Fibrinolysis in Traumatic Brain Injury: Diagnosis, Management, and Clinical Considerations

Abstract

Posttraumatic coagulopathy involves disruption of both the coagulation and fibrinolytic pathways secondary to tissue damage, hypotension, and inflammatory upregulation. This phenomenon contributes to delayed complications after traumatic brain injury (TBI), including intracranial hemorrhage progression and systemic disseminated intravascular coagulopathy. Development of an early hyperfibrinolytic state may result in uncontrolled bleeding and is associated with increased mortality in patients with TBI. Although fibrinolytic assays are not routinely performed in the assessment of posttraumatic coagulopathy, circulating biomarkers such as D-dimer and fibrin degradation products have demonstrated potential utility in outcome prediction. Unfortunately, the relatively delayed nature of these tests limits their clinical utility. In contrast, viscoelastic tests are able to provide a rapid global assessment of coagulopathy, although their ability to reliably identify disruptions in the fibrinolytic cascade remains unclear. Limited evidence supports the use of hypertonic saline, cryoprecipitate, and plasma to correct fibrinolytic disruption; however, some studies suggest more harm than benefit. Recently, early use of tranexamic acid in patients with TBI and confirmed hyperfibrinolysis has been proposed as a strategy to further improve clinical outcomes. Moving forward, further delineation of TBI phenotypes and the clinical implications of fibrinolysis based on phenotypic variation is needed. In this review, we summarize the clinical aspects of fibrinolysis in TBI, including diagnosis, treatment, and clinical correlates, with identification of targeted areas for future research efforts.

頭部外傷患者における頭部造影CT検査での造影剤血管外漏出像と予後との関係(Relationship between extravascular leakage and clinical outcome on computed tomography of traumatic brain injury)

“…サマリデータは，連続変数は中央値（四分位範囲）で示し，カテゴリカル変数は数（%）で示した。血管外漏出像がある患者と血管外漏出像がない患者の2群間差の検出は，連続変数の項目ではMann–Whitney U検定を行い，名義変数を用いた項目についてはカイ二乗検定またはFisherの正確検定を行った。主要評価項目である死亡と造影剤の血管外漏出像との関連を評価するためにロジスティック回帰分析を行い，オッズ比と95%信頼区間を算出した。調整因子は先行論文 10), 11)に準じて死亡に関連するとされる年齢と単純CT検査で評価できるMarshall CT分類を選択した。なお，Marshall CT分類は連続変数として取り扱った場合でも死亡と関連するとされており 12)，今回ロジスティック回帰分析をする際はMarshall CT分類を1～6の連続変数として取り扱った。副次評価項目である手術の実施と造影剤の血管外漏出像との関連を評価するために，ロジスティック回帰分析を行った。調整因子は背景となる年齢，性別に加え，手術適応に関連すると考えられる来院時GCSを選択した。次にサブグループ解析として緊急手術をせず経過観察を行った患者を対象にロジスティック回帰分析を行った。…”

Blood Type O Is a Risk Factor for Hyperfibrinolysis and Massive Transfusion After Severe Injury

“…As far as the levels of von Willebrand factor in those who are severely injured, there are little to no data with regard to the levels at which replacement is needed. Moreover, cryoprecipitate was initially used to treat both hemophilia A and von Willebrand's disease and is a vital component of MT and directly helps to correct the TEG-based coagulation parameters, namely, R-time, angle, and MA, in severely injured patients (24)(25)(26)(27). In addition, during clot formation, von Willebrand factor incorporates into the fibrin mesh and recruits platelets, and lack of such platelet recruitment will result in an unstable clot (28).…”

Derivation of coagulation phenotypes and the association with in-hospital mortality in traumatic brain injury

“…Since coagulopathy is becoming increasingly more important as a poor prognostic factor in TBI, [39] identifying the severity of coagulopathy in TBI is essential for predicting the outcome. Although tailor-made treatment recommendations are di cult to make since this study is limited to the derivation of phenotypes only, we propose the possibility of coagulation correction therapy in each cluster based on previous studies.…”