Diagnostic Approach to Abnormal Rosner Index in Prolonged aPTT

Understanding the Condition

A Rosner index ≥11% indicates the presence of an inhibitor rather than simple factor deficiency, as factor deficiencies would correct when mixed with normal plasma, according to the American Society of Hematology 1
The mixing test failure distinguishes acquired hemophilia A from congenital hemophilia and confirms an inhibitory substance (autoantibody) is present, as stated by the International Society on Thrombosis and Haemostasis 1

Factor VIII activity level measurement is the most critical next step, as reduced Factor VIII with a non-correcting mixing study is the hallmark of acquired hemophilia A, recommended by the American College of Clinical Pathology 1, 3
Lupus anticoagulant testing must be performed to exclude antiphospholipid syndrome, which is the other major cause of non-correcting mixing studies, as suggested by the British Committee for Standards in Haematology 1, 2, 4
Bethesda assay to quantify Factor VIII inhibitor titer if Factor VIII activity is low, though this may underestimate autoantibody potency due to type 2 kinetics, according to the National Hemophilia Foundation 1, 3

Exclude heparin contamination by checking thrombin time or reviewing clinical history, as heparin can interfere with aPTT interpretation, recommended by the American College of Chest Physicians 4
If the patient is on warfarin with INR 1.5-3.0, interpretation becomes difficult and testing should ideally be performed when INR <1.5 or 1-2 weeks after discontinuation, as stated by the European Society of Cardiology 4
The presence or absence of bleeding helps differentiate acquired hemophilia A (typically presents with bleeding) from lupus anticoagulant (typically no bleeding tendency), according to the World Federation of Hemophilia 3

If Factor VIII is Low (<40% activity): Proceed immediately to Bethesda assay for inhibitor quantification and initiate hematology consultation for potential acquired hemophilia A management, recommended by the American Society of Hematology 1, 3
If Factor VIII is Normal and Lupus Anticoagulant is Positive: Perform confirmatory lupus anticoagulant testing with high phospholipid concentration (integrated tests) and check anticardiolipin and anti-β2-glycoprotein I antibodies for complete antiphospholipid antibody profile, as suggested by the International Society on Thrombosis and Haemostasis 4