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\begin{document}

\title{A prospective, controlled study on the utility of rotational
thromboelastometry in surgery for acute type A aortic dissection}



\author[1]{Mårten Larsson}%
\author[1]{Igor Zindovic}%
\author[1]{Johan Sjögren}%
\author[2]{Peter Svensson J}%
\author[3]{Karin Strandberg}%
\author[1]{Shahab Nozohoor}%
\affil[1]{Lund University Skåne University Hospital Department of Clinical Sciences Lund Department of Cardiothoracic Surgery Lund Sweden}%
\affil[2]{Department of Coagulation Disorders Skåne University Hospital Lund University Malmö Sweden}%
\affil[3]{Department of Clinical Chemistry Malmö Sweden}%


\vspace{-1em}



  
  \date{May 27, 2024}


\begingroup
\let\center\flushleft
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\selectlanguage{english}
\begin{abstract}
\textbf{Objective:} To evaluate the hemostatic system with ROTEM in
patients undergoing surgery for acute type aortic dissection (ATAAD)
using elective aortic procedures as controls. \textbf{Design:} This was
a prospective, controlled, observational study. \textbf{Setting:} The
study was performed at a tertiary referral center and university
hospital. \textbf{Participants:} Twenty-three patients with ATAAD were
compared to 20 control patients undergoing elective surgery of the
ascending aorta or the aortic root. \textbf{Results:} ROTEM (INTEM,
EXTEM, HEPTEM and FIBTEM) was tested at 6 points in time before, during
and after surgery for ATAAD or elective aortic surgery. The ATAAD group
had an activated coagulation coming into the surgical theatre. The two
groups showed activation of both major coagulation pathways during
surgery, but the ATAAD group consistently had larger deficiencies.
Reversal of the coagulopathy was successful, although none of the groups
reached elective baseline until postoperative day 1. ROTEM did not
detect low levels of clotting factors at heparin reversal nor low levels
of platelets. \textbf{Conclusions:} This study demonstrated that ATAAD
is associated with a coagulopathic state. Surgery causes additional
damage to the hemostatic system in ATAAD patients as well as in patients
undergoing elective surgery of the ascending aorta or the aortic root.
ROTEM does not adequately catch the full coagulopathy in ATAAD. A
transfusion protocol in ATAAD should be specifically created to target
this complex coagulopathic state and ROTEM does not negate the need for
routine laboratory tests.%
\end{abstract}%



\sloppy


\textbf{A prospective, controlled study on the utility of rotational
thromboelastometry in surgery for acute type A aortic dissection}

M\selectlanguage{ngerman}årten Larsson MD\textsuperscript{1}, Igor Zindovic, MD
PhD\textsuperscript{1}, Johan Sjögren MD PhD\textsuperscript{1}, Peter J
Svensson MD PhD\textsuperscript{2}, Karin Strandberg MD
PhD\textsuperscript{3}, Shahab Nozohoor MD PhD\textsuperscript{1}

\textsuperscript{1}Lund University, Skåne University Hospital,
Department of Clinical Sciences, Lund, Department of Cardiothoracic
Surgery, Lund, Sweden; \textsuperscript{2}Department of Coagulation
Disorders, Skåne University Hospital, Lund University, Malmö,
Sweden;\textsuperscript{3}Department of Clinical Chemistry, Malmö,
Sweden

Corresponding author: Mårten Larsson, MD

Department of Cardiothoracic Surgery

Skåne University Hospital, SE-221 85 Lund, Sweden

Phone: +46 46-171000; E-mail: marten.larsson@med.lu.se

Funding: This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest: None to declare

Data availability: Not possible due to ethics approval

This study was approved by the Ethics Committee for Clinical Research at
Lund University, Sweden (ref. 2015/197)

Patient consent: Before inclusion a consent was gathered from the
patient or the next of kin (oral and/or written)

\textbf{ABSTRACT}

\textbf{Objective:} To evaluate the hemostatic system with ROTEM in
patients undergoing surgery for acute type aortic dissection (ATAAD)
using elective aortic procedures as controls.

\textbf{Design:} This was a prospective, controlled, observational
study.

\textbf{Setting:} The study was performed at a tertiary referral center
and university hospital.

\textbf{Participants:} Twenty-three patients with ATAAD were compared to
20 control patients undergoing elective surgery of the ascending aorta
or the aortic root.

\textbf{Results:}

ROTEM (INTEM, EXTEM, HEPTEM and FIBTEM) was tested at 6 points in time
before, during and after surgery for ATAAD or elective aortic surgery.
The ATAAD group had an activated coagulation coming into the surgical
theatre. The two groups showed activation of both major coagulation
pathways during surgery, but the ATAAD group consistently had larger
deficiencies. Reversal of the coagulopathy was successful, although none
of the groups reached elective baseline until postoperative day 1. ROTEM
did not detect low levels of clotting factors at heparin reversal nor
low levels of platelets.

