BACKGROUND: Prehospital resuscitation with crystalloid exacerbates fibrinolysis, which is associated with high mortality. We hypothesized that plasma compared with crystalloid resuscitation prevents hyperfibrinolysis in a tissue plasminogen activator (tPA)-rich environment via preservation of proteins essential for regulation of fibrinolysis. STUDY DESIGN: Healthy individuals donated blood, which was assayed using a native (nonactivated) thrombelastography (TEG). Whole-blood was mixed with normal saline (NS) or platelet poor plasma (PPP) at progressive dilutions. Tissue plasminogen activator was added to promote a fibrinolytic environment. In a separate experiment, PPP was run through a 100 kDa filter and liquid remaining on top of the filter (TFP) and below the filter (BFP) was obtained. Whole blood was diluted by 50% with TFP, BFP, and NS and assayed with a tPA TEG challenge. The TFP and BFP were assayed for protein concentration and protein composition. RESULTS: Normal saline and PPP dilution of whole blood without tPA did not affect clot lysis at 30 minutes (LY30) (NS Spearman's rho 0.300, p = 0.186 and PPP 0.294, p = 0.288). When tPA was added, NS dilution of whole blood increased LY30 in a percentage-dependent manner (0.844, p < 0.001), but did not significantly increase with PPP dilution (0.270, p = 0.202). The difference in LY30 from whole blood to diluted whole blood with PPP (mean change, -1.05, 95% CI, -9.42 to 7.33) was similar with TFP (1.23, 95% CI, -5.20 to 7.66, p = 0.992). However, both BFP (37.65, 95% CI 24.47 to 50.82, p = 0.001) and NS (47.36, 95% CI 34.3 to 60.45, p < 0.001) showed large increases in fibrinolysis compared with PPP. CONCLUSIONS: Crystalloid and plasma dilution of whole blood does not increase fibrinolysis. However, NS dilution of whole blood increases susceptibility to tPA-mediated fibrinolysis. Plasma resuscitation, simulated by plasma dilution of whole blood, attenuates increased susceptibility to tPA-mediated fibrinolysis. The benefits of plasma resuscitation are mediated through preservation of plasma proteins.
BACKGROUND: Prehospital resuscitation with crystalloid exacerbates fibrinolysis, which is associated with high mortality. We hypothesized that plasma compared with crystalloid resuscitation prevents hyperfibrinolysis in a tissue plasminogen activator (tPA)-rich environment via preservation of proteins essential for regulation of fibrinolysis. STUDY DESIGN: Healthy individuals donated blood, which was assayed using a native (nonactivated) thrombelastography (TEG). Whole-blood was mixed with normal saline (NS) or platelet poor plasma (PPP) at progressive dilutions. Tissue plasminogen activator was added to promote a fibrinolytic environment. In a separate experiment, PPP was run through a 100 kDa filter and liquid remaining on top of the filter (TFP) and below the filter (BFP) was obtained. Whole blood was diluted by 50% with TFP, BFP, and NS and assayed with a tPA TEG challenge. The TFP and BFP were assayed for protein concentration and protein composition. RESULTS: Normal saline and PPP dilution of whole blood without tPA did not affect clot lysis at 30 minutes (LY30) (NS Spearman's rho 0.300, p = 0.186 and PPP 0.294, p = 0.288). When tPA was added, NS dilution of whole blood increased LY30 in a percentage-dependent manner (0.844, p < 0.001), but did not significantly increase with PPP dilution (0.270, p = 0.202). The difference in LY30 from whole blood to diluted whole blood with PPP (mean change, -1.05, 95% CI, -9.42 to 7.33) was similar with TFP (1.23, 95% CI, -5.20 to 7.66, p = 0.992). However, both BFP (37.65, 95% CI 24.47 to 50.82, p = 0.001) and NS (47.36, 95% CI 34.3 to 60.45, p < 0.001) showed large increases in fibrinolysis compared with PPP. CONCLUSIONS: Crystalloid and plasma dilution of whole blood does not increase fibrinolysis. However, NS dilution of whole blood increases susceptibility to tPA-mediated fibrinolysis. Plasma resuscitation, simulated by plasma dilution of whole blood, attenuates increased susceptibility to tPA-mediated fibrinolysis. The benefits of plasma resuscitation are mediated through preservation of plasma proteins.
