SUPPLEMENT ARTICLE
Treating the endotheliopathy of SARS-CoV-2 infection with plasma: Lessons learned from optimized trauma resuscitation with blood products
Shibani Pati,
Erin Fennern,
John B. Holcomb,
Mark Barry,
Alpa Trivedi,
Andrew P. Cap,
Matthew J. Martin,
Charles Wade,
Rosemary Kozar,
Jessica C. Cardenas,
Joseph F. Rappold,
Renee Spiegel,
Martin A. Schreiber,
Corresponding Author
Shibani Pati
Department of Lab Medicine, University of California San Francisco School of Medicine, San Francisco, California, USA
Correspondence
Shibani Pati, Department of Laboratory Medicine, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA, USA.
Email: [email protected]
Search for more papers by this authorErin Fennern
Department of Surgery, Mount Sinai Icahn School of Medicine, New York, New York, USA
Search for more papers by this authorJohn B. Holcomb
University of Alabama at Birmingham, Birmingham, Alabama, USA
Search for more papers by this authorMark Barry
Department of Surgery, University of California San Francisco School of Medicine, San Francisco, California, USA
Search for more papers by this authorAlpa Trivedi
Department of Lab Medicine, University of California San Francisco School of Medicine, San Francisco, California, USA
Search for more papers by this authorAndrew P. Cap
U.S. Army Institute of Surgical Research, JBSA-FT Sam Houston, San Antonio, Texas, USA
Search for more papers by this authorMatthew J. Martin
Department of Surgery, Scripps Mercy Hospital, San Diego, California, USA
Search for more papers by this authorCharles Wade
Department of Surgery McGovern School of Medicine, University of Texas Health Science Center, Houston, Texas, USA
Search for more papers by this authorRosemary Kozar
Department of Surgery, University of Maryland, Baltimore, Maryland, USA
Search for more papers by this authorJessica C. Cardenas
Department of Surgery McGovern School of Medicine, University of Texas Health Science Center, Houston, Texas, USA
Search for more papers by this authorJoseph F. Rappold
Department of Surgery Maine Medical Center, Tufts University School of Medicine, Portland, Maine, USA
Search for more papers by this authorRenee Spiegel
Department of Surgery, Elmhurst Hospital Center, Elmhurst, New York, USA
Search for more papers by this authorMartin A. Schreiber
Department of Surgery, Oregon Health and Sciences University, Portland, Oregon, USA
Search for more papers by this authorShibani Pati,
Erin Fennern,
John B. Holcomb,
Mark Barry,
Alpa Trivedi,
Andrew P. Cap,
Matthew J. Martin,
Charles Wade,
Rosemary Kozar,
Jessica C. Cardenas,
Joseph F. Rappold,
Renee Spiegel,
Martin A. Schreiber,
Corresponding Author
Shibani Pati
Department of Lab Medicine, University of California San Francisco School of Medicine, San Francisco, California, USA
Correspondence
Shibani Pati, Department of Laboratory Medicine, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA, USA.
