HPE CSL Managing Perioperative Bleeding handbook | Page 20

Paediatrics
20
1 , 14 – 18 coagulopathy in adults and children .
Plasma and cryoprecipitate are alternative sources 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 Cryoprecipitate contains higher concentrations of fibrinogen than plasma , but was withdrawn from several European countries because of the risk of immunologic reactions and potential transmission of infectious agents .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 doses for plasma of 10 – 15ml / kg might not be adequate to achieve a clinically meaningful improvement in haemostatic potential . 11
Fibrinogen activity can be assessed by the Clauss assay , and current recommendations emphasise a trigger level of 150 – 200mg / dl for initiating fibrinogen substitution therapy in a bleeding patient . 19 Ideally , functional fibrinogen activity can be assessed reliably and much faster using the ROTEM ® or TEG ® . As such , fibrinogen substitution can be initiated if maximum clot firmness ( MCF ) at 10 minutes ( A10 ) is ≤ 7mm , which approximates to a Clauss assay of ≤ 150 mg / dl . 3
Clinical studies in adults have demonstrated a beneficial role for intraoperative substitution with human fibrinogen concentrate to treat hypofibrinogenaemia 20 – 25 with a very good safety profile . 26 , 27 A randomised clinical trial in children who underwent major craniofacial surgery has demonstrated that early intraoperative fibrinogen substitution at a dose of 30mg / kg using a threshold of ROTEM ® FIBTEM MCF < 13mm has led to a significant and clinically relevant reduction of transfused red blood cell concentrates compared with a lower threshold of a FIBTEM MCF < 8mm . 10 Although blood loss was still considerable , neither transfusion of plasma nor platelet was necessary . At the same time , earlier substitution with fibrinogen decreased calculated blood loss from a median of 156.9 % to 89.7 %. No postoperative RBC transfusion in any child was necessary , which is in sharp contrast to published data for children who underwent major craniofacial surgeries , where postoperative transfusion occurred relatively frequently ( 26 – 40 %). Notably , this management was not linked to a significant increase in total costs for transfused allogeneic blood products and coagulation factors thus offering an economically equivalent approach to coagulation management . 28
Data from a randomised clinical trial in children undergoing cardiac surgery
showed that fibrinogen concentrate was as efficient and safe as transfusion of cryoprecipitate in the management of bleeding after cardiopulmonary bypass weaning . 29 In the same setting , a retrospective data analysis in children who underwent cardiopulmonary bypass surgery revealed a significant reduction in transfusion requirements for cryoprecipitate and fresh frozen plasma , if fibrinogen concentrate at a dose of 70mg / kg was given in the rewarming phase . 30 A meta-analysis of 14 randomised clinical trials in adult and paediatric cardiosurgical patients demonstrated that all-cause mortality was lower in the fibrinogen concentrate group , and bleeding and transfusion requirements were significantly lower versus placebo or a comparator group . 31 There were no differences in the rates of
“ 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 ”
thrombotic events and myocardial infarction .
Analysis of our own data showed that a dose of 30mg / kg can increase FIBTEM clot firmness approximately 3mm , which may be insufficient in most cases of more severe bleeding conditions with acquired hypofibrinogenaemia . Thus , a dose of 50mg / kg has become standard in our hospital , which is likely to increase the FIBTEM MCF at least 5mm .
In summary , fibrinogen concentrate is 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 .
Prothrombin complex concentrate Prothrombin complex concentrates ( PCCs ) 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 .
Besides that , PCC is frequently used in adult patients to correct coagulopathy with low vitamin K-dependent coagulation factor levels and perioperative bleeding . 32 , 33 However , data on its off-label use in children are very limited . Analysis of a 5-year retrospective case series in patients aged from 0 – 16 years has demonstrated favourable efficacy and safety of PCCs . 34 In that study , 11 patients were treated for vitamin K antagonist-related reversal of high international normalised ratio ( INR ), two children were treated for elevated INR not related to vitamin K antagonist use , and for intractable bleeding postcardiopulmonary bypass surgery in three children . However , total sample size was small , and dosing regimen was not based on evidence-based data . One thrombotic event was documented , but true contribution to PCC was unclear . Data from ex vivo supplemention of PCC to blood samples obtained from neonates after cardiopulmonary bypass showed that even a very low dose of 4.7 – 14U / kg was sufficient to enhance lag time , the peak amount , and the rate of thrombin generation . 35 A case report has described the effective use of PCC in a newborn suffering from spontaneous intracranial bleeding , and who did not receive vitamin K supplementation at birth . 36
As a result , there is little evidence on the safety and efficacy of PCC in children . However , for treatment of severe bleeding episodes , where plasma is unavailable as a source of coagulation factors , or where there is a risk of hypervolaemia due to large amounts of plasma , use of PCC might offer a useful approach .
Factor FXIII concentrate Factor XIII represents another major contributor in achieving clot stability by cross-linking fibrin monomers , and preventing clot lysis by covalent binding of α 2
-plasmin inhibitor to fibrin molecules . Although congenital FXIII deficiency is a very rare bleeding disorder , there are clinical data proving that acquired FXIII deficiency can be observed frequently during major paediatric surgery . 37 , 38 In the latter study , FXIII levels decreased to minimal levels of activity of 33 % ( 15 – 61 %), which has been determined to be the lower threshold in adults to initiate FXIII supplementation . 3
hospitalpharmacyeurope . com