Theoretical modelling of fibrinogen supplementation with therapeutic plasma, cryoprecipitate, or fibrinogen concentrate

Abstract

BackgroundWe aimed to create a theoretical tool to model the effect of three haemostatic agents containing fibrinogen (therapeutic plasma, cryoprecipitate, and fibrinogen concentrate) on the patient's plasma fibrinogen level.MethodsA mathematical model was developed step-wise. The relationship between the amount of haemostatic agent and plasma fibrinogen level was plotted for each agent. A fibrinogen concentration simulator (FCSamount) was developed, where the amount of haemostatic agent was calculated from patient characteristics, agent characteristics, and target plasma fibrinogen level. Refinements were introduced so that (i) FCSamount would account for in vivo fibrinogen recovery, (ii) circulatory volume would not increase ad infinitum with increasing amounts, and (iii) red blood cells would be included in the simulation if haematocrit decreased below a certain level. A second FCS (FCSlevel) was created to calculate fibrinogen levels resulting from specified amounts of haemostatic agents.ResultsFibrinogen concentration in haemostatic agents has a critical impact on their ability to increase patients' fibrinogen levels. If the target plasma fibrinogen level approaches the concentration of the fibrinogen source, the required amounts increase exponentially; it is impossible to achieve a target above the concentration of the fibrinogen source.ConclusionsWe successfully developed two theoretical tools answering the questions: ‘How much therapeutic plasma, cryoprecipitate, or fibrinogen concentrate would be needed to achieve a specified target fibrinogen level?’ and ‘What would be the resultant fibrinogen level for a specified amount of haemostatic agent?’ The current tools are not intended for clinical application, but they are potentially useful for educational purposes.

Fibrinogen in traumatic haemorrhage: A narrative review

“…Fibrinogen can be replaced with: fibrinogen concentrate (FC), cryoprecipitate or plasma, each containing different amounts of fibrinogen: 20g/L, 8-16g/l and 2g/L, respectively, and therefore different volumes are required to achieve replacement (65). A study by Rourke et al (37) demonstrated that standard protocol driven transfusion ratios were ineffective in maintaining fibrinogen levels and the addition of cryoprecipitate was required.…”

How I use fibrinogen replacement therapy in acquired bleeding

“…67 There is a perceived risk of triggering a thromboembolic event associated with fibrinogen supplementation, and that administering excessive fibrinogen, particularly with high thrombin generation, may increase the risk of systemic microthrombogenicity. However, post hoc analysis of a randomized clinical trial of fibrinogen concentrate reported fibrinogen supplementation was not associated with significant alterations of hemostatic parameters.…”

Monitoring the coagulation status of trauma patients with viscoelastic devices

“…It was also reported that abnormalities of R and MA values measured by TEG® were independent predictive factors for poor outcome [33][34][35][36]. It has been demonstrated that prolongation of CFT and a decrease in MCF which indicate a decrease in platelet count measured by ROTEM® were correlated more strongly with poor outcome than with mortality calculated with the Trauma and Injury Severity Score (TRISS) equation [32,37]. It has been reported that a decrease in fibrinogen level which is detectable in the early stage of coagulopathy was also correlated with poor outcome, suggesting the use of fibrinogen level as the standard for administration of cryoprecipitate and fibrinogen preparations [30].…”