Bottio, Tomaso

Buratto, Edward

Gerosa, Gino

Simioni, Paolo

Spiezia, Luca

Tarzia, Vincenzo

Elsevier - Publisher Connector 

LETTERS TO THE EDITORTHE HAZARD OF COMPARING
APPLES AND ORANGES: THE
PROPER INDICATION FOR THE
USE OF RECOMBINANT
ACTIVATED
CLOTTING FACTOR VII IN
CARDIAC SURGERY
To the Editor:
We read with interest the article by
Uber and colleagues1 regarding the
use of recombinant activated clotting
factor VII (rFVIIa) after complex car-
diovascular surgery and would like to
raise the following issues.
First, in our opinion it is inappropri-
ate to compare the pharmacologic
management of bleeding with surgical
reexploration, especially when the
origin of the bleeding is unknown.
Postoperative bleeding is a common
complication after cardiac surgery
and a major cause of reexploration.
Bleeding after cardiac surgery has 2
principle causes: multifactorial coa-
gulopathy and surgical bleeding, each
accounting for about 50% of cases.2
When bleeding arises from a coa-
gulopathy and we can identify a defect
of primary hemostasis (platelets), sec-
ondary hemostasis (clotting factors),
or both, it is appropriate to replace
the deficient circulating factors. In
such cases, rFVIIa may play a role,3
as may other blood products and clot-
ting factors. Conversely, when the
hemorrhage is the result of a surgi-
cal-problem, reintervention to correct
the defect is the necessary course of
action. Thus it is extremely important
to distinguish between surgicalThe Editor welcomes submissions for possible publica-
tion in the Letters to the Editor section that consist
of commentary on an article published in the Journal
or other relevant issues. Authors should:  Include
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Letters commenting on an article published in the
JTCVS will be considered if they are received
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1588 The Journal of Thoracic andbleeding and coagulopathy to choose
the appropriate treatment. In identify-
ing the cause of bleeding after cardiac
surgery, rotational thromboelasto-
metry plays an important, emerging
role. Rotational thromboelastometry
allows point-of-care testing of whole
blood with respect to clot quality and
intrinsic and extrinsic pathways, iden-
tifying both hypercoagulable and
hypocoagulable states. Moreover, ro-
tational thromboelastometry is able
to guide the use of hemostatic agents,
such as rFVIIa.2
In recent years, in our center we
have treated 10 patients with rFVIIa,
all according to a specific diagnostic
and therapeutic algorithm (Figure 1).
All patients presenting with posto-
perative bleeding undergo classic co-
agulation studies, platelet count, and
rotational thromboelastometric profile
to discriminate between surgical
bleeding and coagulopathy. The rota-
tional thromboelastometry tests adop-
ted are INTEM and EXTEM, for
the intrinsic and extrinsic pathways re-
spectively, FIBTEM for the qualitativeFIGURE 1. Management of refractory bleeding di
vated partial thromboplastin time; PT, prothrombin
antithrombin III; ROTEM, rotational thromboelast
thromboelastometric test for extrinsic pathway.
Cardiovascular Surgery c December 20study of fibrinogen status, and HEP-
TEM to monitor heparin effects. Pa-
tients with important bleeding but
essentially normal coagulation pro-
files are treated with surgical reex-
ploration. Conversely, patients with
coagulopathy are treated with fresh-
frozen plasma, platelets, fibrinogen,
and protamine as guided by rotational
thromboelastometric results. When-
ever refractorybleedingpersists despite
this treatment, rotational thromboela-
stometry is reperformed, and if a state
of hypocoagulability persists (pro-
longed clotting time in the EXTEM
test with a cutoff point greater than
180 seconds), a dose of rFVIIa (80–
120 mg/kg) is administered.4,5 Among
our 10 patients, hemostasis was
successfully achieved in 100% of
cases, and there have been no cases of
thromboembolism.
Indeed, rFVIIa can play a role in
the management of bleeding after
cardiac surgery; however, it carries
significant attendant risks of thrombo-
embolic complication.2,4,5 In our
opinion, it should be used with care,agnostic and therapeutic algorithm. aPTT, Acti-
time; INR, international normalized ratio; ATIII,
ometry; CT, clotting time; EXTEM, rotational
11
Letters to the Editorand only for patients presenting with a
coagulopathy as confirmed by rota-
tional thromboelastometric analysis.
Ideally, the lowest dose capable
of correcting the coagulopathy should
be given, avoiding a hypercoagulable
state and thus thromboembolic events.
Adopting this protocol avoids placing
patients with a surgical cause of
bleeding at an unjustified risk of
thromboembolism and reserves rFVIIa
for thosewho truly need it.
In conclusion, rFVIIa represents
a treatment with its own specific indi-
cations, and we should not consider it
as an alternative to reexploration in
cardiac surgery. Indeed, the two are
‘‘horses for courses.’’
Vincenzo Tarzia, MDa
Tomaso Bottio, MD, PhDa
Edward Buratto, MDa
Luca Spiezia, MDb
Paolo Simioni, MDb
Gino Gerosa, MDa
aCardiac Surgery
bSecond Chair of Internal Medicine
Department of Cardiac, Thoracic, and
Vascular Sciences
Padua University Medical School
Padova, ItalyReferences
1. Uber WE, Toole JM, Stroud MR, Haney JS,
Lazarchick J, Crawford FA Jr, et al. Administration
of recombinant activated factor VII in the intensive
care unit after complex cardiovascular surgery:
