Blood management during cardiac surgery starts with risk identification of bleeding and thrombosis, treatment of anemia, and optimizing antithrombotic treatments. Preoperative consultation of the patient for PBM in clinics may provide excellent care in these patient populations. Subsequently, intraoperative bloodconserving strategies including a meticulous surgical technique, optimal management of anticoagulation, and appropriate use of hemostatic agents would serve to protect patient's blood. Finally, the optimal treatment of coagulopathy and bleeding with an appropriate use of blood products would definitely decrease the risk for complications.
This consensus report is an extended summary of the book prepared by the authors who are the task members assigned by the Turkish Society of Cardiovascular Surgery, Cardio-Vascular-Thoracic Anaesthesia and Intensive Care Society, and Turkish Society of Cardiology. This book has been recently published to raise the awareness of PBM and to educate members of the Heart Team in cardiac surgery.[3] This book, written in Turkish, is a synopsis of information in the latest literature and international guidelines.
In this report, you can find recommendations about all blood-conservation strategies using expressions such as "should be used", "is reasonable", "may be used" or "it is not recommended". This judgment is achieved by assessing the effectiveness of the treatment according to the latest literature and guidelines.
CLASSIFICATION OF STRATEGIES FOR
BLOOD CONSERVATION
In this report, each technique is classified according
to the application period. This classification provides
a better understanding and systematic approach
for clinicians. Table 1 shows the classification of
techniques.
Table 1: Blood conservative strategies classified according to application period
RISK IDENTIFICATION FOR
TRANSFUSION AND BLEEDING
Transfusion
Transfusion, related to bleeding or not, carries
a risk for infective (viral diseases, pneumonia,
wound infection) and non-infective (renal failure,
TRALI, TACO, TRIM) complications. This effect on
morbidity and mortality is strongly confirmed by many
studies.[4] Therefore, transfusion should be applied
for the appropriate target at the right time. Instead of
laboratory tests (hemoglobin [Hb] or hematocrit [Hct]),
inadequate tissue oxygenation markers are suggested
to make a decision for transfusion.[5] To date, many
risk scoring systems have been developed, and the
most recent one is the ACTA-PORT which is useful to
predict the number of packed cells to transfuse during
cardiac surgery.[6-9]
Bleeding
Bleeding after cardiac surgery is seen in 2 to 9%
of cases and increases the risk for morbidity and
mortality up to six fold.[10,11] The risk for bleeding
should be identified and, then, preventive and blood conservative strategies should be planned before the
operation. Until present, different risk scoring systems
for bleeding have been used, but have not been widely
accepted. Therefore, the common causes for bleeding
should be recognized by the Heart Team (Table 2).
Table 2: Risk factors for bleeding and re-operation for bleeding
Recommendations
1. The risk score for transfusion (ACTA-PORT)
should be calculated (predicted number of
packed cells) preoperatively, and preventive
strategies should be applied during the whole
perioperative period.
2. The risk factors for bleeding should be examined preoperatively. The level of bleeding risk should be identified, and all preventive strategies should be planned, when necessary.
PREOPERATIVE ANEMIA: DIAGNOSIS
AND TREATMENT
Anemia is a common comorbidity which occurs
in 25 to 40% of patients undergoing elective
cardiac surgery.[13,14] P erioperative a nemia a nd
blood transfusion can be considered as preventable
surgical risk factors, as both anemia and transfusion
contribute to poor outcomes.[15] Preoperative anemia
should be defined, evaluated, and managed to
minimize the use of blood products in patients
undergoing cardiac surgery. It is considered, with
the treatment of anemia, complications such as
transfusion-related mortality and morbidity are
reduced and long intensive care and hospital stay
are shortened.[16,17]
Irrespective of male or female gender, Hb levels below 13 g/dL are considered anemia.[18] All patients undergoing a major elective surgery should be evaluated for anemia. Iron deficiency is the most common cause of anemia in the perioperative period. Intravenous iron should be used as the first-line treatment option in patients who do not respond to oral iron or have iron intolerance, or surgery is planned within 6 weeks after the diagnosis of iron deficiency.[18,19]
Recommendations
1. The laboratory testing for anemia (iron, ferritin,
transferrin saturation) should be evaluated
preoperatively and surgery needs to be scheduled
in this context.
2. In untreated anemia patients, it is reasonable to
postpone elective surgery for the diagnosis and
treatment of anemia.
3. Investigation of ferritin levels, even if the patient
is not anemic, may be used in high-risk patients
for bleeding.
4. In the treatment of preoperative anemia, Hb level
should be targeted as ≥13 g/dL for both genders.
5. Preoperative iron replacement:
• Oral iron replacement therapy is reasonable in
case of iron deficiency, either anemic or nonanemic,
if the procedure can be postponed for
6 to 8 weeks.
• Intravenous iron therapy should be used in patients who are scheduled for surgery less than 6 weeks or who do not respond to or tolerate oral iron therapy.
• In case of iron sequestration (non-anemic), preoperative erythropoietin therapy may be used in selected high-risk patients for bleeding.
• In case of anemia, combined iron replacement and erythropoietin treatment may be used preoperatively in selected patients.
6. Dietary supplements (such as vitamin B12, vitamin D, folic acid) may be used in selected patients.
7. Routine preoperative red blood cell (RBC) transfusion is not recommended in case of anemia.
8. Iron replacement and erythropoietin treatment may be used in groups of patients who are scheduled for preoperative autologous blood donation (rare blood groups, insufficient blood stock, and alloimmunization, etc.).
