Endogenous Procoagulant Activity in Trauma Patients and Its Relationship to Trauma Severity

Prior, Shannon M.; Park, Myung S.; Mann, Kenneth G.; Butenas, Saulius

doi:10.1055/s-0038-1677030

Cited by 4 publications

(3 citation statements)

References 29 publications

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“…However, repeated measurements during and after surgery showed an increase of FXIa levels in plasma, which became statistically significant mid-operatively, reaching levels of 9.38-10.13 pmol/L. These data agree well with previous studies in which median FXIa levels of 5.7-6.8 pmol/L were measured in patients with injuries of varying severity without shock 36) , and mean FXIa levels of 10.6 pmol/L were measured in patients after penetrating trauma 37) , clinical situations comparable with surgical trauma. Besides the increase of FXIa levels, there was an increase of free thrombin and indirect markers of thrombin activation in the surgery cohort that has been described and discussed thoroughly in a previous report 26) .…”

Section: Resultssupporting

confidence: 91%

Activated Factor XI is Increased in Plasma in Response to Surgical Trauma but not to Recombinant Activated FVII-Induced Thrombin Formation

Rühl

Friemann

Reda

et al. 2022

JAT

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Aim: Feedback activation of factor XI (FXI) by thrombin is believed to play a critical role in the amplification phase of thrombin generation and to contribute to thrombosis development and hemostasis. However, the activation of FXI by thrombin has been shown in vitro to require a cofactor. In this study, the role of thrombin in activated FXI (FXIa) formation in vivo is investigated. Methods: The study population comprised probands in whom coagulation activation was triggered by low-dose (15 µg/kg) recombinant activated factor VII (rFVIIa, n =89), of whom 34 with (VTE+) and 45 without a history of venous thromboembolism (VTE−), and patients undergoing major orthopedic surgeries ( n =45). FXIa was quantified via an enzyme capture assay using a monoclonal FXI-specific antibody. Thrombin formation was monitored using an oligonucleotide-based enzyme capture assay and the thrombin activation markers prothrombin fragment 1＋2 (F1＋2) and thrombin–antithrombin complex (TAT). Results: In the rFVIIa cohort, FXIa and thrombin remained below their lower limit of quantification of 3.48 and 1.06 pmol/L, respectively. By contrast, during the surgeries, median FXIa levels increased from 3.69 pmol/L pre-operatively to 9.41 pmol/L mid-operatively ( P =4·10 −4 ) and remained significantly elevated 24 h thereafter, with 9.38 pmol/L ( P =0.001). Peak levels of F1+2 were comparable in the VTE+, VTE−, and surgery cohort (235, 268, and 253 pmol/L), whereas peak TAT levels were higher in the surgery cohort (53.1, 33.9, and 147.6 pmol/L). Conclusions: Under in vivo conditions, the activation of FXI requires specific local features that are present at the wounded site including potential cofactors of thrombin.

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Section: Resultssupporting

confidence: 91%

Activated Factor XI is Increased in Plasma in Response to Surgical Trauma but not to Recombinant Activated FVII-Induced Thrombin Formation

Rühl

Friemann

Reda

et al. 2022

JAT

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“…It should be mentioned that due to the limited sensitivity of flow cytometry in 2001, we called this "EV-depleted plasma". However, as shown recently for foetal calf serum [7,8], most small EVs cannot be removed from plasma or serum by (ultra) centrifugation. To this plasma (120 µL), either EVs, Innovin (50-fold diluted; 6.1 pmol/mL final concentration) or Synthasil (fivefold diluted before use) were added, the last two to initiate the extrinsic or intrinsic coagulation, respectively (20 µL).…”

Section: Coagulationmentioning

confidence: 94%

Extracellular vesicles and coagulation in blood from healthy humans revisited

Berckmans

Lacroix

Hau

et al. 2019

J of Extracellular Vesicle

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Background: In 2001, we studied the presence and coagulant properties of "microparticles" in the blood of healthy humans. Since then, multiple improvements in detection, isolation and functional characterization of the now called "extracellular vesicles" (EVs) have been made, and shortcomings were identified. Aim: To revisit the presence and function of EVs in blood from healthy humans. Methods: Blood was collected from 20 healthy donors. EV-containing plasma was prepared according to new guidelines, and plasma was diluted to prevent swarm detection. Single EVs were measured by flow cytometry with known sensitivity of fluorescence and light scatter. The haemostatic properties of EVs were measured by thrombin-, fibrin-, and plasmin generation. Plasma concentrations of thrombin-antithrombin complexes and prothrombin fragment 1 + 2 were measured to assess the coagulation status in vivo. Results: Compared to 2001, the total concentrations of detected EVs increased from 190-to 264-fold. In contrast to 2001, however, EVs are non-coagulant which we show can be attributed to improvements in blood collection and plasma preparation. No relation is present between the plasma concentrations of EVs and either TAT or F1 + 2. Finally, we show that EVs support plasmin generation. Discussion: Improvements in blood collection, plasma preparation and detection of EVs reveal that results from earlier studies have to be interpreted with care. Compared to 2001, higher concentrations of EVs are detected in blood of healthy humans which promote fibrinolysis rather than coagulation.

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“…Trauma patients are procoagulant [93] and show enhanced thrombin generation [94]. Thrombin contributes to fibrinolysis resistance by reducing profibrinolytic effects of thrombomodulin (TM) and activated protein C (APC) [73].…”

Section: Relation To Fibrinolytic Activitymentioning

confidence: 99%

Evolving Paradigms in Laboratory Biomarkers of Fibrinolysis Phenotypes and Association with Post-Traumatic Vascular Thrombosis

Ogweno¹,

Murungi²

2023

Microcirculation - Updates in the Next Frontier of Vascular Disease

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Traumatic tissue injury triggers blood coagulation to stanch bleeding and concomitant blood clot lysis to restore vascular patency. Approximately, 40% of trauma cases potentially present with trauma-induced coagulopathy that may coexist with clot dissolution or fibrinolysis. Laboratory test results of fibrinolysis biomarkers stratify fibrinolytic phenotypes into hyperfibrinolysis, physiological, hypofibrinolysis, and fibrinolytic shutdown. However, often, there is incongruence between laboratory findings and clinical presentation of bleeding or vascular thrombosis. Increasingly, it is becoming clear that laboratory findings transiently depend on the timing of blood sampling. The spectrum of evolving fibrinolysis phenotypes, a component of nature’s adaptation to wound healing that ranges from initial promotion of blood fluidity to subsequent thrombosis, presents a clinical diagnostic dilemma with regard to the timing of antifibrinolytics or anticoagulants intervention. This chapter will review the available literature on post-traumatic fibrinolytic phenotypes, diagnostic challenges, evolution over time, clinical outcomes following therapeutic interventions, and association with vascular thrombosis.

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Endogenous Procoagulant Activity in Trauma Patients and Its Relationship to Trauma Severity

Cited by 4 publications

References 29 publications

Activated Factor XI is Increased in Plasma in Response to Surgical Trauma but not to Recombinant Activated FVII-Induced Thrombin Formation

Activated Factor XI is Increased in Plasma in Response to Surgical Trauma but not to Recombinant Activated FVII-Induced Thrombin Formation

Extracellular vesicles and coagulation in blood from healthy humans revisited

Evolving Paradigms in Laboratory Biomarkers of Fibrinolysis Phenotypes and Association with Post-Traumatic Vascular Thrombosis

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