Email: [email protected]
Search for more papers by this authorErin Fennern
Department of Surgery, Mount Sinai Icahn School of Medicine, New York, New York, USA
Search for more papers by this authorJohn B. Holcomb
University of Alabama at Birmingham, Birmingham, Alabama, USA
Search for more papers by this authorMark Barry
Department of Surgery, University of California San Francisco School of Medicine, San Francisco, California, USA
Search for more papers by this authorAlpa Trivedi
Department of Lab Medicine, University of California San Francisco School of Medicine, San Francisco, California, USA
Search for more papers by this authorAndrew P. Cap
U.S. Army Institute of Surgical Research, JBSA-FT Sam Houston, San Antonio, Texas, USA
Search for more papers by this authorMatthew J. Martin
Department of Surgery, Scripps Mercy Hospital, San Diego, California, USA
Search for more papers by this authorCharles Wade
Department of Surgery McGovern School of Medicine, University of Texas Health Science Center, Houston, Texas, USA
Search for more papers by this authorRosemary Kozar
Department of Surgery, University of Maryland, Baltimore, Maryland, USA
Search for more papers by this authorJessica C. Cardenas
Department of Surgery McGovern School of Medicine, University of Texas Health Science Center, Houston, Texas, USA
Search for more papers by this authorJoseph F. Rappold
Department of Surgery Maine Medical Center, Tufts University School of Medicine, Portland, Maine, USA
Search for more papers by this authorRenee Spiegel
Department of Surgery, Elmhurst Hospital Center, Elmhurst, New York, USA
Search for more papers by this authorMartin A. Schreiber
Department of Surgery, Oregon Health and Sciences University, Portland, Oregon, USA
Search for more papers by this author
CONFLICT OF INTEREST
SPati has a contract for a research project with CSL Behring Inc. JBH is a co-founder and on the Board of Directors of Decisio Health, on the Board of Directors of QinFlow and Zibrio, a Co-inventor of the Junctional Emergency Tourniquet Tool, and an adviser to Arsenal Medical, Cellphire, Spectrum, and PotentiaMetrics. MAS is a consultant to Velico Medical Inc. Dr. Martin has none to report. JCC has funding from and is an adviser to Grifols. RK has none to report. AC is an active duty officer in the US Army and has no conflicts of interest to declare. EF has none to report. RS has none to report. CW is a co-founder of Decisio Health and receives funding through his institution from Grifols. AT and MB have disclosed no conflicts of interest.
REFERENCES
- 1Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020; 382: 727–33.
- 2Chen L, Li X, Chen M, Feng Y, Xiong C. The ace2 expression in human heart indicates new potential mechanism of heart injury among patients infected with sars-cov-2. Cardiovasc Res. 2020; 116: 1097–100.
- 3Alvarado-Moreno JA, Majluf-Cruz A. Covid-19 and dysfunctional endothelium: the mexican scenario. Arch Med Res. 2020; 51: 587–8.
- 4Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in covid-19. N Engl J Med. 2020; 383: 120–8.
- 5Perlman S, Netland J. Coronaviruses post-sars: update on replication and pathogenesis. Nat Rev Microbiol. 2009; 7: 439–50.
- 6Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med. 2020; 382: 1199–207.
- 7Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, et al. Washington State-nCo VCIT. First case of 2019 novel coronavirus in the United States. N Engl J Med. 2020; 382: 929–36.
- 8Ferrario CM, Jessup J, Chappell MC, Averill DB, Brosnihan KB, Tallant EA, et al. Effect of angiotensin-converting enzyme inhibition and angiotensin ii receptor blockers on cardiac angiotensin-converting enzyme 2. Circulation. 2005; 111: 2605–10.
- 9Ferrario CM, Jessup J, Gallagher PE, Averill DB, Brosnihan KB, Ann Tallant E, et al. Effects of renin-angiotensin system blockade on renal angiotensin-(1-7) forming enzymes and receptors. Kidney Int. 2005; 68: 2189–96.
- 10Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, et al. A sars-cov-2 protein interaction map reveals targets for drug repurposing. Nature. 2020; 583: 459–68.
- 11Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in covid-19. Lancet. 2020; 395: 1417–8.
- 12Zuo Y, Yalavarthi S, Shi H, Gockman K, Zuo M, Madison JA, et al. Neutrophil extracellular traps in covid-19. JCI Insight. 2020;e138999: 1–11.
- 13Barnes BJ, Adrover JM, Baxter-Stoltzfus A, Borczuk A, Cools-Lartigue J, Crawford JM, et al. Targeting potential drivers of covid-19: neutrophil extracellular traps. J Exp Med. 2020; 217: 1–7.
- 14Fox SE, Akmatbekov A, Harbert JL, Li G, Quincy Brown J, Vander Heide RS. Pulmonary and cardiac pathology in african american patients with covid-19: an autopsy series from New Orleans. Lancet Respir Med. 2020; 8: 681–6.
- 15Spiezia L, Boscolo A, Poletto F, Cerruti L, Tiberio I, Campello E, et al. Covid-19-related severe hypercoagulability in patients admitted to intensive care unit for acute respiratory failure. Thromb Haemost. 2020; 120: 1474–7.
