Coagulofibrinolytic changes in patients with post-cardiac arrest syndrome

Frontiers in Medicine

Volumn 4, Issue SEP, 2017, Pages

  Wada, Takeshi ^a  

^a HOKKAIDO UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

Activation of coagulation; Disseminated intravascular coagulation; Fibrinolytic shutdown; Impaired anticoagulant; No reflow phenomenon; Post cardiac arrest syndrome; Systemic ischemia reperfusion

Indexed keywords

EID: 85051670900     PISSN: None     EISSN: 2296858X     Source Type: Journal    
DOI: 10.3389/fmed.2017.00156     Document Type: Review

References (117)

1. Negovsky VA. The second step in resuscitation-the treatment of the 'post-resuscitation disease'. Resuscitation (1972) 1:1-7. doi:10.1016/0300-9572(72)90058-5
2. Neumar RW, Nolan JP, Adrie C, Aibiki M, Berg RA, Böttiger BW, et al. Post-cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A consensus statement from the International Liaison Committee on Resuscitation (American Heart Association, Australian and New Zealand Council on Resuscitation, European Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Asia, and the Resuscitation Council of Southern Africa); the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; and the Stroke Council. Circulation (2008) 118:2452-83. doi:10.1161/CIRCULATIONAHA.108.190652
3. Adrie C, Adib-Conquy M, Laurent I, Monchi M, Vinsonneau C, Fitting C, et al. Successful cardiopulmonary resuscitation after cardiac arrest as a "sepsis-like" syndrome. Circulation (2002) 106:562-8. doi:10.1161/01.CIR.0000023891.80661.AD
4. Mehta B, Briggs DK, Sommers SC, Karpatkin M. Disseminated intravascular coagulation following cardiac arrest: a study of 15 patients. Am J Med Sci (1972) 264:353-63. doi:10.1097/00000441-197211000-00002
5. Levi M, Ten Cate H. Disseminated intravascular coagulation. N Engl J Med (1999) 341:586-92. doi:10.1056/NEJM199908193410807
6. Taylor FB Jr, Toh CH, Hoots WK, Wada H, Levi M. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost (2001) 86:1327-30
7. Gando S. Microvascular thrombosis and multiple organ dysfunction syndrome. Crit Care Med (2010) 38:S35-42. doi:10.1097/CCM.0b013e3181c9e31d
8. Ames A III, Wright RL, Kowada M, Thurston JM, Majno G. Cerebral ischemia. II. The no-reflow phenomenon. Am J Pathol (1968) 52:437-53
9. Hossmann KA, Hossmann V. Coagulopathy following experimental cerebral ischemia. Stroke (1977) 8:249-54. doi:10.1161/01.STR.8.2.249
10. Fischer EG, Ames A III, Hedley-Whyte ET, O'Gorman S. Reassessment of cerebral capillary changes in acute global ischemia and their relationship to the "no-reflow phenomenon". Stroke (1977) 8:36-9. doi:10.1161/01.STR.8.1.36
11. Adrie C, Monchi M, Laurent I, Um S, Yan SB, Thuong M, et al. Coagulopathy after successful cardiopulmonary resuscitation following cardiac arrest: implication of the protein C anticoagulant pathway. J Am Coll Cardiol (2005) 46:21-8. doi:10.1016/j.jacc.2005.03.046
12. Böttiger BW, Motsch J, Bohrer H, Boker T, Aulmann M, Nawroth PP, et al. Activation of blood coagulation after cardiac arrest is not balanced adequately by activation of endogenous fibrinolysis. Circulation (1995) 92:2572-8. doi:10.1161/01.CIR.92.9.2572
13. Castellheim A, Brekke OL, Espevik T, Harboe M, Mollnes TE. Innate immune responses to danger signals in systemic inflammatory response syndrome and sepsis. Scand J Immunol (2009) 69:479-91. doi:10.1111/j.1365-3083.2009.02255.x