PREOPERATIVE ANTITHROMBOTIC
DRUG MANAGEMENT
Recommendations for Antiplatelet Therapy
1. The risk for thrombosis following percutaneous
coronary intervention (PCI) should be identified
preoperatively to optimize antithrombotic drug
management.[20]
2. The thrombotic risk following PCI should be identified, irrespective of the stent type (bare metal stent [BMS] or drug-eluting stent [DES]) according to the time to surgery after stent implantation, angiographic features of the coronary lesions, and clinical characteristics of every individual patient.[21-24]
3. High thrombotic risk group comprises the patients having balloon angioplasty within 2 weeks, stent implantation within 3 months (particularly within the past month), and acute coronary syndrome (ACS) or complex PCI within 6 months. Intermediate risk includes balloon angioplasty between 2 to 4 weeks, stent implantation between 3 to 6 months, and ACS or complex PCI between 6 to 12 months.[25]
Preoperative use of acetylsalicylic acid (ASA)[26,27]
4. If cardiac surgery is elective and the risk for
bleeding is high (complex or redo surgery,
severe renal insufficiency, hematological
disease, and hereditary thrombocyte
dysfunction); ASA may be interrupted at least
5 days before surgery.
5. If cardiac surgery is urgent or emergent, the risk for bleeding is low or moderate, or the risk for thrombosis is moderate or high, ASA should not be discontinued before surgery.
Preoperative use of dual antiplatelet therapy
(DAPT)[26-29]
6. ASA should not be interrupted preoperatively.
7. Ticagrelor, clopidogrel and prasugrel should be
interrupted 3, 5 and 7 days, respectively before
surgery in patients who have an intermediate
thrombotic risk (excluding low bleeding risk
patients).
8. In case of a high thrombotic risk with a low bleeding risk, surgery can be performed without any interruption. If the bleeding risk intermediate or high, the patient should be evaluated by the Heart Team for the necessity of bridging therapy (Figure 1).
9. Bridging therapy with eptifibatide, tirofiban, and cangrelor may be used in patients with a high thrombotic and bleeding risk for cardiac surgery which cannot be postponed (Figure 2).
10. It is reasonable to use platelet function test to analyze the residual effect of P2Y12 inhibitors to optimize the time of surgery or to identify the risk for bleeding.[30-32]
Recommendations for Anticoagulant Therapy
1. The risk for thrombosis should be identified
preoperatively to optimize anticoagulant drug
management. The thrombotic risk assessment
are based on the type of prosthetic heart valve,
the position of valve, a history of cerebrovascular
event due to valve thrombosis, CHA2DS2-VASc
score, etiology of atrial fibrillation (AF) and
thrombophilia.[29,33]
2. Thrombotic risk is associated with the indication of anticoagulation therapy.
3. Prosthetic mitral valve, tricuspid valve (including biological valve), aortic monoleaflet valve, and stroke/transient ischemic attack (TIA) within the past 6 months due to valve thrombosis constitute the high thrombotic risk for patients with prosthetic heart valves. The CHA2DS2- VASc score 7-9, stroke/TIA within the past 3 months and AF due to rheumatic mitral valve disease and new venous thromboembolism, severe thrombophilia comprise the high-risk group.
4. Prosthetic aortic valve plus one risk factor (AF, stroke/TIA >6 months, diabetes mellitus [DM], congestive heart failure [CHF], and age >75 years) for prosthetic heart valve, CHA2DS2-VASc score 5-6, and stroke/TIA history within the past 3 months due to AF and venous thromboembolism within the past 3 to 12 months, and non-severe thrombophilia for venous thromboembolism indicate an intermediate risk.
5. Prosthetic aortic valve without any risk factor, CHA2DS2-VASc score 1-4 without stroke/ TIA, and venous thromboembolism more than 12 months prior constitute a low risk.
Preoperative use of Vitamin K antagonist
(VKA )[26,34,35]
1. VKA should be stopped at least 5 days before
cardiac surgery and bridged with low-molecularweight
heparin (LMWH) or unfractionated heparin (UFH) in patients with a high thrombotic
risk (Figure 3).
2. Patients with a prosthetic aortic valve plus at least one risk factor should be considered a high thrombotic risk and managed accordingly. Other patients in the intermediate- and low-risk group should undergo cardiac surgery with VKA interruption 5 days before surgery without bridging.
3. In case of an emergent surgery, prothrombin complex concentrate (PCC) can be preferred to fresh frozen plasma (FFP) to reverse the effect of VKA and to prevent complications due to transfusion.[36-38]
Preoperative Use of Direct Oral Anticoagulants
(DOACs)[39]
4. DOACs are rapid-acting drugs, and bridging is
not recommended, if the timing is optimal.
5. The time of discontinuation of dabigatran should be managed (48 to 96 hours) according to the creatinine clearance levels (Figure 3).
6. The time of discontinuation of rivaroxaban, apixaban, and edoxaban is 48 hours before cardiac surgery, irrespective of the creatinine clearance levels.
7. In case of an emergent surgery, it is reasonable to use idarucizumab to reverse the effect of dabigatran.[40,41]
8. In case of an emergent surgery, it is reasonable to use Andexanet Alfa to reverse the effect of apixaban and rivaroxaban.[38,42,43]
PREOPERATIVE COAGULATION TEST
An important component of preoperative
preparation is the patient's coagulation status. The first
and most important way to evaluate coagulation status
is to question the standardized history of personalized
or familial bleeding. Patients" history (including the
patients" and the families" bleeding history) and a
careful preoperative physical examination are essential
to identify pre-existing hemorrhagic disorders.[44]
Coagulation tests should be performed in patients with
an acute pathology which may cause hemorrhage.[45]
In addition to standard laboratory tests (prothrombin
time [PT] and activated partial thromboplastin
time [aPTT]), viscoelastic tests (VETs) have also
an important role in perioperative (pre-, intra-, and
postoperative) evaluation and treatment of coagulation
status. Fibrinogen level is the only test which has been
shown to be a predictor of bleeding in many recent
guidelines.[2] Platelets should be functionally evaluated
in selected patients besides thrombocytopenia.
