Efficacy and safety of recombinant factor VIIa in the treatment
of bleeding episodes in patients with aplastic anemia
A. M. AL HAMMADI* and S. SALLAH?
*Department of Hematology, Bone Marrow Transplantation Center, University of Baghdad, Iraq; and ?Novo Nordisk A/S International
Operations, Athens, Greece
To cite this article: Al Hammadi AM, Sallah S. Efficacy and safety of recombinant factor VIIa in the treatment of bleeding episodes in patients with
aplastic anemia. J Thromb Haemost 2007; 5: 435–6.
Aplastic anemia is characterized by severe compromise of
hematopoiesis and by a hypocelullar bone marrow .
Hemorrhagic episodes in patients with aplastic anemia occur
usually secondary to thrombocytopenia and require frequent
support with platelet concentrates and other blood products.
Repeated transfusion often results in alloimmunization and
lack of increments to further platelet transfusion, and increases
the demand load on transfusion centers.
Activated recombinant factor VII (rFVIIa, NovoSeven?;
Novo Nordisk A/S, Bagsvaerd, Denmark) has been used to
control bleeding episodes in a wide spectrum of congenital and
acquired bleeding disorders . In this letter, we describe our
experience in the management of hemorrhagic episodes in
patients with aplastic anemia and severe thrombocytopenia.
Over the past two years, seven patients with aplastic anemia
and thrombocytopenia have been treated in our institution for
a variety of bleeding episodes. The etiology of aplastic anemia
The platelet counts in these patients ranged between 2000 and
10 000 per microliter at the time of admission. A total of 17
bleeding episodes were observed, which consisted of nine
vaginal bleedings grade IV (>three vaginal packs over 24 h),
V (no response to any measure), and one episode of hematuria
grade III (passage of clots with urine).
All patients received rFVIIa at a dose of 90 mcg kg)1after
failure of platelet concentrates to achieve adequate hemostasis
(10 bleeding episodes) or lack of availability of apheresis
platelets (seven bleeding episodes).
Bleeding was controlled in all patients after an average
of two doses (range of one to three doses), and approximately
10–25 min after the administration of rFVIIa. The interval of
administration of rFVIIa in patients requiring more than a
single dose to achieve hemostasis was 2–3 h. The requirements
for blood products were reduced from an average of four
units of platelets (range of three to six units) and three units
of red blood cells (range of two to five units) prior to rFVIIa,
to zero to one units of red blood cells and no further
requirements for platelets following rFVIIa. No adverse events
The use of rFVIIa in patients with thrombocytopenia and
is the first description of a case series on the administration of
rFVIIa in patients with aplastic anemia.
In a cell-based in vitro model of thrombocytopenia, it was
demonstrated that rFVIIa increases the efficiency of thrombin
generation [8,9]. Even in the presence of low platelet number,
thrombin-activated platelets appear to provide sufficient sur-
face to bind FXa and FVa to form the prothrombinase
complex . The prothrombinase complex can catalyze the
conversion of large amounts of prothrombin to thrombin,
which subsequently converts fibrinogen to fibrin. In addition,
recently, it has been shown that rFVIIa enhances platelet
compensate for the reduced platelet count .
Although the current experience is based on a small number
of patients, our results provide supportive evidence of the
efficacy and safety of rFVIIa in patients with thrombocyto
penia. The dose used in our patients (90 mcg kg)1) is based on
the experience in hemophilic patients. It is worth noting that
control the bleeding episodes, regardless of severity, in all
patients in this series and without any safety issues. Based on
with aplastic anemia and bleeding episodes refractory to
Disclosure of Conflict of Interests
Sabah Sallah is an employee of Novo Nordisk A/S.
1 Kurzrock R. Thrombopoietic factors in chronic bone marrow
failure states: the platelet problem revisited. Clin Cancer Res 2005; 11:
2 Roberts HR, Monroe DM, White GC. The use of recombinant factor
VIIa in the treatment of bleeding disorders. Blood 2004; 104: 3858–64.
Correspondence: Sabah Sallah, Novo Nordisk A/S International
Operations, Athinas Avenue and Areos 2a, Athens, 16671, Greece.
Tel.: +30 6948620906; fax: +30 210 9670663; e-mail: asll@
Received 1 November 2006, accepted 17 November 2006
Letters to the Editor 435
? 2006 International Society on Thrombosis and Haemostasis