Thrombocytopenia-associated multiple organ failure syndrome

Pediatric Critical Care Medicine: Volume 3: Gastroenterological, Endocrine, Renal, Hematologic, Oncologic and Immune Systems

Volumn , Issue , 2014, Pages 481-492

  Nguyen, Trung C ^a   Han, Yong Y ^b   Fortenberry, James D ^c   Zhou, Zhou ^d   Cruz, Miguel A ^e   Carcillo, Joseph A ^f  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

^b CHILDREN S MERCY HOSPITAL   (United States)

^c EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d FUWAI HOSPITAL   (China)

^e Section of Cardiovascular Research   (United States)

^f CHILDREN S HOSPITAL OF PITTSBURGH   (United States)

Author keywords

ADAMTS 13; Alternative complement pathway; DIC; Disseminated microvascular thrombosis; Fibrin; HUS; Plasma exchange; Platelets; TAMOF; Thrombocytopenia; Thrombocytopenia associated multiple organ failure; Thrombotic microangiopathy; TTP; VWF

Indexed keywords

EID: 84948977535     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-4471-6416-6_31     Document Type: Chapter

References (145)

1. Nadel S, Goldstein B, Williams M.D., et al. Drotrecogin alfa (activated) in children with severe sepsis: a multicentre phase III randomised controlled trial. Lancet. 2007;369(9564):836-43.
2. Khemani RG, Bart RD, Alonzo TA, Hatzakis G, Hallam D, Newth CJ. Disseminated intravascular coagulation score is associated with mortality for children with shock. Intensive Care Med. 2009; 35(2):327-33.
3. Dhainaut JF, Yan SB, Joyce DE, et al. Treatment effects of drotrecogin alfa (activated) in patients with severe sepsis with or without overt disseminated intravascular coagulation. J Thromb Haemost. 2004;2(11):1924-33.
4. Szczepiorkowski ZM, Winters JL, Bandarenko N, et al. Guidelines on the use of therapeutic apheresis in clinical practice-evidencebased approach from the apheresis applications committee of the American Society for Apheresis. J Clin Apher. 2010;25(3): 83-177.
5. Bell WR, Braine HG, Ness PM, Kickler TS. Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Clinical experience in 108 patients. N Engl J Med. 1991; 325(6):398-403.
6. Rock GA, Shumak KH, Buskard NA, et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group. N Engl J Med. 1991;325(6):393-7.
7. Frank C, Werber D, Cramer JP, et al. Epidemic profile of Shigatoxin-producing Escherichia coli O104:H4 outbreak in Germany. N Engl J Med. 2011;365(19):1771-80.
8. Garg AX, Suri RS, Barrowman N, et al. Long-term renal prognosis of diarrhea-associated hemolytic uremic syndrome: a systematic review, meta-analysis, and meta-regression. JAMA J Am Med Assoc. 2003;290(10):1360-70.
9. Kaplan BS, Meyers KE, Schulman SL. The pathogenesis and treatment of hemolytic uremic syndrome. J Am Soc Nephrol. 1998;9(6):1126-33.
10. Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med. 2009;361(17):1676-87.
11. Kwan HC. Thrombotic microangiopathy. Semin Hematol. 1987; 24:69-81.
12. Kwan HC. Miscellaneous secondary thrombotic microangiopathy. Semin Hematol. 1987;24:141-7.
13. Besbas N, Karpman D, Landau D, et al. A classification of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and related disorders. Kidney Int. 2006;70(3):423-31.
14. Asada Y, Sumiyoshi A, Hayashi T, Suzumiya J, Kaketani K. Immunohistochemistry of vascular lesion in thrombotic thrombocytopenic purpura, with special reference to factor VIII related antigen. Thromb Res. 1985;38(5):469-79.
