Cold-stored platelets have better preserved contractile function in comparison with room temperature-stored platelets over 21 days
Corresponding Author
Prajeeda M. Nair
Blood and Coagulation Research Department, Combat Mortality Prevention Division, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, San Antonio, Texas, USA
Correspondence
Prajeeda M. Nair, Blood and Coagulation Research Department, US Army Institute of Surgical Research, 3650 Chambers Pass, Bldg 3610, JBSA Fort Sam Houston, San Antonio, TX 78234-4504, USA.
Email: [email protected]
Search for more papers by this authorMichael A. Meledeo
Blood and Coagulation Research Department, Combat Mortality Prevention Division, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, San Antonio, Texas, USA
Search for more papers by this authorAdrienne R. Wells
Severe Burns Research Department, Combat Wound Repair Division, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, San Antonio, Texas, USA
Search for more papers by this authorXiaowu Wu
Blood and Coagulation Research Department, Combat Mortality Prevention Division, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, San Antonio, Texas, USA
Search for more papers by this authorJames A. Bynum
Blood and Coagulation Research Department, Combat Mortality Prevention Division, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, San Antonio, Texas, USA
Search for more papers by this authorKai P. Leung
Severe Burns Research Department, Combat Wound Repair Division, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, San Antonio, Texas, USA
Search for more papers by this authorBin Liu
Blood and Coagulation Research Department, Combat Mortality Prevention Division, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, San Antonio, Texas, USA
Search for more papers by this authorAswathi Cheeniyil
Department of Biomedical Engineering, University of Texas at San Antonio, San Antonio, Texas, USA
Search for more papers by this authorAnand K. Ramasubramanian
Department of Biomedical Engineering, University of Texas at San Antonio, San Antonio, Texas, USA
Department of Chemical and Materials Engineering, San Jose State University, San Jose, California, USA
Search for more papers by this authorJohn W. Weisel
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Search for more papers by this authorAndrew P. Cap
Blood and Coagulation Research Department, Combat Mortality Prevention Division, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, San Antonio, Texas, USA
Search for more papers by this authorCorresponding Author
Prajeeda M. Nair
Blood and Coagulation Research Department, Combat Mortality Prevention Division, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, San Antonio, Texas, USA
Correspondence
Prajeeda M. Nair, Blood and Coagulation Research Department, US Army Institute of Surgical Research, 3650 Chambers Pass, Bldg 3610, JBSA Fort Sam Houston, San Antonio, TX 78234-4504, USA.
Email: [email protected]
Search for more papers by this authorMichael A. Meledeo
Blood and Coagulation Research Department, Combat Mortality Prevention Division, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, San Antonio, Texas, USA
Search for more papers by this authorAdrienne R. Wells
Severe Burns Research Department, Combat Wound Repair Division, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, San Antonio, Texas, USA
Search for more papers by this authorXiaowu Wu
Blood and Coagulation Research Department, Combat Mortality Prevention Division, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, San Antonio, Texas, USA
Search for more papers by this authorJames A. Bynum
Blood and Coagulation Research Department, Combat Mortality Prevention Division, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, San Antonio, Texas, USA
Search for more papers by this authorKai P. Leung
Severe Burns Research Department, Combat Wound Repair Division, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, San Antonio, Texas, USA
Search for more papers by this authorBin Liu
Blood and Coagulation Research Department, Combat Mortality Prevention Division, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, San Antonio, Texas, USA
Search for more papers by this authorAswathi Cheeniyil
Department of Biomedical Engineering, University of Texas at San Antonio, San Antonio, Texas, USA
Search for more papers by this authorAnand K. Ramasubramanian
Department of Biomedical Engineering, University of Texas at San Antonio, San Antonio, Texas, USA
Department of Chemical and Materials Engineering, San Jose State University, San Jose, California, USA
Search for more papers by this authorJohn W. Weisel
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Search for more papers by this authorAndrew P. Cap
Blood and Coagulation Research Department, Combat Mortality Prevention Division, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, San Antonio, Texas, USA
Search for more papers by this authorAbstract
Although it is well established that transfusion of platelets in cases of severe bleeding reduces mortality, the availability of platelets is hampered by harsh restrictions on shelf life due to elevated risks of microbial contamination and functional losses with room temperature-stored platelets (RTP) kept at 22°C. In contrast, many recent studies have shown that 4°C cold-stored platelets (CSP) are able to overcome these shortcomings leading to the recent Food and Drug Administration licensure for 14-day stored CSP when conventional platelets are unavailable. This work expands the evidence supporting superiority of CSP function by assaying the less explored platelet-mediated clot retraction of RTP and CSP in either autologous plasma (AP) or platelet additive solution (PAS) for up to 21 days. The results demonstrate that CSP have better preservation of contractile function, exhibiting retraction for up to 21 days in both AP and PAS and forming highly ordered fibrin scaffolds similar to those of fresh platelets. In contrast, RTP stored in AP showed impaired contractile function by Day 5 with no retraction after 10 days, whereas PAS-stored RTP retained contractile function for up to 21 days. Collectively, these findings support extended storage of CSP and suggest that storage in PAS can mitigate functional losses in RTP.
