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 (T0), which
developed to a coagulopathy during CPB (T1 and
T2) and was not fully recovered compared to elective
controls at wound closure (T3) 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 ATAAD21, 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 23. ROTEM at
day 4-5 (T5) 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 previously17.
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 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 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 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%) <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 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 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. 26who 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 protocols9, 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,
>80% for fibrinogen, but only 50% met the criteria for
platelets and RBC at T2. 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 ROTEM11, 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 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.