15. Burke AP, Mont E, Kolodgie F, Virmani R. Thrombotic thrombocytopenic purpura causing rapid unexpected death: value of CD61 immunohistochemical staining in diagnosis. Cardiovasc Pathol. 2005;14(3):150-5.
16. Tsai HM, Chandler WL, Sarode R, et al. von Willebrand factor and von Willebrand factor-cleaving metalloprotease activity in Escherichia coli O157:H7-associated hemolytic uremic syndrome. Pediatr Res. 2001;49(5):653-9.
17. Richardson SE, Karmali MA, Becker LE, Smith CR. The histopathology of the hemolytic uremic syndrome associated with verocytotoxin-producing Escherichia coli infections. Hum Pathol. 1988;19(9):1102-8.
18. Hosler GA, Cusumano AM, Hutchins GM. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are distinct pathologic entities. A review of 56 autopsy cases. Arch Pathol Lab Med. 2003;127(7):834-9.
19. Levi M, Ten Cate H. Disseminated intravascular coagulation. N Engl J Med. 1999;341(8):586-92.
20. Taylor FB, Jr Toh CH, Hoots WK, Wada H, Levi M. Towards defi-nition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001; 86(5):1327-30.
21. Gando S, Saitoh D, Ogura H, 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(1):145-50.
22. Levi M, van der Poll T. Disseminated intravascular coagulation: a review for the internist. Intern Emerg Med. 2013;8(1):23-32.
23. Levi M. Disseminated intravascular coagulation. Crit Care Med. 2007;35(9):2191-5.
24. Conkling PR, Greenberg CS, Weinberg JB. Tumor necrosis factor induces tissue factor-like activity in human leukemia cell line U937 and peripheral blood monocytes. Blood. 1988;72(1):128-33.
25. Nawroth PP, Stern DM. Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med. 1986;163(3): 740-5.
26. van der Poll T, Levi M, Hack CE, et al. Elimination of interleukin 6 attenuates coagulation activation in experimental endotoxemia in chimpanzees. J Exp Med. 1994;179(4):1253-9.
27. Levi M, van der Poll T, ten Cate H, van Deventer SJ. The cytokinemediated imbalance between coagulant and anticoagulant mechanisms in sepsis and endotoxaemia. Eur J Clin Investig. 1997; 27(1):3-9.
28. Pixley RA, De La Cadena R, Page JD, et al. The contact system contributes to hypotension but not disseminated intravascular coagulation in lethal bacteremia. In vivo use of a monoclonal antifactor XII antibody to block contact activation in baboons. J Clin Investig. 1993;91(1):61-8.
29. Biemond BJ, Levi M, ten Cate H, et al. Complete inhibition of endotoxin-induced coagulation activation in chimpanzees with a monoclonal Fab fragment against factor VII/VIIa. Thromb Haemost. 1995;73(2):223-30.
30. Levi M, ten Cate H, Bauer KA, et al. Inhibition of endotoxininduced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees. J Clin Investig. 1994;93(1):114-20.
31. Taylor Jr FB, Chang A, Ruf W, et al. Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody. Circ Shock. 1991;33(3):127-34.
32. Del Conde I, Shrimpton CN, Thiagarajan P, Lopez JA. Tissue-factorbearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood. 2005;106(5):1604-11.
33. Mandal SK, Iakhiaev A, Pendurthi UR, Rao LV. Acute cholesterol depletion impairs functional expression of tissue factor in fibroblasts: modulation of tissue factor activity by membrane cholesterol. Blood. 2005;105(1):153-60.
34. Levi M, de Jonge E, van der Poll T. Rationale for restoration of physiological anticoagulant pathways in patients with sepsis and disseminated intravascular coagulation. Crit Care Med. 2001; 29(7 Suppl):S90-S94.
35. Madach K, Aladzsity I, Szilagyi A, et al. 4G/5G polymorphism of PAI-1 gene is associated with multiple organ dysfunction and septic shock in pneumonia induced severe sepsis: prospective, observational, genetic study. Crit Care. 2010;14(2):R79.
