Shock-induced systemic hyperfibrinolysis is attenuated by plasma-first resuscitation

Abstract

Background We developed a hemorrhagic shock animal model to replicate an urban prehospital setting where resuscitation fluids are limited to assess the effect of saline versus plasma in coagulopathic patients. An in vitro model of whole blood dilution with saline exacerbated tPA mediated fibrinolysis, while plasma dilution did not change fibrinolysis. We hypothesize that shock induced hyperfibrinolysis can be attenuated by resuscitation with plasma while exacerbated by saline. Methods Sprague Dawley rats were hemorrhaged to a mean arterial pressure (MAP) of 25 mmHg and maintained in shock for 30 minutes. Animals were resuscitated with either normal saline (NS) or platelet free plasma (PFP) with a 10% total blood volume bolus, followed by an additional 5 minutes of resuscitation with NS to increase blood pressure to a MAP of 30 mmHg. Animals were observed for 15 minutes for assessment of hemodynamic response and survival. Blood samples were analyzed with thrombelastography (TEG) paired with protein analysis. Results The median percent of total blood volume shed per group were similar (NS 52.5% vs PFP 55.7 p=0.065). Survival was 50% in NS compared to 100% in PFP. The change in LY30 and tPA levels from baseline to shock was similar between groups (LY30 PFP10 IQR 4.3 to 11.2, NS 4.5 IQR 4.1 to 14.2 p=1.00; tPA PFP 16.6 ng/ml IQR 13.7–27.8, NS 22.4 IQR 20.1 to 25.5 p=0.240). After resuscitation, the median change in LY30 was greater in the NS group (13.5 IQR 3.5 to 19.9) compared to PFP (−4.9 % IQR −9.22 to 0.25 p=0.004) but tPA levels did not significantly change (NS 1.4 IQR-6.2 to 7.1 vs PFP 1.7 IQR-5.2 to 6.8 p=0.699). Conclusions Systemic hyperfibrinolysis is driven by hypoperfusion and associated with increased levels of tPA. Plasma is a superior resuscitation fluid to normal saline in a prehospital model of severe hemorrhagic shock as it attenuates hyperfibrinolysis and improves systemic perfusion.

Acute Fibrinolysis Shutdown after Injury Occurs Frequently and Increases Mortality: A Multicenter Evaluation of 2,540 Severely Injured Patients

“…In current clinical practice, early empiric plasma resuscitation appears to be a rationale approach for hypotensive trauma trauma patients as it is a buffer of fibrinolysis(42). Animal models have shown that plasma attenuates hemorrhagic shock induced hyperfibrinolysis (43) and reduces post resuscitation hypercoagulability(44). Ultimately, the debate on the optimal ratios of blood components for initial resuscitation has not become as critical as the timing of early plasma administration.…”

Tranexamic acid is associated with increased mortality in patients with physiological fibrinolysis

“…Plasma is an effective buffer of fibrinolytic activity (19) and effectively reverses hyperfibrinolysis and reduces mortality in hyperfibrinolytic rodents (20). This effective colloid also has been shown to enhance metabolic recovery (21) from hemorrhagic shock, restore the endothelial glycoalyx (22), reduce pulmonary injury (23) and reduce gastrointestinal damage (24).…”

Plasma-first resuscitation to treat haemorrhagic shock during emergency ground transportation in an urban area: a randomised trial

“…14 Prehospital plasma infusion has been shown to be feasible during helicopter transport, 15 but the logistics of storage and thawing in fast ground transport have been challenging. 1,16 Anticipation of approval of the lyophilised plasma by the US Food and Drug Administration (FDA) prompted the US Department of Defense to fund several randomised controlled trials across the USA to produce robust evidence on early plasma resuscitation.…”