Measurement of bleeding parameters

Although traditional teaching of perioperative haemostasis revolved around a “cascade” of events, contemporary “cell-based model” of haemostasis now discusses three overlapping stages. The first stage is initiation, which takes place on a tissue factor-bearing cell followed by amplification, during which platelets and cofactors are activated to set the stage for a large-scale thrombin generation and lastly propagation, during which large amounts of thrombin are generated on the platelet surface. ^{Reference Hoffman and Monroe11} During cardiopulmonary bypass, close monitoring of the patient’s coagulation status with traditional measurements of prothrombin time, partial thromboplastin time, international normalised ratio, activated clotted time, fibrinogen levels, and platelet count is routinely used. However, these tests mainly assess the initiation phase of coagulation and are poor predictors of post-operative bleeding. ^{Reference Faraoni, Fenger-Eriksen, Gillard, Willems, Levy and Van der Linden12} Furthermore, the challenge in understanding which coagulation factors are affected the most, both quantitatively and qualitatively, has resulted in tremendous practice variations across institutions.

Viscoelastic methods are increasingly employed in addition or as an alternative to standard laboratory tests to provide a more global assessment of clot initiation, strength, and stability. Viscoelastic parameters recorded with ROTEM^® (Instrumentation Lab, Bedford, MA, USA), TEG® (Haemonetics, Boston, MA, USA), or more recent Quantra® Hemostasis Analyzer (HemoSonics LLC, Charlottesville, VA, USA) can be obtained at the point of care, and has been shown to decrease the need for transfused blood products in both adult and paediatric cardiac surgery. ^{Reference Royston and von Kier13–Reference Nakayama, Nakajima and Tanaka15}

ROTEM^® allows for the global assessment of clot formation, clot firmness, and lysis. ^{Reference Faraoni, Savan and Levy16} The initiation phase can be assessed with either viscoelastic tests or traditional laboratory clotting tests (prothrombin time/partial thromboplastin time). ROTEM^® has been used to assess the early beginning of clot formation: clotting time (the onset of coagulation) and clot formation time (the initial rate of fibrin polymerisation). While the latter amplification and propagation phases, corresponding to the ability to form a “strong clot” could be assessed via thrombin generation assays, these tests are generally not clinically ready or easily available.

As it usually takes 30–45 minutes to obtain the results from standard coagulation assays, limited information is provided by these tests in the context of acute bleeding. ^{Reference Segal and Dzik17} Haas and colleagues validated ROTEM^® for bedside use with no significant difference in results when compared with traditional laboratory assays, but a mean time saving of 11 (8–16) minutes. ^{Reference Haas, Spielmann, Mauch, Speer, Schmugge and Weiss18} In another study, the authors demonstrated that early values of clot amplitudes measured as soon as 5, 10, or 15 minutes after clotting time could be used to predict maximum clot firmness in all ROTEM® assays. Those results support the timing-saving benefit of using transfusion algorithms based on viscoelastic tests compared to traditional tests.

A series of assays are employed with the ROTEM^® device.

1. 1. EXTEM provides information on the coagulation process via the extrinsic pathway and its interaction with thrombocytes and fibrinogen in citrated blood; the reagent contains tissue factor and phospholipids is used for extrinsic activation (a prolonged clotting time on EXTEM implies a deficiency in the tissue factory activation pathway, while a decreased amplitude suggests a low platelet count and/or fibrinogen level).

2. 2. INTEM provides information about factors in the contact activation pathway.

3. 3. HEPTEM provides information on the coagulation process via the intrinsic pathway in the presence of unfractionated heparin (the ratio between clotting times obtained with HEPTEM and INTEM provide an estimate of the anticoagulation effect of heparin).