\textbf{Conclusions:} This study demonstrated that ATAAD is associated
with a coagulopathic state. Surgery causes additional damage to the
hemostatic system in ATAAD patients as well as in patients undergoing
elective surgery of the ascending aorta or the aortic root. ROTEM does
not adequately catch the full coagulopathy in ATAAD. A transfusion
protocol in ATAAD should be specifically created to target this complex
coagulopathic state and ROTEM does not negate the need for routine
laboratory tests.

\textbf{KEY WORDS:} Aorta, Aneurysm, Dissection, Bleeding, Rotational
thromboelastometry, ROTEM

\textbf{INTRODUCTION}

Acute type A aortic dissection (ATAAD) is a lethal condition requiring
emergent aortic surgery. The procedure is challenging and associated
with high rates of peri-operative bleeding and blood product
transfusions. Mortality is high with rates ranging from 16-18\% after
surgery in large registries \textsuperscript{1-3}. A significant cause
of the high mortality and morbidity is peri-operative
bleeding\textsuperscript{4}. The impairment of the coagulation system is
caused by the contact of blood with the non-endothelialized walls of the
false lumen, but other triggers also have been
suggested\textsuperscript{5-7}. Surgery for acute type A aortic
dissection is conducted using a cardiopulmonary bypass circuit and
usually a deep hypothermic state, both of which further increase the
coagulopathy.

Transfusion strategy in major aortic surgery may either be
reactive,~with the administration of blood products in response to the
development of a clinical coagulopathy, or pre-emptive,~based on the
administration of blood products to prevent a clinically detectable
coagulopathy. Both approaches lead to a significant use of blood
products. A recent review of bleeding management in vascular surgery
concluded that hemostasis should be monitored, and goal
directed\textsuperscript{8}.~This calls for alternative bleeding
management, and the adoption of a transfusion algorithm guided by
rotational thromboelastometry (ROTEM) could be an option.

At many centers, management of perioperative bleeding is carried out
according to rotational ROTEM-guided protocol for transfusion of blood
products and procoagulants, reducing the need for transfusions and
decreasing the risk of bleeding after cardiac
surgery\textsuperscript{9-12}.

A prospective study by Ogawa et al. \textsuperscript{13} compared values
obtained using standard laboratory coagulation tests (PT(INR), APTT and
fibrinogen) with ROTEM CT and MCF values for the parameters INTEM,
EXTEM, HEPTEM, and FIBTEM in adult patients undergoing cardiac surgery
and demonstrated that some ROTEM measurements could act as surrogates
for standard coagulation tests. However, although reference ROTEM values
in patients undergoing elective and non-complex cardiac surgery have
been described \textsuperscript{14-16}, similar data are lacking in the
acute and complex setting. Furthermore, few studies have investigated
the dynamics of the key components of the coagulation system visualized
by ROTEM in association with the complex coagulopathic setting of ATAAD
surgery. It is therefore unclear whether the ROTEM-guided treatment
algorithm utilized in routine surgery also may be used when performing
ATAAD repair.

To assess the performance of ROTEM during surgery for ATAAD, we reviewed
ROTEM in surgically treated patients with ATAAD compared to a control
group undergoing elective aortic surgery.

\textbf{METHODS}

This study was approved by the Ethics Committee for Clinical Research at
Lund University, Sweden (ref. 2015/197). As this was one of several
studies derived from the same prospective project, the study population
and methods have been described previously \textsuperscript{17}.

\textbf{Study population}

A total of 27 patients with ATAAD were selected for the study. Of those,
four patients were excluded: two because they did not follow surgical
protocol, one because of intraoperative death, and one because of a lack
of resources. The control group consisted of 20 patients who underwent
elective surgery of the ascending aorta and/or the aortic root. A
preoperative written or oral consent by the patient or the next of kin
was retrieved before any collection of data in all ATAAD patients. A
preoperative written consent was obtained by all elective control
patients.

\textbf{Study Design}

This was a prospective, single center, observational study comparing
patients undergoing surgery for ATAAD with a control group consisting of
patients undergoing elective aortic surgery of the ascending aorta
and/or the aortic root. The ATAAD group consisted of patients over the
age of 18 with symptom duration \textless{}48h undergoing surgery for
ATAAD at Skåne University Hospital, Lund, Sweden, between September 2015
and April 2018. ATAAD was confirmed by contrast-enhanced computed
tomography. The anatomical extent of the dissection was defined
according to the Stanford \textsuperscript{18} and
Debakey\textsuperscript{19} classification. Exclusion criteria were
preoperative use of anti-coagulants or anti-platelet drugs other than
aspirin (both groups) and if surgical approach deviated from routine (as
described below) (ATAAD group).

