Review

Clinical and Applied

Thrombosis/Hemostasis
A Snapshot of Coagulopathy 1-7
ª The Author(s) 2016

After Cardiopulmonary Bypass Reprints and permission:

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DOI: 10.1177/1076029616651146
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Judith Höfer, MD1, Dietmar Fries, MD2,

Cristina Solomon, MD, MBA3,4,5,
Corinna Velik-Salchner, MD1, and Julia Ausserer, MD1

Abstract
Cardiac surgery involving cardiopulmonary bypass (CPB) is often associated with important blood loss, allogeneic blood product
usage, morbidity, and mortality. Coagulopathy during CPB is complex, and the current lack of uniformity for triggers and
hemostatic agents has led to a wide variability in bleeding treatment. The aim of this review is to provide a simplified picture of the
data available on patients’ coagulation status at the end of CPB in order to provide relevant information for the development of
tailored transfusion algorithms. A nonsystematic literature review was carried out to identify changes in coagulation parameters
during CPB. Both prothrombin time and activated partial thromboplastin time increased during CPB, by a median of 33.3% and
17.9%, respectively. However, there was marked variability across the published studies, indicating these tests may be unreliable
for guiding hemostatic therapy. Some thrombin generation (TG) parameters were affected, as indicated by a median increase in
TG lag time of 55.0%, a decrease in TG peak of 17.5%, and only a slight decrease in endogenous thrombin potential of 7%. The
most affected parameters were fibrinogen levels and platelet count/function. Both plasma fibrinogen concentration and FIBTEM
maximum clot firmness decreased during CPB (median change of 36.4% and 33.3%, respectively) as did platelet count (44.5%) and
platelet component (34.2%). This review provides initial information regarding changes in coagulation parameters during CPB but
highlights the variability in the reported results. Further studies are warranted to guide physicians on the parameters most
appropriate to guide hemostatic therapy.

Keywords
bleeding, blood coagulation factors, cardiology, hemostasis, vascular and endovascular surgery

Introduction employed in addition to standard laboratory tests. Conventional

An epidemiological survey of transfusion in the United States,
England, Australia, and Denmark showed that cardiovascular
surgery utilizes a high percentage of all units of red blood cells
(RBCs), platelets, and plasma.1 Surgery involving cardiopul-
monary bypass (CPB) is well known to be associated with
increased blood loss, allogeneic blood products usage, morbid-
ity, and mortality.2 Activation of the hemostatic system during
surgery can lead to important blood loss, and during CPB, addi-
tional factors such as hemodilution, anticoagulation, or contact
activation with the extracorporeal circulation system can
further contribute to the disruption of normal hemostasis.3-7
During CPB, close monitoring of the patient’s coagulation
status is crucial and traditionally done using standard labora-
tory parameters, including prothrombin time (PT), activated
partial thromboplastin time (aPTT), international normalized
ratio (INR), activated clotted time (ACT), fibrinogen concen-
tration, and platelet count. Although these tests are widely and
routinely used, they involve long turnaround times, a critical
limitation in settings where the patient’s coagulation status can
change very quickly. Viscoelastic methods are increasingly
viscoelastic parameters recorded with TEG (Haemoscope Inc,
Niles, Illinois) or ROTEM (Tem International GmbH, Munich,
Germany) devices during CPB include ROTEM clotting time
(CT), ROTEM maximum clot firmness (MCF), TEG reaction
time (R), and TEG maximum amplitude (MA). Viscoelastic
tests can be easily run at the point of care, thereby decreasing
1
Department of Anesthesiology and Critical Care Medicine, Medical University
Innsbruck, Innsbruck, Austria
2
Department of Surgical and General Critical Care Medicine, Medical Uni-
3
versity Innsbruck, Innsbruck, Austria
Department of Anesthesiology, Perioperative Care and General Intensive
Care, Paracelsus Medical University, Salzburg University Hospital, Salzburg,
Austria
4
Ludwig Boltzmann Institute for Experimental and Clinical Traumatology and
AUVA Research Centre, Vienna, Austria
5
CSL Behring, Marburg, Germany
Corresponding Author:
Dietmar Fries, Department of Surgical and General Critical Care Medicine,
Medical University Innsbruck, Innsbruck 6020, Austria.
Email: dietmar.fries@tirol-kliniken.at