14. Gando S, Otomo Y. Local hemostasis, immunothrombosis, and systemic disseminated intravascular coagulation in trauma and traumatic shock. Crit Care (2015) 19:72. doi:10.1186/s13054-015-0735-x
15. Wada T, Gando S, Mizugaki A, Yanagida Y, Jesmin S, Yokota H, et al. Coagulofibrinolytic changes in patients with disseminated intravascular coagulation associated with post-cardiac arrest syndrome-fibrinolytic shutdown and insufficient activation of fibrinolysis lead to organ dysfunction. Thromb Res (2013) 132:e64-9. doi:10.1016/j.thromres.2013.05.010
16. Gando S, Kameue T, Nanzaki S, Nakanishi Y. Massive fibrin formation with consecutive impairment of fibrinolysis in patients with out-of-hospital cardiac arrest. Thromb Haemost (1997) 77:278-82
17. Gando S, Nanzaki S, Morimoto Y, Kobayashi S, Kemmotsu O. Tissue factor and tissue factor pathway inhibitor levels during and after cardiopulmonary resuscitation. Thromb Res (1999) 96:107-13. doi:10.1016/S0049-3848(99)00073-0
18. Gertler JP, Abbott WM. Prothrombotic and fibrinolytic function of normal and perturbed endothelium. J Surg Res (1992) 52:89-95. doi:10.1016/0022-4804(92)90284-7
19. Gotoh O, Asano T, Koide T, Takakura K. Ischemic brain edema following occlusion of the middle cerebral artery in the rat. I: The time courses of the brain water, sodium and potassium contents and blood-brain barrier permeability to 125I-albumin. Stroke (1985) 16:101-9. doi:10.1161/01.STR.16.1.101
20. Gando S, Levi M, Toh CH. Disseminated intravascular coagulation. Nat Rev Dis Primers (2016) 2:16037. doi:10.1038/nrdp.2016.37
21. Mackman N. Regulation of the tissue factor gene. FASEB J (1995) 9:883-9
22. Hayakawa M, Sawamura A, Yanagida Y, Sugano M, Kubota N, Hoshino H, et al. Insufficient production of urinary trypsin inhibitor for neutrophil elastase release after cardiac arrest. Shock (2008) 29:549-52. doi:10.1097/shk.0b013e31815cfcd6
23. Shyu KG, Chang H, Lin CC, Huang FY, Hung CR. Concentrations of serum interleukin-8 after successful cardiopulmonary resuscitation in patients with cardiopulmonary arrest. Am Heart J (1997) 134:551-6. doi:10.1016/S0002-8703(97)70094-2
24. Coughlin SR. Thrombin signalling and protease-activated receptors. Nature (2000) 407:258-64. doi:10.1038/35025229
25. McDonald B, Pittman K, Menezes GB, Hirota SA, Slaba I, Waterhouse CC, et al. Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science (2010) 330:362-6. doi:10.1126/science.1195491
26. Liaw PC, Ito T, Iba T, Thachil J, Zeerleder S. DAMP and DIC: the role of extracellular DNA and DNA-binding proteins in the pathogenesis of DIC. Blood Rev (2016) 30:257-61. doi:10.1016/j.blre.2015.12.004
27. Arnalich F, Menendez M, Lagos V, Ciria E, Quesada A, Codoceo R, et al. Prognostic value of cell-free plasma DNA in patients with cardiac arrest outside the hospital: an observational cohort study. Crit Care (2010) 14:R47. doi:10.1186/cc8934
28. Huang CH, Tsai MS, Hsu CY, Chen HW, Wang TD, Chang WT, et al. Circulating cell-free DNA levels correlate with postresuscitation survival rates in out-of-hospital cardiac arrest patients. Resuscitation (2012) 83:213-8. doi:10.1016/j.resuscitation.2011.07.039
