30 Jun 2022

1/6/21: Factor VIII Inhibitor Secondary to Urothelial Carcinoma

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

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 TestMeasured PathwayFactorsDifferential Diagnosis
PTExtrinsic & CommonVII, X, V, II, ILiver Disease
Vitamin K deficiency Warfarin Factor Xa inhibitors (i.e.rivaroxaban) Congenital deficiency of factor VII (rare)
aPTTIntrinsic & CommonXII, XI, IX,
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 TimeCommonI (fibrinogen)Hypo/dys fibrinogenemia Increased fibrinogen degradation products Monoclonal gammopathy Heparin or heparin-like inhibitors Direct thrombin inhibitors Thrombin antibodies

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.