000			05829nam a22006137a 4500
008			190521s20192019 xxu||||| |||| 00| 0 eng d
022			_a0026-4075
024			_a10.1093/milmed/usy397 [doi]
024			_a5418659 [pii]
040			_aOvid MEDLINE(R)
099			_a30901410
245			_aUtilizing Plasma Composition Data to Help Determine Procoagulant Dynamics in Patients with Thermal Injury: A Computational Assessment.
251			_aMilitary Medicine. 184(Suppl 1):392-399, 2019 03 01.
252			_aMil Med. 184(Suppl 1):392-399, 2019 03 01.
253			_aMilitary medicine
260			_c2019 _fFY2019
265			_sppublish
266			_d2019-05-21
501			_aAvailable in print through MWHC library: 1999 - 2005
520			_aCONCLUSIONS: Thrombin and FXa generation are increased in burn patients at admission compared to mean physiological simulations. Over the first 48 hours, burn survivors became more procoagulant while non-survivors became less procoagulant. Differences between survivors and non-survivors appear to be present in the underlying dynamics that contribute to FXa dynamics. Understanding how the individual specific balance of procoagulant and anticoagulant proteins contributes to thrombin and FXa generation could ultimately guide therapy and potentially reduce burn injury-related morbidity and mortality.
520			_aCopyright (c) Association of Military Surgeons of the United States 2019. All rights reserved. For permissions, please e-mail: [email protected].
520			_aINTRODUCTION: The development of methods that generate individualized assessments of the procoagulant potential of burn patients could improve their treatment. Beyond its role as an essential intermediate in the formation of thrombin, factor (F)Xa has systemic effects as an agonist to inflammatory processes. In this study, we use a computational model to study the FXa dynamics underlying tissue factor-initiated thrombin generation in a small cohort of burn patients.
520			_aMATERIALS AND METHODS: Plasma samples were collected upon admission (Hour 0) from nine subjects (five non-survivors) with major burn injuries and then at 48 hours. Coagulation factor concentrations (II, V, VII, VIII, IX, X, TFPI, antithrombin (AT), protein C (PC)) were measured and used in a computational model to generate time course profiles for thrombin (IIa), FXa, extrinsic tenase, intrinsic tenase and prothrombinase complexes upon a 5 pM tissue factor stimulus in the presence of 1 nM thrombomodulin. Parameters were extracted from the thrombin and FXa profiles (including max rate (MaxRIIa and MaxRFXa) and peak level (MaxLIIa and MaxLFXa)). Procoagulant potential was also evaluated by determining the concentration of the complexes at select times. Parameter values were compared between survivors and non-survivors in the burn cohort and between the burn cohort and a simulation based on the mean physiological (100%) concentration for all factor levels.
520			_aRESULTS: Burn patients differed at Hour 0 (p < 0.05) from 100% mean physiological levels for all coagulation factor levels except FV and FVII. The concentration of FX, FII, TFPI, AT and PC was lower; FIX and FVIII were increased. The composition differences resulted in all nine burn patients at Hour 0 displaying a procoagulant phenotype relative to 100% mean physiological simulation (MaxLIIa (306 +/- 90 nM vs. 52 nM), MaxRIIa (2.9 +/- 1.1 nM/s vs. 0.3 nM/s), respectively p < 0.001); MaxRFXa and MaxLFXa were also an order of magnitude greater than 100% mean physiological simulation (p < 0.001). When grouped by survival status and compared at the time of admission, non-survivors had lower PC levels (56 +/- 18% vs. 82 +/- 9%, p < 0.05), and faster MaxRFXa (29 +/- 6 pM/s vs. 18 +/- 6 pM/s, p < 0.05) than those that survived; similar trends were observed for all other procoagulant parameters. At 48 hours when comparing non-survivors to survivors, TFPI levels were higher (108 +/- 18% vs. 59 +/- 18%, p < 0.05), and MaxRIIa (1.5 +/- 1.4 nM/s vs. 3.6 +/- 0.7 nM/s, p < 0.05) and MaxRFXa (13 +/- 12 pM/s vs. 35 +/- 4 pM/s, p < 0.05) were lower; similar trends were observed with all other procoagulant parameters. Overall, between admission and 48 hours, procoagulant potential, as represented by MaxR and MaxL parameters for thrombin and FXa, in non-survivors decreased while in survivors they increased (p < 0.05). In patients that survived, there was a positive correlation between FX levels and MaxLFXa (r = 0.96) and reversed in mortality (r= -0.91).
546			_aEnglish
650			_a*Burns/bl [Blood]
650			_a*Burns/pp [Physiopathology]
650			_a*Coagulants/an [Analysis]
650			_aAnalysis of Variance
650			_aArea Under Curve
650			_aBlood Coagulation Tests/mt [Methods]
650			_aBurns/en [Enzymology]
650			_aCoagulants/bl [Blood]
650			_aCohort Studies
650			_aFactor Xa/an [Analysis]
650			_aHumans
650			_aPilot Projects
650			_aROC Curve
650			_aThrombin/an [Analysis]
650			_aTime Factors
651			_aMedStar Health Research Institute
651			_aMedStar Washington Hospital Center
656			_aFirefighters' Burn and Surgical Research Laboratory
656			_aSurgery/Burn Services
657			_aJournal Article
657			_aResearch Support, U.S. Gov't, Non-P.H.S.
700			_aMcLawhorn, Melissa M
700			_aMoffatt, Lauren T
700			_aShupp, Jeffrey W
700			_aTejiram, Shawn
790			_aBravo MC, Brummel-Ziedins KE, Jett-Tilton M, McLawhorn MM, Moffatt LT, Orfeo T, Pusateri AE, Shupp JW, Tejiram S
856			_uhttps://dx.doi.org/10.1093/milmed/usy397 _zhttps://dx.doi.org/10.1093/milmed/usy397
942			_cART _dJournal article
999			_c12535 _d12535