29. Gornik I, Wagner J, Gasparovic V, Milicic D, Degoricija V, Skoric B, et al. Prognostic value of cell-free DNA in plasma of out-of-hospital cardiac arrest survivors at ICU admission and 24h post-admission. Resuscitation (2014) 85:233-7. doi:10.1016/j.resuscitation.2013.10.008
30. Jeppesen AN, Hvas AM, Grejs AM, Duez CH, Sorensen BS, Kirkegaard H. Post-cardiac arrest level of free-plasma DNA and DNA-histone complexes. Acta Anaesthesiol Scand (2017) 61:523-31. doi:10.1111/aas.12882
31. Oda Y, Tsuruta R, Fujita M, Kaneda K, Kawamura Y, Izumi T, et al. Prediction of the neurological outcome with intrathecal high mobility group box 1 and S100B in cardiac arrest victims: a pilot study. Resuscitation (2012) 83:1006-12. doi:10.1016/j.resuscitation.2012.01.030
32. Oehmcke S, Morgelin M, Herwald H. Activation of the human contact system on neutrophil extracellular traps. J Innate Immun (2009) 1:225-30. doi:10.1159/000203700
33. Swystun LL, Mukherjee S, Liaw PC. Breast cancer chemotherapy induces the release of cell-free DNA, a novel procoagulant stimulus. J Thromb Haemost (2011) 9:2313-21. doi:10.1111/j.1538-7836.2011.04465.x
34. Gould TJ, Vu TT, Swystun LL, Dwivedi DJ, Mai SH, Weitz JI, et al. Neutrophil extracellular traps promote thrombin generation through platelet-dependent and platelet-independent mechanisms. Arterioscler Thromb Vasc Biol (2014) 34:1977-84. doi:10.1161/atvbaha.114.304114
35. Fuchs TA, Brill A, Duerschmied D, Schatzberg D, Monestier M, Myers DD Jr, et al. Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci U S A (2010) 107:15880-5. doi:10.1073/pnas.1005743107
36. Nakahara M, Ito T, Kawahara K, Yamamoto M, Nagasato T, Shrestha B, et al. Recombinant thrombomodulin protects mice against histone-induced lethal thromboembolism. PLoS One (2013) 8:e75961. doi:10.1371/journal.pone.0075961
37. Fuchs TA, Bhandari AA, Wagner DD. Histones induce rapid and profound thrombocytopenia in mice. Blood (2011) 118:3708-14. doi:10.1182/blood-2011-01-332676
38. Abrams ST, Zhang N, Manson J, Liu T, Dart C, Baluwa F, et al. Circulating histones are mediators of trauma-associated lung injury. Am J Respir Crit Care Med (2013) 187:160-9. doi:10.1164/rccm.201206-1037OC
39. Kim JE, Lee N, Gu JY, Yoo HJ, Kim HK. Circulating levels of DNA-histone complex and dsDNA are independent prognostic factors of disseminated intravascular coagulation. Thromb Res (2015) 135:1064-9. doi:10.1016/j.thromres.2015.03.014
40. Scaffidi P, Misteli T, Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature (2002) 418:191-5. doi:10.1038/nature00858
41. Wang H, Bloom O, Zhang M, Vishnubhakat JM, Ombrellino M, Che J, et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science (1999) 285:248-51. doi:10.1126/science.285.5425.248
42. Ito T, Kawahara K, Nakamura T, Yamada S, Nakamura T, Abeyama K, et al. High-mobility group box 1 protein promotes development of microvascular thrombosis in rats. J Thromb Haemost (2007) 5:109-16. doi:10.1111/j.1538-7836.2006.02255.x
43. Engelmann B, Massberg S. Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol (2013) 13:34-45. doi:10.1038/nri3345
44. Gando S, Nanzaki S, Morimoto Y, Kobayashi S, Kemmotsu O. Alterations of soluble L-and P-selectins during cardiac arrest and CPR. Intensive Care Med (1999) 25:588-93. doi:10.1007/s001340050907