- 16Han H, Yang L, Liu R, Liu F, Wu KL, Li J, et al. Prominent changes in blood coagulation of patients with sars-cov-2 infection. Clin Chem Lab Med. 2020; 58: 1116–20.
- 17Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020; 18: 844–7.
- 18Zhang L, Yan X, Fan Q, Liu H, Liu X, Liu Z, et al. D-dimer levels on admission to predict in-hospital mortality in patients with covid-19. J Thromb Haemost. 2020; 18: 1324–9.
- 19Panigada M, Bottino N, Tagliabue P, Grasselli G, Novembrino C, Chantarangkul V, et al. Hypercoagulability of covid-19 patients in intensive care unit: a report of thromboelastography findings and other parameters of hemostasis. J Thromb Haemost. 2020; 18: 1738–42.
- 20Aid M, Busman-Sahay K, Vidal SJ, Maliga Z, Bondoc S, Starke C, et al. Vascular disease and thrombosis in sars-cov-2-infected rhesus macaques. Cell. 2020; 183: 1354–66.e1313.
- 21Aird WC. Endothelium as a therapeutic target in sepsis. Curr Drug Targets. 2007; 8: 501–7.
- 22Aird WC. Phenotypic heterogeneity of the endothelium: ii. Representative vascular beds. Circ Res. 2007; 100: 174–90.
- 23Aird WC. Endothelium in health and disease. Pharmacol Rep. 2008; 60: 139–43.
- 24Aird WC. Endothelium as an organ system. Crit Care Med. 2004; 32: S271–9.
- 25Varga Z. Endotheliitis in covid-19. Pathologe. 2020;( Supp. 2): 99–102.
- 26Jaffe S. Regulators split on antimalarials for covid-19. Lancet. 2020; 395: 1179.
- 27Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-ncov lung injury. Lancet. 2020; 395: 473–5.
- 28Shang L, Zhao J, Hu Y, Du R, Cao B. On the use of corticosteroids for 2019-ncov pneumonia. Lancet. 2020; 395: 683–4.
- 29Atluri S, Manchikanti L, Hirsch JA. Expanded umbilical cord mesenchymal stem cells (uc-mscs) as a therapeutic strategy in managing critically ill covid-19 patients: the case for compassionate use. Pain Physician. 2020; 23: E71–83.
- 30Leng Z, Zhu R, Hou W, Feng Y, Yang Y, Han Q, et al. Transplantation of ace2-mesenchymal stem cells improves the outcome of patients with covid-19 pneumonia. Aging Dis. 2020; 11: 216–28.
- 31Whyte CS, Morrow GB, Mitchell JL, Chowdary P, Mutch NJ. Fibrinolytic abnormalities in acute respiratory distress syndrome (ards) and versatility of thrombolytic drugs to treat covid-19. J Thromb Haemost. 2020; 18: 1548–55.
- 32 Group RC, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, et al. Dexamethasone in hospitalized patients with covid-19 - preliminary report. N Engl J Med. 2020; 384: 693–704.
- 33Dean CL, Hooper JW, Dye JM, Zak SE, Koepsell SA, Corash L, et al. Characterization of ebola convalescent plasma donor immune response and psoralen treated plasma in the United States. Transfusion. 2020; 60(5): 1024–31.
- 34Simonovich VA, Burgos Pratx LD, Scibona P, Beruto MV, Vallone MG, Vazquez C, et al. A randomized trial of convalescent plasma in covid-19 severe pneumonia. N Engl J Med. 2020; 384(7): 619–29.
- 35Libster R, Perez Marc G, Wappner D, Coviello S, Bianchi A, Braem V, et al. Early high-titer plasma therapy to prevent severe covid-19 in older adults. N Engl J Med. 2021; 384: 610–8.
- 36Joyner MJ, Wright RS, Fairweather D, Senefeld JW, Bruno KA, Klassen SA, et al. Early safety indicators of covid-19 convalescent plasma in 5000 patients. J Clin Invest. 2020; 130: 4791–7.
- 37Holcomb JB, Pati S. Optimal trauma resuscitation with plasma as the primary resuscitative fluid: the surgeon's perspective. Hematology Am Soc Hematol Educ Program. 2013; 2013: 656–9.
