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

ABSTRACT: Guidelines for the treatment of severe bleeding comprise viscoelastic-test-guided use of coagulation factor concentrates as part of their recommendations. The aim of this study is to investigate the effects of substituting fibrinogen, prothrombin complex concentrate, and a combination of both on conventional coagulation tests, viscoelastic test results, and thrombin generation. Blood was drawn from seven healthy volunteers to obtain platelet-free plasma, which later was diluted by replacing 40%, 60%, 80%, 90%, 95%, and 99% with a crystalloid solution. The diluted samples were spiked with fibrinogen concentrate, prothrombin complex concentrate, a combination of both, or a corresponding amount of crystalloid solution. Up to a dilution level of 95%, viscoelastically determined clotting time was significantly shorter in the group substituted with fibrinogen only in comparison with the additional use of prothrombin complex concentrate. Clot firmness and endogenous thrombin potential remained at relatively stable values up to a dilution level of 95% with the substitution of fibrinogen but not prothrombin complex concentrate. Substitution of prothrombin complex concentrate led to an excessive overshoot of thrombin generation. The results of our study question currently propagated treatment algorithms for bleeding patients that include the use of prothrombin complex concentrate for patients without former intake of oral anticoagulants. Even in severely bleeding patients, thrombin generation might be sufficient to achieve adequate hemostasis.

SUBMITTER: Gratz J

PROVIDER: S-EPMC7760770 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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

Gratz Johannes J Schlimp Christoph J CJ Honickel Markus M Hochhausen Nadine N Schöchl Herbert H Grottke Oliver O

Journal of clinical medicine 20201125 12

Guidelines for the treatment of severe bleeding comprise viscoelastic-test-guided use of coagulation factor concentrates as part of their recommendations. The aim of this study is to investigate the effects of substituting fibrinogen, prothrombin complex concentrate, and a combination of both on conventional coagulation tests, viscoelastic test results, and thrombin generation. Blood was drawn from seven healthy volunteers to obtain platelet-free plasma, which later was diluted by replacing 40%, ...[more]

PMID: 33255530

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Project description:The two sides of trauma-induced coagulopathy, the hypocoagulable and the hypercoagulable states, are poorly understood. To identify potential mechanisms for venous thromboembolism and bleeding after acute trauma, we estimated changes in circulating procoagulant microparticles (MPs) and thrombin activity during hospitalization for trauma.Whole blood was collected by venipuncture into 3.2% trisodium citrate at 0, 6, 12, 24, and 72 hours after injury and discharge. Platelet-poor plasma was harvested and stored at -80°C until analysis. Thrombin generation was determined using the calibrated automated thrombogram (CAT), reported as lag time (minutes), peak height (nM thrombin), and time to reach peak height (ttPeak, minutes). The concentration of total procoagulant MPs (number/?L) was measured by flow cytometry. Data are presented as median (interquartile range [IQR]).Among 443 trauma patients (1,734 samples; Injury Severity Score [ISS], 13.0 [IQR, 6.0-22.0]; hospital length of stay, 4.0 days [IQR, 2.0-10.0]; age, 48 years [IQR, 28-65]; 70.7% male; 95% with blunt mechanism; mortality, 3.2%), no discernable patterns in thrombin generation or MP concentration were observed over time. The peak height and MPs were significantly different from healthy volunteers and were 337 nM (IQR, 285-395) and 400/?L plasma (IQR, 211-772), respectively. Extreme (defined as highest or lowest 5%) values reflecting a possible "hypercoagulable state" (lag time ? 1.98, peak height ? 486.2, ttPeak ? 3.61, and total procoagulant MP ? 2,278) were reached within 12 hours after acute trauma, while extreme values representing a possible "hypocoagulable state" (lag time ? 18.6, peak height ? 17.8, and ttPeak ? 29.45) were not reached until 1 day to 3 days.Although there was no predictable pattern of coagulopathy observed in each patient after trauma, those who reached extreme values did so relatively early after injury. These findings should be taken into account when designing risk model tools involving coagulation laboratory parameters.Epidemiologic study, level III.

Dataset Information

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

Publications

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

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