Introduction: Factor VIII inhibitor (acquired hemophilia) is a rare bleeding disorder rdue to autoantibodies
to factor VIII resulting in reduction in factor VIII levels and mucocutaneous bleeding
complications. The incidence is estimated to be 1.5 cases per million population.
The management requires various bypassing agents to rapidly restore hemostasis in
patients with active bleeding or in patients in need of an urgent invasive procedure.
For eradication of the inhibitor, the generally accepted first line treatment thus
far has been steroids with Rituximab or Cyclophosphamide as salvage treatment. However,
in recent past a combination therapy has been recommended in patients with factor
VIII level of<1% or high titer inhibitor (>20 BU).
Method: Here we presented a case of a 69-year-old Caucasian lady who had initially presented
to ER with extensive bruising of left forearm. She had IV draw 4 days prior and had
significant ecchymosis around the wrist and hand, which had spread down the elbow.
She also complained of fatigue and intermittent dark black stool for the previous
6 weeks. Her hemoglobin was 7.5 gm with a platelet count of 447K. No coagulation studies
were done. An EGD showed LA grade A esophagitis and patchy gastritis without overt
bleeding. A subsequent colonoscopy was entirely normal.
The patient was subsequently noted to have bleeding upon removal of IV from right
arm with progressive bruising that eventually spread to dorsum of her right hand with
a large subcutaneous hematoma but no skin breakdown.
Laboratory studies: PT 11.7 seconds, aPTT 126 seconds, fibrinogen 365, Thrombin time
14.3 seconds
Mixing studies:
aPTT (Patient) 126 seconds
aPTT (Control) 34 seconds
aPTT 1:1 mix (immediate) 49 seconds
aPTT 1:1mix (2-hour incubation) 114 seconds
factor VIII activity<1%, factor VIII inhibitor 63 BU
factor IX activity 91%, factor X activity 64%, factor XII activity 55%, von Willebrand
activity 453%
A diagnosis of acquired factor VIII inhibitor was made. The patient had no history
of an underlying autoimmune disease. No evidence of an underlying malignancy was found
on body CT scans or endoscopic procedures.
Because of concerns regarding recent GI bleed and possible need for surgical management
of her large subcutaneous hematoma, rapid eradication of factor VIII inhibitor was
warranted. She was treated with a combination of weekly Rituximab x 4 and initially
IV and subsequently oral steroids.
Results:
Fig. 1 aPTT and Factor VIII Activity Table
Fig. 2 aPTT and Factor VIII Activity Levels Over Time
She had an excellent response with a step wise decrease in her aPTT and increase in
her factor VIII activity ([Fig. 1], [Fig. 2]). She was tapered off her steroids and remains in complete remission [1].
Conclusion: A combination of upfront Rituximab and steroids can achieve a rapid clearance of
high titer factor VIII inhibitor.
