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Fibrinogen depletion in trauma: early, easy to estimate and central totrauma-induced coagulopathy
Critical Care volume 17, Article number: 190 (2013)
Fibrinogen is fundamental to hemostasis and falls rapidly in trauma hemorrhage,although levels are not routinely measured in the acute bleeding episode. Promptidentification of critically low levels of fibrinogen and early supplementationhas the potential to correct trauma-induced coagulation and improve outcomes.Early estimation of hypofibrinogenemia is possible using surrogate markers ofshock and hemorrhage; for example, hemoglobin and base excess. Rapid replacementwith fibrinogen concentrate or cryoprecipitate should be considered a clinicalpriority in major trauma hemorrhage.
Fibrinogen is the primary substrate of the coagulation system and is fundamental tohemostasis. Fibrinogen falls to critical levels soon after the onset of major traumahemorrhage but is not considered part of routine clotting assays. To maintain theintegrity of coagulation function it is recommended that fibrinogen is replaced whenit falls below 150 to 200?mg/dl. Early recognition and replacement has the potentialto rapidly reverse trauma-induced coagulopathy, arrest hemorrhage and improveoutcomes. Schlimp and colleagues have demonstrated that it is possible to estimatefibrinogen in the emergency department using widely available point-of-care assays .
The literature contains numerous reports of improved outcomes when early high-doseplasma is administered as part of a massive hemorrhage protocol. Fibrinogensupplementation with either cryoprecipitate (the UK or USA) or fibrinogenconcentrate (Europe) is often delayed or considered second line in the empiricdelivery of hemostatic coagulation therapy. The therapeutic mechanism by whichplasma controls hemorrhage or corrects coagulopathy remains unknown. Earlyfibrinogen supplementation is commonplace in postpartum hemorrhage and cardiacsurgery, with only limited data indicating a potential therapeutic benefit in trauma . Each unit of plasma contains approximately 500?mg fibrinogen, andtherefore the efficacy of large-volume plasma transfusions in massive hemorrhageprotocols may in part be due to restoration of fibrinogen levels. For this reason,early fibrinogen replacement is the subject of two pilot randomized controlledtrials in the UK (CRYOSTAT)  and Austria (FiTIC)  due to report later this year.
Fibrinogen falls early , rapidly reaches critical threshold values relative to other coagulationfactors  and is associated with higher transfusion requirements and increasedmortality. Schlimp and colleagues have confirmed that hypofibrinogenemia is commonin major trauma and is an almost universal problem in those patients presenting withhemoglobin <8?g/dl . The identification of early hypofibrinogenemia requires a laboratoryassay; for example, the Clauss method. Fibrinogen levels are rarely available to thetrauma physician in a clinically relevant timeframe and thus fibrinogensupplementation (for example, cryoprecipitate) is often delayed.
Rotational thromboelastometry and thromboelastography provide a more rapid and globalassessment of coagulation and can provide an estimate of the contribution offunctional fibrinogen to clot strength . These tests are expensive, however, and although available at point ofcare they require further modification, simplification and validation before thistechnology has global appeal for the trauma community. This study has shown it ispossible to risk stratify patients for low or critical fibrinogen levels, usinghemoglobin and base excess that are rapidly available in emergency trauma care.However, even with the addition of the Injury Severity Score, which is not availablewithin the first few hours of care, the regression model only accounted for 51% ofthe variation in fibrinogen. Other important, iatrogenic and patient factorstherefore contribute significantly to the depletion of fibrinogen in traumahemorrhage.
The mechanism by which fibrinogen loss occurs in trauma continues to be the subjectof ongoing debate and research. There is limited evidence to support a consumptiveprocess such as disseminated intravascular coagulation [8, 9], although clearly fibrinogen will be utilized because the coagulationsystem is activated following hemorrhage. Acidosis and hypothermia compoundtrauma-induced coagulopathy and have profound effects on fibrinogen breakdown andsynthesis , which is supported by the findings of the current study thatdemonstrated critical and low levels of fibrinogen in 81% and 63% of shockedpatients, respectively . Finally, resuscitation with gelatins and hydroxyethyl starch solutionreduce the concentration of fibrinogen through dilution and interfere with fibrinpolymerization . Fibrinogen is thought to only contribute approximately one-third ofviscoelastic strength to the overall clot, with platelets being the majordeterminant of clot firmness in rotational thromboelastometry/thromboelastography .Estimation of fibrinogen deficit alone risks missing the global derangement ofhemostasis typified by trauma-induced coagulopathy.
The estimation of fibrinogen levels by Schlimp and colleagues reminds us thatfibrinogen loss is not only rapid and significant in trauma but is detectable in theemergency department. Metabolic acidosis, injury severity and hemorrhage reducefibrinogen, but other endogenous and iatrogenic factors contribute to the depletionof this primary substrate of coagulation. Rapid identification of hypofibrinogenemiashould be routine in all injured patients and a priority in major trauma hemorrhage,either through estimation or functional assessment with rotationalthromboelastometry/thromboelastography. Understanding the mechanism by whichfibrinogen is lost and the efficacy of early fibrinogen replacement are researchimperatives, and are likely to yield significant therapeutic benefit.
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RD and KB both received departmental funding for study support costs from HaemoneticsCorporation (Braintree, MA, USA) and equipment/reagent grants from Tem InnovationsGmbH (Munich, Germany).
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Davenport, R., Brohi, K. Fibrinogen depletion in trauma: early, easy to estimate and central totrauma-induced coagulopathy. Crit Care 17, 190 (2013). https://doi.org/10.1186/cc13021
- Injury Severity Score
- Disseminate Intravascular Coagulation
- Fibrinogen Level
- Hydroxyethyl Starch