All patients with acute aortic syndromes (\emph{e.g.} ATAAD and
intramural hematomas) referred to our clinic during the study period
were registered and screened for inclusion (Fig 1). Routinely, a ROTEM
Delta (Tem Innovations GmgH, Germany) and standard lab test guided
bleeding management protocol was used at our clinic (Fig 2). Red blood
cell transfusions were given at B-Hemoglobin \textless{}90g/L. Platelets
were administered at maximum clot firmness (MCF) EXTEM \textless{}50mm
and MCF FIBTEM \textgreater{}10mm or platelet count
\textless{}100x10\textsuperscript{9}/L. Fibrinogen and/or plasma were
used at MCF FIBTEM \textless{}15mm or P-fibrinogen \textless{}2g/l.
Plasma or prothrombin complex concentrate (PCC) were used at coagulation
time (CT) EXTEM \textgreater{}100s, CT INTEM \textgreater{}240s,
P-PT(INR) \textgreater{}1.5 or P-APTT \textgreater{}1.5 x normal value.
Additional Tranexamic acid was used when maximum lysis (ML) exceeded
15\%. However, final decision regarding transfusions was at the
surgeon's discretion.

\textbf{Endpoints}

The primary endpoints were measurements of ROTEM values of clotting time
(CT) in INTEM, EXTEM, and HEPTEM and maximum clot firmness (MCF) in
EXTEM and FIBTEM. Secondary endpoints were need for transfusion with
blood products, procoagulants used, 30-day mortality, bleeding at 24h,
and reoperation for bleeding.

\textbf{Definitions}

An acute type A aortic dissection was defined as a separation of the
aortic layers providing a true and a false lumen for the blood flow,
presenting within 14 days of symptom onset and extending distally from
the aortic root or ascending aorta (Stanford A). Surgical mortality was
defined as death within 30 days of surgery. Intraoperative bleeding was
defined as blood loss collected and quantified using intraoperative cell
salvage and surgical gauze swabs. Postoperative stroke was defined as a
permanent loss of neurological function caused by an ischemic event with
or without confirmation with computed tomography or magnetic resonance
imaging. Renal replacement therapy (RRT) was defined as any need for
continuous hemofiltration or hemodialysis postoperatively. Cardiac
tamponade was defined as pericardial effusion that required pericardial
drainage or re-exploration.

\textbf{Biomarker Measurements}

Samples of blood were collected at six points in time:
T\textsubscript{0}- anesthesia induction; T\textsubscript{1}- lowest
core temperature (only collected in elective patients with core
temperature \selectlanguage{english}[?]32degC, n=14); T\textsubscript{2}- just before protamine
administration; T\textsubscript{3}- end of surgery; T\textsubscript{4}-
24h after surgery; T\textsubscript{5}- 96-120h after surgery. A central
venous line was used for samples collected at T\textsubscript{0},
T\textsubscript{4}, and T\textsubscript{5}. A circuit from the
cardiopulmonary bypass machine was used for samples collected at
T\textsubscript{1} and T\textsubscript{2}. A radial artery line was used
for the samples collected at T\textsubscript{3}.

All samples were analyzed at the Dept. of Clinical Chemistry, Division
of Laboratory Medicine, Skane University Hospital, Lund, Sweden, on a
ROTEM. Parameters tested were INTEM, EXTEM, HEPTEM, and FIBTEM and
variables clotting time (CT), which is time from start until clotting is
initiated in seconds (s) and maximum clot firmness (MCF), which is
maximum diameter of clot in millimeters (mm).

\textbf{Surgical Procedures}

The surgical technique for ATAAD used at our center has been described
previously \textsuperscript{17}. Median sternotomy, cardiopulmonary
bypass (CPB) with hypothermic circulatory arrest and cold blood
cardioplegia was used in all cases. Heparin was reversed with protamine
after weaning from CPB and transfusion of procoagulants and blood
products initiated. The cooling strategy used in the elective controls
were hemiarch procedure 25degC; valve sparing root replacement (ad modum
David): 30degC; root replacement (ad modum Bentall) or aortic valve
replacement with supracoronary replacement of the ascending aorta: 32degC;
isolated replacement of the ascending aorta: 32-36degC.

During the study period, all patients received preoperative tranexamic
acid (2-3g preoperatively and 1-2g after termination of CPB for a total
of 4g) to prevent hyperfibrinolysis. A Dideco Electa (Sorin Group,
Electa, Italy) cell saver machine was used to process and re-infuse
salvaged blood. Heparin dose was calculated using the Hepcon HMS Plus
system (Medtronic, Minneapolis, MN, USA) to reach an activated clotting
time (ACT) of \textgreater{}480s and monitored serially during CPB to
maintain ACT \textgreater{}480s with additional heparin added if
necessary. Antithrombin was administered if the heparin dose response
slope was low (\textless{}70s/U/ml) and a subsequent test was conducted
ten minutes later. Two patients in each group received 2000IE of
antithrombin during surgery. ACT was routinely controlled at the end of
surgery, and additional protamine was given if ACT exceeded 120 seconds.

