Abstract We present two patients who acquired factor
VIII antibodies in the immediate postoperative period.
One patient was receiving warfarin that was temporarily
discontinued but reintroduced after the procedure. Preoper-
atively, none gave a history of bleeding, even with past
surgeries, and both had normal coagulation tests. Within
days of surgery, hemorrhage with prolonged activated
partial thromboplastin time, low factor VIII levels, and
demonstrable factor VIII antibodies were observed. For
the patient who was receiving warfarin the severe bleeding
was attributed, at the beginning, only to the high interna-
tional normalized ratio (INR), which resulted in a fatal
delay in diagnosis and appropriate treatment. We would
like to raise awareness of surgery as a precipitating cause
of acquired hemophilia, which is something to be
considered with unusual postoperative bleeding. This
syndrome is remarkable for its abrupt onset within days
of surgery, severe bleeding but potential successful
outcome with combined hemostatic control with recombi-
nant activated FVII (rFVIIa) and elimination of the
antibody by immunosuppression.
Keywords Surgery · Acquired hemophilia A ·
Warfarin · Recombinant activated FVII (rFVIIa)
Introduction
Acquired hemophilia is a rare bleeding disorder caused
by the development of specific autoantibodies which are
capable of inhibiting the action of naturally occurring
factor VIII. The incidence of acquired hemophilia is
uncertain, but has been estimated in Caucasian populations
to be in excess of 1 per million of the population per
year. Bleeding is often severe, particularly during the
first few weeks after presentation, resulting in a mortality
of between 13% and 22%. Approximately half of the
patients with acquired hemophilia have an associated
identifiable disorder at the time the autoantibody is
discovered. Conditions most commonly encountered are
rheumatoid arthritis (15%), systemic lupus erythematosus
(10%), and the peripartum period (14%). Other conditions
include drug reactions, other autoimmune, respiratory
and dermatological disorders, malignancy, and multiple
transfusions [1, 4]. Surgery, although implicated in
isolated case reports in acquired hemophilia [3, 5], has
only very recently been recognized as a possible etiologic
factor [9].
We report our experience with two nonhemophilic
patients who developed factor VIII inhibitors in the
immediate postoperative period. We also describe the
complex bleeding problems that may coexist during this
period, as one patient was receiving warfarin which was
associated with a fatal delay in diagnosis.
Case reports
Case 1
Table 1 provides a summary of the cases. A 75-year-old man with
a history of in situ carcinoma of the colon, which was resected
15 years ago, was admitted to the hospital for surgical correction
of a postoperative hernia of the abdominal wall. He had no bleeding
history, and apart from the colectomy, he had undergone two
surgical procedures 8and 5 years previously for inguinal hernias.
Laboratory findings on admission included: hemoglobin (Hb)
14 g/dl, platelet count 250,000/mm
3
, prothrombin time (PT) 11 s
(INR 1.0), and activated partial thromboplastin time (APTT) 32 s
(NR 27–36 s). He was given once 1 g of cefamandole i.v. 2 hours
prior to surgery and underwent the procedure without any compli-
cation. On the 4th postoperative day, he developed diffuse subcuta-
neous hematomas on the abdomen and a large hematoma in the
operative bed. His Hb level felt to 7.5 g/dl, platelet count and PT
were normal but a marked prolongation of the APTT (71.6 s) was
observed. Further coagulation studies showed normal levels of
factors II, IX, X, XI, and XII, but the factor VIIIc level was 2%
and a factor VIII inhibitor of 10.4 Bethesda units (BU) was identified.
He was transfused and was given i.v. gamma globulin (0.4 g/kg
G. Theodossiades (
✉
) · V. Tsevrenis · E. Nomikou · L. Dadiotis
I. Kontopoulou-Griva
First Regional Transfusion and Haemophilia Centre,
Hippokration Hospital, Vassilissis Sophias 114, Ambelokipi 11527,
Athens, Greece
e-mail: blood@hellasnet.gr
Tel.: +301-7795814, Fax: +301-7702959
Ann Hematol (2001) 80:691–693
DOI 10.1007/s002770100367
CASE REPORT
G. Theodossiades · V. Tsevrenis · E. Nomikou
L. Dadiotis · I. Kontopoulou-Griva
Surgery-associated acquired hemophilia A
Received: 5 October 2000 / Accepted: 30 July 2001 / Published online: 12 September 2001
© Springer-Verlag 2001