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2 Clinical and Applied Thrombosis/Hemostasis
Table 1. Standard Laboratory Parameters.
Baselinea, Range
PT, n ¼ 16, seconds 11.0, 14.6
aPTT, n ¼ 23, seconds 26.3, 35.0
INR, n ¼ 5 0.8, 1.1
ACT, n ¼ 5, seconds 110.2, 153.0
Fibrinogen, n ¼ 25, g/L 1.8, 4.0
Platelets, n ¼ 23, 103/mL 187.0, 276.0
Abbreviations: ACT, activated clotting time; aPTT, activated partial thromboplastin time; CPB, cardiopulmonary bypass; INR, international normalized ratio; PT,
prothrombin time.
a
Mean or median as provided in the original publications.
the time required to obtain informative data on patients’ coa-
gulation status. Moreover, multiple tests can be run simultane-
ously on a single viscoelastic device, allowing for the
assessment of various aspects of hemostasis and a more precise
diagnosis of the underlying cause of coagulopathy.
The major causes of bleeding, complexity of coagulopathy,
and available hemostatic therapies in cardiac surgery involving
CPB have been extensively described.3-7 However, it is not
clear which hemostatic or coagulation parameters are affected
the most and consequently whether the current triggers for
hemostatic therapy in this setting are appropriate. Therefore,
a large variation in practice across institutes exists with regard
to blood product usage in cardiac surgery.8,9 Furthermore, a
study involving patients undergoing primary elective coronary
artery bypass graft demonstrated that 27% of transfusions were
deemed unnecessary and 15%, 32%, and 47% of RBCs,
plasma, and platelets, respectively, were inappropriate.10
We undertook a nonsystematic search of publications
describing changes in hemostatic and coagulation parameters
during cardiovascular surgery involving CPB in adults, with
the aim of depicting common and less common reported para-
meters usually considered as triggers in transfusion algorithms.
Literature Search and Data Collection
A nonsystematic search for publications describing both com-
mon and less common coagulation parameters during CPB was
undertaken using PubMed. We retrieved data from original
research articles providing both values at baseline and post-
CPB (ranging from after protamine infusion up to intensive
care unit admission). Studies were discarded if they did not
provide numerical data.
A total of 25 publications were retrieved, covering studies
involving cardiac surgery with CPB such as coronary artery
bypass grafting, valve surgery/replacement, or other complex
aortic cardiac procedures. The percentage change in hemostatic
and coagulation parameters after CPB compared to baseline
was calculated for each study using the mean or median values
provided in the retrieved publications (Supplementary Tables
1-5). Parameters of interest were as follows:
– PT, aPTT, INR, ACT, and fibrinogen concentration.
– ROTEM EXTEM CT, MCF; ROTEM FIBTEM, MCF;
and kaolin-activated TEG R, MA.
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End of CPBa, Range Median Change (Range), %
11.7, 21.3 33.0 (6.3, 49.0)
31.0, 53.0 17.9 (5.7, 55.9)
1.2, 1.8 33.3 (27.9, 125.0)
118.4, 158.0 3.3 (14.6, 7.4)
1.2, 3.2 36.4 (54.5, 6.2)
82.0, 192.3 44.5 (58.2, 25.8)
– Platelet count, platelet component (ROTEM EXTEM
maximum clot elasticity [MCE]–ROTEM FIBTEM
MCE), Multiplate (Roche Diagnostics Ltd, Rotkreuz,
Switzerland) adenosine diphosphate (ADP), COL, and
TRAP tests data.
– Factor (F) II, FV, FVII, FVIII, FIX, FX, FXI, FXIII
activity; von Willebrand factor concentration (vWF);
vWF antigen activity (vWF: Ag); vWF collagen-binding
activity (vWF: CB); vWF ristocetin cofactor activity.
– Thrombin generation (TG) test lag time, peak, and endo-
genous thrombin potential (ETP); antithrombin activity
(AT); thrombin–antithrombin III complex concentration
(TAT); prothrombin fragment 1 þ 2 (F 1 þ 2) concen-
tration; D -dimers concentration, plasmin-alpha-2-
antiplasmin complexes (PAP) concentration.
Standard Laboratory Parameters
Described mean and median values at baseline and after CPB,
and calculated percentage changes in standard laboratory para-
meters, are presented in Table 1.
Prothrombin time, INR, and aPTT. Prothrombin time and INR
(a normalized parameter derived from the PT) allow for the
detection of defects within the extrinsic and common coagula-
tion pathways; aPTT, on the other hand, provides information
on the intrinsic and common coagulation pathways. These
tests are run on citrated plasma samples and are therefore not
affected by platelet numbers. Both PT and aPTT increase
during CPB by 33.3% and 17.9%, respectively. The INR was
increased by 33.3% during CPB. However, there was marked
variability between studies with increases ranging from 27.9%
to 125.0% after CPB compared to the baseline.
Activated clotted time. The ACT is commonly performed during
CPB, as it allows the anticoagulant effect of heparin to be
monitored. In addition, the extent of heparin neutralization
by protamine at the end of the procedure can be assessed. This
test is run on fresh whole blood samples and is known to be less
sensitive than the aPTT.11 Activated clotted time is only mod-
erately affected during CPB, with an average increase of 3.3%.
Reported values varied across studies, ranging from a 14.6%
decrease to a 7.4% increase after CPB compared to baseline.
Höfer et al 3

