K antagonists raise the INR value to an extent that mirrors their anticoagulant effect, DOACs do not, in general, alter standard clotting values in any consistent way. Thus, there is a risk that abnormal INR and aPTT values can be misinterpreted.

Case illustration: A woman taking rivaroxaban, a DOAC, presented with ileus and was scheduled for urgent surgery. A prolonged aPTT was, at first, wrongly attributed to rivaroxaban, delaying the correct diagnosis of autoantibody-associated acquired hemophilia (a rare condition with incidence, 1.34-1.48 cases per million people per year). The patient had a history of unusually intense bleeding in the skin and mucous membranes during anticoagulant treatment. Her aPTT had been prolonged even before any anticoagulants were taken.

Course: The operation was delayed to await the elimination of rivaroxaban. The aPTT was still prolonged 24 hours later. The diagnosis of autoantibody-associated acquired hemophilia was suspected and then confirmed by the measurement of a factor VIII residual activity of 1% and the demonstration of factor VIII inhibition at an intensity of 9.2 Bethesda units per mL.

Conclusion: The causes of abnormal clotting test results must be clarified before beginning anticoagulant therapy. Unusually intense bleeding during oral anticoagulation should arouse suspicion of a previously undiagnosed acquired coagulopathy, e.g., antibody-associated acquired hemophilia.

Figure

Changes in aPTT and INR over time, in relation to different anticoagulant drugs in a patient with acquired hemophilia with inhibitors. She presented to the emergency department on day 0. aPTT remained above the normal range at all times and was not perceptibly affected by any of the anticoagulants. Until the inhibitor had been eliminated by immunosuppressant therapy, factor VIII activity did not increase and APTT did not return to normal. Other points in time: t3: eight weeks before day 0; t2: six weeks before day 0; t1: one week before day 0. t4: four weeks after day 0. INR: international normalized ratio; aPTT: actviated partial thromboplastin time; VKA: vitamin K antagonists