4. 4. FIBTEM provides information on the fibrinogen level and quality of fibrin polymerisation in citrated blood by inhibiting thrombocytes; the reagent contains thrombocyte inhibitor (Cytochalasin D) (a decreased amplitude suggested a low fibrinogen level). The difference between EXTEM MCF and FIBTEM MCF (maximum clot firmness) gives you an estimation of platelet contribution to clot formation. ^{Reference Willems, Savan and Faraoni19}

A strong correlation has been shown between FIBTEM maximum clot firmness and fibrinogen levels in paediatric cardiac surgical patients with results available to the anaesthesiologist in 5 minutes. ^{Reference Tirotta, Lagueruela and Madril20} Having results in this brief, a window should theoretically assist the paediatric cardiac anaesthesiologist in making a more rapid decision with regards to providing the appropriate therapy to the right patient at the right time. In a study of 161 paediatric cardiac surgery patients, ROTEM assays were performed prior to surgery on cardiopulmonary bypass prior to platelet administration, following platelet administration, and post-cardiopulmonary bypass after protamine and fibrinogen. ^{Reference Tirotta, Lagueruela and Salyakina21} The investigators found that cardiopulmonary bypass induced profound perturbations in ROTEM values in children undergoing cardiac surgery. Administration of fibrinogen concentrate improved FIBTEM maximum clot firmness by 2.7 mm and led to an average increase in fibrinogen concentration of 73 mg/dl. Use of ROTEM has also been shown to reduce the need and amount of transfused blood products in paediatric cardiac surgery patients and by administering fibrinogen concentrate at a dose of 70 mg/kg to neonates and infants undergoing cardiac surgery reduced the fresh frozen plasma and cryoprecipitate requirements. A recent publication by Emani et al showed that a TEG maximal amplitude <45 during the rewarming phase of the bypass was helpful in predicting an increased risk of perioperative bleeding and the need for platelet transfusion. ^{Reference Emani, Emani and Diallo22} Moreover, based on an increasing number of studies, it appears that viscoelastic tests are excellent surrogates for traditional laboratory clotting values and the rapidity with which the results are ascribed to the patient allow for a more rapid and adjudicated plan of action.

The role of a bleeding algorithm

Post-cardiopulmonary bypass bleeding relates to either surgical bleeding, coagulopathic bleeding, or a combination of both. Despite a battery of traditional coagulation tests, no single laboratory test has emerged as the sole deciding coagulation test predicting bleeding. In a study by Miller et al, thrombocytopenia, platelet dysfunction, and hypofibrinogenemia as well as TEG K, α, and maximum amplitude values (all dependent on platelet–fibrinogen interactions) at the conclusion of CPB demonstrated a positive correlation to post-operative chest tube (bleeding) output. ^{Reference Miller, Mochizuke and Jerrold23} As such anaesthesiologists are often challenged, based on laboratory non-predictability to individualise care based on traditional laboratory or viscoelastic tests. Whether laboratory tests reveal a prolonged prothrombin time, partial thromboplastin time, or ROTEM abnormality, nothing is more important than what the anaesthesiologist is assessing when visualising the operative field. Is there active bleeding? Does the field appear profoundly “wet”? Clinical judgement should always supersede an individual laboratory result, and coagulopathy should only be treated with procoagulants products in the presence of clinically significant bleeding. Most recent guidelines recommend the use of intraoperative monitoring of haemostasis to guide the administration of blood products in the presence of excessive bleeding (Grade 1B). The authors suggest that intraoperative monitoring of haemostasis should be integrated into institution-specific transfusion algorithms (Grade 2C) and suggest viscoelastic tests as an alternative to standard coagulation assays for intraoperative bleeding management (Grade 2C). ^{Reference Faraoni, Meier, New, Van der Linden and Hunt24}