Table 2. Viscoelastic Parameters.

Baselinea, Range End of CPBa, Range Median Change (Range), %

EXTEM CT, n ¼ 12, seconds 49.0, 71.0 58.0, 92.0 31.9 (11.5, 48.1)
EXTEM MCF, n ¼ 10, mm 59.5, 64.0 48.6, 57.0 12.7 (18.3, 10.9)
TEG R, n ¼ 3, minutes 5.9, 7.3 8.3, 9.3 34.3 (13.7, 57.6)
TEG MA, n ¼ 4, mm 32.0, 70.0 17.0, 60.0 23.8 (46.9, 7.2)
FIBTEM MCF, n ¼ 13, mm 14.0, 19.7 8.7, 17.0 33.3 (47.1, 5.6)
Platelet component, (MCEExt-MCEFib), n ¼ 4, mm 132.0, 159.0 87.0, 102.0 34.2 (35.8, 27.3)
Abbreviations: CPB, cardiopulmonary bypass; CT, clotting time; MA, maximum amplitude; MCF, maximum clot firmness; R, reaction time.
a
Mean or median as provided in the original publications.

Fibrinogen Concentration Table 3. Platelet Function Parameters.

Plasma fibrinogen levels can be assessed by various methods, Baselinea, End of CPBa, Median Change
the most routinely used being the Clauss method run on Range Range (Range), %
citrated platelet-poor plasma samples.12 Fibrinogen concen-
ADP test, 51.0, 78.0 12.0, 43.7 70.6 (78.2, 39.4)
tration after CPB was consistently decreased by an average
n ¼ 5, U
of 36.4%. However, there were marked differences between COL test, 61.0, 69.0 17.0, 37.6 65.1 (73.0, 41.3)
studies with decreases ranging from 6.2% to 54.5%. n ¼ 5, U
TRAP test, 89.0, 111.0 35.0, 86.8 53.8 (60.7, 21.8)
n ¼ 5, U
Platelet Count
Abbreviations: ADP, adenosine diphosphate; CPB, cardiopulmonary bypass.
Platelets play various roles within the coagulation process from a
Mean or median as provided in the original publications.
the activation of coagulation factors to the physical mainte-
nance of the clot.13 Therefore, patients with a low platelet count
during CPB as shown by an average decrease in FIBTEM MCF
are considered to be at risk of bleeding. The platelet count is
by 33.3% (ranging from 47.1% to 5.6%).
traditionally monitored during CPB and was found to be
strongly affected as shown by an average reduction of 44.5%
Platelet component. The platelet component provides an indi-
(range: 58.2% to 25.9%).
cation of the contribution of platelets to the clot and is calcu-
lated by subtracting FIBTEM MCF from EXTEM MCF. The
Viscoelastic Parameters overall contribution of platelets to the clot is reduced after
Described mean and median values at baseline and after CPB CPB compared to baseline by an average of 34.2% (ranging
and calculated percentage changes in viscoelastic parameters from 35.8% to 27.3%).
are presented in Table 2.
Platelet Function
Overall clot parameters. The ROTEM EXTEM test and the stan-
dard TEG test are both run on whole blood samples in the Described mean and median values at baseline and after CPB
presence of activators of the coagulation cascade (tissue factor and calculated percentage changes in platelet function para-
in the EXTEM test and kaolin in the standard TEG test). These meters are presented in Table 3. Platelet function tests, which
tests allow close monitoring of the kinetics of clot formation, can identify potential platelet disorders, are often run in addi-
thereby providing an indication for the time to initiation of tion to the platelet count. Multiplate analyses allow the quanti-
coagulation (CT and R, respectively) and the time to maximum fication of platelet activation triggered by different pathways:
firmness (or strength) of the clot (MCF and MA, respectively). the ADP receptor-dependent pathway in the ADP test; the
Prolonged CTs after CPB are observed with viscoelastic tests collagen-dependent pathway in the COL test; and the TRAP-
as shown by increased EXTEM CT and TEG R (31.9% and 6-dependent pathway in the TRAP test. Platelet function
34.3%, respectively). The strength of the clot is also affected declines during CPB, as shown by reductions in Multiplate
during CPB as shown by reductions in both EXTEM MCF and parameter by an average of 70.0%, 65.1%, and 53.8% in the
TEG MA (12.7% and 23.8%, respectively). ADP test, COL test, and TRAP test, respectively.

