Paediatrics
However, clinical efficacy of FXIII
administration to treat acquired FXIII
deficiency in paediatric surgery is
currently based on clinical observation
rather than on evidence-based data. a significantly less volume than plasma
transfusion. Although more clinical data
in children are needed, this approach
seems very likely to permit rapid and
effective targeted management.
Recombinant activated FVII
Management of intractable bleeding has
led to a call for a defined rescue therapy.
Although it is well known that some
prerequisites including normothermia,
undisturbed acid–base status, and
normal calcium levels, as well as sufficient
platelet count and plasma fibrinogen
levels are the mainstay for adequate clot
building, many authors have declared
a special role in improving thrombin
potential to enable cessation of bleeding.
Therefore, administration of recombinant
activated FVII (rFVIIa) has been
advocated, whereby clinical evidence
to support its use are lacking.
Activated rFVII is licensed for the
treatment of patients with haemophilia
A or B with inhibitors, and patients with
congenital FVII deficiency. In Europe,
additional approval was granted for
treatment of Glanzmann’s
thrombasthenia. There are published data
for the off-label treatment using rFVIIa
to stop severe bleeding in children with
bleeding during neurosurgical
procedures 39,40 and cardiac surgery. 41
It has been hypothesised that
administration of rFVIIa for treatment
of severe bleeding in adults may only
be efficacious if critical amounts of
fibrinogen and platelets have been
established. 3 As no clear dose has been
established, sound evidence-based data
are lacking, and the treatment using
rFVIIa increases thromboembolic risk
considerably, a recent Cochrane analysis
has advocated against the use of rFVIIa
outside its licensed indications. 42 References
1 Haas T et al. Management of dilutional
coagulopathy during pediatric major surgery. Transfus
Med Hemother 2012;39:114–19.
2 American Society of Anesthesiologists Task Force on
Perioperative Blood M. Practice guidelines for
perioperative blood management: an updated report
by the American Society of Anesthesiologists Task
Force on Perioperative Blood Management.
Anesthesiology 2015;122:241–75.
3 Kozek-Langenecker SA et al. Management of
severe perioperative bleeding: guidelines from the
European Society of Anaesthesiology: First update
2016. Eur J Anaesthesiol 2017;34:332–95.
4 El Kady N et al. Perioperative assessment of
coagulation in paediatric neurosurgical patients using
thromboelastography. Eur J Anaesthesiol
2009;26:293–7.
5 Romlin BS et al. Earlier detection of coagulopathy
with thromboelastometry during pediatric cardiac
surgery: a prospective observational study. Paediatr
Anaesth 2013;23:222–7.
6 Faraoni D et al. Developm ent of a specific algorithm
to guide haemostatic therapy in children undergoing
cardiac surgery: a single-centre retrospective study.
Eur J Anaesthesiol 2015;32:320–9.
7 Faraoni D et al. Plasma fibrinogen concentration is
correlated with postoperative blood loss in children
undergoing cardiac surgery. A retrospective review.
Eur J Anaesthesiol 2014;31:317–26.
8 Nakayama Y et al. Thromboelastometry-guided
intraoperative haemostatic management reduces
bleeding and red cell transfusion after paediatric
cardiac surgery. Br J Anaesth 2015;114:91–102.
9 Weber CF et al. Point-of-care testing: a prospective,
randomized clinical trial of efficacy in coagulopathic
cardiac surgery patients. Anesthesiology
2012;117:531–47.
10 Haas T et al. Higher fibrinogen concentrations for
reduction of transfusion requirements during major
paediatric surgery: A prospective randomised
controlled trial. Br J Anaesth 2015;115:234–43.
11 Levy JH, Welsby I, Goodnough LT. Fibrinogen as
a therapeutic target for bleeding: a review of critical
levels and replacement therapy. Transfusion
2014;54:1389–1405; quiz 1388.
12 Levy JH et al. Fibrinogen and hemostasis:
a primary hemostatic target for the management
of acquired bleeding. Anesth Analg 2012;114:261–74.
13 Sorensen B et al. Fibrinogen as a hemostatic
agent. Semin Thromb Haemost 2012;38:268–73.
14 Fenger-Eriksen C et al. Mechanisms of hydroxyethyl
starch-induced dilutional coagulopathy. J Thromb
Haemost 2009;7:1099–105.
15 Levy JH. Massive transfusion coagulopathy. Semin
Hematol 2006;43:S59–S63.
16 Fries D. [Dilutional coagulopathy: development,
diagnostic options and management].
Haemostaseologie 2006;26:S15–S19.
17 Kozek-Langenecker S. Management of massive
operative blood loss. Minerva Anestesiol
2007;73:401–15.
18 Innerhofer P, Kienast J. Principles of perioperative
coagulopathy. Best practice and research. Clin
Anaesthesiol 2010;24:1–14.
19 Rossaint R et al. Management of bleeding
following major trauma: an updated European
guideline. Crit Care 2010;14:R52.