Recommendations
1. The use of routine coagulation tests for the
prediction of perioperative bleeding is not recommended in non-selected patients prior to
surgery and other invasive procedures.
2. A standardized bleeding questionnaire should be used for screening the perioperative bleeding risk. It is reasonable to perform VET and/or standard coagulation test (SCT) in the following patients:
i. Positive bleeding history
ii. Surgical procedure with a high risk for
bleeding
iii. Presence of comorbidities with a high risk for
bleeding (such as disseminated intravascular
coagulation, sepsis, and liver disease)
3. Routine testing of platelet function is not
recommended. It is reasonable to use if,
i. Hemorrhage is not diagnosed by SCT and
VET.
ii. A potent (P2Y12 inhibitors) antiplatelet drug
is used.
AUTOLOGOUS BLOOD DONATION
Preoperative autologous donation (PAD) is
known, but not commonly used as blood conservation
strategy. Through the PAD, the patient is protected
against febrile and non-febrile transfusion reactions,
alloimmunization, and graft-versus-host disease
(GVHD). However, the risk for infection or hemolysis
persists, and the risk for transfusion due to anemia
induced by donation and availability of autologous blood is increased with a high cost. On the other
hand, PAD should be limited to healthy individuals
with a long life expectancy requiring intense blood
transfusion or those without cross-match compatible
blood. The eligibility criteria for PAD are good
health condition, being tolerant to iron replacement
and surgery with the risk for bleeding more than
500 to 1000 mL. It is contraindicated in case of
cardiovascular risk factors (unstable angina, recent
myocardial infarction, heart failure, aortic stenosis,
angina at rest, or TIA), organ dysfunction, and active
infection.
Recommendations
1. Routine use of PAD is not recommended, as PAD
is associated with lower preoperative Hb levels
leading to higher amounts of transfusion.[46-48]
2. PAD may be used in case of rare blood type, or if identification of alloantibody is not possible and cross-match compatible blood is not available.[49,50]
BLOOD CONSERVATIVE SURGICAL
TECHNIQUES
Operative technique is one of the most important
steps in the prevention of morbidity related to bleeding
and transfusion. The decision should be made by
the multidisciplinary Heart Team. Hemodilution and
coagulopathy due to CPB are prevented by off-pump
cardiac surgery which may reduce transfusion.
However, meta-analyses and randomized trials have not reached a final judgment about this issue.[51,52] Therefore, it is recommended only in selected patients in accordance with the recent guidelines.[2] Minimally invasive approaches cause less surgical trauma which reduce bleeding. Most of studies have concluded that the use of blood products would be restricted by minimally invasive surgery.[53-55]
Recommendations
1. The decision of the multidisciplinary team
(a surgeon, cardiologist, anesthesiologist, and
perfusionist) is strongly recommended in terms
of treatment strategy, incision, and operative
technique to prevent complications due to
bleeding and transfusion.
2. Off-pump surgery may be preferred to reduce perioperative use of blood products, if optimal surgical treatment is provided.
3. Minimally invasive techniques (minithoracotomy, mini-sternotomy transcatheter aortic valve implantation [TAVI], other transcatheter techniques) may be performed to reduce perioperative use of blood products, where applicable.
THE USE OF FRESH WHOLE BLOOD (FWB)
The FWB identifies the donor blood stored at
room temperature less than 24 hours after donation.[56]
Hemostatic properties of FWB gradually decrease by
lowering FV and FVIII levels, and viable platelets
yield in course of time. In addition, the increase
in the extracellular potassium and lactate and the
decrease in glucose and pH levels during the storage
of whole blood result in metabolic imbalances after
transfusion.[57,58]
Although, several clinical studies have demonstrated the superiority of FWB to reconstituted blood which is composed of FFP, RBC, and single donor platelet concentrate (dPC) units in terms of bleeding control, overall studies have concluded that the only advantage of FWB against reconstituted blood is less donor exposure.[57-59]
Recommendation
1. The use of FWB is not recommended in cardiac
surgery, if blood components are avalibale.
ANTIFIBRINOLYTICS
Antifibrinolytics (tranexamic acid [TXA],
Epsilon-aminocaproic acid [EACA], and aprotinin)
are used to reduce blood loss, blood transfusion, and the need for reoperation in cardiac surgery.[60,61] This
triple effect has been demonstrated for aprotinin
and TXA.[60,62] However, the effect of EACA on the
reduction of reoperation has not been demonstrated,
yet.[60]
The multi-center Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) study showed that blood transfusion requirement (p<0.001) and reoperation rate (1.4% and 2.8%, p=0.001) were lower in the TXA group, despite increased neurological events such as convulsions.[62] Several meta-analyses also demonstrated that aprotinin reduced the need for reoperation and blood transfusion.[60] However, this drug has not been licensed, except for some countries, due to its adverse effect on cardiovascular events and mortality. Thus, care should be taken to ensure that it is approved by the local authority and the balance of benefit/harm should be considered. Although there is a limited number of studies comparing EACA to other antifibrinolytic agents, there are meta-analyses showing similar effects to other antifibrinolytic agents.[63]
Recommendation
1. Antifibrinolytics should be used to reduce
bleeding and transfusion.[60,62,64]
ACUTE NORMOVOLEMIC
HEMODILUTION (ANH )
Acute normovolemic hemodilution is one of the
strategies to decrease the need for allogeneic blood
transfusion in cardiac surgery. It is commonly used,
reliable, easy-to-apply, and low-cost technique. The
ANH has been shown to regulate microcirculation by
reducing blood mass, blood cell damage, and preserving
organ functions by reducing the inflammatory
response.[65] The amount of transfusion has been
reduced by 18 to 90% through ANH.[66]
Recommendations
1. ANH may be used to reduce perioperative
transfusions in selected cases.[67]
2. It is reasonable to use ANH in patients with autologous blood transfusion, rare blood group, alloantibody positivity, and refusing allogenic transfusion for special reasons.[67]
3. ANH is not recommended:
• In the presence of severe anemia (Hb <11 g/dL or Hct <33%) or platelet dysfunction.[67]
• Coronary artery disease (critical stenosis, unstable angina, left ventricle dysfunction).[68]
• In the presence of severe pulmonary disease, impaired renal function and hepatic dysfunction.[68]
4. Each center should establish their own protocol (patient selection, vascular access, ANH volume, fluid to be replaced, blood collection, and storage) in ANH applications.
