At resident morning report, PGY2 Jacqueline Cervantes presented the case of a 79 yo M with PMH of atrial fibrillation (on rivaroxaban until 1 week prior to presentation), hyperlipidemia, COPD, BPH and NIDDM who arrived to the ED with one week of dark urine. He had his first episode of hematuria 2 months prior to presentation, at which time his symptoms were thought to be due to UTI or urolithiasis. His symptoms briefly paused after cessation of anticoagulation; however, they resumed shortly thereafter. He has no history of heavy bleeding, nor does he have recent fevers/chills, coffee ground emesis or hematochezia/melena. ROS otherwise was notable for dark brown blood oozing from his ears during an at home ear lavage.

Medications: metoprolol succinate, rivaroxaban, atorvastatin, metformin, pantoprazole, finasteride, tamsulosin, escitalopram, trazodone

Social history: 50 pack year smoking history

Physical Exam:
                HEENT: poor dentition, no mucocutaneous bleeding
                CV: irregularly irregular rhythm
                Lungs: b/l crackles to mid-lungs
                GU: rash in inguinal area
                MSK: LLE cool to touch with 0/1+ pulses, mild erythema, 2 cm bullae with violaceous discoloration. RLE warm to touch, erythematous, scaling and discoloration, pulses 2+, R knee with small effusion
                Neuro: intermittently confused, answer questions inappropriately

Labs:
WBC: 9.87, Hgb 10.3 (MCV 92), Platelets: 101
Cr: 0.66
Liver panel: ALP 84, Protein 6.5, Albumin 3.6, AST 15, ALT 19, T Bili 0.4
PT: 15.2, INR 1.2, PTT 109.2
UA: Blood 1.0 (RBCs on micro: 60+)
Blood cultures: negative, UCx: negative, HIV: negative

CTH: Negative for intracranial hemorrhage
Arterial Duplex: negative for arterial thrombus  

Mixing study:
PTT Baseline: 109.2
PTT NPP: 30.9
PTT Mix 60 mins: 100.9 (suggestive of inhibitor)

Factor VIII Activity Level: <1%
Factor VIII Inhibitor Level: 705.5 Bethesda Units

At this point, a diagnosis of acquired hemophilia was established; however, the cause was still unknown and further workup was warranted. Causes of acquired hemophilia include malignancy, autoimmune, medications, and the postpartum state.

Autoimmune Workup:
ANA: positive (1:320)
RF: 15 IU/ml (non-specific); anti-CCP: Negative
All other rheumatologic labs negative, including lupus anticoagulant testing

CT Abdomen/Pelvis:

24 mm length focal thickening of the right anterolateral bladder wall
Biopsy showed urothelial carcinoma in this patient

Diagnosis: Factor VIII Inhibitor secondary to urothelial carcinoma

Teaching points:

Coagulation Cascade Review (the best method per the chief residents): https://www.ashclinicalnews.org/education/coagulation-cascade/

Abnormal Test	Measured Pathway	Factors	Differential Diagnosis
PT	Extrinsic & Common	VII, X, V, II, I	Liver Disease Vitamin K deficiency Warfarin Factor Xa inhibitors (i.e.rivaroxaban) Congenital deficiency of factor VII (rare)
aPTT	Intrinsic & Common	XII, XI, IX, VIII, X, V, II,I	Factor deficiencies (VII, IX, XI and XII) Factor inhibitors Heparin type products Direct thrombin inhibitors (lepirudin, aragtroban and bivalrudin) Lupus anticoagulant Von Willebrand Dz
Thrombin Time	Common	I (fibrinogen)	Hypo/dys fibrinogenemia Increased fibrinogen degradation products Monoclonal gammopathy Heparin or heparin-like inhibitors Direct thrombin inhibitors Thrombin antibodies