CONFLICT OF INTEREST
The authors have disclosed no conflicts of interest. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.
Supporting Information
Filename | Description |
---|---|
trf16530-sup-0001-supinfo.docxWord 2007 document , 15.7 KB | Appendix S1 Supporting information |
trf16530-sup-0002-FigureS1.pptxPowerPoint 2007 presentation , 48 KB | Figure S1 Platelets were collected in accordance with a US Army Institute of Surgical Research approved protocol. Apheresis platelets in PAS was prepared by diluting a hyperconcentrated platelet product to a final ratio of 65% T-PAS+ (Terumo BCT)/35% plasma through addition of T-PAS+ directly to the platelet bag after collection. For storage studies, 10 ml aliquots were obtained from the donor bag and sterilely transferred into 15-ml mini-bags (BCSI, Seattle, WA), with one minibag used for each time point and condition. The mini bags were stored for 5, 10, 15, or 21 days at 22°C (RTP) in an FDA-approved PLT incubator with agitation or at 4°C without agitation (CSP). Composition of T-PAS+ as per the manufacturer SDS is as follows: 0.030% magnesium chloride hexahydrate, 0.037% potassium chloride, 0.105% sodium dihydrogen phosphate dihydrate, 0.318% sodium citrate dihydrate, 0.405% sodium chloride, 0.442% sodium acetate trihydrate, 0.769% disodium hydrogen phosphate dodecahydrate. Further, number of donors per experiment is specified on the figure legends. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012; 380(9859): 2095–128.
- 2Cannon JW. Hemorrhagic Shock. N Engl J Med. 2018; 378(4): 370–9.
- 3Tisherman SA, Schmicker RH, Brasel KJ, Bulger EM, Kerby JD, Minei JP, et al. Detailed description of all deaths in both the shock and traumatic brain injury hypertonic saline trials of the Resuscitation Outcomes Consortium. Ann Surg. 2015; 261(3): 586–90.
- 4Holcomb 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(3): 447–58.
- 5Holcomb JB, del Junco DJ, Fox EE, Wade CE, Cohen MJ, Schreiber MA, et al. The prospective, observational, multicenter, major trauma transfusion (PROMMTT) study: comparative effectiveness of a time-varying treatment with competing risks. JAMA Surg. 2013; 148(2): 127–36.
- 6Holcomb 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(5): 471–82.
- 7Cannon JW, Khan MA, Raja AS, Cohen MJ, Como JJ, Cotton BA, et al. Damage control resuscitation in patients with severe traumatic hemorrhage: a practice management guideline from the Eastern Association for the Surgery of Trauma. J Trauma Acute Care Surg. 2017; 82(3): 605–17.
- 8Brown LM, Call MS, Margaret Knudson M, Cohen MJ, Trauma Outcomes Group, Holcomb JB, et al. A normal platelet count may not be enough: the impact of admission platelet count on mortality and transfusion in severely injured trauma patients. J Trauma. 2011; 71(2 Suppl 3): S337–42.
- 9Kutcher ME, Redick BJ, McCreery RC, Crane IM, Greenberg MD, Cachola LM, et al. Characterization of platelet dysfunction after trauma. J Trauma Acute Care Surg. 2012; 73(1): 13–9.
- 10Wohlauer MV, Moore EE, Thomas S, Sauaia A, Evans E, Harr J, et al. Early platelet dysfunction: an unrecognized role in the acute coagulopathy of trauma. J Am Coll Surg. 2012; 214(5): 739–46.
- 11Becker GA, Tuccelli M, Kunicki T, Chalos MK, Aster RH. Studies of platelet concentrates stored at 22 C nad 4 C. Transfusion. 1973; 13(2): 61–8.
- 12Ketter PM, Kamucheka R, Arulanandam B, Akers K, Cap AP. Platelet enhancement of bacterial growth during room temperature storage: mitigation through refrigeration. Transfusion. 2019; 59(S2): 1479–89.
- 13Marini I, Aurich K, Jouni R, Nowak-Harnau S, Hartwich O, Greinacher A, et al. Cold storage of platelets in additive solution: the impact of residual plasma in apheresis platelet concentrates. Haematologica. 2019; 104(1): 207–14.
- 14Montgomery RK, Reddoch KM, Evani SJ, Cap AP, Ramasubramanian AK. Enhanced shear-induced platelet aggregation due to low-temperature storage. Transfusion. 2013; 53(7): 1520–30.