HEPARIN-PROTAMINE MANAGEMENT
Optimal anticoagulation during CPB and its
adequate neutralization after CPB is important to
maintain the balance between thrombosis and bleeding
in cardiac surgery. Less anticoagulation may cause
thrombi, more consumption of coagulation factors, and
vice versa, it may cause bleeding and consumption of
coagulation factors. For heparin, dosing, its application,
measurement of anticoagulation, appropriate reversal
by protamine, alternatives of heparin are the main
challenges during CPB.
Recommendations
1. The bolus administration of UFH based on the
body weight (300 to 400 IU/kg) is reasonable to
ensure adequate anticoagulation.[69]
2. The efficacy of anticoagulation should be measured by therapeutic functional test or maximum activated clotting time (ACT) at regular intervals before and during CPB. The ACT should be kept for more than 480 sec during CPB.[69,70]
3. Heparin concentration analysis may be used in addition to ACT.[71]
4. If anticoagulation is inadequate before CPB, despite additional doses of heparin, FFP transfusion or antithrombin III infusion may be used.[72]
5. Protamine dose adjustment according to heparin level is reasonable to prevent bleeding and to minimize blood product use.[71]
6. It is reasonable to provide a protamine/heparin ratio of 1:1. The ratio above 2.6:1 is associated with platelet dysfunction, coagulopathy, and bleeding.[70]
7. In patients requiring high-dose UFH use, lowdose protamine infusion may be used for 6 hours after CPB to prevent heparin rebound.[73]
8. The adverse effects of protamine (i.e., vascular collapse, pulmonary hypertension, and anaphylaxis) should be recognized and resuscitative care should be planned.[74]
9. In case of heparin-induced thrombocytopenia (HIT) diagnosed based on functional serum tests, it is reasonable to postpone (about 2 to 3 months) elective surgery requiring CPB.
10. In case of an emergent surgery, it is reasonable to use bivalirudin as an alternative to heparin. Its efficacy can be monitored by the ecarin clotting time (ECT). The reversal of its effect by any antidote is not possible, which may cause bleeding after CPB and require additional hemostatic strategy.[70]
HEPARIN-INDUCED
THROMBOCYTOPENIA
Heparin-induced thrombocytopenia is an adverse
drug reaction of heparin which may result in potentially
fatal clinical entities. It is not uncommon and caused
by risk factors similar to cardiac surgery.[75,76] It
develops within 1 to 2 weeks after heparin, and
antibodies to the heparin-platelet factor 4 complex
play a key role in the clinical status of the patient.[2]
The risk for HIT development is independent of the
type, dose, and route of administration of heparin.
Clinical picture includes thrombocytopenia and both
arterial and venous thrombosis due to activation of
platelets. The 4T score should be assessed for the
likelihood of HIT by thrombocytopenia, time of
platelet decline, presence of thrombosis, and other
causes of thrombocytopenia.[77] Discontinuation of
heparin alone is not sufficient to reduce the risk for
thrombosis, and non-heparin anticoagulant treatment
is necessary.[78-80]
If cardiac surgery cannot be postponed, bivalirudin or argatroban may be used as an alternative for anticoagulation during CPB. However, the use of non-heparin anticoagulants (bivalirudin, argatroban, danaparoid, fondaparinux, or DOACs) have not been approved for use in the treatment of acute HIT. The treatment agent and application amounts to be selected should be based on the patient-specific evaluation.
Recommendations
1. 4T score should be calculated in case of
HIT suspicious clinical findings such as
thrombocytopenia accompanied by a thrombotic
event.[77]
• If score is 0-3, heparin treatment is regulated according to the indication and non-heparin anticoagulants are discontinued, if possible.
• If score is ?4, heparin is discontinued and non-heparin anticoagulant is initiated.
If immunological assay yields negative results, it is treated as a low 4T score. Otherwise (in case of positivity), a functional assay may be performed to confirm.
• If the score is 6-8, the probability of the diagnosis is high, even the functional test is negative.
2. In case of elective cardiac surgery requiring heparin, it is reasonable to postpone the procedure until HIT antibodies become negative.
3. If cardiac surgery cannot be postponed, it is reasonable to use bivalirudin or argatroban as an alternative for anticoagulation during CPB.
4. In case of HIT, the use of heparin (UFH or LMWH) should be avoided in the perioperative period.
5. Non-heparin anticoagulants may be used in case of HIT, even if it is off-label use.
VOLUME THERAPY
The aim of fluid (crystalloid or colloid) therapy in
cardiac surgery is to maintain adequate blood pressure,
cardiac output, tissue perfusion, and oxygenation.