Authors: Michael P Chapman; Ernest E Moore; Christopher R Ramos; Arsen Ghasabyan; Jeffrey N Harr; Theresa L Chin; John R Stringham; Angela Sauaia; Christopher C Silliman; Anirban Banerjee Journal: J Trauma Acute Care Surg Date: 2013-12 Impact factor: 3.313
Authors: Bryan A Cotton; John A Harvin; Vadim Kostousouv; Kristin M Minei; Zayde A Radwan; Herbert Schöchl; Charles E Wade; John B Holcomb; Nena Matijevic Journal: J Trauma Acute Care Surg Date: 2012-08 Impact factor: 3.313
Authors: Joshua B Brown; Mitchell J Cohen; Joseph P Minei; Ronald V Maier; Michael A West; Timothy R Billiar; Andrew B Peitzman; Ernest E Moore; Joseph Cuschieri; Jason L Sperry Journal: J Trauma Acute Care Surg Date: 2013-05 Impact factor: 3.313
Authors: Gregory R Stettler; Ernest E Moore; Hunter B Moore; Geoffrey R Nunns; Julia R Coleman; Arthur Colvis; Arsen Ghasabyan; Mitchell J Cohen; Christopher C Silliman; Anirban Banerjee; Angela Sauaia Journal: J Trauma Acute Care Surg Date: 2019-09 Impact factor: 3.313
Authors: Ernest E Moore; Hunter B Moore; Eduardo Gonzalez; Michael P Chapman; Kirk C Hansen; Angela Sauaia; Christopher C Silliman; Anirban Banerjee Journal: J Trauma Acute Care Surg Date: 2015-06 Impact factor: 3.313
Authors: Hunter B Moore; Ernest E Moore; Clay C Burlew; Walter L Biffl; Fredric M Pieracci; Carlton C Barnett; Denis D Bensard; Gregory J Jurkovich; Charles J Fox; Angela Sauaia Journal: J Am Coll Surg Date: 2016-04-21 Impact factor: 6.113
Authors: Hunter B Moore; Angelo D'Alessandro; Ernest E Moore; Matthew Wither; Peter J Lawson; Benjamin R Huebner; Kirk Hansen; Rashikh Choudhury; Trevor L Nydam Journal: Blood Transfus Date: 2019-02-04 Impact factor: 3.443
Authors: Benjamin R Huebner; Ernest E Moore; Hunter B Moore; Angela Sauaia; Gregory Stettler; Monika Dzieciatkowska; Kirk Hansen; Anirban Banerjee; Christopher C Silliman Journal: Transfusion Date: 2017-05-12 Impact factor: 3.157
Authors: Hunter B Moore; Ernest E Moore; Ioannis N Liras; Eduardo Gonzalez; John A Harvin; John B Holcomb; Angela Sauaia; Bryan A Cotton Journal: J Am Coll Surg Date: 2016-01-22 Impact factor: 6.113
Authors: Hunter B Moore; Ernest E Moore; Benjamin R Huebner; Gregory R Stettler; Geoffrey R Nunns; Peter M Einersen; Christopher C Silliman; Angela Sauaia Journal: J Surg Res Date: 2017-05-08 Impact factor: 2.192
Authors: H B Moore; E E Moore; M P Chapman; E Gonzalez; A L Slaughter; A P Morton; A D'Alessandro; K C Hansen; A Sauaia; A Banerjee; C C Silliman Journal: J Thromb Haemost Date: 2015-09-22 Impact factor: 5.824