In a randomised prospective study of adults undergoing cardiac surgery with cardiopulmonary bypass, patients managed with a point-of-care-based transfusion algorithm received fewer red blood cell transfusions, platelet transfusion, and had less post-operative bleeding. ^{Reference Karkouti, Callum and Wijeysundera25} Whitney and colleagues performed a 12-month QI study on the role of a paediatric designed algorithm and its potential positive effects in reducing the need for transfusion. Two groups of patients with similar demographics (complexity of surgery and duration of bypass) were evaluated to determine the transfusion(s) required prior to the algorithm (Group I: 303 patients) and those after the implementation of the algorithm (Group II: 246 patients). A blood product utilisation algorithm was established with transfusions based on specific quantitative values. If the platelet count was < 100,000 with bleeding, or a haematocrit < 30 (biventricular patients), or a fibrinogen < 70 mg·dl⁻¹, the patient would receive a transfusion of platelets, red blood cells, or cryoprecipitate, respectively. When compared with the 12 months preceding implementation of the algorithm, blood utilisation per case in the operating room decreased by 66% for red cells and 86% for cryoprecipitate. Blood utilisation during the first 12 hours of ICU care also decreased 56% for plasma and 41% for red cells, indicating that the decrease in operating room transfusion did not shift the transfusion burden to the ICU. ^{Reference Whitney, Daves and Hughes26} Romlin et al conducted an observational study in which 50 paediatric cardiac surgical patients underwent intraoperative transfusion guided by ROTEM performed during cardiopulmonary bypass. Compared with historical controls, the study group received 30% fewer transfusions; specifically, the study group received 20% fewer red cells and 66% fewer plasma transfusions. ^{Reference Romlin, Wahlander and Berggren14} Faraoni retrospectively evaluated a ROTEM-based algorithm in 150 children undergoing cardiopulmonary bypass and its ability to predict bleeding risk. Analysis of our ROTEM parameters revealed that clotting time ≥ 111 seconds, clot amplitude 10 minutes after administration of protamine (A10) ≤ 38 mm measured on the EXTEM, and A10 ≤ 3 mm obtained on the FIBTEM tests were the three relevant parameters to guide haemostatic therapy. If the ROTEM-based algorithm was applied according to the bleeding risk, 93% of the high-blood loss (>10% of the child’s estimated blood volume) would have been treated. ^{Reference Faraoni, Willems, Romlin and Van der Linden27}

In the only randomised control study, Nakayama randomised patients (n = 50) to ROTEM-guided transfusion versus a control group (n = 50), where ACT and platelet count guided transfusion. The ROTEM study group experienced a 50% reduction in RBC transfusion and a 30% reduction in chest tube output within the first 12 post-operative hours. Additionally, the study group had a 10% reduction in ICU stay. ^{Reference Nakayama, Nakajima and Tanaka15}

In contrast to adults, children with CHD are heterogeneous both anatomically and physiologically. As such coming up with a single algorithm for all paediatric CHD patients is an enormous undertaking and may not be realistic.

Constructing a post-operative bleeding algorithm

The creation of an algorithm in part has to be based on predicting which children are likely to bleed in conjunction with point-of-care testing. A number of algorithms, often institutionally specific, have been established based on the risk of the procedure and risk of bleeding (i.e., low-risk procedure/low risk of bleeding; low-risk procedure/high risk of bleeding; high-risk procedure/high risk of bleeding). ^{Reference Machovec and Jooste28} Building a practical transfusion algorithm to reduce post-cardiopulmonary bypass bleeding necessitates choosing the ideal targets and thresholds.

Haemoglobin target

The ideal haemoglobin for a patient with CHD is highly individualised and considers the age of the patient, presence or absence of cyanosis, and the need for a particular haemoglobin to assure adequate oxygen delivery to the tissues without metabolic acidosis. Willems and colleagues in fact showed no difference in levels of multisystem organ dysfunction with a restrictive transfusion strategy (transfusion when haemoglobin <7 mg/dl) was followed compared with a liberal transfusion strategy (transfusion when haemoglobin <9.5 mg/dl). ^{Reference Willems, Harrington and Lacroix29} Chollete and colleagues performed a prospective randomised clinical control trial of 60 single-ventricle patients undergoing a cavopulmonary connection. Patients were randomised to either a restrictive (haemoglobin of < 9.0 g/dl), or liberal (haemoglobin of ≥ 13.0 g/dl) transfusion strategy for 48 hours post-operation. While the liberal cohort received a great number of red blood cell transfusions and donor exposures, there was no change in lactate, or cardiac output as assessed by the arterial-venous oxygen difference or the clinical outcome. ^{Reference Cholette, Rubenstein, Alfieris, Powers, Eaton and Lerner30}

