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.
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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
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The phosphodiesterase 4D gene for early onset ischemic stroke
among normotensive patients
H.-F. LIN,*??1Y.-C. LIAO,§1C.-W. LIOU,– C.-K. LIU*? and S.-H. H. JUO§**??
*Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung; ?Department of Neurology, Kaohsiung Medical University,
Kaohsiung; ?Department of Neurology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung; §Graduate Institute
of Medical Genetics, Kaohsiung Medical University, Kaohsiung; –Department of Neurology, Kaohsiung Medical Center, Chang Gung University
College of Medicine, Kaohsiung; **Department of Clinical Research, Kaohsiung Medical University Hospital, Kaohsiung; and ??Department of
Medical Research, Mackay Memorial Hospital, Taipei, Taiwan, China
To cite this article: Lin HF, Liao YC, Liou CW, Liu CK, Juo SHH. The phosphodiesterase 4D gene for early onset ischemic stroke among
normotensive patients. J Thromb Haemost 2007; 5: 436–8.
The phosphodiesterase 4D (PDE4D) gene was recently
reported as a risk gene for stroke . Although several
studies tried to replicate the results, only one study focused
primarily on early onset stroke , where the study subjects
were Caucasian women and African–American women. Our
aim was to study four commonly investigated single
nucleotide polymorphisms (SNPs) of the PDE4D gene in
young stroke subjects recruited in southern Taiwan. In
addition, we stratified the subjects based on the presence of
hypertension because two studies reported that the PDE4D
genetic effect is more significant in non-hypertensive subjects
[3,4]. An interaction between the gene and smoking was also
explored in the present study.
the Southern Taiwan Young Stroke Study . Our patients
included 57 cases of large-artery atherosclerosis, 18 cases of
cardioembolism, 66 cases of small-vessel occlusion, 16 cases of
other determined etiology, and 33 cases of undetermined
recruited from the general population between 2002 and 2006.
We selected four SNPs that have been implicated to be
associated with stroke: rs12188950 (i.e. SNP45, indicated in the
original article ); rs702553 (SNP56); rs966221 (SNP83); and
rs2910829 (SNP87). Polymorphisms were genotyped using
TaqMan?technology (Applied Biosystems, Foster City, CA,
USA). Each SNP was in Hardy–Weinberg equilibrium
for cases and controls. SNP45 was monomorphic in our
For SNP56, the results indicated that genotypes TT [crude
odds ratio (OR) ¼ 2.0, P ¼ 0.014] and AT (crude OR ¼ 1.4,
P ¼ 0.157) carried a higher risk than the reference AA
genotype (Table 1). It appeared that the T allele had an
additive effect, and thus we used the additive model to estimate
adjusted OR. After adjusting for significant covariates inclu-
ding diabetes, hypertension, and current smoking, the OR was
1.36 (P ¼ 0.052). The final multivariate regression model
suggested that smoking, diabetes and hypertension were the
major risk factors for early onset stroke. Further analysis
according to the hypertensive status found that the genetic
Correspondence: Suh-Hang H. Juo, Kaohsiung Medical University,
100 TzYou First Road, Kaohsiung City 807, Taiwan, China.
Tel.: 886 7 312 1101 ext. 6470; fax: 886 7 321 3931; e-mail:
1These authors contributed equally to this work.
Received 16 November 2006, accepted 17 November 2006
436 Letters to the Editor
? 2006 International Society on Thrombosis and Haemostasis