36. Nguyen TC, Han YY, Kiss JE, et al. Intensive plasma exchange increases a disintegrin and metalloprotease with thrombospondin motifs-13 activity and reverses organ dysfunction in children with thrombocytopenia-associated multiple organ failure*. Crit Care Med. 2008;36(10):2878-87.
37. Green J, Doughty L, Kaplan SS, Sasser H, Carcillo JA. The tissue factor and plasminogen activator inhibitor type-1 response in pediatric sepsis-induced multiple organ failure. Thromb Haemost. 2002;87(2):218-23.
38. Madoiwa S, Nunomiya S, Ono T, et al. Plasminogen activator inhibitor 1 promotes a poor prognosis in sepsis-induced disseminated intravascular coagulation. Int J Hematol. 2006;84(5):398-405.
39. Di Nisio M, Baudo F, Cosmi B, et al. Diagnosis and treatment of disseminated intravascular coagulation: guidelines of the Italian Society for Haemostasis and Thrombosis (SISET). Thromb Res. 2012;129(5):e177-84.
40. Levi M, Toh CH, Thachil J, Watson HG. Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Committee for Standards in Haematology. Br J Haematol. 2009;145(1):24-33.
41. Wada H, Thachil J, Di Nisio M, et al. Guidance for diagnosis and treatment of DIC from harmonization of the recommendations from three guidelines. J Thromb Haemost. 2013. Epub ahead of print.
42. Wada H, Asakura H, Okamoto K, et al. Expert consensus for the treatment of disseminated intravascular coagulation in Japan. Thromb Res. 2010;125(1):6-11.
43. Moschcowitz E. A hitherto undescribed disease. Proc N Y Pathol Soc. 1924;24:21-4.
44. Moake JL, Rudy CK, Troll JH, et al. Unusually large plasma factor VIII:von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. N Engl J Med. 1982;307(23):1432-5.
45. Moake JL. Thrombotic microangiopathies. N Engl J Med. 2002;347(8):589-600.
46. Levy GG, Nichols WC, Lian EC, et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature. 2001;413(6855):488-94.
47. Kokame K, Matsumoto M, Soejima K, et al. Mutations and common polymorphisms in ADAMTS13 gene responsible for von Willebrand factor-cleaving protease activity. Proc Natl Acad Sci U S A. 2002;99(18):11902-7.
48. Matsumoto M, Kokame K, Soejima K, et al. Molecular characterization of ADAMTS13 gene mutations in Japanese patients with Upshaw-Schulman syndrome. Blood. 2004;103(4):1305-10.
49. Pimanda JE, Maekawa A, Wind T, Paxton J, Chesterman CN, Hogg PJ. Congenital thrombotic thrombocytopenic purpura in association with a mutation in the second CUB domain of ADAMTS13. Blood. 2004;103(2):627-9.
50. Schneppenheim R, Budde U, Oyen F, et al. von Willebrand factor cleaving protease and ADAMTS13 mutations in childhood TTP. Blood. 2003;101(5):1845-50.
51. Uchida T, Wada H, Mizutani M, et al. Identification of novel mutations in ADAMTS13 in an adult patient with congenital thrombotic thrombocytopenic purpura. Blood. 2004;104(7): 2081-3.
52. Tsai HM, Lian EC. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med. 1998;339(22):1585-94.
53. Furlan M, Robles R, Galbusera M, et al. von Willebrand factorcleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med. 1998;339(22): 1578-84.
54. Fowler WE, Fretto LJ, Hamilton KK, Erickson HP, McKee PA. Substructure of human von Willebrand factor. J Clin Investig. 1985;76(4):1491-500.
55. Wagner DD, Lawrence SO, Ohlsson-Wilhelm BM, Fay PJ, Marder VJ. Topology and order of formation of interchain disulfide bonds in von Willebrand factor. Blood. 1987;69(1):27-32.
