Effect of ascorbic acid concentrations on hemodynamics and inflammation following lyophilized plasma transfusion

McCully, Sean P.; Martin, David T.; Cook, Mackenzie R.; Gordon, Nicole; McCully, Belinda H.; Lee, Tim H.; Dean, Rondi K.; Rick, Elizabeth A.; Moren, Alexis M.; Fair, Kelly A.; Undurraga, Vicente J.; Watson, Kathrine M.; Anderson, Nathan; Schreiber, Martin A.

doi:10.1097/ta.0000000000000684

Cited by 11 publications

(16 citation statements)

References 30 publications

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“…[16][17][18] These data suggest pFDP is equivalent to PP in restoring clot formation. [16][17][18] However, animal models are consistently unable to produce systemic hyperfibrinolysis, which is the most deadly form of TIC. Therefore, the role of FDP in systemic hyperfibrinolysis remains undefined.…”

Section: Discussionmentioning

confidence: 80%

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

Huebner¹,

Moore

Moore³

et al. 2017

Transfusion

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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.

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Section: Discussionmentioning

confidence: 80%

“…Renewed interest of FDP in trauma has prompted recent animal studies . These data suggest pFDP is equivalent to PP in restoring clot formation . However, animal models are consistently unable to produce systemic hyperfibrinolysis, which is the most deadly form of TIC.…”

Section: Discussionmentioning

confidence: 99%

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

Huebner¹,

Moore

Moore³

et al. 2017

Transfusion

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“…No difference in physiology, coagulation parameters, or blood loss was noted, but animals receiving ascorbic acid had lower IL-6 levels and less oxidative DNA damage [57]. Using higher concentrations of ascorbic acid didn't affect the physiologic benefits of LP, but no improvement in the anti-inflammatory effects or further decrease in DNA oxidative damage was detected [53].…”

Section: Buffering and Reconstitutionmentioning

confidence: 97%

“…Reconstituted porcine lyophilized plasma is alkalotic with a pH >8.5, making it highly lethal when injected in swine due to their lack of ability to buffer their plasma [53]. Human lyophilized plasma is also alkalotic with a pH near 8; however, it is well tolerated clinically in humans [54].…”

Section: Buffering and Reconstitutionmentioning

confidence: 99%

Dried Plasma

Zaza¹,

Kalkwarf²,

Holcomb³

2019

Damage Control Resuscitation

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“…In contrast, these results may not be as applicable in rural America and the developing world, where RBCs, thawed plasma and platelets are in limited supply, limiting access to therapies, such as damage control resuscitation. To improve trauma care in these settings, novel blood products 10, 11 , such as lyophilized plasma 12 , and freeze dried platelets are being developed but are not yet available in the United States.…”

Section: Discussionmentioning

confidence: 99%

Damage-control resuscitation and emergency laparotomy

Perl

Cook

Watson

et al. 2016

Journal of Trauma and Acute Care Surgery

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Background The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial has demonstrated that damage control resuscitation, a massive transfusion strategy targeting a balanced delivery of plasma-platelet-RBC in a ratio of 1:1:1, results in improved survival at 3 hours and a reduction in deaths due to exsanguination in the first 24 hours compared to a 1:1:2 ratio. In light of these findings, we hypothesized that patients receiving 1:1:1 ratio would have improved survival after emergency laparotomy. Methods Severely injured patients predicted to receive a massive transfusion admitted to 12 level I North American trauma centers were randomized to 1:1:1 versus 1:1:2 as described in the PROPPR trial. From these patients, the subset that underwent an emergency laparotomy, defined previously in the literature as laparotomy within 90 minutes of arrival, were identified. We compared rates and timing of emergency laparotomy as well as post-surgical survival at 24-hours and 30-days. Results Of the 680 enrolled patients, 613 underwent a surgical procedure, 397 underwent a laparotomy, and 346 underwent an emergency laparotomy. The percentages of patients undergoing emergency laparotomy were 51.5% (174/338) and 50.3% (172/342) for 1:1:1 and 1:1:2, respectively (p=0.20). Median time to laparotomy was 28 minutes in both treatment groups. Among patients undergoing an emergency laparotomy, the proportions of patients surviving to 24 hours and 30 days were similar between treatment arms, 24-hour survival was 86.8% (151/174) for 1:1:1 and 83.1% (143/172) for 1:1:2 (p=0.29), and 30-day 79.3% (138/174) for 1:1:1 and 75.0% (129/172) for 1:1:2 (p=0.30). Conclusions We found no evidence that resuscitation strategy affects whether a patient requires an emergency laparotomy, time to laparotomy, or subsequent survival. Level of Evidence Level IV, therapeutic study.

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Effect of ascorbic acid concentrations on hemodynamics and inflammation following lyophilized plasma transfusion

Abstract: Concentrations of AA were well tolerated and did not diminish the procoagulant activity of LP. Within our tested range of concentrations, AA can safely be used to buffer LP.

Cited by 11 publications

References 30 publications

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

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

Dried Plasma

Damage-control resuscitation and emergency laparotomy

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