Sufficient Thrombin Generation Despite 95% Hemodilution: An In Vitro Experimental Study

Gratz, Johannes; Schlimp, Christoph J.; Honickel, Markus; Hochhausen, Nadine; Schöchl, Herbert; Grottke, Oliver

doi:10.3390/jcm9123805

Cited by 15 publications

(27 citation statements)

References 45 publications

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“…Our study revealed prolonged EXTEM CT values in the HES group despite of no differences in PT between the groups. Although EXTEM CT values primarily represent clot initiation dynamics, a relevant influence of the substrate fibrinogen on EXTEM CT has been described before [ 30 , 31 ]. Consequently, current guidelines for the management of major bleeding recommend further procoagulant medication only once fibrinogen levels, as represented by FIBTEM MCF, have been corrected [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Goal-Directed Crystalloid versus Colloid Administration on Perioperative Hemostasis in Partial Hepatectomy: A Randomized, Controlled Trial

Gratz

Zotti

Pausch

et al. 2021

JCM

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The use of colloids may impair hemostatic capacity. However, it remains unclear whether this also holds true when colloids are administered in a goal-directed manner. The aim of the present study was to assess the effect of goal-directed fluid management with 6% hydroxyethyl starch 130/0.4 on hemostasis compared to lactated Ringer’s solution in patients undergoing partial hepatectomy. We included 50 patients in this prospective, randomized, controlled trial. According to randomization, patients received boluses of either hydroxyethyl starch or lactated Ringer’s solution within the scope of goal-directed fluid management. Minimum perioperative FIBTEM maximum clot firmness (MCF) served as the primary outcome parameter. Secondary outcome parameters included fibrinogen levels and estimated blood loss. In the hydroxyethyl starch (HES) group the minimum FIBTEM MCF value was significantly lower (effect size −6 mm, 95% CI −10 to −3, p < 0.001) in comparison to the lactated Ringer’s solution (RL) group. These results returned to normal within 24 h. We observed no difference in plasma fibrinogen levels (RL 3.08 ± 0.37 g L−1 vs HES 2.65 ± 0.64 g L−1, p = 0.18) or the amount of blood loss between the two groups (RL 470 ± 299 mL vs HES 604 ± 351 mL, p = 0.18). We showed that goal-directed use of HES impairs fibrin polymerization in a dose-dependent manner when compared with RL. Results returned to normal on the first postoperative day without administration of procoagulant drugs and no differences in blood loss were observed.

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Section: Discussionmentioning

confidence: 99%

Effect of Goal-Directed Crystalloid versus Colloid Administration on Perioperative Hemostasis in Partial Hepatectomy: A Randomized, Controlled Trial

Gratz

Zotti

Pausch

et al. 2021

JCM

Self Cite

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“…If SLT are useful for the diagnosis of coagulopathy or to guide hemostatic therapy is questionable [20,22,23]; their turnaround times of 45-60 min disqualify SLT, as median time to death due to exsanguination was 106 min [24]. However, if no other laboratory test is available, SLT may be preferable to no testing [22].…”

Section: Definitionsmentioning

confidence: 99%

“…[22] Perioperative use of SLT Review Gratz J et al J Clin Med. 2020 [23] Thrombin generation Laboratory, healthy volunteers Holcomb JB et al JAMA. 2015 [24] ratio Pragmatic, phase 3, multisite, randomized, clinical Connelly CR et al J Surg Res.…”

Section: Lier/friesmentioning

confidence: 99%

“…Fibrinogen Fibrinogen, coagulation factor I, is the precursor of fibrin and is an important mediator of PLT aggregation, namely via the PLT receptor glycoprotein IIb/IIIa [4]. It is the first factor to reach critical levels [23,68]. Rapid depletion and dysfunction of fibrinogen are an integral part of TIC [1,4,15].…”

