CASE REPORT

Effectiveness of recombinant activated factor VII in haemorragic cancer-

related disseminated intravascular coagulation: a case report

Matteo Giorgi Pierfranceschi1, Davide Imberti4, Sergio Orlando1, Daniele Vallisa2, Emanuele
Michieletti3
1
Thrombosis and Haemostasis Unit; 2Haematology Department; 3Radiology Department, Piacenza Hospital,
Piacenza; 4Internal Medicine, University Hospital of Ferrara, Ferrara, Italy

Introduction
Bleeding in disseminated intravascular coagulation
(DIC) associated with advanced or metastatic tumours
is often difficult to control by conventional therapies,
such as transfusion of red blood cells, fresh-frozen
plasma, cryoprecipitate, and platelet concentrates1.
Furthermore, this support and replacement therapy is
associated with an increased risk of morbidity and
mortality2.
We present the case of a woman, without a known
history of cancer, who presented with pyramidal
syndrome of sudden onset due to an intracranial bleed.
She had DIC and was successfully treated with
recombinant activated factor VII (rFVIIa).

Case Report
A 76-year old woman was admitted to our
Department because of a sudden headache, blurred
speech and right hemiparesis. On physical examination,
she was slightly confused and her Glasgow Coma Scale
score was 12. Computed tomography (CT) of the brain
revealed a subdural haematoma with a diameter of 14
mm, cerebral oedema causing a mild mass effect with
right midline shift and a tentorial cerebellar
haemorrhage (Figure 1).
Laboratory findings on admission indicated the
presence of acute DIC: fibrinogen 98 mg/dL (n.v. 150-
400 mg/dL), prothrombin time 19 sec, activated
partial prothrombin time 42.3 sec, D-dimer 48,055
ng/mL (n.v. 0-243 ng/mL), platelet count 48x109/L,
and antithrombin 58%.
Suspecting an acute myeloid leukaemia, bone
marrow aspiration and biopsy were performed and
showed metastases of an adenocarcinoma of uncertain
origin.
Figure 1 - CT scan of the brain at the time of the patient's
admission to hospital.
Four units of fresh-frozen plasma, six units of
platelets, four units of packed red blood cells and an
intravenous bolus of 10 mg vitamin K were
administered, without correction of the haemostatic
parameters.
Approximately 6 hours after admission to hospital
the patient's neurological status worsened
considerably (Glasgow Coma Scale score 3) and
another CT scan demonstrated substantial expansion
of the intracranial haematoma with a left hemispheric
subdural haematoma of 18 mm in diameter, a midline
shift of 17 mm, with evidence of uncal trans-tentorial
herniation and a posterior parafalcine haematoma
(Figure 2).

Blood Transfus 2011;9:336-8 DOI 10.2450/2010.0053-10

© SIMTI Servizi Srl
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Factor VII in haemorrhagic disseminated coagulation
Figure 2 - CT scan of the brain 6 hours after admission to
hospital.
The patient's critical condition with a life-
threatening, expanding intracranial mass and the long
distance between our hospital and the nearest
Neurosurgery Unit led us to use rFVIIa therapy; a
single dose of 90 µ g/kg was administered to limit the
patient's bleeding and to bridge the time to a
neurosurgical intervention. The patient arrived alive
at the Neurosurgery Unit. The haematoma was
evacuated successfully and the bleeding stopped
definitively; no thromboembolic complications were
observed following rVIIa administration. Seven days
later the patient was discharged from the Neurosurgery
Unit and received chemotherapy for the newly
Figure 3 - CT scan of the brain 10 days after surgery.
Blood Transfus 2011;9:336-8 DOI 10.2450/2010.0053-10
diagnosed, disseminated adenocarcinoma of unknown
origin. Her neurological symptoms resolved completely
and a CT scan of the brain performed 10 days later
showed complete resolution of the haemorrhagic mass
and no recurrent bleeding (Figure 3). The patient is
still alive after 9 months of follow-up.
Discussion
rFVIIa is a potent, synthetic haemostatic agent; its
mechanism of action is dependent on forming a
complex with tissue factor and generating sufficient
thrombin at the site of the injured vessel wall. The
haemostatic effect of rFVIIa is related to two different
mechanisms of action: (i) binding of rFVIIa to tissue
factor starts the coagulation pathway by activating
factor X and factor IX3; (ii) rFVIIa binds to the surface
of activated platelets, causing activation of factor X
and generation of thrombin4.
This drug has been effectively used in different
bleeding disorders: patients with haemophilia and
inhibitors5,6, Glanzmann's thromboasthenia7, post-
surgical and post-partum bleeding and in critically
injured patients8. Many cases and case-series of
treatment of bleeding episodes in patients with
advanced underlying malignancy have also been
reported1,9.
DIC is characterised by an uncontrolled activation
of coagulation and fibrinolytic pathways with an
excessive release of thrombin and fibrin, resulting in
consumption of coagulation factors and platelets and
diffuse deposition of fibrin in the vasculature of
organs. Bleeding, blood clotting and organ failure are
the clinical consequences of this process10. Because
337