\textbf{Statistical Analysis}

Categorical variables were expressed as numbers and percentages.
Continuous variables were expressed as mean (+-SD) when normally
distributed, otherwise as median {[}IQR{]}. ROTEM variables were
visualized using box plots. ROTEM reference values are illustrated as
dashed lines and shaded areas and are based on reference ranges by Lang
et al \textsuperscript{20}. Proportions were compared using the
chi-square test. Fisher's exact test was used when the number of cases
was less than 5, and continuous variables were evaluated using the
Mann-Whitney test. Wilcoxon signed-rank test was used for analyzing
related samples. Missing values were not analyzed. A \emph{p} -value
\textless{} 0.05 was considered statistically significant and analyses
were performed using standard software (IBM Corp. Released 2019. IBM
SPSS Statistics, Version 26. Armonk, NY: IBM Corp).

\textbf{RESULTS}

\textbf{Baseline and Intraoperative Data}

Patient characteristics are presented in Table 1. Bicuspid aortic valve
was less common in the ATAAD group (0\% vs 32\%,\emph{p\textless{}}
0.01), and proximal surgery was less extensive with fewer root
replacements in the ATAAD group (\emph{p\textless{}} 0.001) compared to
the control group. Cardiopulmonary bypass time was shorter in the ATAAD
group (160 (+-36) min vs 208 (+-60) min,\emph{p\textless{}} 0.01) as well
as aortic cross-clamping (75 (+-31) min vs 139 (+-44) min,
\emph{p\textless{}} 0.001). The lowest core temperature was
significantly lower in the ATAAD group (20.0 (+-2.8)degC vs 30.5 (+-3.1)degC,
\emph{p\textless{}} 0.001).

\textbf{Biomarker Measurements}

ROTEM data is presented in Figure 3. At T\textsubscript{0} there was no
significant difference in clotting time (CT) in INTEM or HEPTEM between
groups (159s {[}140-170{]} vs 170s {[}159-180{]}, \emph{p=} 0.08 and
156s {[} 138-168{]} vs 163s {[}150-180{]}, \emph{p=} 0.21). During CPB,
HEPTEM CT increased markedly in both groups and was significantly higher
in the ATAAD group at T\textsubscript{2} (212s {[}202-239{]} vs 198s
{[}193-236{]}, \emph{p=} 0.05). At the end of surgery
(T\textsubscript{3}), the HEPTEM CT recovered, although not to
preoperative levels and was significantly higher in the ATAAD group
(187s {[}166-203{]} vs 166s {[}151-173{]}, \emph{p\textless{}} 0.01).
The CT in INTEM and HEPTEM was significantly more prolonged in the ATAAD
group at T\textsubscript{3} compared to T\textsubscript{0} (191s
{[}179-211{]} vs 159s {[}140-170{]}, \emph{p\textless{}} 0.01 and 187s
{[}166-203{]} vs 156s {[}138-168{]}, \emph{p\textless{}} 0.01). In the
control group, INTEM CT was significantly longer at
T\textsubscript{3}compared to T\textsubscript{0} (184s {[}162-196{]} vs
170s {[}159-180{]}, \emph{p=} 0.03) but not HEPTEM CT (166s
{[}151-173{]} vs 163s {[}150-180{]}, \emph{p=} 0.93).

EXTEM

There was a significant difference in EXTEM CT at T\textsubscript{2}(87s
{[}76-107{]} vs 76s {[}73-84{]}, \emph{p} =0.03) and a trend towards it
at T\textsubscript{3} (59s {[}54-67{]} vs 64s {[}60-68{]},\emph{p}
=0.07). At the end of surgery, CT in the control group was significantly
longer than preoperative levels (64s {[}60-68{]} vs 60s {[}56-65{]},
\emph{p=} 0.05) and in the ATAAD group there was a trend towards shorter
CT compared to preoperative (59s {[}54-67{]} vs 62s {[}56-71{]},
\emph{p} =0.06).

The maximum clot firmness (MCF) in EXTEM was lower in the ATAAD group
compared to the control group at T\textsubscript{1},
T\textsubscript{2,}and T\textsubscript{5} (41mm {[}34-41{]} vs 55mm
{[}51-61{]},\emph{p\textless{}} 0.001, 50mm {[}44-55{]} vs 57mm
{[}54-62{]},\emph{p=} 0.001 and 69mm {[}66-72{]} vs 73mm
{[}72-74{]},\emph{p=} \textless{}0.01, respectively) and had a similar
trend at T\textsubscript{0} (59mm {[}56-65{]} vs 64mm
{[}58-68{]},\emph{p=} 0.07). EXTEM MCF was also lower in the control
group at the end of surgery compared to preoperative levels (61mm
{[}59-65{]} vs 64mm {[}58-68{]}, \emph{p=} 0.02) but not in the ATAAD
group (61mm {[}58-64{]} vs 59mm {[}56-65{]}, \emph{p=} 0.15).