A consensus has not yet been reached upon on the
optimal choice of fluids, either crystalloid or colloid.
However, it is known that hemodilution is caused by
priming and volume resuscitation, and both increase
the use of blood products.[81]
Crystalloid solutions are routinely used in cardiac surgery, since they cause lower rates of coagulopathy, infection, and anaphylaxis with a lower cost. However, high-volume normal saline solution (0.9%) has been shown to alter serum osmolarity, increase the blood product use, cause hyperchloremic acidosis, and postoperative acute renal failure. Stable isotonic solutions such as ringer lactate or ringer solution are therefore recommended.[82]
The most commonly used colloid solutions are hydroxyethyl starch (HES) solutions, albumin and gelatin which are more effective to expand intravascular volume.[83,84] However, t he main disadvantages i nclude impaired renal function, need for renal replacement therapy, tendency to bleed, and an increased risk for mortality. There are conflicting results in the literature and yet a single consensus has not been established for the use of colloid solutions.[85-87] Nonetheless, newgeneration HES solutions seem to be safer in terms of coagulopathy and renal complications.[88]
Recommendations
1. The target is the hemodynamic stability in
the perioperative period provided by volume
therapy.[89]
2. Preoperative risk factors, hemodilution, high Hct values, and coagulation status should be considered during volume therapy in the perioperative period.[72]
3. In addition to fluid selection, timing, monitoring (particularly dynamic, transesophageal echocardiography), and evaluation of hemodynamics are crucial.[72]
4. There is no advantage in using HES as the prime solution to reduce bleeding and blood product use.[90]
5. Hemodilution should be avoided to reduce bleeding and blood transfusion.[81]
6. The use of new-generation HES solutions are not recommended to reduce hemorrhage, although limitation of hemodilution is reasonable to reduce bleeding and transfusion.[72]
7. The use of HES solutions in volume therapy should be restricted to prevent renal complications and reduce mortality.[91]
8. Stable and isosmotic electrolyte solutions may be used, if crystalloid solutions are preferred.[92]
9. The colloid solution use should not exceed 30 mL/kg per day; new-generation HES solutions or gelatin may be preferred, if colloids are to be used.[93]
10. In the postoperative period, balanced solutions (ringer, ringer lactate) should be preferred as the maintenance fluid therapy.[82]
11. FFP should not be used for volume extension.[72]
MINIMALLY INVASIVE
EXTRACORPOREAL CIRCULATION
AND STRATEGIES
Hemodilution, excess activation of coagulation
system, loss of platelets, and its function are associated
with systemic inflammatory syndrome caused by
CPB which increase the risk for transfusion in the
perioperative period.[94-96]
The Minimal Invasive Extracorporeal Minimally Invasive Extracorporeal Circulation (MiECC) defines essentially closed, shortened, biocompatible circuit without venous reservoir which requires less prime volume and anticoagulation.[97] Metaanalyses and studies have shown the beneficial effect of the use of MiECC in terms of packed red cell transfusion.[98-100] Retrograde or antegrade autologous priming techniques are also used to reduce hemodilution during CPB. This beneficial effect has been confirmed in several studies and recommended by the recent guidelines.[72,101,102]
Recommendations
1. The use of MiECC is reasonable to decrease the
risk for transfusion.
2. The RAP and AAP can be used to reduce hemodilution and to decrease the amount of transfusion.
AUTOTRANSFUSION
In cardiac surgery, blood taken from the
mediastinal shed and remaining into the CPB circuit
are collected, processed, and infused to the patient
intra- and postoperatively through the autotransfusion
techniques.[72,103] As a result, allogenic blood transfusion,
particularly RBC transfusion, can be reduced by the cellsalvage
system.[72,103] Besides, systemic inflammatory
response related to CPB may cause postoperative organ
dysfunction and complications which can be reduced
by autotransfusion.[104] The use of autotransfusion
system improve the anti-inflammatory cytokine/proinflammatory
cytokine ratio.[105]
Recommendations
1. It is reasonable to use autotransfusion (cellsalvage
system) to reduce transfusion,
particularly in high-risk patients.
ULTRAFILTRATION (UF )
Hemodilution during CPB may result in an
increased total body water, interstitial edema of vital
organs, hypoxia, hypotension, coagulopathy, renal
dysfunction, myocardial and cerebral ischemia, and
even mortality. Ultrafiltration is a hemoconcentration
technique which filtrates the plasma from blood
via semi-permeable membrane which is used as a
blood conversation strategy in cardiac surgery. The
beneficial effects of UF in cardiac surgery patients
are uncertain and, although some studies have shown
a benefit, some others have provided controversial
results.[106] Several studies have also demonstrated
reduced RBC transfusions with the use of UF. In a
randomized-controlled study from Brazil, modified
ultrafiltration (MUF) groups had reduced chest tube
drainage compared to control group after 48 hours
and the Hct levels were higher and transfusion
requirement was less in the MUF group.[107] Metaanalysis
conducted by Boodhwani et al.[108] found a benefit of UF in lower rates of postoperative bleeding
and blood transfusions. Mongero et al.[109] analyzed
a total of 40,650 (propensity-matched) adult cardiac
surgery cases for a 61-month period and concluded
that UF was not associated with a reduction of risk for
RBC transfusion during cardiac surgery.
Recommendations
1. There is no adequate evidence to recommend
the routine use of UF as a blood conversation
technique or to decrease postoperative bleeding
in adult cardiac surgery.
2. The UF, particularly MUF, may be used in selected patients such as volume overload or excessive use of crystalloid cardioplegia.