56. Vischer UM, Wagner DD. von Willebrand factor proteolytic processing and multimerization precede the formation of Weibel-Palade bodies. Blood. 1994;83(12):3536-44.
57. Bowie EJ, Solberg LA, Jr Fass DN, et al. Transplantation of normal bone marrow into a pig with severe von Willebrand’s disease. J Clin Investig. 1986;78(1):26-30.
58. Sadler JE. Biochemistry and genetics of von Willebrand factor. Ann Rev Biochem. 1998;67:395-424.
59. Tsai HM, Nagel RL, Hatcher VB, Seaton AC, Sussman II. The high molecular weight form of endothelial cell von Willebrand factor is released by the regulated pathway. Br J Haematol. 1991; 79(2):239-45.
60. Bernardo A, Ball C, Nolasco L, Moake JF, Dong JF. Effects of inflammatory cytokines on the release and cleavage of the endothelial cell-derived ultralarge von Willebrand factor multimers under flow. Blood. 2004;104(1):100-6.
61. Wagner DD. Cell biology of von Willebrand factor. Annu Rev Cell Biol. 1990;6:217-46.
62. Sporn LA, Marder VJ, Wagner DD. Inducible secretion of large, biologically potent von Willebrand factor multimers. Cell. 1986; 46(2):185-90.
63. Moake JL, Turner NA, Stathopoulos NA, Nolasco LH, Hellums JD. Involvement of large plasma von Willebrand factor (vWF) multimers and unusually large vWF forms derived from endothelial cells in shear stress-induced platelet aggregation. J Clin Investig. 1986;78(6):1456-61.
64. Arya M, Anvari B, Romo GM, et al. Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein Ib-IX complex: studies using optical tweezers. Blood. 2002;99(11):3971-7.
65. Chow TW, Turner NA, Chintagumpala M, et al. Increased von Willebrand factor binding to platelets in single episode and recurrent types of thrombotic thrombocytopenic purpura. Am J Hematol. 1998;57(4):293-302.
66. Zhou W, Inada M, Lee TP, et al. ADAMTS13 is expressed in hepatic stellate cells. Lab Investig J Tech Methods Path. 2005;85(6):780-8.
67. Liu L, Choi H, Bernardo A, et al. Platelet-derived VWF-cleaving metalloprotease ADAMTS-13. J Thromb Haemost. 2005;3(11): 2536-44.
68. Turner N, Nolasco L, Tao Z, Dong JF, Moake J. Human endothelial cells synthesize and release ADAMTS-13. J Thromb Haemost. 2006;4(6):1396-404.
69. Moake J. Thrombotic microangiopathies: multimers, metalloprotease, and beyond. Clin Transl Sci. 2009;2(5):366-73.
70. Noris M, Remuzzi G. Hemolytic uremic syndrome. J Am Soc Nephrol. 2005;16(4):1035-50.
71. Constantinescu AR, Bitzan M, Weiss LS, et al. Non-enteropathic hemolytic uremic syndrome: causes and short-term course. Am J Kidney Dis. 2004;43(6):976-82.
72. Tarr PI, Gordon CA, Chandler WL. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet. 2005;365(9464):1073-86.
73. Gould LH, Demma L, Jones TF, et al. Hemolytic uremic syndrome and death in persons with Escherichia coli O157:H7 infection, foodborne diseases active surveillance network sites, 2000-2006. Clin Infect dis. 2009;49(10):1480-5.
74. Johannes L, Romer W. Shiga toxins-from cell biology to biomedical applications. Nat Rev Microbiol. 2010;8(2):105-16.
75. van Setten PA, Monnens LA, Verstraten RG, van den Heuvel LP, van Hinsbergh VW. Effects of verocytotoxin-1 on nonadherent human monocytes: binding characteristics, protein synthesis, and induction of cytokine release. Blood. 1996;88(1):174-83.