45. Geppert A, Zorn G, Karth GD, Haumer M, Gwechenberger M, Koller-Strametz J, et al. Soluble selectins and the systemic inflammatory response syndrome after successful cardiopulmonary resuscitation. Crit Care Med (2000) 28:2360-5. doi:10.1097/00003246-200007000-00030
46. Gando S, Nanzaki S, Morimoto Y, Kobayashi S, Kemmotsu O. Out-of-hospital cardiac arrest increases soluble vascular endothelial adhesion molecules and neutrophil elastase associated with endothelial injury. Intensive Care Med (2000) 26:38-44. doi:10.1007/s001340050009
47. Bro-Jeppesen J, Johansson PI, Hassager C, Wanscher M, Ostrowski SR, Bjerre M, et al. Endothelial activation/injury and associations with severity of post-cardiac arrest syndrome and mortality after out-of-hospital cardiac arrest. Resuscitation (2016) 107:71-9. doi:10.1016/j.resuscitation.2016.08.006
48. Johansson P, Stensballe J, Ostrowski S. Shock induced endotheliopathy (SHINE) in acute critical illness-a unifying pathophysiologic mechanism. Crit Care (2017) 21:25. doi:10.1186/s13054-017-1605-5
49. Madoiwa S. Recent advances in disseminated intravascular coagulation: endothelial cells and fibrinolysis in sepsis-induced DIC. J Intensive Care (2015) 3:8. doi:10.1186/s40560-015-0075-6
50. Gando S, Kameue T, Nanzaki S, Igarashi M. Protein C activation during cardiopulmonary resuscitation following out-of-hospital cardiac arrest. J Anesth (1997) 11:239-41. doi:10.1007/BF02480047
51. Ammollo CT, Semeraro F, Xu J, Esmon NL, Esmon CT. Extracellular histones increase plasma thrombin generation by impairing thrombomodulin-dependent protein C activation. J Thromb Haemost (2011) 9:1795-803. doi:10.1111/j.1538-7836.2011.04422.x
52. Adrie C, Laurent I, Monchi M, Cariou A, Dhainaou JF, Spaulding C. Postresuscitation disease after cardiac arrest: a sepsis-like syndrome? Curr Opin Crit Care (2004) 10:208-12. doi:10.1097/01.ccx.0000126090.06275.fe
53. Wada T, Gando S, Ono Y, Maekawa K, Katabami K, Hayakawa M, et al. Disseminated intravascular coagulation with the fibrinolytic phenotype predicts the outcome of patients with out-of-hospital cardiac arrest. Thromb J (2016) 14:43. doi:10.1186/s12959-016-0116-y
54. Ono Y, Hayakawa M, Maekawa K, Kodate A, Sadamoto Y, Tominaga N, et al. Fibrin/fibrinogen degradation products (FDP) at hospital admission predict neurological outcomes in out-of-hospital cardiac arrest patients. Resuscitation (2017) 111:62-7. doi:10.1016/j.resuscitation.2016.11.017
55. Wada T, Jesmin S, Gando S, Yanagida Y, Mizugaki A, Sultana SN, et al. Angiogenic factors and their soluble receptors predict organ dysfunction and mortality in post-cardiac arrest syndrome. Crit Care (2012) 16:R171. doi:10.1186/cc11648
56. Levi M, van der Poll T. Inflammation and coagulation. Crit Care Med (2010) 38:S26-34. doi:10.1097/CCM.0b013e3181c98d21
57. Gando S, Tedo I. Increased neutrophil elastase release in patients with cardiopulmonary arrest: role of elastase inhibitor. Intensive Care Med (1995) 21:636-40. doi:10.1007/BF01711540
58. Schochl H, Cadamuro J, Seidl S, Franz A, Solomon C, Schlimp CJ, et al. Hyperfibrinolysis is common in out-of-hospital cardiac arrest: results from a prospective observational thromboelastometry study. Resuscitation (2013) 84:454-9. doi:10.1016/j.resuscitation.2012.08.318
59. Mangum M, Venable RH, Boatwright JD, Cocke TB. Hypoxia: a stimulus for tissue plasminogen activator release in humans? Aviat Space Environ Med (1987) 58:1093-6