Heparin dosing

Heparin is a requirement for cardiac surgery and is traditionally dosed based on weight and followed by measuring the activated clotting time. However, the activated clotting time can be erroneously offset by anaemia, thrombocytopenia, hypofibrinogenemia, and hypothermia. There is some encouraging data on the use of heparin concentration point-of-care measurement testing in infants undergoing cardiopulmonary bypass surgery to reduce transfusion needs. ^{Reference Machovec, Jooste and Walczak31}

At the end of the bypass, protamine is given and the anaesthesiologist at that point is faced with the decision regarding how to manage ongoing bleeding. It is at this juncture were clinical observation, point-of-care traditional laboratory tests, and viscoelastic testing have a role.

The role of fibrinogen

A growing body of literature suggests that fibrinogen is the first coagulation factor to decrease during significant bleeding and is a major contributor to post-bypass bleeding (Fig 2). Hypofibrinogenemia post-cardiopulmonary bypass surgery occurs as a result of hemodilution and in neonates and small children may result in fibrinogen values 30% below baseline. ^{Reference Moganasundram, Hunt and Sykes32} Giving fibrinogen concentrate has proven to be an alternative to cryoprecipitate to treat the post-cardiopulmonary bypass hypofibrinogenemia. Fibrinogen concentrate is plasma-derived but pasteurised, which minimises the risk of transfusion-transmitted disease, immunologic, and allergic reactions. Fibrinogen concentrate provides a standard and more consistent dose of fibrinogen compared to FFP and cryoprecipitate at a lower volume. Siemens and colleagues performed a single-centre randomised prospective study (FC cohort n = 60; placebo n = 30) using an intraoperative point-of-care test, ROTEM, to screen patients at low risk of post-operative bleeding and then guide individualised fibrinogen concentrate dosing in high-risk patients. ^{Reference Siemans, Hunt, Harris, Nyman, Parmar and Tibby33} Amongst randomised patients, the median (range) fibrinogen concentrate administered dose was 114 mg/kg (51–218). Fibrinogen levels increased from a mean (SD) of 0.91 (0.22)–1.7 g/L (0.41). The post-dose fibrinogen range was 1.2–3.3 g/L (72% within the desired range). The corresponding FIBTEM maximum clot firmness values were as follows: pre-dose, 5.3 mm (1.9); post-dose, 13 mm (3.2). While not powered for efficacy, there was a clear trend towards less mediastinal chest tube drainage in the first 24 hours after surgery (11.2 ml versus 17.1 ml), lower need for blood products (59 versus 40%), and less chest re-exploration for bleeding (1.7 versus 3.3%). In a similar study, Downey and colleagues randomised 60 infants (< 12 months of age) to receive either fibrinogen concentrate or cryoprecipitate in a post-cardiopulmonary bypass transfusion algorithm. Patients were randomised both by the institution and surgical complexity. If a patient continued to have post-bypass bleeding in either arm, the anaesthesiologist used point-of-care testing, TEG, or clinical judgment to determine appropriate products for transfusion. Overall, the fibrinogen concentrate group received significantly fewer total intraoperative allogenic blood transfusions when compared to patients in the cryoprecipitate group, 4 units (interquartile range: 3.0–5.0) versus 5.5 units (IQR: 4.0–7.0). The fibrinogen concentrate group received a mean of 1.79 (95% confidence interval, 0.64, 2.93; p = .003) less allogenic donor exposures than the cryoprecipitate group when adjusted for institution and complexity. ^{Reference Downey, Andrews and Hedlin34} Increased donor exposures to allogenic products is of great concern for children who likely will need multiple procedures over the course of their lifetime and even further particularly challenging if heart transplantation will need to be considered.