76. Karpman D, Papadopoulou D, Nilsson K, Sjogren AC, Mikaelsson C, Lethagen S. Platelet activation by Shiga toxin and circulatory factors as a pathogenetic mechanism in the hemolytic uremic syndrome. Blood. 2001;97(10):3100-8.
77. Nestoridi E, Tsukurov O, Kushak RI, Ingelfinger JR, Grabowski EF. Shiga toxin enhances functional tissue factor on human glomerular endothelial cells: implications for the pathophysiology of hemolytic uremic syndrome. J Thromb Haemost. 2005;3(4):752-62.
78. Nolasco LH, Turner NA, Bernardo A, et al. Hemolytic uremic syndrome-associated Shiga toxins promote endothelial-cell secretion and impair ADAMTS13 cleavage of unusually large von Willebrand factor multimers. Blood. 2005;106(13):4199-209.
79. Stahl AL, Sartz L, Karpman D. Complement activation on platelet-leukocyte complexes and microparticles in enterohemorrhagic Escherichia coli-induced hemolytic uremic syndrome. Blood. 2011;117(20):5503-13.
80. Thurman JM, Marians R, Emlen W, et al. Alternative pathway of complement in children with diarrhea-associated hemolytic uremic syndrome. Clin J Am Soc Nephrol. 2009;4(12):1920-4.
81. Monnens L, Molenaar J, Lambert PH, Proesmans W, van Munster P. The complement system in hemolytic-uremic syndrome in childhood. Clin Nephrol. 1980;13(4):168-71.
82. Morigi M, Galbusera M, Gastoldi S, et al. Alternative pathway activation of complement by Shiga toxin promotes exuberant C3a formation that triggers microvascular thrombosis. J Immunol. 2011;187(1):172-80.
83. Turner NA, Moake J. Assembly and activation of alternative complement components on endothelial cell-anchored ultra-large von Willebrand factor links complement and hemostasis-thrombosis. PLoS One. 2013;8(3):e59372.
84. Noris M, Mescia F, Remuzzi G. STEC-HUS, atypical HUS and TTP are all diseases of complement activation. Nat Rev Nephrol. 2012;8(11):622-33.
85. Dragon-Durey MA, Sethi SK, Bagga A, et al. Clinical features of anti-factor H autoantibody-associated hemolytic uremic syndrome. J Am Soc Nephrol. 2010;21(12):2180-7.
86. Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: a key system for immune surveillance and homeostasis. Nat Immunol. 2010;11(9):785-97.
87. Legendre CM, Licht C, Muus P, et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med. 2013;368(23):2169-81.
88. Zuber J, Fakhouri F, Roumenina LT, Loirat C, Fremeaux-Bacchi V. French Study Group for a HCG. Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies. Nat Rev Nephrol. 2012;8(11):643-57.
89. Colic E, Dieperink H, Titlestad K, Tepel M. Management of an acute outbreak of diarrhoea-associated haemolytic uraemic syndrome with early plasma exchange in adults from southern Denmark: an observational study. Lancet. 2011;378(9796):1089-93.
90. Kim JJ, Goodship TH, Tizard J, Inward C. Plasma therapy for atypical haemolytic uraemic syndrome associated with heterozygous factor H mutations. Pediatr Nephrol. 2011;26(11):2073-6.
91. Kielstein JT, Beutel G, Fleig S, et al. Best supportive care and therapeutic plasma exchange with or without eculizumab in Shiga-toxin-producing E. coli O104:H4 induced haemolyticuraemic syndrome: an analysis of the German STEC-HUS registry. Nephrol Dial Transplant. 2012;27(10):3807-15.
92. Lapeyraque AL, Malina M, Fremeaux-Bacchi V, et al. Eculizumab in severe Shiga-toxin-associated HUS. N Engl J Med. 2011; 364(26):2561-3.