Section: Coagulation Factor Concentratesmentioning

confidence: 99%

“…The concentration of clotting factors is approximately 25-fold that of plasma [15,29]. Even in severely bleeding trauma patients, thrombin generation might be sufficient to achieve adequate hemostasis [3,23]. This might be different for trauma patients in shock [76].…”

Section: Coagulation Factor Concentratesmentioning

confidence: 99%

See 2 more Smart Citations

Emergency Blood Transfusion for Trauma and Perioperative Resuscitation: Standard of Care

Lier

Fries

2021

Transfus Med Hemother

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Uncontrolled and massive bleeding with derangement of coagulation is a major challenge in the management of both surgical and seriously injured patients. The underlying mechanism of trauma-induced or -associated coagulopathy is tissue injury in the presence of shock and acidosis provoking endothelial damage, activation of inflammation, and coagulation disbalancing. Furthermore, the combination of ongoing blood loss and consumption of blood components that are essential for effective coagulation worsens uncontrolled hemorrhage. Additionally, therapeutic actions, such as resuscitation with replacement fluids or allogeneic blood products, can further aggravate coagulopathy. Of the coagulation factors essential to the clotting process, fibrinogen is the first to be consumed to critical levels during acute bleeding and current evidence suggests that normalizing fibrinogen levels in bleeding patients improves clot formation and clot strength, thereby controlling hemorrhage. Three different therapeutic approaches are discussed controversially. Whole blood transfusion is used especially in the military scenario and is also becoming more and more popular in the civilian world, although it is accompanied by a strong lack of evidence and severe safety issues. Transfusion of allogeneic blood concentrates in fixed ratios without any targets has been investigated extensively with disappointing results. Individualized and target-controlled coagulation management based on point-of-care diagnostics with respect to the huge heterogeneity of massive bleeding situations is an alternative and advanced approach to managing coagulopathy associated with massive bleeding in the trauma as well as the perioperative setting.

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Engineering a Two‐Component Hemostat for the Treatment of Internal Bleeding through Wound‐Targeted Crosslinking

Hong

Bowen

et al. 2023

Adv Healthcare Materials

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Primary hemostasis (platelet plug formation) and secondary hemostasis (fibrin clot formation) are intertwined processes that occur upon vascular injury. Researchers have sought to target wounds by leveraging cues specific to these processes, such as using peptides that bind activated platelets or fibrin. While these materials have shown success in various injury models, they are commonly designed for the purpose of treating solely primary or secondary hemostasis. In this work, a two‐component system consisting of a targeting component (azide/GRGDS PEG‐PLGA nanoparticles) and a crosslinking component (multifunctional DBCO) is developed to treat internal bleeding. The system leverages increased injury accumulation to achieve crosslinking above a critical concentration, addressing both primary and secondary hemostasis by amplifying platelet recruitment and mitigating plasminolysis for greater clot stability. Nanoparticle aggregation is measured to validate concentration‐dependent crosslinking, while a 1:3 azide/GRGDS ratio is found to increase platelet recruitment, decrease clot degradation in hemodiluted environments, and decrease complement activation. Finally, this approach significantly increases survival relative to the particle‐only control in a liver resection model. In light of prior successes with the particle‐only system, these results emphasize the potential of this technology in aiding hemostasis and the importance of a holistic approach in engineering new treatments for hemorrhage.

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Sufficient Thrombin Generation Despite 95% Hemodilution: An In Vitro Experimental Study

Cited by 15 publications

References 45 publications

Effect of Goal-Directed Crystalloid versus Colloid Administration on Perioperative Hemostasis in Partial Hepatectomy: A Randomized, Controlled Trial

Effect of Goal-Directed Crystalloid versus Colloid Administration on Perioperative Hemostasis in Partial Hepatectomy: A Randomized, Controlled Trial

Emergency Blood Transfusion for Trauma and Perioperative Resuscitation: Standard of Care

Engineering a Two‐Component Hemostat for the Treatment of Internal Bleeding through Wound‐Targeted Crosslinking

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