- 15Nair PM, Pandya SG, Dallo SF, Reddoch KM, Montgomery RK, Pidcoke HF, et al. Platelets stored at 4 degrees C contribute to superior clot properties compared to current standard-of-care through fibrin-crosslinking. Br J Haematol. 2017; 178(1): 119–29.
- 16Nair PM, Pidcoke HF, Cap AP, Ramasubramanian AK. Effect of cold storage on shear-induced platelet aggregation and clot strength. J Trauma Acute Care Surg. 2014; 77(3 Suppl 2): S88–93.
- 17NasrEldin E. Effect of cold storage on platelets quality stored in a small containers: Implications for pediatric transfusion. Pediatr Hematol Oncol J. 2017; 2(2): 29–34.
10.1016/j.phoj.2017.07.001 Google Scholar
- 18Reddoch KM, Montgomery RK, Rodriguez AC, Meledeo MA, Pidcoke HF, Ramasubramanian AK, et al. Endothelium-derived inhibitors efficiently attenuate the aggregation and adhesion responses of refrigerated platelets. Shock. 2016; 45(2): 220–7.
- 19Reddoch KM, Pidcoke HF, Montgomery RK, Fedyk CG, Aden JK, Ramasubramanian AK, et al. Hemostatic function of apheresis platelets stored at 4 degrees C and 22 degrees C. Shock. 2014; 41(Suppl 1): 54–61.
- 20Rosenfeld SI, Looney RJ, Leddy JP, Phipps DC, Abraham GN, Anderson CL. Human platelet Fc receptor for immunoglobulin G. Identification as a 40,000-molecular-weight membrane protein shared by monocytes. J Clin Invest. 1985; 76(6): 2317–22.
- 21Yang JC, Liu FH, Sun Y, Ma T, Xu CX, Wang WH, et al. Good hemostatic effect of platelets stored at 4 degrees C in an in vitro model of massive blood loss and thrombocytopenia. Medicine (Baltimore). 2019; 98(18):e15454.
- 22Torres Filho IP, Torres LN, Valdez C, Salgado C, Cap AP, Dubick MA. Refrigerated platelets stored in whole blood up to 5 days adhere to thrombi formed during hemorrhagic hypotension in rats. J Thromb Haemost. 2017; 15(1): 163–75.
- 23Reddoch-Cardenas KM, Peltier GC, Chance TC, Nair PM, Meledeo MA, Ramasubramanian AK, et al. Cold storage of platelets in platelet additive solution maintains mitochondrial integrity by limiting initiation of apoptosis-mediated pathways. Transfusion. 2021; 61(1): 178–90.
- 24Reddoch-Cardenas KM, Sharma U, Salgado CL, Cantu C, Darlington DN, Pidcoke HF, et al. Use of specialized pro-resolving mediators to alleviate cold platelet storage lesion. Transfusion. 2020; 60(Suppl 3): S112–S8.
- 25Tutwiler V, Litvinov RI, Lozhkin AP, Peshkova AD, Lebedeva T, Ataullakhanov FI, et al. Kinetics and mechanics of clot contraction are governed by the molecular and cellular composition of the blood. Blood. 2016; 127(1): 149–59.
- 26Cohen I. The contractile system of blood platelets and its function. Methods Achiev Exp Pathol. 1979; 9: 40–86.
- 27Ting LH, Feghhi S, Taparia N, Smith AO, Karchin A, Lim E, et al. Contractile forces in platelet aggregates under microfluidic shear gradients reflect platelet inhibition and bleeding risk. Nat Commun. 2019; 10(1): 1204.
- 28Kim OV, Litvinov RI, Alber MS, Weisel JW. Quantitative structural mechanobiology of platelet-driven blood clot contraction. Nat Commun. 2017; 8(1): 1274.
- 29Stubbs JR, Tran SA, Emery RL, Hammel SA, Haugen DAL, Zielinski MD, et al. Cold platelets for trauma-associated bleeding: regulatory approval, accreditation approval, and practice implementation-just the "tip of the iceberg". Transfusion. 2017; 57(12): 2836–44.
- 30Holme S. Effect of additive solutions on platelet biochemistry. Blood Cells. 1992; 18(3): 421–30. discussion 31-4.
- 31van der Meer PF. PAS or plasma for storage of platelets? A concise review. Transfus Med. 2016; 26(5): 339–42.
- 32Skripchenko A, Turgeon A, Thompson-Montgomery D, Awatefe H, Wagner SJ. Value of calcium and phosphate in a bicarbonate-containing platelet additive solution with low plasma levels in maintaining key in vitro platelet storage parameters. Transfusion. 2017; 57(2): 349–56.