93. Trachtman H, Austin C, Lewinski M, Stahl RA. Renal and neurological involvement in typical Shiga toxin-associated HUS. Nat Rev Nephrol. 2012;8(11):658-69.
94. Stephan F, Hollande J, Richard O, CheffiA, Maier-Redelsperger M, Flahault A. Thrombocytopenia in a surgical ICU. Chest. 1999; 115(5):1363-70.
95. Vanderschueren S, De Weerdt A, Malbrain M, et al. Thrombocytopenia and prognosis in intensive care. Crit Care Med. 2000;28(6):1871-6.
96. Corrigan Jr JJ. Thrombocytopenia: a laboratory sign of septicemia in infants and children. J Pediatr. 1974;85(2):219-21.
97. Akca S, Haji-Michael P, de Mendonca A, Suter P, Levi M, Vincent JL. Time course of platelet counts in critically ill patients. Crit Care Med. 2002;30(4):753-6.
98. Moreau D, Timsit JF, Vesin A, et al. Platelet count decline: an early prognostic marker in critically ill patients with prolonged ICU stays. Chest. 2007;131(6):1735-41.
99. Baughman RP, Lower EE, Flessa HC, Tollerud DJ. Thrombocytopenia in the intensive care unit. Chest. 1993;104(4): 1243-7.
100. Nguyen TC, Liu A, Liu L, et al. Acquired ADAMTS-13 defi-ciency in pediatric patients with severe sepsis. Haematologica. 2007;92(1):121-4.
101. Nguyen TCH, Han YY, Mai RA, Dong JF, Jaffe R, Carcillo JA. Microvascular thrombosis is common in children with multiple organ failure: an autopsy study. Crit Care Med. 2007;35(12):A200.
102. Bockmeyer CL, Claus RA, Budde U, et al. Inflammationassociated ADAMTS13 deficiency promotes formation of ultralarge von Willebrand factor. Haematologica. 2008;93(1):137-40.
103. Martin K, Borgel D, Lerolle N, et al. Decreased ADAMTS-13 (A disintegrin-like and metalloprotease with thrombospondin type 1 repeats) is associated with a poor prognosis in sepsis-induced organ failure*. Crit Care Med. 2007;35(10):2375-82.
104. Ono T, Mimuro J, Madoiwa S, et al. Severe secondary deficiency of von Willebrand factor-cleaving protease (ADAMTS13) in patients with sepsis-induced disseminated intravascular coagulation: its correlation with development of renal failure. Blood. 2006;107(2):528-34.
105. Ohshiro M, Kuroda J, Kobayashi Y, et al. ADAMTS-13 activity can predict the outcome of disseminated intravascular coagulation in hematologic malignancies treated with recombinant human soluble thrombomodulin. Am J Hematol. 2012;87(1):116-9.
106. Studt JD, Hovinga JA, Antoine G, et al. Fatal congenital thrombotic thrombocytopenic purpura with apparent ADAMTS13 inhibitor: in vitro inhibition of ADAMTS13 activity by hemoglobin. Blood. 2005;105(2):542-4.
107. Zhou Z, Han H, Cruz MA, Lopez JA, Dong JF, Guchhait P. Haemoglobin blocks von Willebrand factor proteolysis by ADAMTS-13: a mechanism associated with sickle cell disease. Thromb Haemost. 2009;101(6):1070-7.
108. Ware LB, Eisner M.D., Thompson BT, Parsons PE, Matthay MA. Significance of von Willebrand factor in septic and nonseptic patients with acute lung injury. Am J Respir Crit Care Med. 2004; 170(7):766-72.
109. Flori HR, Ware LB, Milet M, Matthay MA. Early elevation of plasma von Willebrand factor antigen in pediatric acute lung injury is associated with an increased risk of death and prolonged mechanical ventilation. Pediatr Crit Care Med. 2007;8(2): 96-101.
110. Nguyen TC, Balll C, Cruz MA, Liang X, Zhou Z, Dong J. A negative feedback mechanism of regulating VWF proteolysis by ADAMTS-13. J Thromb Haemost. 2011;9 Suppl 2:206.