clinical and economic outcomes. J Thorac Cardio-
vasc Surg. 2011;141:1469-77.
2. Luddington RJ. Thrombelastography/thromboelas-
tometry. Clin Lab Haematol. 2005;27:81-90.
3. Gill R, Herbertson M, Vuylsteke A, Olsen PS, von
Heymann C,MythenM, et al. Safety and efficacy of
recombinant activated factor VII: a randomized
placebo-controlled trial in the setting of bleeding
after cardiac surgery. Circulation. 2009;120:21-7.
4. Romagnoli S, Bevilacqua S, Gelsomino S,
Pradella S, Ghilli L, Rostagno C, et al. Small-
dose recombinant activated factor VII (NovoS-
even) in cardiac surgery. Anesth Analg. 2006;
102:1320-6.
5. Gelsomino S, Lorusso R, Romagnoli S,
Bevilacqua S, De Cicco G, Bille G, et al. Treatment
of refractory bleeding after cardiac operations with
low-dose recombinant activated factor VII (Novo-
Seven): a propensity score analysis. Eur J Cardio-
thorac Surg. 2008;33:64-71.
doi:10.1016/j.jtcvs.2011.08.028The JournalReply to the Editor:
WeappreciateTarzia andcolleagues’
letter regarding our article.1 They take
exception to comparing reexploration
with pharmacologic management us-
ing recombinant activated factor VII
(rFVIIa) in the intensive care unit be-
cause the source of bleeding is not
known. They also elucidate a well–
thought out algorithm for the manage-
ment of postoperative bleeding.
Our initial experience with rFVIIa
was in the operating room, where we
found it to be highly effective at con-
trolling intraoperative bleeding and
to reduce the incidence of packing
and delayed closure for hemostasis.2
We developed criteria for correction
of coagulopathy (including platelet
count, prothrombin time, partial
thromboplastin time, and fibrinogen
levels), acid–base status, temperature,
and ionized calcium levels before the
administration of rFVIIa. We found
that patients who continued to bleed
despite correction of these variables
responded quickly to rFVIIa.
All intensive care unit patients in our
current study had undergone similar
evaluations in the operating room and
were considered not to have surgical
bleeding. Unfortunately, the source of
significant bleeding in the intensive
care unit is always unknown, and this
is the clinical conundrum our study at-
tempted to address. In this study, we
found 1 case of surgical bleeding out
of the 12 patients who received rFVIIa.
This is substantially lower than the
50% quoted by Tarzia and colleagues.
This emphasizes the importance of
having a well–thought out algorithm
for the management of bleeding. Ours
begins by defining significant bleeding
as 3 mL/kg/h for 2 or more consecutive
hours. Correction of the previously
mentioned variables is accomplished
as early as possible. Hemothorax and
pericardial tamponade are considered
indications for reoperation. Finally,
the attending surgeon’s index of suspi-
cion for surgical bleeding is the final
determinant of therapy. As we hadof Thoracic and Cardiovascular Surgerpreviously observed in the operating
room, bleeding intensive care unit pa-
tients with corrected coagulation fac-
tors, temperature, ionized calcium,
and acidosis quickly responded to
rFVIIa.This suggests thatwe are not ca-
pable of measuring a clinically signifi-
cant coagulation deficiency. Perhaps
rotational thromboelastometry will be
able to shed light on these difficult pa-
tients. Rotational thromboelastometry
was only recently approved by the
Food and Drug Administration in 2010
(after our study period), and further-
more only 2 of the 4 reagents described
by Tarzia and colleagues, INTEM and
HEPTEM, have been approved.
We anxiously await new tools for
the diagnosis and treatment of postop-
erative coagulopathic bleeding. It is
important that they be incorporated
into a well-designed and well–thought
out algorithm for the treatment of
postoperative bleeding.
J. Matthew Toole, MD
Walter E. Uber, PharmD
John S. Ikonomidis, MD, PhD
Division of Cardiothoracic Surgery
and Department of Pharmacy Services
Medical University of South Carolina
Charleston, SCReferences
1. Uber WE, Toole JM, Stroud MR, Haney JS,
Lazarchick J, Crawford FA Jr, et al. Administration
of recombinant activated factor VII in the intensive
care unit after complex cardiovascular surgery:
clinical and economic outcomes. J Thorac Cardio-
vasc Surg. 2011;141:1469-77.
2. BowmanLJ,UberWE, StroudMR,ChristiansenLR,
Lazarchick J, CrumbleyAJ III, et al. Use of recombi-
nant activated factor VII concentrate to control post-
operative hemorrhage in complex cardiovascular
surgery. Ann Thorac Surg. 2008;85:1669-77.
doi:10.1016/j.jtcvs.2011.08.027CANNULATION SITES AND
TYPES FOR ANTEGRADE
CEREBRAL PERFUSION
DURING ARCH SURGERY
To the Editor:
We read with great interest the re-
cent published paper by Shi andy c Volume 142, Number 6 1589


The hazard of comparing apples and oranges: The proper indication for the use of recombinant activated clotting factor VII in cardiac surgery 

Tarzia V

Buratto E

Spiezia L

BOTTIO, TOMASO

SIMIONI, PAOLO

GEROSA, GINO

Archivio istituzionale della ricerca - Università di Padova

The hazard of comparing apples and oranges: the proper indication for the use of recombinant activated clotting factor VII in cardiac surgery.

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The hazard of comparing apples and oranges: The proper indication for the use of recombinant activated clotting factor VII in cardiac surgery

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