- 33Reddoch-Cardenas KM, Sharma U, Salgado CL, Montgomery RK, Cantu C, Cingoz N, et al. An in vitro pilot study of apheresis platelets collected on Trima Accel system and stored in T-PAS+ solution at refrigeration temperature (1-6 degrees C). Transfusion. 2019; 59(5): 1789–98.
- 34Tutwiler V, Peshkova AD, Le Minh G, Zaitsev S, Litvinov RI, Cines DB, et al. Blood clot contraction differentially modulates internal and external fibrinolysis. J Thromb Haemost. 2019; 17(2): 361–70.
- 35Weisel JW. Structure of fibrin: impact on clot stability. J Thromb Haemost. 2007; 5(Suppl 1): 116–24.
- 36Nguyen TH, Palankar R, Bui VC, Medvedev N, Greinacher A, Delcea M. Rupture forces among human blood platelets at different degrees of activation. Sci Rep. 2016; 6: 25402.
- 37Zhang Y, Qiu Y, Blanchard AT, Chang Y, Brockman JM, Ma VPY, et al. Platelet integrins exhibit anisotropic mechanosensing and harness piconewton forces to mediate platelet aggregation. Proc Natl Acad Sci U S A. 2018; 115(2): 325–30.
- 38Brzoska T, Suzuki Y, Sano H, Suzuki S, Tomczyk M, Tanaka H, et al. Imaging analyses of coagulation-dependent initiation of fibrinolysis on activated platelets and its modification by thrombin-activatable fibrinolysis inhibitor. Thromb Haemost. 2017; 117(4): 682–90.
- 39Mondoro TH, Vostal JG. Cold temperatures reduce the sensitivity of stored platelets to disaggregating agents. Platelets. 2002; 13(1): 11–20.
- 40Moroff G, Chang CH. Aggregation response of human platelets stored at 22 C as platelet-rich plasma. Transfusion. 1979; 19(6): 704–18.
- 41Ryan EA, Mockros LF, Stern AM, Lorand L. Influence of a natural and a synthetic inhibitor of factor XIIIa on fibrin clot rheology. Biophys J. 1999; 77(5): 2827–36.
- 42Ryan EA, Mockros LF, Weisel JW, Lorand L. Structural origins of fibrin clot rheology. Biophys J. 1999; 77(5): 2813–26.
- 43Kotova YN, Podoplelova NA, Obydennyy SI, Kostanova EA, Ryabykh AA, Demyanova AS, et al. Binding of coagulation factor xiii zymogen to activated platelet subpopulations: roles of integrin alphaiibbeta3 and fibrinogen. Thromb Haemost. 2019; 119(6): 906–15.
- 44Byrnes JR, Duval C, Wang Y, Hansen CE, Ahn B, Mooberry MJ, et al. Factor XIIIa-dependent retention of red blood cells in clots is mediated by fibrin alpha-chain crosslinking. Blood. 2015; 126(16): 1940–8.
- 45Cohen I, De Vries A. Platelet contractile regulation in an isometric system. Nature. 1973; 246(5427): 36–7.
- 46Kasahara K, Kaneda M, Miki T, Iida K, Sekino-Suzuki N, Kawashima I, et al. Clot retraction is mediated by factor XIII-dependent fibrin-alphaIIbbeta3-myosin axis in platelet sphingomyelin-rich membrane rafts. Blood. 2013; 122(19): 3340–8.
- 47Kasahara K, Souri M, Kaneda M, Miki T, Yamamoto N, Ichinose A. Impaired clot retraction in factor XIII A subunit-deficient mice. Blood. 2010; 115(6): 1277–9.
- 48Niewiarowski S, Markiewicz M, Nath N. Inhibition of the platelet-dependent fibrin retraction by the fibrin stabilizing factor (FSF, factor 13). J Lab Clin Med. 1973; 81(5): 641–50.
- 49Rao KM, Newcomb TF. Clot retraction in a factor XIII free system. Scand J Haematol. 1980; 24(2): 142–8.
- 50Helms CC, Ariens RA, Uitte de Willige S, Standeven KF, Guthold M. Alpha-alpha Cross-links increase fibrin fiber elasticity and stiffness. Biophys J. 2012; 102(1): 168–75.
- 51Kattula S, Byrnes JR, Martin SM, Holle LA, Cooley BC, Flick MJ, et al. Factor XIII in plasma, but not in platelets, mediates red blood cell retention in clots and venous thrombus size in mice. Blood Adv. 2018; 2(1): 25–35.
- 52Leeper CM, Yazer MH, Cladis FP, Saladino R, Triulzi DJ, Gaines BA. Cold-stored whole blood platelet function is preserved in injured children with hemorrhagic shock. J Trauma Acute Care Surg. 2019; 87(1): 49–53.
- 53Condron M, Scanlan M, Schreiber M. Massive transfusion of low-titer cold-stored O-positive whole blood in a civilian trauma setting. Transfusion. 2019; 59(3): 927–30.