Vol 41 # 3 September 2009 - Kma.org.kw

September 2009
KUWAIT MEDICAL JOURNAL 243
Case Report
Acquired Hemophilia in a Child: Response to Rituximab
Najwa Ali Akar 1 , Adekunle Adekile 2
1
Department of Pediatrics, Mubarak Hospital, Kuwait
2
Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait
Kuwait Medical Journal 2009; 41 (3): 243-245
ABSTRACT
Acquired hemophilia, secondary to factor VIII inhibitors,
is very rare especially in childhood. We present the case
of an otherwise healthy Kuwaiti boy who presented with
spontaneous factor VIII inhibitors at the age of two years,
making him one of the youngest to be reported. There was
no associated acute illness, recent vaccination or drug intake
except a history of mild bronchial asthma. He presented
with multiple ecchymoses, but no frank bleeding. His
lowest factor VIII level was 8% and highest inhibitor level
was 400 Bethesda units (BU)/ml. He initially responded
to a combination of intravenous immunoglobulin,
prednisolone and azathioprine. However he relapsed
and later became refractory to treatment. He had a trial of
mycophenolate, to which he did not respond. He eventually
received rituximab 375 mg/m 2 as a six-week IV course, to
which he had a prompt response without any major side
effects. More than two years later, his factor VIII level is
about 150% and inhibitor is not detectable. It appears
therefore, that even in childhood, rituximab is useful for
the management of acquired factor VIII inhibitors.
KEY WORDS: acquired hemophilia, factor VIII inhibitors, rituximab
INTRODUCTION
Acquired inhibitors of coagulation may be
alloantibodies or autoantibodies. The former are
well-recognized in patients with severe congenital
coagulation factor deficiencies, especially of factors
VIII and IX. They are clotting factor-specific and
generally retained for variable periods of time.
Autoantibodies are seen in non-hemophiliacs and are
of two general types - specific (directed against a single
clotting factor) and non-specific inhibitors (interfering
in some fashion with clotting factor interaction). The
lupus antagonist (LA) is the most common nonspecific
inhibitor; it occurs in approximately 10% of
adult patients with systemic lupus erythematosus.
Specific inhibitors of coagulation are monofactorspecific
and are directed at specific regions of the
coagulation factor molecule [1-3] .
Acquired factor VIII inhibitors are uncommon
in adults and even rarer in children [2] . They have
been reported in patients with underlying disorders
like lymphoproliferative disorders, leukemia and
autoimmune diseases; following vaccination, ingestion
of drugs (e.g., penicillins) and postpartum [1-3] . The
presence of these inhibitors has been associated with
serious and life-threatening bleeding. Treatment
is mainly directed at controlling the bleeding and
eliminating the inhibitors. Spontaneous disappearance
of the inhibitors has also been reported [3] . Here we
report the case of acquired factor VIII inhibitor in a boy
who presented at the age of two years, making him
probably the youngest such patient in literature.
Case Report
A two-year old Kuwaiti boy presented for the first
time in April 1995 with multiple bruises, mainly on
his chest. There was no history of significant trauma,
infection, recent vaccination or drug intake. There was
no previous history of prolonged bleeding or excessive
bruising. He had normal perinatal and developmental
history and he had been quite well except for mild
bronchial asthma. His parents were well and there
was no family history of a bleeding disorder.
Physical examination was unremarkable except for
significant ecchymosis. There was no lymphadenopathy
and no hepatosplenomegaly. Imaging studies including
X-ray and CT chest and abdomen were normal. Complete
blood count (CBC), bleeding time and prothrombin time
were normal, but activated partial thromboplastin time
(APTT) was prolonged (82 seconds; control 31 seconds)
and INR was 1.1. Factor VIII level was 8% and inhibitor
screen showed the presence of a time-dependent inhibitor.
Anti-nuclear and anti-dsDNA antibodies were negative.
He was referred to the Royal Free Hospital London, UK
in June 1995. Repeat investigations showed a normal PT,
APTT was 91 seconds (control 28-38 seconds), factor VIII
bioassay was < 1 u/dl and investigations confirmed the
presence of type II acquired factor VIII inhibitors at a
level of 14-24 Bethesda Units (BU)/ml.
Address Correspondence to:
Professor Adekunle D. Adekile, Department of Pediatrics, Faculty of Medicine, Kuwait University, PO Box 24923, Safat 13110, Kuwait. Tel: +965
531-9486, Fax: +965 533-8940, E-mail: adekile@hsc.edu.kw