Follow-up
The patient has been followed for three years since discontinuing
immunosuppressive therapy and continues to do well. She has not had any
additional abnormal bleeding events, FVIII activity has remained normal,
and FVIII inhibitor levels remain undetectable.
DISCUSSION
AHA is rare in pediatric patients. A systematic literature review
identified 42 cases of de novo acquired coagulation factor
inhibitors in pediatric patients, including 29 cases of acquired
hemophilia A12. Of the reported cases, 14/29 were
idiopathic, 5/29 were associated with prior penicillin/ampicillin use,
5/29 with prior infection, and 3/29 with autoimmune disease. Bleeding
episodes typically were mucosal bleeds, bleeding into muscles and soft
tissues, and subcutaneous bleeds. Hemarthrosis was observed in only one
patient. Resolution of disease was reported in 22/29 cases.
AHA treatment entails achieving hemostasis with factor replacement
therapy, reduction of the autoantibody via immunosuppression, and
supportive care. Due to the rarity of the condition, there is no data
from randomized clinical trials to guide management. Control of bleeding
by FVIII replacement or desmopressin (DDAVP) to increase FVIII levels is
typically not recommended, even if inhibitor titers are
low13,14. Control of bleeding with such bypassing
agents as rFVIIa or prothrombin complex concentrates appears to be more
effective, and there does not appear to be a significant difference in
efficacy between the two13,15–17. Emicizumab is a
manufactured bispecific antibody that mimics the effects of activated
factor VIII by bridging factors IX and X. Emicizumab successfully
prevents bleeding in patients with congenitally acquired hemophilia
A18. Several case reports describe successful bleeding
control in adult onset AHA, but its efficacy has not been evaluated in
prospective trials19,20.
Immunosuppressive therapy is typically employed to eliminate the
inhibitor, although spontaneous loss of the inhibitor may occur in
one-third of patients21. A retrospective study of 331
adult patients with AHA observed improved rates of complete remission
with cyclophosphamide combined with steroids (70%) compared to steroids
alone (48%) or rituximab-based regimens (59%)13.
Given the scarcity of pediatric cases, little evidence exists regarding
the optimal immunosuppressive regimen in children.
In summary, we present two cases of acquired hemophilia A with
hemarthrosis as the sentinel bleeding event. AHA should thus be
considered in pediatric patients presenting with sudden onset
hemarthrosis. It is notable that both cases also had a possible
triggering event — recent infection or vaccination — that may have
been related to development of AHA. Finally, as demonstrated with these
two cases, immunosuppression with steroids +/- IVIG may be curative in
pediatric AHA.
CONFLICT OF INTEREST
STATEMENT
The authors declare no conflicts of interest.
ACKNOWLEDGMENTS
L.H.D. was supported by the Stanford Medical Scientist Training Program
NIH training grant T32GM007365.
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LEGENDS
FIGURE 1: FVIII inhibitor levels and FVIII activity versus time since
diagnosis in case #1. Bleeding events are indicated with an asterix.
IVIG doses are indicated with an arrowhead. a, prednisone started at
1mg/kg/dose twice daily; b, prednisone taper initiated; c, prednisone
discontinued.
FIGURE 2: FVIII inhibitor levels and FVIII activity versus time since
diagnosis in case #2. Bleeding events are indicated with an asterix. a,
prednisone started at 1 mg/kg/dose twice daily; b, prednisone taper
initiated with 5 mg/dose decrease each week; c, prednisone discontinued.