Effect of Coagulation Factor Concentrates on Markers of Endothelial Cell Damage in Experimental Hemorrhagic Shock

Abstract

Background: Plasma-based resuscitation showed protective effects on the endothelial glycocalyx compared with crystalloid resuscitation. There is paucity of data regarding the effect of coagulation factor concentrates (CFC) on the glycocalyx in hemorrhagic shock (HS). We hypothesized that colloid-based resuscitation supplemented with CFCs offers a therapeutic value to treat endothelial damage following HS. Methods: Eighty-four rats were subjected to pressure-controlled (mean arterial pressure (MAP) 30–35 mm Hg) and lab-guided (targeted cutoff: lactate >2.2. mmol/L and base deficit > 5.5 mmol/L) HS. Animals were resuscitated with fresh frozen plasma (FFP), human albumin (HA) or Ringer's lactate (RL) and RL or HA supplemented with fibrinogen concentrate (FC) or prothrombin complex concentrate (PCC). Serum epinephrine and the following markers of endothelial damage were assessed at baseline and at the end-of-observation (120 min after shock was terminated): syndecan-1, heparan sulfate, and soluble vascular endothelial growth factor receptor 1 (sVEGFR 1). Results: Resuscitation with FFP had no effect on sVEGFR1 compared with crystalloid-based resuscitation (FFP: 19.3 ng/mL vs. RL: 15.9 ng/mL; RL+FC: 19.7 ng/mL; RL+PCC: 18.9 ng/mL; n.s.). At the end-of-observation, syndecan-1 was similar among all groups. Interestingly, HA+FC treated animals displayed the highest syndecan-1 concentration (12.07 ng/mL). Resuscitation with FFP restored heparan sulfate back to baseline (baseline: 36 ng/mL vs. end-of-observation: 36 ng/mL). Conclusion: The current study revealed that plasma-based resuscitation normalized circulating heparan sulfate but not syndecan-1. Co-administration of CFC had no further effect on glycocalyx shedding suggesting a lack of its therapeutic potential. Level of evidence: V Experimental in vivo study.

Normalization Of Blood Clotting Characteristics Using Prothrombin Complex Concentrate, Fibrinogen And FXIII In An Albumin Based Fluid: Experimental Studies In Thromboelastometry.

“…Experimental studies show that albumin-based colloid solutions provide stabilizing effects on the endothelial barrier and show intravascular plasma expander effects of nearly 100% 22,23 . By contrast, no such effects on the endothelial barrier could be demonstrated for CFCs 24 . The administration of well-balanced coagulation factors in carrier solutions with constant intravascular volume effects might be a safe way to treat bleeding associated coagulopathies, as "overshot" peak plasma concentrations caused by the infusion of highly concentrated factor formulas (as under nondiluted CFC administration) would be avoided.…”

Normalization of Blood Clotting Characteristics Using Prothrombin Complex Concentrate, Fibrinogen and Fxiii In an Albumin Based Fluid: Experimental Studies In Thromboelastometry.

“…By contrast, no such effects on the endothelial barrier could be demonstrated for CFCs 24 . The administration of well-balanced coagulation factors in carrier solutions with constant intravascular volume effects might be a safe way to treat bleeding associated coagulopathies, as "overshooted" peak plasma concentrations caused by the infusion of highly concentrated factor formulas (as under nondiluted CFC administration) would be avoided.…”

Thromboelastometry fails to detect autoheparinization after major trauma and hemorrhagic shock

“…Glycosaminoglycans, such as heparan sulfate, dermatan sulfate, and chondroitin sulfate, exert anticoagulant effects, thereby helping to maintain hemostatic balance at the endothelial surface 13 . Experimental and clinical data from previous studies have shown that damage to the glycocalyx causes constituents, such as syndecan-1 and heparan sulfate, to be released into the bloodstream 14–19 . In major trauma patients, the severity of endothelial cell dysfunction and glycocalyx damage is driven by the severity of shock-related hypoperfusion and the extent of tissue trauma, inflammation and catecholamine release 5 .…”

“…13 Experimental and clinical data from previous studies have shown that damage to the glycocalyx causes constituents, such as syndecan-1 and heparan sulfate, to be released into the bloodstream. [14][15][16][17][18][19] In major trauma patients, the severity of endothelial cell dysfunction and glycocalyx damage is driven by the severity of shock-related hypoperfusion and the extent of tissue trauma, inflammation and catecholamine release. 5 Rahbar et al 20 reported median plasma heparan sulfate levels of 177 ng/mL to 180 ng/mL in severely injured patients.…”