Thorsten Haas, MD
Management of perioperative bleeding in children is a major challenge for anaesthetists and this is one of the topics to be discussed next November, in Sofia, in the framework of the ESA annual Focus Meeting.
The reasons for haemostatic changes during paediatric major surgery are multifactorial and may be related to dilutional coagulopathy, loss and consumption of coagulation factors, hyperfibrinolysis, or surgical bleeding.1Although optimal thresholds to initiate transfusion therapy in children are still controversially discussed, it has become more evident that the transfusion of allogeneic blood productsis linked to increased morbidity and mortality in bleeding children.2-5
Timely laboratory testing is crucial in detecting and guiding adequate management. The use of viscoelastic testing such as ROTEM® or TEG® has been shown to be effective in guiding paediatric perioperative bleeding management.6-11In addition, such tests are effective at reducing transfusion requirements and related costs.12,13However, the implementation of a fast and reliable haemostatic testing is just half of the equation. It additionally needs a tailored and individualised administration of blood products and factors to further improve effectiveness of adequate bleeding management.
The targeted use of purified coagulation factors offers a great alternative to transfusion of allogeneic blood products, as they are easy to reconstitute and thus are available in a short period of time, there is no need for blood group compatible administration, and it is not linked to transfusion-associated side effects, such as transfusion related immunomodulation (TRIM) or transfusion-related acute lung injury (TRALI). In addition, the total volume of reconstituted purified coagulation factors is markedly less and, therefore, transfusion-related cardiac overload (TACO) is less likely.
Therapeutic modalities for treating haemostatic derangements caused by critical bleeding were traditionally composed of the administration of allogeneic blood products such as therapeutic plasma or cryoprecipitate. However, specific factor replacements, such as fibrinogen concentrate, prothrombin complex concentrate, or factor XIII concentrate, may offer definite advantages.
Fibrinogen is the first coagulation factor that achieves critically low levels during massive blood loss, while all other factors seem to be less affected by haemodilution and blood loss.14This has been observed in adult as well as in the paediatric perioperative setting.1
Besides the use of plasma or cryoprecipitate, fibrinogen concentrate is an alternative source of fibrinogen. Cryoprecipitate contains higher concentrations of fibrinogen than plasma, but was withdrawn from several European countries because of the risk of immunologic reactions and potential transmission of infectious agents. It should be acknowledged that recommended dosages for plasma of 10–15 mL/kg may not be adequate to achieve a clinically meaningful improvement in adequate amounts of fibrinogen to ensure sufficient clot building.14Ideally, functional fibrinogen activity can be assessed reliably and much faster using viscoelastic testing such as the ROTEM® or TEG®. Fibrinogen concentrate has been demonstrated to be highly efficient in treating acquired hypofibrinogenaemia, offers a good safety profile, is almost immediately available, can be stored at room temperature, can be timely and reliably guided by viscoelastic testing, and can be administered in a very short time.
Tranexamic acid (TXA) is an antifibrinolytic that has been proven effective in paediatric cardiac, craniofacial, orthopaedic, and neurosurgery in reducing blood loss and blood transfusion requirements and therefore has been recommended universally in the management of critical paediatric bleeding.7-15TXA is a potent antifibrinolytic and therefore in pathological hyperfibrinolytic states induced by trauma and surgery, TXA stabilizes the vulnerable fibrin clot.
Prothrombin complex concentrates (PCC) are licensed for rapid reversal of low vitamin K-dependent coagulation factor levels due to vitamin K antagonists in the setting of active bleeding and for urgent prophylaxis of bleeding. Data about its off-label use in children is very limited. Analysis of a 5-year retrospective case series in patients aged 0-16 years has demonstrated favourable efficacy and safety of PCCs.15Although evidence on the safety and efficacy of PCC in children is limited, for treatment of severe bleeding episodes, where plasma is unavailable as a source of coagulation factors, or where there is a risk of hypervolemia due to large amounts of plasma, using PCC might offer a useful approach.
Factor XIII represents another major contributor in achieving clot stability by cross-linking fibrin monomers, and preventing clot lysis. Although congenital FXIII deficiency is a very rare bleeding disorder, there is clinical data proving that acquired FXIII deficiency can be frequently observed during major paediatric surgery.16,17
In summary, prompt and timely identification of the underlying coagulopathy and in consequence individualised treatment of depleted factors are the mainstay of a modern and advanced coagulation management. The use of coagulation factors as part of an algorithm offers great advantages for effective bleeding management, as it does not require cross-matching or thawing, is almost immediately available, it does not alter serum ionized calcium level, it is less immunogenic, the increase in desired coagulation factor levels can be reliably calculated, and it can be administered in significantly less volume compared to empiric plasma transfusion. Although more clinical data in children are needed, this approach seems very likely to warrant a targeted effective management that can be established within a very short time.
- Haas T, Mauch J, Weiss M, Schmugge M. Transfus Med Hemother2012;39:114-9.
- Goobie SM, DiNardo JA, Faraoni D. Transfusion2016;56:2487-94.
- Bolton-Maggs PH. Pediatr Clin North Am2013;60:1527-40.
- Demaret P, Tucci M, Karam O, Trottier H, Ducruet T, Lacroix J. Pediatr Crit Care Med2015;16:505-14.
- Lavoie J. Paediatr Anaesth2011;21:14-24.
- American Society of Anesthesiologists Task Force on Perioperative Blood Management. Practice guidelines for perioperative blood management. Anesthesiology2015;122:241-75.
- El Kady N, Khedr H, Yosry M, El Mekawi S. Eur J Anaesthesiol2009;26:293-7.
- Romlin BS, Wahlander H, Synnergren M, Baghaei F, Jeppsson AE. Paediatr Anaesth2013;23:222-7.
- Faraoni D, Willems A, Romlin BS, Belisle S, Van der Linden P. Eur J Anaesthesiol2015;32:320-9.
- Faraoni D, Willems A, Savan V, Demanet H, De Ville A, Van der Linden P. Eur J Anaesthesiol2014;31:317-26.
- Nakayama Y, Nakajima Y, Tanaka KA, et al. Br J Anaesth2015;114:91-102.
- Weber CF, Gorlinger K, Meininger D, et al. Anesthesiology2012;117:531-47.
- Haas T, Spielmann N, Restin T, et al. Br J Anaesth2015;115:234-43.
- Levy JH, Welsby I, Goodnough LT. Transfusion2014;54:1389-405; quiz 1388.
- Noga T, Bruce AA, Blain H, Nahirniak S. Vox Sang2016;110:253-7.
- Korte W. Hamostaseologie2006;26:S30-5.
- Haas T, Korte W, Spielmann N, et al. Paediatr Anaesth2012;22:641-6.