FIBTEM

The preoperative FIBTEM MCF was significantly lower in the ATAAD group
compared to the control group (12.0mm {[}10.0-15.0{]} vs 16.5mm
{[}13.5-20.0{]}, \emph{p=} 0.03), and the pattern persisted during the
operation (at T\textsubscript{1} 9.0mm {[}5.5-11.5{]} vs 13.0mm
{[}10.0-16.3{]}, \emph{p\textless{}} 0.01 and at T\textsubscript{2}
9.0mm {[}7.0-12.0{]} vs 13.5mm {[}11.3-15.0{]}, \emph{p\textless{}}
0.01). There was no difference in FIBTEM MCF at the end of surgery
(T\textsubscript{3}) or the first postoperative day (T\textsubscript{4})
(\emph{p=} 0.91 and \emph{p=} 0.51, respectively), however at
T\textsubscript{5}, MCF was again lower in the ATAAD group (28.5mm
{[}25.0-37.3{]} vs 37.0mm {[}35.0-38.0{]}, \emph{p\textless{}} 0.01).

\textbf{Bleeding, Transfusions and Medical Management}

Data presented in Table 2 reveal that patients in the ATAAD group
received significantly more transfusions and procoagulants during
surgery and the first 24 hours after surgery. Transfusion of packed red
blood cells (3.3U (+-4.0) vs 1.2U (+-1.5), \emph{p=} 0.03), platelets
(4.3U (+-1.7) vs 2.5U (+-1.6), \emph{p=} 0.001) and FFP (2.4U (+-2.6) vs
0.6U (+-1.2), \emph{p\textless{}} 0.01) was larger in the ATAAD group.
The use of fibrinogen (6.0g (+-3.4) vs 3.1g (+-2.5), \emph{p\textless{}}
0.01), PCC (1780IU (+-1050) vs 775IU (+-896), \emph{p\textless{}} 0.01)
and recombinant factor VIIa (5 (22\%) vs 0 (0\%) patients, \emph{p=}
0.03) also were significantly larger in the ATAAD group. No patient was
reoperated for bleeding in both groups and postoperative bleeding
volumes at 12h (492ml (+-235) vs 498ml (+-175), \emph{p=} 0.64) and 24h
(810ml (+-400) vs 740ml (+-215), \emph{p=} 0.78) did not show any
difference between groups.

\textbf{DISCUSSION}

The results of this study demonstrate that there are predictable and
quantifiable changes in ROTEM values during surgery in ATAAD and
elective aortic surgery with CPB. Surgery significantly and negatively
impacted all ROTEM values assessed in this study (EXTEM CT, INTEM CT,
HEPTEM CT, EXTEM MCF, and FIBTEM MCF). The greatest impairment in
coagulation parameters occurred consistently in patients with ATAAD.
This study demonstrated that ATAAD caused an activation of the
coagulation shown in ROTEM prior to surgery (T\textsubscript{0}), which
developed to a coagulopathy during CPB (T\textsubscript{1} and
T\textsubscript{2}) and was not fully recovered compared to elective
controls at wound closure (T\textsubscript{3}) despite significantly
greater use of procoagulants and transfusions. Our ROTEM-guided
transfusion protocol does not seem to catch the full need of
transfusions as most of our patients received more transfusions than
what ROTEM would suggest. However, bleeding volumes and the need for
re-exploration for bleeding or tamponade did not differ and had
favorable outcomes in both groups.

Aortic dissection leads to blood being exposed to tissue factor,
extracellular collagen, and other subendothelial structures that
activate the coagulation process. This is evident by the decreased MCF
in FIBTEM indicating consumption of fibrinogen. MCF in EXTEM also was
decreased but did not reach the level of significance. Both EXTEM and
INTEM CT showed a trend towards longer clotting time indicating reduced
amounts of clotting factors. Combined, this indicates an established
activation of coagulation when ATAAD develops resulting in a consumption
coagulopathy. During surgery, both groups showed similar trends in all
ROTEM variables, but the ATAAD group had consistently more impaired
values, which could indicate that the dissection consumed coagulation
factors, platelets, and fibrinogen prompted by more profound
hypothermia.

At the end of surgery, both groups showed similar ROTEM findings. The
ATAAD group had longer HEPTEM CT than the control group, but not INTEM
CT. This indicates a reduction of factors in the intrinsic pathway in
the ATAAD group and a remaining heparin effect in the control group. In
the ATAAD group, FIBTEM is normalized and equal to the control group.
These findings are in line with similar work by Liu et al. and Guan et
al. who did serial TEG analysis on patients with
ATAAD\textsuperscript{21, 22}. Data in both studies demonstrated that
ATAAD initiates a consumption coagulopathy, and surgery affects
fibrinogen and clotting factors more than platelets. However, TEG is not
able to detect differences between intrinsic and extrinsic pathways. The
studies lacked either a control group or did not provide differences
between samples with heparinase.