Figure 2. A depiction of the coagulation cascade with a focus on factor–enzyme complexes and target locations for direct factor repletion by prothrombin complex concentrates (in black), activated recombinant factor VII (in blue), and cryoprecipitate (in yellow).

Post-CPB platelet challenges

Aside from the negative effects on fibrinogen, hemodilution post-bypass can also result in quantitative effects on platelets in addition to platelet dysfunction. Following cardiopulmonary bypass, there is a disruption of factors specific to platelets, which normally bind the von Willebrand factor to elicit platelet aggregation. Activation and aggregation of platelets following blood contact with foreign material, systemic inflammation, negative effects of heparin on platelets and the fibrinolytic system, and hypothermia collectively contribute to both thrombocytopenia and platelet dysfunction. No studies have assessed the effect of platelet transfusion on post-operative bleeding in children undergoing cardiac surgery or compared different volumes and types of platelet transfusion. Thus, the recommendations for platelet transfusion are mainly consensus, considering transfusion guidelines. However, the use of thromboelastography during the rewarming phase may help predict the overall need for platelets. ^{Reference Emani, Emani and Diallo22}

Recombinant factor VIIA and anti-inhibitor complexes

While recombinant activated factor VII (rFVIIa; NovoSeven RT, Novo Nordisk, Plainsboro, NJ, USA) has been used in treating haemophilia A and B, it has also extensively been used off-label in post-CPB bleeding. Recombinant factor VIIa enhances the initiation phase of clot formation and, consequently, the amount of thrombin generated at the site of blood vessel injury. Not unlike many paediatric therapies embraced for use in medicine, much of the evidence for using rFVIIa has been extrapolated from adult studies. While rFVIIa has achieved widespread use as a procoagulant agent in post-cardiopulmonary bypass paediatric bleeding, much of the data has been based on anecdotal cases or small case series. However, not all studies have shown rFVIIa to reduce post-op bleeding. In a randomised, double-blind, parallel-group, placebo-controlled study prospective study of rFVIIa and standard haemostatic replacement therapy versus standard haemostatic replacement therapy alone did not shorten the time to chest closure or reduce blood loss and need for transfusions. ^{Reference Ekert, Brizard and Eyers35} However, there is some evidence that a higher initial loading dose may be required. Recombinant factor VIIa in isolation without other coagulation factors, platelets, and fibrinogen is not a panacea to curtail all post-op bleeding. Additionally, rFVIIa is not recommended for routine prophylaxis against bleeding in neonates under congenital heart surgery. Current task force guidelines recommend an initial dose of 90 mcg/kg of rFVIIa with a one-time option to repeat the dose in 2 hours in patients with massive post-bypass bleeding having failed traditional first-line therapies. ^{Reference Guzzetta, Russell and Williams36}

A recent retrospective review of 33 patients who received rFVIIa (29 patients) or anti-inhibitor coagulant complex (FEIBA; FEIBA NF, Baxter Healthcare Corporation, Westlake Village, CA, USA; 9 patients) reported a reduced amount of FFP, cryoprecipitate, platelets, and RBCs required after paediatric cardiac surgery. FEIBA is an anti-inhibitor coagulant complex that contains non-activated factors II, IX, and X and activated factor VII. FEIBA bypasses factor VIII by shortening the activated PTT of plasma with factor VIII inhibitor. While rFVIIa and FEIBA were both shown to reduce the need for blood products and chest tube output, thromboembolic events occurred in 17% of rFVIIA recipients and 22% of FEIBA patients. ^{Reference Carroll, Zaki, McCracken, Figueroa and Guzzetta37} No prospective study has compared rFVIIa to FEIBA to ascertain which product is more likely to reduce the need for product replacement therapy. Moreover, Wise-Faberowski et al examined their use of FEIBA at a 10–15 U/kg in a large series of children undergoing unifocalisation in Tetralogy of Fallot with major aortopulmonary collaterals at their institution. ^{Reference Wise-Faberowski, Irvin and Quinonez38} They concluded that the intraoperative use of FEIBA was not associated with a decrease in the amount of blood products, days of mechanical ventilation, length of stay, or an increase in recognised thrombotic events compared to those patients who did not receive FEIBA.