111. Mannucci PM, Capoferri C, Canciani MT. Plasma levels of von Willebrand factor regulate ADAMTS-13, its major cleaving protease. Br J Haematol. 2004;126(2):213-8.
112. Chen J, Fu X, Wang Y, et al. Oxidative modification of von Willebrand factor by neutrophil oxidants inhibits its cleavage by ADAMTS13. Blood. 2010;115(3):706-12.
113. Iba T, Kidokoro A, Fukunaga M, Sugiyama K, Sawada T, Kato H. Association between the severity of sepsis and the changes in hemostatic molecular markers and vascular endothelial damage markers. Shock. 2005;23(1):25-9.
114. Crawley JT, Lam JK, Rance JB, Mollica LR, O’Donnell JS, Lane DA. Proteolytic inactivation of ADAMTS13 by thrombin and plasmin. Blood. 2005;105(3):1085-93.
115. Shelat SG, Smith P, Ai J, Zheng XL. Inhibitory autoantibodies against ADAMTS-13 in patients with thrombotic thrombocytopenic purpura bind ADAMTS-13 protease and may accelerate its clearance in vivo. J Thromb Haemost. 2006;4(8):1707-17.
116. Rieger M, Mannucci PM, Kremer Hovinga JA, et al. ADAMTS13 autoantibodies in patients with thrombotic microangiopathies and other immunomediated diseases. Blood. 2005;106(4):1262-7.
117. Kox WJ, Volk T, Kox SN, Volk HD. Immunomodulatory therapies in sepsis. Intensive Care Med. 2000;26 Suppl 1:S124-8.
118. Hall MW, Knatz NL, Vetterly C, et al. Immunoparalysis and nosocomial infection in children with multiple organ dysfunction syndrome. Intensive Care Med. 2011;37(3):525-32.
119. Genton C, Wang Y, Izui S, et al. The Th2 lymphoproliferation developing in LatY136F mutant mice triggers polyclonal B cell activation and systemic autoimmunity. J Immunol. 2006;177(4): 2285-93.
120. Feys HB, Roodt J, Vandeputte N, et al. Thrombotic thrombocytopenic purpura directly linked with ADAMTS13 inhibition in the baboon (Papio ursinus). Blood. 2010;116(12):2005-10.
121. Bockmeyer CL, Reuken PA, Simon TP, et al. ADAMTS13 activity is decreased in a septic porcine model. Significance for glomerular thrombus deposition. Thromb Haemost. 2011;105(1):145-53.
122. Aoki N, Matsuda T, Saito H, et al. A comparative double-blind randomized trial of activated protein C and unfractionated heparin in the treatment of disseminated intravascular coagulation. Int J Hematol. 2002;75(5):540-7.
123. Jaimes F, De La Rosa G, Morales C, et al. Unfractioned heparin for treatment of sepsis: a randomized clinical trial (the HETRASE study). Crit Care Med. 2009;37(4):1185-96.
124. Sakuragawa N, Hasegawa H, Maki M, Nakagawa M, Nakashima M. Clinical evaluation of low-molecular-weight heparin (FR-860) on disseminated intravascular coagulation (DIC)-a multicenter co-operative double-blind trial in comparison with heparin. Thromb Res. 1993;72(6):475-500.
125. Warren BL, Eid A, Singer P, et al. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA J Am Med Assoc. 2001;286(15):1869-78.
126. Abraham E, Reinhart K, Opal S, et al. Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA J Am Med Assoc. 2003;290(2):238-47.
127. Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001;344(10):699-709.
128. Ranieri VM, Thompson BT, Barie PS, et al. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med. 2012;366(22): 2055-64.
129. de Kleijn ED, de Groot R, Hack CE, et al. Activation of protein C following infusion of protein C concentrate in children with severe meningococcal sepsis and purpura fulminans: a randomized, double-blinded, placebo-controlled, dose-finding study. Crit Care Med. 2003;31(6):1839-47.