Contribution of fibrin/fibrinogen to the clot. In addition to the

EXTEM test, the FIBTEM test is often run simultaneously
on the ROTEM device. In addition to tissue factor, the FIB-
TEM test contains the platelet inhibitor cytochalasin D; there-
fore, FIBTEM parameters provide information on the quality of
the fibrin-based clot. The fibrin-based clot firmness is reduced
Coagulation Factors Activity
Described mean and median values at baseline and after CPB
and calculated percentage changes in the activity of coagula-
tion factors are presented in Table 4. Most coagulation factors
investigated show an overall decrease in activity during CPB.

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4 Clinical and Applied Thrombosis/Hemostasis

Table 4. Coagulation Factor Activity.

Baselinea, Range End of CPBa, Range Median Change (Range), %

FII, n ¼ 8, % activity 81.0, 108.0 43.0, 78.0 47.0 (51.1, 12.3)

FV, n ¼ 8, % activity 88.0, 140.0 50.0, 83.0 39.9 (44.4, 30.7)
FVII, n ¼ 4, % activity 82.0, 121.0 55.0, 98.0 23.5 (41.5, 16.0)
FVIII, n ¼ 9, % activity 89.0, 194.0 88.0, 175.0 9.8 (29.9, 34.8)
FIX, n ¼ 4, % activity 77.0, 149.0 87.0, 143.0 8.4 (22.3, 13.0)
FX, n ¼ 6, % activity 81.0, 104.0 41.0, 72.0 40.3 (53.4, 14.5)
FXI, n ¼ 3, % activity 90.0, 117.0 55.0, 91.0 35.6 (40.2, 22.2)
FXIII, n ¼ 8, % activity 85.0, 135.0 60.0, 97.0 33.6 (40.2, 28.1)
vWF, n ¼ 1, mg/mL 1.6 1.8 9.3
vWF: Ag, n ¼ 3, % activity 108.0, 194.0 122.0, 144.0 8.3 (33.0, 13.0)
vWF: CB, n ¼ 3, % activity 128.0, 236.0 133.0, 153.0 3.1 (35.2, 18.8)
vWF: RiCo, n ¼ 1, % activity 113.0 133.0 17.7
Abbreviations: Ag, antigen; CB, collagen-binding; CPB, cardiopulmonary bypass; FII, factor II; RiCo, ristocetin co-factor; vWF, von Willebrand factor.
a
Mean or median as provided in the original publications.

Table 5. Thrombin Generation and Clot Lysis Parameters.