HEMOSTATIC AGENTS
A. Fresh Frozen Plasma
Recommendations
1. FFP should not be used prophylactically to
reduce blood loss or reduce the need for blood
products in cardiac surgery.[110,111]
2. The use of FFP is reasonable to decrease bleeding due to coagulation factor deficiency and the need for blood transfusion, particularly by the VET guidance.
3. FFP may be used to reverse the effect of oral VKAs preoperatively.[110,111]
B. Factor XIII
Factor XIII (FXIII) is a coagulation factor acting
at the end of the coagulation cascade, provide a tight
and strong clot formation by cross-linking fibrin
monomers. There is no evidence that the use of FXIII
which reduces bleeding, the need for blood products,
and reoperation for bleeding.[112]
Recommendation
1. Prophylactic use of FXIII is not recommended,
but may be beneficial in selected patients with
postoperative plasma FXIII level less than 70%
of normal value.[112]
C. Fibrinogen
In cardiac surgery, hypofibrinogenemia is a common
coagulopathy associated with CPB, hemodilution, and
bleeding which strongly causes bleeding.[113]
Recommendations
1. Fibrinogen concentrate should not be used
prophylactically to reduce bleeding or the need
for transfusion.[114]
2. It is reasonable to use fibrinogen concentrate in case of bleeding related to hypofibrinogenemia (lower than 1.5-2 g/dL).[115]
D. Prothrombin complex concentrate
Prothrombin complex concentrate comprises
coagulation factors (Factors II, VII, IX, X) whose
production is vitamin K-dependent. It (4 factors or
activated form) is used to treat bleeding related to
VKA or coagulation factor deficiency, and to reverse
VKA effect in case of an emergent surgery. In patients
with elevated international normalized ratio (INR)
values (>4-5) under VKA treatment, it is aimed to
reverse the effect of VKA with PCC or FFP, when an
urgent surgical intervention is required.[116]
Recommendations
1. It is reasonable to use PCC in case of bleeding
associated with VKA therapy or coagulation
factor deficiency.
2. PCC may be preferred to FFP with the intent of rapid and effective reversal of VKA to prevent complications related to FFP.[116]
E. Desmopressin
Desmopressin (1-deamino-8-D-a rginine
vasopressin; DDAVP) is a vasopressin analog which
induces the von Willebrand factor (vWF) release from
endothelial cells.[117] A lthough it has been argued that
perioperative DDAVP use in cardiac surgery may lead
to a slight decrease in the postoperative bleeding, this
effect has been found to be more prominent in patients
with platelet dysfunction or preoperative ASA use.
Recommendation
1. Desmopressin should not be used prophylactically
to reduce blood loss. However, in patients with
bleeding related to platelet dysfunction (inherited
or acquired), the use of DDAVP is reasonable to
reduce blood loss and transfusion requirements.[118]
F. Recombinant Factor VIIa
After tissue damage, Factor VIIa (FVIIa), formed
by the effect of tissue factor, plays a role in the
coagulation cascade by activating Factor X. Although it
is suggested to use in the management of hemorrhages
refractory to conventional methods in adult and
pediatric cardiac surgery, there are some reports of
increased thromboembolic events.[119-121]
Recommendation
1. FVIIa should not be used prophylactically to
reduce bleeding in cardiac surgery.
2. FVIIa may be used in case of life-threatening hemorrhage refractory to conventional hemostatic methods.[120]
G. Topical hemostatic agents (THAs)
Topical hemostatic agents can be used to support
the coagulation system in case of bleeding which
cannot be controlled by conventional methods.[122]
These agents are classified according to characteristics
as active (containing anti-bleeding agents) and passive
(without anti-bleeding agents), or both.
G.1. Active THAs
Active THAs induce coagulation system by
stimulating conversion of fibrinogen to fibrin at the site
of bleeding via a high concentration of thrombin.[123]
Recommendation
1. The use of human-derived thrombin is reasonable
in case of a high risk for bleeding in surgical
sites.[124]
G.2. Passive THAs
Passive THAs (collagen, cellulose, gelatin, and
polysaccharides) do not contain coagulation factors,
but have physical properties which lead to compression
and platelet aggregation.[125]
Recommendation
1. The routine use of passive THAs in cardiac
surgery is not recommended, although it may
be used in case of bleeding from anastomosis
and suture sites in patients with a high risk for
transfusion.[126]
G.3. Fibrin sealants
Fibrin sealants contain fibrinogen and thrombin,
leading to clot formation in the bleeding site.[127]
Recommendation
1. The use of fibrin sealants is reasonable in case
of bleeding which arises from the needle hole in
cardiac and aortic surgery.[126]
MANAGEMENT OF BLEEDING
Transfusion Criteria
Cardiac surgery carries a high risk for transfusion;
however, transfusion should be administered for
therapeutic, but not preventive purposes.[128] Transfusion
criteria may vary according to personal approaches and
decisions, which is not based on scientific evidence.
The following transfusion principles should be adopted:
i. Transfusion should be applied in case of acute blood loss, hypoxia due to anemia, and coagulopathy causing bleeding.
ii. The balance between benefit/harm should be considered before transfusion.
iii. Laboratory values are not a trigger for transfusion.
iv. Transfusion should be applied, if there is a sufficient amount of knowledge and equipment to treat complications.
v. Patients need to be monitored during transfusion.