60. Lowenstein CJ, Morrell CN, Yamakuchi M. Regulation of Weibel-Palade body exocytosis. Trends Cardiovasc Med (2005) 15:302-8. doi:10.1016/j.tcm.2005.09.005
61. Viersen VA, Greuters S, Korfage AR, Van der Rijst C, Van Bochove V, Nanayakkara PW, et al. Hyperfibrinolysis in out of hospital cardiac arrest is associated with markers of hypoperfusion. Resuscitation (2012) 83:1451-5. doi:10.1016/j.resuscitation.2012.05.008
62. Schwameis M, Schober A, Schorgenhofer C, Sperr WR, Schochl H, Janata-Schwatczek K, et al. Asphyxia by drowning induces massive bleeding due to hyperfibrinolytic disseminated intravascular coagulation. Crit Care Med (2015) 43:2394-402. doi:10.1097/ccm.0000000000001273
63. Lijnen HR, Collen D. Mechanisms of physiological fibrinolysis. Baillieres Clin Haematol (1995) 8:277-90. doi:10.1016/S0950-3536(05)80268-9
64. Pinsky DJ, Liao H, Lawson CA, Yan SF, Chen J, Carmeliet P, et al. Coordinated induction of plasminogen activator inhibitor-1 (PAI-1) and inhibition of plasminogen activator gene expression by hypoxia promotes pulmonary vascular fibrin deposition. J Clin Invest (1998) 102:919-28. doi:10.1172/jci307
65. Geppert A, Zorn G, Delle-Karth G, Heinz G, Maurer G, Siostrzonek P, et al. Plasminogen activator inhibitor type 1 and outcome after successful cardiopulmonary resuscitation. Crit Care Med (2001) 29:1670-7. doi:10.1097/00003246-200109000-00003
66. Komissarov AA, Florova G, Idell S. Effects of extracellular DNA on plasminogen activation and fibrinolysis. J Biol Chem (2011) 286:41949-62. doi:10.1074/jbc.M111.301218
67. Longstaff C, Varju I, Sotonyi P, Szabo L, Krumrey M, Hoell A, et al. Mechanical stability and fibrinolytic resistance of clots containing fibrin, DNA, and histones. J Biol Chem (2013) 288:6946-56. doi:10.1074/jbc.M112.404301
68. Machovich R, Owen WG. The elastase-mediated pathway of fibrinolysis. Blood Coagul Fibrinolysis (1990) 1:79-90. doi:10.1097/00001721-199003000-00011
69. Madoiwa S, Tanaka H, Nagahama Y, Dokai M, Kashiwakura Y, Ishiwata A, et al. Degradation of cross-linked fibrin by leukocyte elastase as alternative pathway for plasmin-mediated fibrinolysis in sepsis-induced disseminated intravascular coagulation. Thromb Res (2011) 127:349-55. doi:10.1016/j.thromres.2010.12.008
70. Wada T, Gando S, Mizugaki A, Kodate A, Sadamoto Y, Murakami H, et al. The differences in the coagulofibrinolytic changes between post-cardiac arrest syndrome of cardiac causes and hypoxic insults: a pilot study. Acute Med Surg (2017) 4:371-2. doi:10.1002/ams2.270
71. Kim J, Kim K, Lee JH, Jo YH, Kim T, Rhee JE, et al. Prognostic implication of initial coagulopathy in out-of-hospital cardiac arrest. Resuscitation (2013) 84:48-53. doi:10.1016/j.resuscitation.2012.09.003
72. Duvekot A, Viersen VA, Dekker SE, Geeraedts LM Jr, Schwarte LA, Spoelstra-Man AM, et al. Low cerebral oxygenation levels during resuscitation in out-of-hospital cardiac arrest are associated with hyperfibrinolysis. Anesthesiology (2015) 123:820-9. doi:10.1097/aln.0000000000000806
73. Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med (2002) 346:557-63. doi:10.1056/NEJMoa003289
74. Tieu BH, Holcomb JB, Schreiber MA. Coagulopathy: its pathophysiology and treatment in the injured patient. World J Surg (2007) 31:1055-64. doi:10.1007/s00268-006-0653-9