Baselinea, Range End of CPBa, Range Median Change (range), %

TG lag time, n ¼ 2, seconds 1.7, 3.8 2.9, 5.3 55.0 (39.5, 70.6)
TG peak, n ¼ 2, nmol/L 145.0, 327.0 135.0, 235.0 17.5 (28.1, 6.9)
ETP, n ¼ 2, nmol/min 1059.0, 1485.0 981.0, 1382.0 7.2 (7.4, 6.9)
AT, n ¼ 12, % activity 74.0, 105.0 48.0, 78.0 34.3 (41.1, 20.2)
TAT complex, n ¼ 1, mg/mL 5.3 95.0 1692.0
F 1 þ 2, n ¼ 4, pmol/L 160.0, 992.0 575.6, 1731.0 173.5 (74.5, 476.3)
D-dimers, n ¼ 5, mg/L 0.1, 0.7 0.2, 4.4 58.6 (6.7, 633.3)
PAP, n ¼ 3, ng/mL 135.0, 938.0 267.0, 1746.0 276.3 (71.5, 1193.3)
Abbreviations: AT, antithrombin activity; CPB, cardiopulmonary bypass; ETP, endogenous thrombin potential; F1þ2, prothrombin fragment 1 þ 2; PAP, plasmin-
alpha-2 antiplasmin; TAT, thrombin-antithrombin III complex; TG, thrombin generation.
a
Mean or median as provided in the original publications.

Factor II, FV, FVII, FX, FXI, and FXIII all strongly decrease
by an average of 47.0%, 39.9%, 23.5%, 40.3%, 35.6%, and
33.6%, respectively. Changes in the activity of FVIII, FIX, and
vWF are more varied. Factor VIII activity was found to
decrease by an average of 9.8% during CPB; however, changes
varied across studies as shown by a wide range of values (from
a decrease of 29.9% to an increase of 34.8%). Similarly, FIX
activity decreased by an average of 8.4%, ranging from a
decrease of 29.9% to an increase of 13.0%. Finally, calcula-
tions of percentage changes in vWF: Ag and vWF: CB activ-
ities also varied, with increases of up to 13.0% and 18.8%,
respectively, and decreases of 33.0% and 35.2%, respectively.
Thrombin Generation
Described values at baseline and after CPB, and calculated
percentage changes in TG parameters, are presented in Table 5.
Thrombin generation can increase as a consequence of
the activation of the hemostatic system during CPB14 and can
be monitored by calibrated automated thrombography. Among
the parameters provided by the TG curve, the lag time indi-
cates the time to beginning of TG, the peak indicates the
maximum concentration of thrombin generated, and the area
under the curve indicates the ETP. Thrombin generation lag
time increased by an average of 55.0% (range: 39.5%, 70.6%)
after CPB. Furthermore, TG peak showed an average
decrease of 17.5% (range: 28.1%, 6.9%), while TG ETP
is minimally affected with a calculated decrease of 7.2%
(range: 7.4%, 6.9%).
Fibrinolysis
Described values at baseline and after CPB, and calculated
percentage changes in clot lysis parameters, are presented in
Table 5. Similar to TG, fibrinolysis can be strongly induced as
a consequence of the activation of the coagulation cascade
during CPB.14 Fibrinolysis can be assessed by quantifying var-
ious markers, including AT activity, TAT complex levels, F 1
þ 2 levels, and D-dimer levels. Compared to baseline, AT
activity decreased by an average of 34.3% (range: 41.1%,
20.2%) after CPB, whereas F 1 þ 2 levels increased by an
average of 173.5% (range: 74.5%, 476.3%). Changes in
D-dimers and PAP concentrations were found to increase by
an average of 58.6% and 276.3%, respectively. These changes
varied markedly between studies with D-dimer concentrations
ranging from a decrease of 6.7% to an increase of 633.3% and
PAP concentrations ranging from a decrease of 71.5% to an
increase of 1193.0%.