Postoperatively, the patient was hypercoagulable in both groups,
primarily in terms of FIBTEM, which may be explained by an increase in
fibrinogen levels caused by inflammation \textsuperscript{23}. ROTEM at
day 4-5 (T\textsubscript{5}) showed normal CT in INTEM and a prolonged
CT in EXTEM in both groups. The MCF was elevated in FIBTEM and EXTEM.
The increase is likely driven by high fibrinogen levels. The prolonged
CT in EXTEM indicates a higher threshold for extrinsic pathway
activation, likely induced by increased activity by inhibiting factors
such as antithrombin, protein C, and protein S. This is supported by the
normal PT-INR and increased antithrombin at day five as shown
previously\textsuperscript{17}.

Point-of-care testing with either ROTEM or tromboelastography (TEG) has
been proven to reduce the need for red blood cell transfusion and reduce
bleeding in cardiac surgery \textsuperscript{10}. The clotting time (CT)
of INTEM and EXTEM test the same pathways as activated partial
thromboplastin time (APTT) and prothrombin time (PT-INR), respectively.
Maximum clot firmness (MCF) in both INTEM and EXTEM is an estimate of
platelet number and fibrinogen levels while MCF in FIBTEM is primarily a
measurement of fibrinogen levels \textsuperscript{11}. One of the main
benefits of ROTEM are its fast results compared to compared to routine
plasma-based laboratory coagulation tests (RLT) which enables serial
testing of the coagulation and allows for faster response on changes in
the coagulation during and after surgery, and our results generated by
ROTEM are in line with previous reports using RLT \textsuperscript{17,
24}. However, one main difference between ROTEM and RLT is that RLT has
well-established quality assurance programs with imprecision results,
coefficient of variation (CV\%) \textless{}5\%, which is more difficult
to achieve for a whole-blood system like ROTEM, reflected in the
reference values that are wider in ROTEM counterparts. Another benefit
of RLT is that ROTEM is harder to interpret and in the setting of
complex coagulopathy, the use of both RLT and ROTEM provides a more
nuanced picture \textsuperscript{25}.

To be able to use ROTEM as a substitute for RLT in a transfusion
protocol it needs to adequately identify differences in coagulation seen
in RLT. When comparing our ROTEM data with RLT in the same cohort, we
find that ROTEM does not detect as many pathologies as RLT does. ROTEM
identified all cases with low levels of fibrinogen, a finding supported
by previous studies \textsuperscript{13, 26}. However, low levels of
clotting factors and platelets seem to be underdiagnosed by ROTEM. In
this study, ROTEM suggests that 35\% of the patients require PCC or FFP,
but RLT indicates that all patients have decreased levels of coagulation
factors. This is also demonstrated by Rugeri et al.
\textsuperscript{26}who showed poor correlation between CT and
APTT/PT-INR. Platelet levels were also underdiagnosed by ROTEM, where
only one out of seven thrombocytopenic patients were detected compared
to RLT.

Our ROTEM-guided transfusion protocol was introduced in 2015. It follows
a similar structure to previously published protocols\textsuperscript{9,
10, 12}. The adherence to protocol in this study, however, was not
always optimal. When analyzing the transfusions, all patients in the
ATAAD group received platelets, fibrinogen, and PCC and/or FFP. Compared
to the transfusion protocol, all patients in the ATAAD group met the
criteria for PCC/FFP substitution, \textgreater{}80\% for fibrinogen,
but only 50\% met the criteria for platelets and RBC at
T\textsubscript{2}. This could be interpreted in different ways: either
pre-emptive transfusions were used to prevent coagulopathy or the
protocol was bypassed due to clinical coagulopathy not detected by the
protocol. As mentioned earlier, ROTEM failed to identify the patients
with low levels of coagulation factors or platelets indicating that the
ROTEM-guided algorithm used in routine surgery may not be directly
translated to ATAAD or other complex surgery. Also, our ROTEM does not
contain platelet function analysis, which may explain why the algorithm
was not followed for platelet transfusion.

Although ROTEM has been proven to reduce transfusions in cardiac
surgery, some studies show no predictive value of
ROTEM\textsuperscript{11, 14-16, 27}. One potential reason might be its
imprecision. In elective surgery, a preoperative test enables the
patient to act as its own control, and changes in ROTEM could better be
interpreted in that context. However, in the acute setting of surgery
for ATAAD, the patients' preoperative values are impaired, and
preoperative levels have a limited value. This is supported by several
studies of ROTEM and TEG showing that comparing pre- and post CPB levels
is better at predicting bleeding rather than a post CPB ROTEM/TEG
analyzed with predetermined cut-off values \textsuperscript{11, 14-16,
27}.