In a recent study by Downey et al,163 children with post-cardiopulmonary bypass bleeding who received rFVIIa were an estimated 3.9 times (95% confidence interval, 2.6, 5.9) more likely to develop thrombotic complications when compared with propensity-matched controls. ^{Reference Downey, Brown, Faraoni, Zurakowski and DiNardo39} The use of rFVIIa should only be considered in specific cases of intractable bleeding after a careful consideration of the balance between efficacy of the drug and risk of thrombotic complications. This is particularly true in patients known to be at high thrombotic risks like neonates, patients with shunts, and single-ventricle physiology.

The role of prothrombin complex concentrates

Prothrombin complex concentrates are a form of clotting factor concentrates and are available in three-factor (factors II, IX, X) and four-factor (factors II, VII, IX, X, with select anticoagulants) formulations. Prothrombin complex concentrates are derived from cryoprecipitate-free plasma and undergo purification, nanofiltration, vapour-heated treatment, and/or viral inactivation steps, all of which serve to significantly reduce the antigenic load to a negligible amount.

Prothrombin complex concentrates administration rapidly increases vitamin K-dependent clotting factor levels, which makes usage during perioperative bleeding an attractive option for achieving haemostasis. Commercially available prothrombin complex concentrates (Profilnine, Grifols Biologicals, Los Angeles, CA, USA and Kcentra, CSL Behring, Marburg, Germany, and Octaplex Octapharma, Vienna, Austria) improve thrombin generation by replenishing factors in both the extrinsic and intrinsic pathways. As with all procoagulants, the effect of achieving haemostasis is balanced against thromboembolic risk. The unique ability of prothrombin complex concentrate to support the enzymatic conversion of factors II–IIa illustrates its haemostatic efficacy to generate thrombin and its utility in post-operative bleeding. However, it is important to remember that while prothrombin complex concentrates will replace factor II (prothrombin) they in and of themselves will be ineffective in correcting clinically important coagulopathy without adequate repletion of fibrinogen and platelets. Similarly, a prolonged activated partial thromboplastin time (aPTT, a measure of the intrinsic and common coagulation pathways) is independently associated with failure of haemostasis after rFVIIa for refractory haemorrhage. This also supports the need to be mindful of the relationship of rFVIIA and prothrombin complex concentrate together. Investigators in one adult post-CPB propensity-matched study administered 10–15 U/kg of 4F-PCCs prior to low-dose rFVIIa (median: 18 mcg/kg, IQR: 9–16 mcg/kg) and found reduced bleeding after cardiac surgery. ^{Reference Gelsomino, Lorusso and Romagnoli40} This combination of low-dose rFVIIa and prothrombin complex concentrates may confer advantages over the use of rFVIIa alone. The use of ROTEM algorithmic point-of-care testing (EXTEM > 90–100 seconds) with regards to giving prothrombin complex concentrates has been done in adult surgical cases with reduced need for allogenic blood product transfusions. ^{Reference Ghadimi, Levy and Welsby41} In one neonatal study, Guzzetta and colleagues compared rFVIIa with three-factor prothrombin complex concentrate for the ability to augment thrombin generation in neonatal plasma following CPB. Eleven neonates undergoing cardiac surgery were enrolled. Two blood samples were obtained from each neonate: pre-bypass and post-bypass after platelet and cryoprecipitate transfusion. The post-cardiopulmonary bypass products sample was divided into control (no treatment), control plus rFVIIa, and control plus 3F-PCC. Three parameters of thrombin generation were measured ex vivo in a computer-simulated model. The computer-simulated post-CPB model demonstrated that rFVIIa failed to substantially improve lag time, thrombin generation rate, and peak thrombin without supplementing prothrombin. While the addition of rFVIIa post-CPB significantly shortened lag time; however, rate and peak were not statistically significantly improved. Conversely, 3F-PCC improved all thrombin generation parameters in parallel with increased prothrombin levels in both simulated and ex vivo post-CPB samples. ^{Reference Guzzetta, Szlam and Kiser42} In a similar fashion to giving rFVIIA, correction of hypofibrinogenemia and thrombocytopenia prior to the administration of prothrombin complex concentrates may be prudent in order to maximise the efficacy of lower prothrombin complex concentrates dosing and minimise the risk for adverse thromboembolic events. Decisions regarding the administration of prothrombin complex concentrates should be based on clinical observation of bleeding and point-of-care testing into an institutional-based algorithm.

