Freeze‐dried plasma enhances clot formation and inhibits fibrinolysis in the presence of tissue plasminogen activator similar to pooled liquid plasma

Abstract

BACKGROUND Systemic hyperfibrinolysis is an integral part of trauma-induced coagulopathy associated with uncontrolled bleeding. Recent data suggest that plasma-first resuscitation attenuates hyperfibrinolysis; however, the availability, transport, storage, and administration of plasma in austere environments remain challenging and have limited its use. Freeze-dried plasma (FDP) is a potential alternative due to ease of storage, longer shelf life, and efficient reconstitution. FDP potentially enhances clot formation and resists breakdown better than normal saline (NS) and albumin and similar to liquid plasma. STUDY DESIGN AND METHODS Healthy volunteers underwent citrated blood draw followed by 50% dilution with NS, albumin, pooled plasma (PP), or pooled freeze-dried plasma (pFDP). Citrated native and tissue plasminogen activator (t-PA)-challenge (75 ng/mL) thrombelastography were done. Proteins in PP, pFDP, and albumin were analyzed by mass spectroscopy. RESULTS pFDP and PP had superior clot-formation rates (angle) and clot strength (maximum amplitude) compared with NS and albumin in t-PA-challenge thrombelastographies (angle: pFDP, 67.9 degrees; PP, 67.8 degrees; NS, 40.6 degrees; albumin, 35.8 degrees; maximum amplitude: pFDP, 62.4 mm; PP, 63.5 mm; NS, 44.8 mm; albumin, 41.1 mm). NS and albumin dilution increased susceptibility to t-PA-induced hyperfibrinolysis compared with pFDP and PP (NS, 62.4%; albumin, 62.6%; PP, 8.5%; pFDP, 6.7%). pFDP was similar to PP in the attenuation of t-PA-induced fibrinolysis. Most proteins (97%) were conserved during the freeze-dry process, with higher levels in 12% of pFDP proteins compared with PP. CONCLUSION pFDP enhances clot formation and attenuates hyperfibrinolysis better than NS and albumin and is a potential alternative to plasma resuscitation in the treatment of hemorrhagic shock.

Thromboelastography as a tool to evaluate blood of healthy volunteers and blood component quality: a review

“…Further dilution to less than 40% blood causes increased initiation times, indicating significant effects of decreased clotting factor concentrations [28]. Observations by others of a shorter initiation time with 33% dilution [29] or 50% dilution (not significant) [30] and a longer initiation time with 60% [23] saline-diluted WB are in line with this. In all cases, propagation rate was not affected or shifted to slower kinetics with increasing dilution grade, while clot strength decreased.…”

“…In all cases, propagation rate was not affected or shifted to slower kinetics with increasing dilution grade, while clot strength decreased. Fibrinolysis was not affected in the absence of tPA, when WB was diluted with saline or albumin, but in the presence of tPA significantly higher fibrinolysis was observed . Summarizing, dilution of WB with colloids has variable effects on thromboelastographic outcomes.…”

“…While no significant effect on initiation times were seen when saline was used, Huebner et al . observed shorter initiation times in case plasma was used when WB samples were diluted to 50%. Also, faster propagation rates and higher clot strength were obtained when plasma was used, which was recently confirmed by Noorman and Hess for a range of PLT concentrations.…”

“…Also, faster propagation rates and higher clot strength were obtained when plasma was used, which was recently confirmed by Noorman and Hess for a range of PLT concentrations. The other authors report corresponding enhanced coagulation or attenuated fibrinolysis when plasma was used as diluent instead of colloids . So, dilution with plasma can counteract dilution effects by colloids by increasing the concentration of clotting factors.…”

“…However, when WB was filtered for leukoreduction, also fibrinogen and FXII levels were affected (both ~−15%), and subsequently the corresponding TEG curves showed longer initiation times (~+10%), no shift in propagation rate and weaker clots (~−15%). The other way around, in case of freeze‐drying of plasma, which resulted in increased levels of FXIII B chain, FXI, thrombin‐activatable fibrinolysis inhibitor (TAFI) and Protein C (all ≥ +50%) but which did not change fibrinogen levels, no impact on thromboelastographic profile was observed, compared to the original plasma .…”