130. Rintala E, Kauppila M, Seppala OP, et al. Protein C substitution in sepsis-associated purpura fulminans. Crit Care Med. 2000;28(7): 2373-8.
131. Saito H, Maruyama I, Shimazaki S, et al. Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial. J Thromb Haemost. 2007;5(1):31-41.
132. Nurnberger J, Philipp T, Witzke O, et al. Eculizumab for atypical hemolytic-uremic syndrome. N Engl J Med. 2009;360(5):542-4.
133. Plaimauer B, Kremer Hovinga JA, Juno C, et al. Recombinant ADAMTS13 normalizes von Willebrand factor-cleaving activity in plasma of acquired TTP patients by overriding inhibitory antibodies. J Thromb Haemost. 2011;9(5):936-44.
134. Jin SY, Xiao J, Bao J, Zhou S, Wright JF, Zheng XL. AA Vmediated expression of an ADAMTS13 variant prevents shigatoxin-induced thrombotic thrombocytopenic purpura. Blood. 2013;121(19):3825-9.
135. Cataland SR, Peyvandi F, Mannucci PM, et al. Initial experience from a double-blind, placebo-controlled, clinical outcome study of ARC1779 in patients with thrombotic thrombocytopenic purpura. Am J Hematol. 2012;87(4):430-2.
136. Callewaert F, Roodt J, Ulrichts H, et al. Evaluation of efficacy and safety of the anti-VWF Nanobody ALX-0681 in a preclinical baboon model of acquired thrombotic thrombocytopenic purpura. Blood. 2012;120(17):3603-10.
137. Firbas C, Siller-Matula JM, Jilma B. Targeting von Willebrand factor and platelet glycoprotein Ib receptor. Expert Rev Cardiovasc Ther. 2010;8(12):1689-701.
138. Perez-Vilar J, Hill RL. The structure and assembly of secreted mucins. J Biol Chem. 1999;274(45):31751-4.
139. Chen J, Reheman A, Gushiken FC, et al. N-acetylcysteine reduces the size and activity of von Willebrand factor in human plasma and mice. J Clin Investig. 2011;121(2):593-603.
140. Nguyen TC, Gushiken F, Dong JF, Cruz MA. Recombinant Von Willebrand Factor A2 Domain Polypeptide Inhibits Platelet Adhesion to Fibrinogen and Decreases Mortality in a Murine Endotoxemia-induced Disseminated Intravascular Coagulation Model. Crit Care Med. 2012;40(12):A179.
141. Chapin J, Weksler B, Magro C, Laurence J. Eculizumab in the treatment of refractory idiopathic thrombotic thrombocytopenic purpura. Br J Haematol. 2012;157(6):772-4.
142. Tsai E, Chapin J, Laurence JC, Tsai HM. Use of eculizumab in the treatment of a case of refractory, ADAMTS13-deficient thrombotic 492 thrombocytopenic purpura: additional data and clinical follow-up. Br J haematol. 2013;162:558-9.
143. Reti M, Farkas P, Csuka D, et al. Complement activation in thrombotic thrombocytopenic purpura. J Thromb Haemost. 2012; 10(5):791-8.
144. Fortenberry JD, Knezevic A, Nguyen TC. Group TNS. Outcome in childrens on ECMO with TAMOF receiving plasma exchange: results from the prospective pediatric TAMOF network study. Crit Care Med. 2012;40(12):A520.
145. Fortenberry JD, Nguyen TC, Toney R, Knezevic A, Rogers K. Group CsTNS. Organ dysfunction and experience with Plasma Exchange (PEx) in children with Thrombocytopenia-Associated Multiple Organ Failure (TAMOF); findings of the prospective children’s TAMOF network. Pediatr Crit Care Med. 2011;12(3):A83.