There are several limitations to this study. First, the sample size is
not large leaving room for type II errors. However, including more
subjects would require a longer inclusion period, and smaller
differences found in a larger cohort may have questionable clinical
value. The use of a control group undergoing aortic surgery is of
benefit, but a better-matched surgical procedure with deep hypothermic
circulatory arrest could possibly have given even more insights. Since
adherence to the transfusion protocol was impaired, the true effect of a
ROTEM-guided protocol could not be evaluated.

\textbf{Conclusion}

ATAAD induces an activation of the coagulation system that affects all
three subsystems: the extrinsic, the intrinsic and the common pathway.
ROTEM does not adequately catch the full coagulopathy in ATAAD. A
transfusion protocol in ATAAD should be specifically created to target
this complex coagulopathic state and ROTEM does not negate the need for
routine laboratory tests.

\textbf{Table 1}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[b]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.22\columnwidth}\raggedright\strut
ATAAD (n=23)\strut
\end{minipage} & \begin{minipage}[b]{0.22\columnwidth}\raggedright\strut
Control (n=20)\strut
\end{minipage} & \begin{minipage}[b]{0.22\columnwidth}\raggedright\strut
p-value\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Age (years)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
64.6 \selectlanguage{ngerman}±11.1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
59.2 \selectlanguage{ngerman}±14.2\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.17\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Sex (Female)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
7 (30\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
3 (15\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.29\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Hypertension\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
14 (61\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
11 (55\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.70\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Marfan\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0 (0\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2 (10\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.21\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Other connective disorder\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0 (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0 (0\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Bicuspid valve\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0 (0\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6 (32\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.01\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Aortic aneurysm\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6 (26\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
20 (100\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Diabetes\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0 (0\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1 (5\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.47\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Smoking history\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
7 (30\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4 (27\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Chronic kidney disease\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1 (4\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0 (0\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
COPD\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0 (0\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1 (5\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.47\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Stroke\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1 (4\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0 (0\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Aspirin\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
3 (13\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2 (10\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Hyperlipidemia\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1 (4\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6 (30\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.04\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Proximal surgical technique\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
- Supracoronary graft\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
21 (91\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
3 (6\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
- Supracoronary graft + AVR\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1 (4\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1 (5\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
- Root replacement\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1 (4\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
16 (80\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
- Valve sparing root replacement\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0 (0\%)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
8 (40\%)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
- Bentall\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1 (4\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
8 (40\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Distal surgical technique\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.04\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
- Supracoronary graft\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
21 (91\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
16 (80\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
- Hemiarch\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0 (0\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4 (20\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
- Arch\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2 (9\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0 (0\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Arterial cannulation\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
- Femoral\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
18 (78\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0 (0\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
- Arch\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1 (4\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
17 (85\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
- Other\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4 (17\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
3 (15\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Symptom duration (h)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
7.0 (3.9)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Operation time (min)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
298 \selectlanguage{ngerman}±72\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
322 \selectlanguage{ngerman}±79\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.10\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
CPB time (min)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
160 \selectlanguage{ngerman}±36\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
208 \selectlanguage{ngerman}±60\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.01\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Cx time (min)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
75 \selectlanguage{ngerman}±31\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
139 \selectlanguage{ngerman}±44\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
HCA time (min)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
21.6 \selectlanguage{ngerman}±10.5\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
3.6 \selectlanguage{ngerman}±8.2\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
SCP modality\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
- Circulatory arrest\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
14 (61\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0 (0\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
- SABP\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
9 (39\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4 (20\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
SCP time\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Lowest core temp (\selectlanguage{ngerman}°C)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
20.0 \selectlanguage{ngerman}±2.8\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
30.5 \selectlanguage{ngerman}±3.1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Circulatory arrest time (min)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
17.9 \selectlanguage{ngerman}±5.8\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.01\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Values are expressed as numbers (\%) or mean \selectlanguage{ngerman}±SD. ATAAD, acute aortic
dissection; COPD, chronic obstructive pulmonary disease; AVR, aortic
valve replacement; CPB, cardiopulmonary bypass; Cx, crossclamp; HCA,
hypothermic circulatory arrest; SCP, selective cerebral perfusion; SABP,
selective antegrade brain perfusion.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Values are expressed as numbers (\%) or mean \selectlanguage{ngerman}±SD. ATAAD, acute aortic
dissection; COPD, chronic obstructive pulmonary disease; AVR, aortic
valve replacement; CPB, cardiopulmonary bypass; Cx, crossclamp; HCA,
hypothermic circulatory arrest; SCP, selective cerebral perfusion; SABP,
selective antegrade brain perfusion.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Values are expressed as numbers (\%) or mean \selectlanguage{ngerman}±SD. ATAAD, acute aortic
dissection; COPD, chronic obstructive pulmonary disease; AVR, aortic
valve replacement; CPB, cardiopulmonary bypass; Cx, crossclamp; HCA,
hypothermic circulatory arrest; SCP, selective cerebral perfusion; SABP,
selective antegrade brain perfusion.\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Values are expressed as numbers (\%) or mean \selectlanguage{ngerman}±SD. ATAAD, acute aortic
dissection; COPD, chronic obstructive pulmonary disease; AVR, aortic
valve replacement; CPB, cardiopulmonary bypass; Cx, crossclamp; HCA,
hypothermic circulatory arrest; SCP, selective cerebral perfusion; SABP,
selective antegrade brain perfusion.\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{ngerman}



