Finding the optimal concentration range for fibrinogen replacement after severe haemodilution: an in vitro model

Abstract

The target plasma concentration for fibrinogen replacement was predicted by these in vitro results to be greater than 200 mg dl(-1) as only these concentrations optimized the rate of clot formation. This concentration is twice the level suggested by the current transfusion guidelines. Although improved, clots were prone to fibrinolysis indicating that the efficacy of fibrinogen therapy may be influenced by co-existing fibrinolytic tendency occurring during dilutional coagulopathy.

A new structural biomarker that quantifies and predicts changes in clot strength and quality in a model of progressive haemodilution

“…Several studies investigating the optimal fibrinogen concentration have recommended a range values (>1.0 g/L to <2.5 g/L). [31][32][33][34] In the present study we report significant changes in the incipient clot microstructure, df, at a dilution of ≥20% (see Figure 3). The df changes from 1.74 ± 0.033 (at 0% dilution) to 1.69 ± 0.032 (at 20% dilution) with a corresponding change in fibrinogen concentration of 2.6 ± 0.3 g/L (at 0% dilution) to 2.1 ± 0.5 g/L (at 20% dilution).…”

Diagnostic Performance and Therapeutic Consequence of Thromboelastometry Activated by Kaolin versus a Panel of Specific Reagents

“…This assay has been used in clinical studies to detect dilutional coagulopathy 33 and to calculate relevant dosages of fibrinogen. 34 Although significant difference where found between the levels of dilutional coagulopathy and thrombocytopenia applied in this study using the INTEM and EXTEM, distinction based on monoactivation without FIBTEM does not seem feasible in a clinical setting with complex coagulopathies of widespread severity. A functional fibrinogen assay is also available from Haemoscope, 35 but has so far not found widespread application in published treatment algorithms and was not evaluated in this study.…”

Increasing concentrations of prothrombin complex concentrate induce disseminated intravascular coagulation in a pig model of coagulopathy with blunt liver injury

“…Second, the relationship between coagulation factor levels and CT/PT values is not linear: in hemodilution, the concentration of coagulation factors needs to drop to Ͻ 40% before prolongation of CT or PT is observed. 40,41 On the other hand, there is a linear relationship between thrombin generation and levels of coagulation factors, making this assay more sensitive to changes in these proteins. Third, neither EXTEM CT nor PT is influenced by antithrombin, whereas thrombin generation is strongly influenced by antithrombin.…”