- 38Klein SL, Pekosz A, Park HS, Ursin RL, Shapiro JR, Benner SE, et al. Sex, age, and hospitalization drive antibody responses in a covid-19 convalescent plasma donor population. J Clin Invest. 2020; 130: 6141–50.
- 39Eastridge BJ, Mabry RL, Seguin P, Cantrell J, Tops T, Uribe P, et al. Death on the battlefield (2001-2011): implications for the future of combat casualty care. J Trauma Acute Care Surg. 2012; 73: S431–7.
- 40Holcomb JB, Fox EE, Wade CE. Mortality and ratio of blood products used in patients with severe trauma–reply. JAMA. 2015; 313: 2078–9.
- 41Kelly JF, Ritenour AE, McLaughlin DF, Bagg KA, Apodaca AN, Mallak CT, et al. Injury severity and causes of death from operation iraqi freedom and operation enduring freedom: 2003–2004 versus 2006. J Trauma. 2008; 64: S21–6.
- 42Holcomb JB, Fox EE, Wade CE. The prospective observational multicenter major trauma transfusion (prommtt) study. J Trauma Acute Care Surg. 2013; 75: S1–2.
- 43Holcomb JB, Tilley BC, Baraniuk S, Fox EE, Wade CE, Podbielski JM, et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the proppr randomized clinical trial. JAMA. 2015; 313: 471–82.
- 44Imam AM, Jin G, Sillesen M, Duggan M, Jepsen CH, Hwabejire JO, et al. Early treatment with lyophilized plasma protects the brain in a large animal model of combined traumatic brain injury and hemorrhagic shock. J Trauma Acute Care Surg. 2013; 75: 976–83.
- 45Imam AM, Jin G, Duggan M, Sillesen M, Hwabejire JO, Jepsen CH, et al. Synergistic effects of fresh frozen plasma and valproic acid treatment in a combined model of traumatic brain injury and hemorrhagic shock. Surgery. 2013; 154: 388–96.
- 46Borgman MA, Spinella PC, Perkins JG, Grathwohl KW, Repine T, Beekley AC, et al. The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. J Trauma. 2007; 63: 805–13.
- 47Holcomb JB, Wade CE, Michalek JE, Chisholm GB, Zarzabal LA, Schreiber MA, et al. Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients. Ann Surg. 2008; 248: 447–58.
- 48Holcomb JB, Zarzabal LA, Michalek JE, Kozar RA, Spinella PC, Perkins JG, et al. Increased platelet:Rbc ratios are associated with improved survival after massive transfusion. J Trauma. 2011; 71: S318–28.
- 49Zink KA, Sambasivan CN, Holcomb JB, Chisholm G, Schreiber MA. A high ratio of plasma and platelets to packed red blood cells in the first 6 hours of massive transfusion improves outcomes in a large multicenter study. Am J Surg. 2009; 197: 565–70. discussion 570.
- 50Hendrickson CM, Howard BM, Kornblith LZ, Conroy AS, Nelson MF, Zhuo H, et al. The acute respiratory distress syndrome following isolated severe traumatic brain injury. J Trauma Acute Care Surg. 2016; 80: 989–97.
- 51Shah CV, Localio AR, Lanken PN, Kahn JM, Bellamy S, Gallop R, et al. The impact of development of acute lung injury on hospital mortality in critically ill trauma patients. Crit Care Med. 2008; 36: 2309–15.
- 52Kozar RA, Pati S. Syndecan-1 restitution by plasma after hemorrhagic shock. J Trauma Acute Care Surg. 2015; 78: S83–6.
- 53Kozar RA, Peng Z, Zhang R, Holcomb JB, Pati S, Park P, et al. Plasma restoration of endothelial glycocalyx in a rodent model of hemorrhagic shock. Anesth Analg. 2011; 112: 1289–95.
- 54Pati S, Matijevic N, Doursout MF, Ko T, Cao Y, Deng X, et al. Protective effects of fresh frozen plasma on vascular endothelial permeability, coagulation, and resuscitation after hemorrhagic shock are time dependent and diminish between days 0 and 5 after thaw. J Trauma. 2010; 69(Suppl 1): S55–63.