\textbf{Table 2.}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
& ATAAD (n=23) & Control (n=20) & p-value\tabularnewline
\midrule
\endhead
Early mortality & 1 (4\%) & 0 (0\%) & 1\tabularnewline
Chest output (ml) & & &\tabularnewline
- 12h & 492 \selectlanguage{ngerman}±235 & 498 \selectlanguage{ngerman}±175 & 0.64\tabularnewline
- 24h & 810 \selectlanguage{ngerman}±400 & 740 \selectlanguage{ngerman}±215 & 0.78\tabularnewline
Transfusions & & &\tabularnewline
Packed red blood cells (U) & 3.3 \selectlanguage{ngerman}±4.0 & 1.2 \selectlanguage{ngerman}±1.5 & 0.03\tabularnewline
Platelets (U) & 4.3 \selectlanguage{ngerman}±1.7 & 2.5 \selectlanguage{ngerman}±1.6 & 0.001\tabularnewline
Fresh frozen plasma (U) & 2.4 \selectlanguage{ngerman}±2.6 & 0.6 \selectlanguage{ngerman}±1.2 &
\textless{}0.01\tabularnewline
Fibrinogen (g) & 6.0 \selectlanguage{ngerman}±3.4 & 3.1 \selectlanguage{ngerman}±2.5 & \textless{}0.01\tabularnewline
Novoseven & 5 (22\%) & 0 (0\%) & 0.03\tabularnewline
Antithrombin & 2 (9\%) & 2 (10\%) & 1\tabularnewline
Tranexamic acid (g) & 3.5 \selectlanguage{ngerman}±0.9 & 3.9 \selectlanguage{ngerman}±0.4 & 0.03\tabularnewline
Desmopressin (\selectlanguage{greek}µ\selectlanguage{english}g) & 11.1 \selectlanguage{ngerman}±14.1 & 14.3 \selectlanguage{ngerman}±14.8 & 0.59\tabularnewline
PCC (IE) & 1780 \selectlanguage{ngerman}±1050 & 775 \selectlanguage{ngerman}±896 & \textless{}0.01\tabularnewline
Re-exploration for bleeding & 0 (0\%) & 0 (0\%) & 1\tabularnewline
Postoperative stroke & 5 (22\%) & 1 (5\%) & 0.19\tabularnewline
Dialysis (RRT) & 3 (13\%) & 0 (0\%) & 0.24\tabularnewline
Prolonged ventilation (\textgreater{}48h) & 8 (35\%) & 0 (0\%) &
\textless{}0.01\tabularnewline
ICU stay (days) & 6.7 \selectlanguage{ngerman}±6.8 & 1.4 \selectlanguage{ngerman}±0.8 & \textless{}0.001\tabularnewline
Values are expressed as numbers (\%) or mean \selectlanguage{ngerman}±SD. ATAAD, acute aortic
dissection; PCC, prothrombin complex concentrate; RRT, continuous renal
replacement therapy; ICU, intensive care unit. & Values are expressed as
numbers (\%) or mean \selectlanguage{ngerman}±SD. ATAAD, acute aortic dissection; PCC,
prothrombin complex concentrate; RRT, continuous renal replacement
therapy; ICU, intensive care unit. & Values are expressed as numbers
(\%) or mean \selectlanguage{ngerman}±SD. ATAAD, acute aortic dissection; PCC, prothrombin
complex concentrate; RRT, continuous renal replacement therapy; ICU,
intensive care unit. & Values are expressed as numbers (\%) or mean \selectlanguage{ngerman}±SD.
ATAAD, acute aortic dissection; PCC, prothrombin complex concentrate;
RRT, continuous renal replacement therapy; ICU, intensive care
unit.\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{ngerman}



\textbf{FIGURE LEGENDS}

\textbf{FIGURE 1.} Flow chart of patients with acute aortic syndromes
referred to the Department of Cardiothoracic Surgery, Skåne University
Hospital, Lund, Sweden, during the inclusion period.

\textbf{FIGURE 2.} Transfusion protocol

\textbf{FIGURE 3.} ROTEM analyses\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\textbf{Figure 1.}

\textbf{Figure 2.}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

\textbf{Figure 3.}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

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