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Höfer et al
Figure 1. Prothrombin time, fibrinogen concentration, and platelet
count percentage change after cardiopulmonary bypass (CPB). Gra-
phical representation of percentage change in prothrombin time (PT),
fibrinogen concentration, and platelet count calculated from published
means/medians values at baseline and after CPB.
Discussion
Cardiac surgery has been shown to utilize a significant percent-
age of allogeneic blood product units transfused,1 and CPB is
known to be associated with increased blood loss, allogeneic
blood products usage, morbidity, and mortality.2 Acquired coa-
gulopathy can develop secondary to blood loss, consumption and
loss of coagulation factors, and hemodilution, and this coagulo-
pathy can lead to progression from initial bleeding to severe
hemorrhage. Early targeted hemostatic therapy may prevent the
development of complex coagulopathies and the progression to
life-threatening hemorrhage. An understanding of the changes in
coagulation status related to CPB would therefore be of use in the
development of recommendations to guide such early treatment.
We initially considered the standard laboratory parameters
due to their widespread availability and use. Prothrombin time
and aPTT are generally described as useful to detect coagula-
tion deficiencies14,15 and are standardly used as hemostatic
triggers to guide transfusion. However, they have been shown
to be very poor predictors of bleeding.16 Although both PT and
aPTT increased during CPB, there was a marked variability
across the studies retrieved (Table 1 and Figure 1). The use
of prolonged PT and aPTT values as triggers to guide hemo-
static therapy, in the absence of a strong relationship with
bleeding tendency, might therefore lead to unnecessary trans-
fusion of allogeneic blood products, exposing patients to an
increased risk of adverse events (ie, transfusion-related acute
lung injury or transfusion-associated circulatory overload),
which may be detrimental to their health.17,18 In addition, PT
and aPTT are often used as triggers for hemostatic therapy with
allogeneic blood products, such as plasma. It should be noted
that there is currently a debate as to the usefulness of plasma,
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5
Figure 2. Endogenous thrombin potential, fibrin-based maximum clot
firmness, and platelet component percentage change after cardiopul-
monary bypass (CPB). Graphical representation of percentage change
in endogenous thrombin potential (ETP), fibrin-based maximum clot
firmness (FIBTEM MCF), and platelet component calculated from
published means/medians values at baseline and after CPB.
with little evidence to support its efficacy for the treatment of
coagulopathic bleeding.16
Viscoelastic tests are increasingly used, particularly at the
point of care, and can reduce the time taken to obtain results.
As part of our review, we considered the changes during CPB
to standard laboratory parameters in conjunction with viscoe-
lastic parameters. We observed an important decrease in
plasma fibrinogen levels and a similar reduction in FIBTEM
MCF (Figures 1 and 2). Interestingly, the extent to which both
fibrinogen concentration and FIBTEM MCF decreased is
comparable with the observed increase in PT; however, unlike
PT, low fibrinogen concentration has been suggested to be
predictive of increased bleeding in cardiac surgery.19-22 Fibri-
nogen is the first coagulation factor to reach critical levels
during massive bleeding,23 and point-of-care–guided hemo-
static therapy, such as fibrinogen concentrate, to replenish
fibrinogen levels is recommended in complex cardiovascular
surgery.24 Indeed, while primary hemostasis is also affected,
various studies showed that fibrinogen has the strongest
decline during CPB, and replacement therapy with fibrinogen
concentrate was reported to be effective and well tolerated.25
Additionally, high plasma fibrinogen concentration may com-
pensate for thrombocytopenia or thrombocytopathia. 26
Furthermore, the recent European Society for Anesthesiology
guidelines for the management of severe perioperative bleed-
ing propose various recommendations in the cardiovascular
setting, including, for example: ‘‘We recommend treatment
with fibrinogen concentrate if significant bleeding is
accompanied by at least suspected low fibrinogen concen-
trations or function. We recommend that a plasma fibrinogen
6 Clinical and Applied Thrombosis/Hemostasis
concentration <1.5 to 2.0 g l1 or ROTEM/TEG signs of
functional fibrinogen deficit should be triggers for fibrinogen
substitution.’’24(p275)
Our observations also show a strong decrease in the platelet
count and platelet component after CPB (Figures 1 and 2).
Platelet transfusion is usually based on the platelet count; cur-
rent guidelines recommend platelet administration in bleeding
patients with characterized thrombocytopenia or with sus-
pected platelet dysfunction.27 Only a few studies have investi-
gated the use of the platelet component as a trigger for platelet
administration. However, it should be noted that the platelet
component provides an indication of the contribution of
platelets to the clot strength and, therefore, depends highly
on both platelet count and function. Furthermore, we found a
low variability in the change of platelet component during CPB
between studies, which suggests this parameter might poten-