75. Kushimoto S, Gando S, Saitoh D, Mayumi T, Ogura H, Fujishima S, et al. The impact of body temperature abnormalities on the disease severity and outcome in patients with severe sepsis: an analysis from a multicenter, prospective survey of severe sepsis. Crit Care (2013) 17:R271. doi:10.1186/cc13106
76. Jacob M, Hassager C, Bro-Jeppesen J, Ostrowski SR, Thomsen JH, Wanscher M, et al. The effect of targeted temperature management on coagulation parameters and bleeding events after out-of-hospital cardiac arrest of presumed cardiac cause. Resuscitation (2015) 96:260-7. doi:10.1016/j.resuscitation.2015.08.018
77. Nielsen AK, Jeppesen AN, Kirkegaard H, Hvas AM. Changes in coagulation during therapeutic hypothermia in cardiac arrest patients. Resuscitation (2016) 98:85-90. doi:10.1016/j.resuscitation.2015.11.007
78. Szymanski FM, Karpinski G, Filipiak KJ, Platek AE, Hrynkiewicz-Szymanska A, Kotkowski M, et al. Usefulness of the D-dimer concentration as a predictor of mortality in patients with out-of-hospital cardiac arrest. Am J Cardiol (2013) 112:467-71. doi:10.1016/j.amjcard.2013.03.057
79. Deng Y, He L, Yang J, Wang J. Serum D-dimer as an indicator of immediate mortality in patients with in-hospital cardiac arrest. Thromb Res (2016) 143:161-5. doi:10.1016/j.thromres.2016.03.001
80. Gando S, Saitoh D, Ogura H, Mayumi T, Koseki K, Ikeda T, et al. Natural history of disseminated intravascular coagulation diagnosed based on the newly established diagnostic criteria for critically ill patients: results of a multicenter, prospective survey. Crit Care Med (2008) 36:145-50. doi:10.1097/01.CCM.0000295317.97245.2D
81. Ferreira FL, Bota DP, Bross A, Melot C, Vincent JL. Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA (2001) 286:1754-8. doi:10.1001/jama.286.14.1754
82. Kowada M, Ames A III, Majno G, Wright RL. Cerebral ischemia. I. An improved experimental method for study; cardiovascular effects and demonstration of an early vascular lesion in the rabbit. J Neurosurg (1968) 28:150-7. doi:10.3171/jns.1968.28.2.0150
83. Fischer EG, Ames A III. Studies on mechanisms of impairment of cerebral circulation following ischemia: effect of hemodilution and perfusion pressure. Stroke (1972) 3:538-42. doi:10.1161/01.STR.3.5.538
84. Safar P, Stezoski W, Nemoto EM. Amelioration of brain damage after 12 minutes' cardiac arrest in dogs. Arch Neurol (1976) 33:91-5. doi:10.1001/archneur.1976.00500020019004
85. Lin SR, O'Connor MJ, Fischer HW, King A. The effect of combined dextran and streptokinase on cerebral function and blood flow after cardiac arrest: and experimental study on the dog. Invest Radiol (1978) 13:490-8. doi:10.1097/00004424-197811000-00003
86. Böttiger BW, Bohrer H, Bach A, Motsch J, Martin E. Bolus injection of thrombolytic agents during cardiopulmonary resuscitation for massive pulmonary embolism. Resuscitation (1994) 28:45-54. doi:10.1016/0300-9572(94)90054-X
87. Böttiger BW, Martin E. Thrombolytic therapy during cardiopulmonary resuscitation and the role of coagulation activation after cardiac arrest. Curr Opin Crit Care (2001) 7:176-83. doi:10.1097/00075198-200106000-00006
88. Fischer M, Böttiger BW, Popov-Cenic S, Hossmann KA. Thrombolysis using plasminogen activator and heparin reduces cerebral no-reflow after resuscitation from cardiac arrest: an experimental study in the cat. Intensive Care Med (1996) 22:1214-23. doi:10.1007/BF01709339