DIC is a secondary phenomenon, no specific therapy
is applicable to all cases.
The usual therapeutic approach in patients with
cancer and DIC is based on two principles:
replacement of deficient blood components and
treatment of the underlying cancer. In 2004 Sallah et
al. reported a series of 18 patients with advanced
cancer and bleeding disorders related to DIC who were
successfully (15/18) treated with serial doses of rFVIIa
(90 µ g/kg) in addition to replacement therapy and, in
three cases, chemotherapy1. These authors concluded
that concomitant occurrence of DIC is not an absolute
contraindication to rFVIIa administration. In our case
a single dose of rFVIIa was able to avoid a potentially
fatal evolution of an intracranial haemorrhage and to
allow a life-saving surgical procedure.
In conclusion, our case suggests that the use of
rFVIIa can be effective and safe in cancer patients
with life-threatening bleeding related to DIC. Thus,
rFVIIa is a possible therapeutic option for
haemorrhagic DIC in cancer patients in whom
conventional management fails.
References
1) Sallah S, Hussain A, Nguyen NP. Recombinant
activated factor VII in patients with cancer and
hemorrhagic disseminated intravascular coagulation.
Blood Coagul Fibrinolysis 2004; 15: 577-82.
2) Malone DL, Dunne J, Tracy JK, et al. Blood
transfusion, independent of shock severity, is
associated with worse outcome in trauma. J Trauma
2003; 54:898-907.
3) Butenas S, Brummel KE, Branda RF, et al.
Mechanisms of factor VIIa-dependent coagulation in
hemophilia blood. Blood 2002; 99: 923-30.
338
Giorgi Pierfranceschi M et al.
4) Hoffman M, Monroe DM, Roberts HR. Platelet-
dependent action of high dose factor VIIa. Blood 2002;
100: 364-6.
5) Shapiro AD, Gilchrist GS, Hoots WK et al.
Prospective randomized trial of two doses of rFVIIa
(NovoSeven) in haemophilia patients with inhibitors
undergoing surgery. Thromb Haemost 1998;
70: 773-8.
6) Franchini M, Manzato F, Salvato GL, et al.
Prophylaxis in congenital hemophilia with inhibitors:
the role of recombinant activated factor VII. Semin
Thromb Hemost 2009;35: 814-9.
7) Poon MC, Demers C, Jobin F, Wu JW. Recombinant
factor VIIa is effective for bleeding and surgery in
patients with Glanzmann thromboasthenia. Blood
1999; 94: 3951-3.
8) Eikelboom JW, Bird R, Blythe D, et al. Recombinant
activated factor VII for the treatment of life-
threatening haemorrage. Blood Coagul Fibrinolysis
2003; 14:713-7.
9) Hatzipantelis ES, Gombakis N, Vasiliki S, et al.
Successful outcome of DIC and life-threatening
bleeding in a toddler with neuroblastoma treated with
recombinant activated factor VII. Intern Emerg Med
2008; 3: 171-3.
10) Franchini M, Lippi G, Manzato F. Recent acquisitions
in the pathophysiology, diagnosis and treatment of
disseminated intravascular coagulation. Thromb J
2006; 4: 4.
Received: 8 June 2010 - Revision accepted: 20 September 2010
Correspondence: Matteo Giorgi Pierfranceschi
Thrombosis and Haemostasis Unit
Emergency Department
Piacenza Hospital
29100 Piacenza, Italy
e-mail: m.giorgi@ausl.pc.it
Blood Transfus 2011;9:336-8 DOI 10.2450/2010.0053-10