tially be considered a more reliable trigger for platelet transfu-
sion. In addition to the decrease in platelet count, platelet
function is found to be greatly reduced. However, there is
currently little evidence on the utility of platelet function tests
to guide platelet administration.
Coagulation factors were not affected equally, with some
showing consistent decreases in activity (FII, FV, FVII, FX,
FXI, and FXIII) and others a varied response (FVIII and FIX).
The significance of these changes is not currently clear, as
blood loss after CPB is not correlated with changes in all
coagulation factors, and differences in correlation were found
between studies. For example, a correlation between blood
loss and decreased FII or FVII has been previously
described.28,29
We also investigated reported changes to TG. Overall, while
the time-related parameters such as TG lag time tended to be
considerably prolonged, the parameters assessing the amount
of thrombin generated, such as ETP, remained almost
unchanged. In this context, immediately following cardiac sur-
gery fibrin formation was shown to be significantly more
impaired than both ETP and the platelet component of the
whole blood clot.30
A variety of mechanisms underlie the development of
coagulopathy among patients undergoing CPB. At the
outset, high-dose heparin is administered to prevent extracor-
poreal coagulation, and the CPB priming solution causes
hemodilution.4,7 Despite administration of heparin, use of the
CPB circuit causes a degree of contact activation of coagula-
tion; platelets may become activated, and inflammatory path-
ways are triggered.5,6 At the surgical site, blood is exposed to
air and tissue factor, further activating coagulation. These
processes result in consumption of coagulation factors and
platelets as well as increased fibrinolysis.5,7 Thus, normal
hemostasis may not be restored upon reversal of heparin at
the end of CPB.
The limitations of this review are related to the amount of
data retrieved, and the variability between reports regarding the
type of change in some of the parameters investigated. This
variability may be due to differences in patient populations or
surgery types between studies. Additionally, there may be
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differences in CPB duration, or information was often not pro-
vided in the studies we retrieved, which may have affected the
results reported. Finally, it is well known that differences in
clinical practice exist among institutions and consequently,
differences in hemostatic therapies used in the various studies
could have also affected the extent to which some of the para-
meters changed during CPB.31
Most of the hemostatic and coagulation parameters we
investigated are affected during CPB, reflecting the overall
destabilization of the clot which can lead to coagulopathic
bleeding if not treated promptly. Coagulopathy during cardiac
surgery involving CPB is complex; bleeding management var-
ies among institutions and is mostly based on a limited number
of triggers, which might not be predictive of bleeding risk (ie,
PT and aPTT). Despite the overall changes throughout the
coagulation system after CPB, not all parameters are affected
to the same extent. Fibrinogen levels (reflected in plasma fibri-
nogen levels and FIBTEM MCF parameters) and platelet
count/function (reflected in platelet count and platelet compo-
nent parameters) are the most affected at the end of CPB. In
contrast, ETP, vWF, and FVIII activities are some of the least
affected parameters (Tables 4 and 5; Figure 2).
Our observations in this review suggest that first-line hemo-
static therapy following CPB should be focused first on cor-
recting impaired fibrinogen levels and/or platelet count/
function before considering supplementation to correct a pos-
sible deficit in TG, vWF, or FVIII. However, further studies,
where larger sets of coagulation and hemostatic parameters are
investigated, are warranted in order to provide physicians with
clearer views on which parameters would be most appropriate
to guide hemostatic therapy during cardiovascular surgery
involving CPB.
Acknowledgments
Editorial assistance with manuscript preparation was provided by
Sandrine Dupré and Claire Crouchley of Meridian HealthComms
Ltd, funded by CSL Behring.
Declaration of Conflicting Interests
The author(s) declared the following potential conflicts of interest
with respect to the research, authorship, and/or publication of this
article. CS was an employee of CSL Behring at the time of writing
and previously received speaker honoraria and research support from
Tem International and CSL Behring and travel support from Haemo-
scope Ltd (former manufacturer of TEG1). CV-F has received
research funding from CSL Behring. DF has received honoraria for
consulting, lecture fees and sponsoring for academic studies from the
following companies: Astra Zeneca, AOP Orphan, Baxter, Bayer, B.
Braun, Biotest, CSL Behring, Cytosorb, Delta Select, Dade Behring,
Edwards, Fresenius, Glaxo, Haemoscope, Hemogem, Lilly, LFB,
Mitsubishi Pharma, NovoNordisk, Octapharma, Pfizer, Tem-
Innovation. JH and JA have no conflict of interests.
Funding
The author(s) received no financial support for the research, author-
ship, and/or publication of this article.
Höfer et al
Supplemental Material
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