Summary

Excessive bleeding following complex congenital heart surgery results in significant morbidity and mortality. Contributory mechanisms include developmental considerations (weight, age, immaturity of the coagulation system), heparinisation, hemodilution, and haemostatic alterations while on bypass, exposure to artificial surfaces, chronic cyanosis, complexity of the surgical procedure, insufficient surgical haemostasis, and perturbations in the coagulation cascade. Collaborative efforts between the paediatric cardiac anaesthesiologist and the cardiac surgeon should always revolve around maintaining haemostasis, blood sparing techniques, and restrictive transfusion protocols. To restore the haemostatic balance, transfusion of packed red blood cells, platelets, cryoprecipitate, and specific coagulation factors is the current standard of care. However, liberal use of such products may result in a significant volume load to the patient, result in infectious and non-infectious morbidity and mortality. Unfortunately, conventional measures of coagulation such as prothrombin time, activated partial thromboplastin time, activated clotting time, plasma fibrinogen, and platelet count do not accurately predict perioperative bleeding or guide administration of haemostatic agents during active bleeding. Results from standard coagulation assays require up to 30 minutes, limiting their effectiveness in the context of acute bleeding. In addition, these standard assays use platelet-poor plasma and do not allow for a global assessment of coagulation, providing no information about clot firmness or clot lysis.

Over the last two decades, efforts to reduce liberal blood product utilisation have centred on the use of point-of-care testing (ROTEM^® or thromboelastography) as an adjunct to traditional laboratory tests. These assays assess the intrinsic (INTEM) and extrinsic (EXTEM) pathways and fibrinogen function (FIBTEM) reflects the overall adequacy of platelet with coagulation factors. These point-of-care assays allow for near-real-time assessment of platelet aggregation, clot formation, and stability of clots. Established ROTEM-guided transfusion algorithms have been shown to reduce post-operative bleeding and red cell transfusion and reduced intensive care length of stay. Platelet abnormalities and hypofibrinogenemia are the most common causes of coagulopathic bleeding after cardiopulmonary bypass surgery.

If bleeding persists following platelet administration, fibrinogen concentrate should be considered to restore haemostasis. If fibrinogen concentrate is not readily available, cryoprecipitate should be considered over FFP as it has been shown to be more effective in improving fibrinogen levels, and TEG parameters. Ongoing bleeding despite the aforementioned approaches, and assurances that there are no obvious surgical causes of bleeding, warrant consideration for use of recombinant factor VIIa or coagulation factor concentrates. Recombinant factor VIIa promotes thrombin formation and plasma-derived coagulation factor concentrates contain all of the concentrates necessary to also form thrombin including vitamin K-dependent coagulation factors. While both rFVIIa and prothrombin complex concentrate are being used off label to attenuate post-cardiopulmonary bypass bleeding, they also carry potential safety concerns regarding thrombogenicity and thromboembolic risk. Future randomised control specific to paediatric post-cardiopulmonary bypass surgical studies are needed. Coagulopathy and bleeding in neonates and children undergoing cardiac surgery are complex and multifactorial. An institutional algorithm using surgical field inspection, restrictive red blood cell transfusion strategies, point-of-care testing directed towards individualised platelet, fibrinogen concentrate (or cryoprecipitate), and rFVIIa and prothrombin complex concentrate care should be considered.