89. Kim YH, Park JH, Hong SH, Koh JY. Nonproteolytic neuroprotection by human recombinant tissue plasminogen activator. Science (1999) 284:647-50. doi:10.1126/science.284.5414.647
90. Tiffany PA, Schultz M, Stueven H. Bolus thrombolytic infusions during CPR for patients with refractory arrest rhythms: outcome of a case series. Ann Emerg Med (1998) 31:124-6. doi:10.1016/S0196-0644(98)70295-1
91. Böttiger BW, Bode C, Kern S, Gries A, Gust R, Glatzer R, et al. Efficacy and safety of thrombolytic therapy after initially unsuccessful cardiopulmonary resuscitation: a prospective clinical trial. Lancet (2001) 357:1583-5. doi:10.1016/s0140-6736(00)04726-7
92. Abu-Laban RB, Christenson JM, Innes GD, van Beek CA, Wanger KP, McKnight RD, et al. Tissue plasminogen activator in cardiac arrest with pulseless electrical activity. N Engl J Med (2002) 346:1522-8. doi:10.1056/NEJMoa012885
93. Fatovich DM, Dobb GJ, Clugston RA. A pilot randomised trial of thrombolysis in cardiac arrest (The TICA trial). Resuscitation (2004) 61:309-13. doi:10.1016/j.resuscitation.2004.01.016
94. Bozeman WP, Kleiner DM, Ferguson KL. Empiric tenecteplase is associated with increased return of spontaneous circulation and short term survival in cardiac arrest patients unresponsive to standard interventions. Resuscitation (2006) 69:399-406. doi:10.1016/j.resuscitation.2005.09.027
95. Spohr F, Böttiger BW. Safety of thrombolysis during cardiopulmonary resuscitation. Drug Safety (2003) 26:367-79. doi:10.2165/00002018-200326060-00001
96. Janata K, Holzer M, Kurkciyan I, Losert H, Riedmuller E, Pikula B, et al. Major bleeding complications in cardiopulmonary resuscitation: the place of thrombolytic therapy in cardiac arrest due to massive pulmonary embolism. Resuscitation (2003) 57:49-55. doi:10.1016/S0300-9572(02)00430-6
97. Böttiger BW, Arntz HR, Chamberlain DA, Bluhmki E, Belmans A, Danays T, et al. Thrombolysis during resuscitation for out-of-hospital cardiac arrest. N Engl J Med (2008) 359:2651-62. doi:10.1056/NEJMoa070570
98. Renard A, Verret C, Jost D, Meynard JB, Tricehreau J, Hersan O, et al. Impact of fibrinolysis on immediate prognosis of patients with out-of-hospital cardiac arrest. J Thromb Thrombolysis (2011) 32:405-9. doi:10.1007/s11239-011-0619-0
99. Logan JK, Pantle H, Huiras P, Bessman E, Bright L. Evidence-based diagnosis and thrombolytic treatment of cardiac arrest or periarrest due to suspected pulmonary embolism. Am J Emerg Med (2014) 32:789-96. doi:10.1016/j.ajem.2014.04.032
100. Lavonas EJ, Drennan IR, Gabrielli A, Heffner AC, Hoyte CO, Orkin AM, et al. Part 10: special circumstances of resuscitation: 2015 American Heart Association Guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation (2015) 132:S501-18. doi:10.1161/cir.0000000000000264
101. Kuriyama N, Isaji S, Hamada T, Kishiwada M, Ohsawa I, Usui M, et al. Activated protein C prevents hepatic ischaemia-reperfusion injury in rats. Liver Int (2009) 29:299-307. doi:10.1111/j.1478-3231.2008.01796.x
102. Hirose K, Okajima K, Taoka Y, Uchiba M, Tagami H, Nakano K, et al. Activated protein C reduces the ischemia/reperfusion-induced spinal cord injury in rats by inhibiting neutrophil activation. Ann Surg (2000) 232:272-80. doi:10.1097/00000658-200008000-00018