Triggers for Packed Red Cell
1. In case of Hb ≥10 g/dL or Hct ≥30%, transfusion
should not be applied.[129]
2. In case of Hb ≥8 g/dL or Hct ≥24%, transfusion should be avoided unless;
a. An emergent surgery
b. Acute coronary syndrome
c. The need for high-dose inotropes or
mechanical circulatory support
d. Venous oxygen saturation below 65%
e. Arterial blood lactate level above 4.0 mmol/L
f. Inadequate global body perfusion
g. Massive bleeding
h. End-organ ischemia (myocardial ischemia,
stroke, or anuria)
3. In case of Hb 7 to 8 g/dL or Hct 21 to 24%, transfusion may be considered, if there is low oxygen delivery to tissues.[128]
4. In case of Hb below 7 g/dL, transfusion is reasonable.[129]
5. In case of Hb below 6 mg/dL, transfusion should be done.
Fresh frozen plasma
1. FFP should not be used to prevent bleeding or to
expand intravascular volume.[130]
2. FFP should not be considered as the first-line
therapy, if coagulopathy can be treated by VKA
dose adjustment or vitamin K.
3. FFP should not be used in case of coagulopathy
without bleeding.[131]
4. FFP may be used in case of coagulopathy due
to massive transfusion or major surgery.[12,131,132]
5. FFP may be used in case of bleeding due to
coagulation factor deficiency, when fractionated
blood products are unable to be obtained.[12,131,132]
6. FFP may be used in case of bleeding due to
VKA therapy, when PCC is not available.[12]
7. The use of PCC (4-factors or activated form)
is reasonable, if emergent reversal of VKA is
needed.[12]
8. FFP can be used empirically or level-guided, in
case of antithrombin III deficiency.[72,131,133]
9. In case of bleeding, off-label use of PCC may be
considered as an alternative to FFP.
Platelet
Transfusion is reasonable:
1. If the platelet count is below 50¥109/L in
patients with bleeding
2. If thrombocytopenia due to massive transfusion
is present
3. If thrombocytopenia due to disseminated
intravascular coagulopathy is present.[72,133,134]
Cryoprecipitate
1. The use of cryoprecipitate is reasonable in case
of bleeding accompanied by low (below 1.5 to 2
g/dL) fibrinogen levels.[135]
2. VET-guided use of cryoprecipitate is reasonable
in case of bleeding.
3. Fibrinogen concentrate can be used instead of
cryoprecipitate, if available.
Viscoelastic test-Guided Coagulopathy Treatment
Bleeding due to coagulopathy has worse
consequences than surgical causes.[136] The treatment
of coagulopathy under the VET guidance may decrease
the use of blood products and may improve clinical
outcomes.[136-140]
Recommendations
Re-Exploration for Bleeding
Recommendations
• Over 300 mL/h within the first hour
5. Early re-exploration (within the first
12 hours) should be done in case of persistent
drainage.[144,145]
POSTOPERATIVE ANTİTHROMBOTIC
DRUG MANAGEMENT
Recommendations
2. It is reasonable to restart within 24 hours
after surgery, when there is no concern about
bleeding in patients undergoing non-coronary
cardiac surgery with a preoperative indication
for ASA.
Dual Antiplatelet Therapy
2. It may be considered to restart P2Y12 inhibitors
within 3 to 4 days postoperatively, when
the risk for ischemia is not high (e.g. recent
stent implantation >1 month or ACS without
stenting).[12,26,147,152-157]
Anticoagulant Therapy
Bioprosthetic valve
2. VKA may be considered for the first 3 months
after surgical implantation of an aortic
bioprosthesis.[166]
Others
2. DAPT may be considered after TAVI, if any of
anticoagulants are not indicated.[167]
BLOOD MANAGEMENT IN PEDIATRIC
CARDIAC SURGERY
Unfortunately, many of the parameters in an
infant/child undergoing cardiac surgery are not
unique. More importantly, it is not possible to
evaluate the algorithms of blood conservation on
evidence-based implementations. Therefore, possible
scenarios for low- and high-risk patients may be
defined and flowcharts for blood conservation may
be recommended.[168]
Preoperative Recommendations
• Hemodilution-optimal Hct level: Although
there is no consensus about an optimal Hct
level in pediatric cardiac surgery, 25% may
be considered.[173]
• Techniques for hemoconcentration:
Conventional or MUF may be used in
reversing the effects of hemodilution.[174]
Optimal management of the composition of
prime solution is recommended.
• Optimal management of hypothermia during
CPB is reasonable.
• Cell-savers may be used in selected pediatric
cases.[175]
• Optimal algorithm for anticoagulation and
neutralization during CPB should be provided.
• Antifibrinolytics may be useful to avoid
bleeding in pediatric population.[176]
• To analyze coagulation system, VET can be
used, particularly in case of bleeding.[177]
• Recombinant coagulation factors may be
administered in case of bleeding.[178]
ULTRA-BRIEF STEPS OF PBM
In conclusion, patient blood management should
be a philosophy for the Heart Team to improve the
outcomes of surgical procedures and postoperative
process. Each center should establish its own algorithm
and train the whole team for a complete application.
This is the first report in Turkey regarding this issue
and will be updated and improved every two years. As
a continuation of this report, a web-based, multi-center
prospective study is planned to be initiated by the
Turkish Society of Cardiovascular Surgery and Society
of Cardio-Vascular-Thoracic Anaesthesia and Intensive
Care. The analysis of this study would provide a great
source of scientific data which would guide future
applications and update current knowledge.
Patient Blood Management Study Group Members
Declaration of conflicting interests
Funding
1. VET-guided coagulopathy treatment is
reasonable in case of bleeding or in selected
patients with a high risk for bleeding.
2. The routine use of VET is not recommended in
cardiac surgery.
3. Easy access, service 24/7, professional
evaluation, and algorithmic application should
be provided for effective use of VET.
