Rapid resolution of factor VIII inhibitor with combination therapy with Rituximab and steroids

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.

Publikationsverlauf

Artikel online veröffentlicht:
13. Februar 2025

• References

• 1 Sridharan M, Pruthi R.K.. ‘Autoimmune (Acquired) Hemophilia: Updates in Diagnosis and Therapy. Journal: The Hematologist. 19. 02 2022