103. Cheng T, Liu D, Griffin JH, Fernandez JA, Castellino F, Rosen ED, et al. Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective. Nat Med (2003) 9:338-42. doi:10.1038/nm826
104. Shibata M, Kumar SR, Amar A, Fernandez JA, Hofman F, Griffin JH, et al. Anti-inflammatory, antithrombotic, and neuroprotective effects of activated protein C in a murine model of focal ischemic stroke. Circulation (2001) 103:1799-805. doi:10.1161/01.CIR.103.13.1799
105. Schoots IG, Levi M, van Vliet AK, Maas AM, Roossink EH, van Gulik TM. Inhibition of coagulation and inflammation by activated protein C or antithrombin reduces intestinal ischemia/reperfusion injury in rats. Crit Care Med (2004) 32:1375-83. doi:10.1097/01.CCM.0000128567.57761.E9
106. Ozden A, Sarioglu A, Demirkan NC, Bilgihan A, Duzcan E. Antithrombin III reduces renal ischemia-reperfusion injury in rats. Res Exp Med (Berl) (2001) 200:195-203
107. Wang J, Wang Y, Wang J, Gao J, Tong C, Manithody C, et al. Antithrombin is protective against myocardial ischemia and reperfusion injury. J Thromb Haemost (2013) 11:1020-8. doi:10.1111/jth.12243
108. Wang J, Yang L, Rezaie AR, Li J. Activated protein C protects against myocardial ischemic/reperfusion injury through AMP-activated protein kinase signaling. J Thromb Haemost (2011) 9:1308-17. doi:10.1111/j.1538-7836.2011.04331.x
109. Teschendorf P, Albertsmeier M, Vogel P, Padosch SA, Spohr F, Kirschfink M, et al. Neurological outcome and inflammation after cardiac arrest-effects of protein C in rats. Resuscitation (2008) 79:316-24. doi:10.1016/j.resuscitation.2008.05.005
110. Teschendorf P, Padosch SA, Del Valle YFD, Peter C, Fuchs A, Popp E, et al. Effects of activated protein C on post cardiac arrest microcirculation: an in vivo microscopy study. Resuscitation (2009) 80:940-5. doi:10.1016/j.resuscitation.2009.04.029
111. Johansson J, Ridefelt P, Basu S, Rubertsson S. Antithrombin administration during experimental cardiopulmonary resuscitation. Resuscitation (2004) 62:71-8. doi:10.1016/j.resuscitation.2004.02.010
112. Wiedermann CJ, Kaneider NC. A systematic review of antithrombin concentrate use in patients with disseminated intravascular coagulation of severe sepsis. Blood Coagul Fibrinolysis (2006) 17:521-6. doi:10.1097/01.mbc.0000245302.18010.40
113. Gando S, Saitoh D, Ishikura H, Ueyama M, Otomo Y, Oda S, et al. A randomized, controlled, multicenter trial of the effects of antithrombin on disseminated intravascular coagulation in patients with sepsis. Crit Care (2013) 17:R297. doi:10.1186/cc13163
114. Yin Q, Liu B, Wu C, Yang J, Hang C, Li C. Effects of Shen-Fu injection on coagulation-fibrinolysis disorders in a porcine model of cardiac arrest. Am J Emerg Med (2016) 34:469-76. doi:10.1016/j.ajem.2015.12.010
115. Hou X, Li C, Gu W, Guo Z, Yin W, Zhang D. Effect of Shenfu on inflammatory cytokine release and brain edema after prolonged cardiac arrest in the swine. Am J Emerg Med (2013) 31:1159-64. doi:10.1016/j.ajem.2013.03.020
116. Ji XF, Yang L, Zhang MY, Li CS, Wang S, Cong LH. Shen-fu injection attenuates postresuscitation myocardial dysfunction in a porcine model of cardiac arrest. Shock (2011) 35:530-6. doi:10.1097/SHK.0b013e31820e2058
117. Zhang MY, Ji XF, Wang S, Li CS. Shen-fu injection attenuates postresuscitation lung injury in a porcine model of cardiac arrest. Resuscitation (2012) 83:1152-8. doi:10.1016/j.resuscitation.2012.01.041