ABSTRACT
Acquired hemophilia A is a rare condition characterized by de
novo development of a coagulation factor VIII inhibitor. Inhibition of
factor VIII activity results in increased susceptibility to bleeding
events, most frequently mucosal or soft tissue bleeding. We report two
cases of acquired hemophilia A in previously healthy pediatric patients.
Notably, both patients presented with hemarthrosis as the sentinel
bleeding event. In both cases, administration of immunosuppressive
therapy was associated with inhibitor loss and patient cure. These cases
emphasize the importance of considering acquired hemophilia A in
pediatric patients presenting with acute onset hemarthrosis.
INTRODUCTION
Acquired hemophilia A (AHA) is a rare bleeding disorder characterized by
loss of coagulation FVIII (FVIII) activity with an estimated incidence
of 0.6 - 1.48 patients per million per year1–4. AHA
predominantly affects elderly populations with a median age at diagnosis
of 64 - 78 years-old; it is extremely rare in pediatric
populations5. Approximately 50% of cases are
idiopathic, but an association with malignancy and autoimmune disease
has been suggested5–10. Typical presenting symptoms
include subcutaneous bleeding in 80% of patients, as well as bleeding
into muscles/soft tissues and from mucus membranes. However,
hemarthrosis is uncommon, in contrast to joint bleeding frequently
observed in hereditary hemophilia A1,5,11. Little is
known about AHA in pediatric patients due to the exceedingly low
incidence of AHA in younger demographics. We present two cases of AHA in
previously healthy pediatric patients who presented with hemarthrosis.
RESULTS
Case 1
The first patient was a previously healthy 4 year-old male who presented
to hematology clinic with right ankle hemarthrosis and increased
bruising. He had no prior history of easy bleeding or bruising and a
negative family history for bleeding disorders. There was a possible
history of a viral infection several weeks prior to presentation. On
presentation, laboratory evaluation demonstrated severe FVIII deficiency
(<1%) as well as a FVIII inhibitor (5.8 Bethesda Units, B.U.;
Fig. 1). He was initially treated with intravenous activated recombinant
factor VII (rFVIIa) with improvement in his ankle bleed and bruising.
One week later, he developed signs concerning for ongoing bleeding. He
was treated with rFVIIa and started on prednisone 1mg/kg/dose twice
daily.
Marked improvement was noted at follow-up four weeks after initiating
steroid treatment. Prednisone was decreased for a two-week taper. During
the taper, he developed recurrent swelling and pain in his ankle related
to overuse and received rFVIIa with improvement of pain and swelling. At
the time, he was noted to have a factor VIII activity of 9% and a FVIII
inhibitor of 2.7 B.U (Figure 1). He had another incident concerning for
a distal phalangeal joint bleed within several days of discontinuing
prednisone and was treated with two doses of rFVIIa. FVIII activity was
noted to have decreased to 1.7% and FVIII inhibitor level increased to
4.3 BU. Given the recurrent bleeding, he was treated with intravenous
immunoglobulin (IVIG, 1g/kg) every two weeks for a total of five doses.
Improvement of joint pain and swelling was noted following the first
IVIG dose. By the fourth IVIG dose, the patient was clinically well,
without active bleeding, and his FVIII activity was 15.7%. At six-week
follow-up, lab values showed FVIII activity 73% and a FVIII inhibitor 0
BU.