- 55Pati S, Peng Z, Wataha K, Miyazawa B, Potter DR, Kozar RA. Lyophilized plasma attenuates vascular permeability, inflammation and lung injury in hemorrhagic shock. PLoS One. 2018; 13:e0192363.
- 56Peng Z, Pati S, Potter D, Brown R, Holcomb JB, Grill R, et al. Fresh frozen plasma lessens pulmonary endothelial inflammation and hyperpermeability after hemorrhagic shock and is associated with loss of syndecan 1. Shock. 2013; 40: 195–202.
- 57Potter DR, Baimukanova G, Keating SM, Deng X, Chu JA, Gibb SL, et al. Fresh frozen plasma and spray-dried plasma mitigate pulmonary vascular permeability and inflammation in hemorrhagic shock. J Trauma Acute Care Surg. 2015; 78: S7–S17.
- 58Spinella PC, Frazier E, Pidcoke HF, Dietzen DJ, Pati S, Gorkun O, et al. All plasma products are not created equal: characterizing differences between plasma products. J Trauma Acute Care Surg. 2015; 78: S18–25.
- 59Pusateri AE, Given MB, Schreiber MA, Spinella PC, Pati S, Kozar RA, et al. Dried plasma: state of the science and recent developments. Transfusion. 2016; 56(Suppl 2): S128–39.
- 60Wataha K, Menge T, Deng X, Shah A, Bode A, Holcomb JB, et al. Spray-dried plasma and fresh frozen plasma modulate permeability and inflammation in vitro in vascular endothelial cells. Transfusion. 2013; 53(Suppl 1): 80S–90S.
- 61Jin G, DeMoya MA, Duggan M, Knightly T, Mejaddam AY, Hwabejire J, et al. Traumatic brain injury and hemorrhagic shock: evaluation of different resuscitation strategies in a large animal model of combined insults. Shock. 2012; 38: 49–56.
- 62Sillesen M, Jin G, Oklu R, Albadawi H, Imam AM, Jepsen CH, et al. Fresh-frozen plasma resuscitation after traumatic brain injury and shock attenuates extracellular nucleosome levels and deoxyribonuclease 1 depletion. Surgery. 2013; 154: 197–205.
- 63Pati S, Potter DR, Baikamunova G, Farrell DH, Holcomb JB, Schreiber MA. Modulating the endotheliopathy of trauma: factor concentrate vs. fresh frozen plasma. J Trauma Acute Care Surg. 2016; 80(4): 576–84.
- 64Jenkins DH, Rappold JF, Badloe JF, Berseus O, Blackbourne L, Brohi KH, et al. Thor position paper on remote damage control resuscitation: definitions, current practice and knowledge gaps. Shock. 2014; 41: 3–12.
- 65Wu F, Chipman A, Pati S, Miyasawa B, Corash L, Kozar RA. Resuscitative strategies to modulate the endotheliopathy of trauma: from cell to patient. Shock. 2020; 53: 575–84.
- 66Rahbar E, Cardenas JC, Baimukanova G, Usadi B, Bruhn R, Pati S, et al. Endothelial glycocalyx shedding and vascular permeability in severely injured trauma patients. J Transl Med. 2015; 13: 117.
- 67Lipowsky HH. The endothelial glycocalyx as a barrier to leukocyte adhesion and its mediation by extracellular proteases. Ann Biomed Eng. 2012; 40: 840–8.
- 68Pati S, Potter DR, Baimukanova G, Farrel DH, Holcomb JB, Schreiber MA. Modulating the endotheliopathy of trauma: factor concentrate versus fresh frozen plasma. J Trauma Acute Care Surg. 2016; 80: 576–84.
- 69Meyer DE, Reynolds JW, Hobbs R, Bai Y, Hartwell B, Pommerening MJ, et al. The incidence of transfusion-related acute lung injury at a large, urban tertiary medical center: a decade's experience. Anesth Analg. 2018; 127: 444–9.