4. Suggested treatment algorithms for
thromboelastography (TEG) and rotational
thromboelastometry (ROTEM) are presented in
the book.[
Bleeding, re-exploration and transfusion, alone
or combined, affect the worst outcomes in cardiac surgery.[1] The rate of re-exploration is about 2 to 8%
and the major causes are surgical sites.[1,141,142] Therefore,
early diagnosis of surgical bleeding, and emergent and
appropriate correction is critical to prevent complications
related to bleeding and blood products.
1. Meticulous surgery should be performed to
prevent bleeding.
2. The team (a surgeon, intensive care specialist,
and nurse) needs to be aware to keep chest tubes
open. Active drainage systems may be used for
this purpose.[143]
3. The team (a surgeon, intensive care specialist,
and nurse) needs to be aware about hemodynamic
changes related to bleeding.
4. Recommended amount of bleeding for
re-exploration:
• Over 250 mL/h within the first 2 hours
• Over 200 mL/h within the first 3 hours or
total 750 mL
• Massive bleeding
• Cardiac arrest accompanied by bleeding
• Cardiac tamponade.
6. In case of massive bleeding or bleeding
associated cardiac arrest, re-exploration may be
done in the intensive care unit.
Medical treatment plays a key role for the success
of perioperative and long-term care in cardiac
surgery which reduces morbidity and mortality.[26]
Postoperatively, antiplatelet and anticoagulant therapy
is crucial to prevent ischemic events, arrhythmias
and to manage thromboembolic risk factors.[146]
However, these agents may increase the risk for
late bleeding complications. Therefore, appropriate
use of antiplatelet or anticoagulant agents should be
recognized by the Heart Team.[147]
Acetylsalicylic Acid
1. Acetylsalicylic acid should be restarted within
24 hours (6 hours, if possible) after coronary artery bypass grafting (CABG), when early
bleeding is not significant.[148]
1. It is reasonable to restart DAPT after CABG
as soon as it is considered safe in patients with
ACS. In patients with a high risk for ischemia,
P2Y12 i nhibitors s hould b e r estarted w ithin
48 hours after surgery.[149-151]
<İ>Mechanical valve
1. Anticoagulant treatment with UFH and VKA
should be started on the first postoperative day
and maintained, until the INR is in therapeutic
range.[158,159]
2. In case of bleeding risk, VKA may be restarted,
whenever it is deemed safe, preferably within
48 hours.
3. In patients with an indication for postoperative
therapeutic bridging, it is reasonable to start
UFH 12 to 24 hours after surgery.
4. Low-molecular-weight heparin may be
considered as an alternative bridging strategy to
UFH 24 to 48 hours after surgery.[
5. It is reasonable to restart VKA on the
first postoperative day, and lifelong oral
anticoagulation with VKA is recommended for
all patients.[2,158]
6. DOACs are not recommended in patients with a
mechanical valve prosthesis.[161]
7. The addition of low-dose ASA
(75 to 100 mg/day) to VKA should be considered
in case of concomitant atherosclerotic disease
or thromboembolism, despite an adequate
INR.[161-165]
1. VKA is reasonable on a lifelong basis for patients
with a surgical or transcatheter bioprothesis who
have other indications for anticoagulation.
1. VKA should be considered for the first 3 months
after mitral or tricuspid valve repair or valvesparing
procedures.
In congenital cardiac surgery, the indications and
complications of transfusion show a considerable
differences than in adults. These differences are
predominantly related to the physiological and
developmental factors, as well as pathophysiology of
the diseases encountered in the pediatric population.
Although developing an evidence-based algorithm
is challenging, the basic principle of transfusion
is always the same: transfusion of the right blood
product to the right patient at the right time, and the
right indication.
1. Anemia, iron deficiency, and history of bleeding
or coagulation disorders should be evaluated
preoperatively.
2. A multidisciplinary approach for the diagnosis
and treatment of preoperative anemia should be
standardized.
3. The discontinuation of antithrombotic treatment
should be optimized.
4. Autologous blood donation may be considered
in selected cases.[17,169-172]
Intraoperative Recommendations
5. Meticulous surgical technique for minimizing
blood loss should be provided. Cyanotic patients,
those undergoing a reoperation, and newborns
are at a higher risk for bleeding.
6. Factors related to CPB:
1. Identify the risk for thrombosis and bleeding.
2. Treat anemia.
3. Optimize cessation and bridging of
antithrombotic drugs.
4. Use antifibrinolytics.
5. Optimize anticoagulation during CPB.
6. Optimize volume therapy.
7. Minimize hemodilution.
8. Diagnose and treat bleeding promptly.
9. Use an individualized and VET-guided approach
for the use of blood products.
10. Choose the optimal timing to restart
antithrombotic drugs.
Aylin Yıldırır, Ahmet Hakan Vural, Aslı Demir, Ertekin
Utku Ünal, Hüseyin İlksen Toprak, Nevzat Erdil, Yeşim
Aydınok, Şahin Bozok, Ersin Kadiroğulları, Yüksel Atay, Tülün
Öztürk, Osman Nuri Tuncer, Şahin Şenay, Serdar Akansel,
Murat Acarel, Uğur Kısa, Suna Gören, Tuğra Gençpınar,
Ozan Onur Balkanay, Seden Kocabaş, Barış Durukan,
Serdar Günaydın, Atike Tekeli Kunt, Muharrem Koçyiğit, Levent
Mavioğlu, Ümit Karadeniz, Cem Alhan, Alper Kararmaz,
Nihan Yapıcı, Elif Başağan Moğol, İsmail Yürekli, Büşra
Yetkin Tezcan, Evren Özçınar, Mehmet Ali Astarcıoğlu, Arda
Özyüksel, Filiz İzgi Coşkun.
The authors declared no conflicts of interest with respect to
the authorship and/or publication of this article.
The authors received no financial support for the research
and/or authorship of this article.
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