20 Haas T et al. Fibrinogen in craniosynostosis
surgery. Anesth Analg 2008;106:725–31.
21 Rahe-Meyer N et al. Thromboelastometry-guided
administration of fibrinogen concentrate for the
treatment of excessive intraoperative bleeding in
thoracoabdominal aortic aneurysm surgery. J Thorac
Cardiovasc Surg 2009;138:694–702.
22 Fenger-Eriksen C et al. Fibrinogen substitution
Conclusions
Prompt and timely identification of the
underlying coagulopathy and,
consequently, 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 ionised calcium level, it is less
immunogeneic, the increase in desired
coagulation factor levels can be reliably
calculated, and it can be administered in
improves whole blood clot firmness after dilution with
hydroxyethyl starch in bleeding patients undergoing
radical cystectomy: a randomized, placebo-controlled
clinical trial. J Thromb Haemost 2009;7:795–802.
23 Fenger-Eriksen C et al. Fibrinogen concentrate
substitution therapy in patients with massive
haemorrhage and low plasma fibrinogen
concentrations. Br J Anaesth 2008;101:769–73.
24 Danes AF et al. Efficacy and tolerability of human
fibrinogen concentrate administration to patients with
acquired fibrinogen deficiency and active or in
high-risk severe bleeding. Vox Sang 2008;94:221–6.
25 Weinkove R, Rangarajan S. Fibrinogen concentrate
for acquired hypofibrinogenaemic states. Transfus
Med 2008;18:151–7.
26 Dickneite G et al. Animal model and clinical
evidence indicating low thrombogenic potential of
fibrinogen concentrate (Haemocomplettan P). Blood
Coagul Fibrinolysis 2009;20:535–40.
27 Manco-Johnson MJ et al. Pharmacokinetics and
safety of fibrinogen concentrate. J Thromb Haemost
2009;7:2064–9.
28 Haas T et al. Economic aspects of intraoperative
coagulation management targeting higher fibrinogen
concentrations during major craniosynostosis surgery.
Paediatr Anaesth 2016;26:77–83.
29 Galas FR et al. Hemostatic effects of fibrinogen
concentrate compared with cryoprecipitate in children
after cardiac surgery: a randomized pilot trial.
J Thorac Cardiovasc Surg 2014;148:1647–55.
30 Tirotta C et al. Use of human fibrinogen
concentrate in pediatric cardiac surgery. Int
J Anesthetic Anesthesiol 2015;2:1–6.
31 Fominskiy E et al. Efficacy and safety of fibrinogen
concentrate in surgical patients: A meta-analysis of
randomized controlled trials. J Cardiothorac Vasc
Anesth 2016;30:1196–1204.
32 Despotis G, Eby C, Lublin DM. A review of
transfusion risks and optimal management of
perioperative bleeding with cardiac surgery.
Transfusion 2008;48:2S–30S.
33 Butchart EG et al. Exercise Physiology ESoC.
Recommendations for the management of patients
after heart valve surgery. Eur Heart J 2005;26:
2463–71.
34 Noga T et al. Four-factor prothrombin complex
concentrates in paediatric patients – a retrospective
case series. Vox Sang 2016;110:253–7.
35 Franklin SW et al. Optimizing thrombin generation
with 4-Factor prothrombin complex concentrates in
neonatal plasma after cardiopulmonary bypass.
Anesth Analg 2016;122:935–42.
36 Rech MA et al. Prothrombin complex concentrate
for intracerebral hemorrhage secondary to vitamin K
deficiency bleeding in a 6-week-old child. J Pediatr
2015;167:1443–4.
37 Korte W. [Fibrin monomer and factor XIII: a new
concept for unexplained intraoperative coagulopathy].
Hamostaseologie 2006;26:S30–35.
38 Haas T et al. Perioperative course of FXIII in
children undergoing major surgery. Paediatr Anaesth
2012;22(7):641–6.
39 Uhrig L et al. Use of recombinant activated factor
VII in intractable bleeding during pediatric
neurosurgical procedures. Pediatr Crit Care Med
2007;8:576–9.
40 Heisel M et al. Use of recombinant factor VIIa
(rFVIIa) to control intraoperative bleeding in pediatric
brain tumor patients. Pediatr Blood Cancer
2004;43:703–05.
41 Ekert H et al. Elective administration in infants of
low-dose recombinant activated factor VII (rFVIIa) in
cardiopulmonary bypass surgery for congenital heart
disease does not shorten time to chest closure or
reduce blood loss and need for transfusions:
a randomized, double-blind, parallel group,
placebo-controlled study of rFVIIa and standard
haemostatic replacement therapy versus standard
haemostatic replacement therapy. Blood Coagul
Fibrinolysis 2006;17:389–95.
42 Simpson E et al. Recombinant factor VIIa for the
prevention and treatment of bleeding in patients
without haemophilia. Cochrane Database Sys Rev
2012;3:CD005011.
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