- 70Fox S, Vashisht R, Siuba M, Dugar S. Evaluation and management of shock in patients with covid-19. Cleve Clin J Med. 2020. https://doi.org/10.3949/ccjm.87a.ccc052.
- 71Peyvandi F, Artoni A, Novembrino C, Aliberti S, Panigada M, Boscarino M, et al. Hemostatic alterations in covid-19. Haematologica. 2020; 106(5): 1472–5.
10.3324/haematol.2020.262634 Google Scholar
- 72Duque P, Mora L, Levy JH, Schochl H. Pathophysiological response to trauma-induced coagulopathy: a comprehensive review. Anesth Analg. 2020; 130: 654–64.
- 73Chang R, Holcomb JB. Choice of fluid therapy in the initial management of sepsis, severe sepsis, and septic shock. Shock. 2016; 46: 17–26.
- 74Chang R, Holcomb JB, Johansson PI, Pati S, Schreiber MA, Wade CE. Plasma resuscitation improved survival in a cecal ligation and puncture rat model of sepsis. Shock. 2018; 49: 53–61.
- 75Cardenas JC, Rahbar E, Pommerening MJ, Baer LA, Matijevic N, Cotton BA, et al. Measuring thrombin generation as a tool for predicting hemostatic potential and transfusion requirements following trauma. J Trauma Acute Care Surg. 2014; 77: 839–45.
- 76McCully BH, Connelly CR, Fair KA, Holcomb JB, Fox EE, Wade CE, et al. Onset of coagulation function recovery is delayed in severely injured trauma patients with venous thromboembolism. J Am Coll Surg. 2017; 225: 42–51.
- 77Park MS, Spears GM, Bailey KR, Xue A, Ferrara MJ, Headlee A, et al. Thrombin generation profiles as predictors of symptomatic venous thromboembolism after trauma: a prospective cohort study. J Trauma Acute Care Surg. 2017; 83: 381–7.
- 78Cardenas JC, Cap AP, Swartz MD, Huby Mdel P, Baer LA, Matijevic N, et al. Plasma resuscitation promotes coagulation homeostasis following shock-induced hypercoagulability. Shock. 2016; 45: 166–73.
- 79Cardenas JC, Wang YW, Karri JV, Vincent S, Cap AP, Cotton BA, et al. Supplementation with antithrombin iii ex vivo optimizes enoxaparin responses in critically injured patients. Thromb Res. 2020; 187: 131–8.
- 80Frankel HL, Magee GA, Ivatury RR. Why is sepsis resuscitation not more like trauma resuscitation? Should it be? J Trauma Acute Care Surg. 2015; 79: 669–77.
- 81Wei S, Kao LS, Wang HE, Chang R, Podbielski J, Holcomb JB, et al. Protocol for a pilot randomized controlled trial comparing plasma with balanced crystalloid resuscitation in surgical and trauma patients with septic shock. Trauma Surg Acute Care Open. 2018; 3:e000220.
- 82Gurney JM, Kozar RA, Cancio LC. Plasma for burn shock resuscitation: is it time to go back to the future? Transfusion. 2019; 59: 1578–86.
- 83Straat M, Muller MC, Meijers JC, Arbous MS, Spoelstra-de Man AM, Beurskens CJ, et al. Effect of transfusion of fresh frozen plasma on parameters of endothelial condition and inflammatory status in non-bleeding critically ill patients: a prospective substudy of a randomized trial. Crit Care. 2015; 19: 163.
- 84Deng X, Cao Y, Huby MP, Duan C, Baer L, Peng Z, et al. Adiponectin in fresh frozen plasma contributes to restoration of vascular barrier function after hemorrhagic shock. Shock. 2016; 45: 50–4.
- 85Hawkins RB, Raymond SL, Stortz JA, Horiguchi H, Brakenridge SC, Gardner A, et al. Chronic critical illness and the persistent inflammation, immunosuppression, and catabolism syndrome. Front Immunol. 2018; 9: 1511.
- 86Watson JJ, Pati S, Schreiber MA. Plasma transfusion: history, current realities, and novel improvements. Shock. 2016; 46: 468–79.
