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Published in: Thrombosis Journal 1/2021

Open Access 01-12-2021 | Disseminated Intravascular Coagulation | Research

ADAMTS13 activity decreases in the early phase of trauma associated with coagulopathy and systemic inflammation: a prospective observational study

Authors: Hironori Matsumoto, Jun Takeba, Kensuke Umakoshi, Satoshi Kikuchi, Muneaki Ohshita, Suguru Annen, Naoki Moriyama, Yuki Nakabayashi, Norio Sato, Mayuki Aibiki

Published in: Thrombosis Journal | Issue 1/2021

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Abstract

Background

We conducted a prospective observational study for investigating the changes in the 13th member of a disintegrin-like and metalloprotease with thrombospondin type 1 motif (ADAMTS13) and its association with the coagulofibrinolytic response in adult trauma patients.

Methods

In 39 trauma patients hospitalized for longer than 7 days, time-course changes in biomarkers of coagulofibrinolysis and systemic inflammation along with ADAMTS13 activity were examined. The patients were stratified into three groups based on ADAMTS13 activities on admission (day 0): normal group (≥70%), mildly decreased group (≥50 and < 70%) and moderately decreased group (< 50%).

Results

Among 39 patients with a median Injury Severity Score (ISS) of 20, 11 patients developed disseminated intravascular coagulation (DIC) and 16 patients required transfusion. Six of 39 patients (15.4%) showed moderate decreased ADAMTS13 activity to < 50%, and 20 patients (51.3%) showed mild drops (≥50 and < 70%). These changes in ADAMTS13 activity on day 0 were significantly correlated with changes in IL-6 and other coagulofibrinolytic markers such as platelet counts, prothrombin time and fibrin/fibrinogen degradation product (FDP). Antithrombin activity (AT) and serum albumin (Alb) level showed significantly positive linear correlations with ADAMTS13 activity (AT: r = 0.513, p < 0.001; Alb: r = 0.647, p < 0.001). Simple logistic regression analyses showed that ADAMTS13 activity, if less than 50%, was significantly correlated with the development of DIC (OR 7.499, 95%CI 1.121–49.242, p = 0.038) and the need for transfusion of fresh frozen plasma (OR 9.000, 95%CI 1.327–61.025, p = 0.028).

Conclusions

ADAMTS13 activity decreased even in the early phase of trauma, which was complicated by coagulopathy and systemic inflammation. Furthermore, the decrease in ADAMTS13 activity was correlated with DIC and plasma transfusion.
Literature
1.
go back to reference Sadler JE. Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura. Blood. 2008;112(1):11–8.CrossRef Sadler JE. Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura. Blood. 2008;112(1):11–8.CrossRef
2.
go back to reference Dong JF, Moake JL, Nolasco L, Bernardo A, Arceneaux W, Shrimpton CN, Schade AJ, McIntire LV, Fujikawa K, López JA. ADAMTS-13 rapidly cleaves newly secreted ultralarge von Willebrand factor multimers on the endothelial surface under flowing conditions. Blood. 2002;100(12):4033–9.CrossRef Dong JF, Moake JL, Nolasco L, Bernardo A, Arceneaux W, Shrimpton CN, Schade AJ, McIntire LV, Fujikawa K, López JA. ADAMTS-13 rapidly cleaves newly secreted ultralarge von Willebrand factor multimers on the endothelial surface under flowing conditions. Blood. 2002;100(12):4033–9.CrossRef
3.
go back to reference Sadler JE. Pathophysiology of thrombotic thrombocytopenic purpura. Blood. 2017;130(10):1181–8.CrossRef Sadler JE. Pathophysiology of thrombotic thrombocytopenic purpura. Blood. 2017;130(10):1181–8.CrossRef
4.
go back to reference Moake JL. Thrombotic microangiopathies. N Engl J Med. 2002;347(8):589–600.CrossRef Moake JL. Thrombotic microangiopathies. N Engl J Med. 2002;347(8):589–600.CrossRef
5.
go back to reference South K, Lane DA. ADAMTS-13 and von Willebrand factor: a dynamic duo. J Thromb Haemost. 2018;16(1):6–18.CrossRef South K, Lane DA. ADAMTS-13 and von Willebrand factor: a dynamic duo. J Thromb Haemost. 2018;16(1):6–18.CrossRef
6.
go back to reference Feng Y, Li X, Xiao J, Li W, Liu J, Zeng X, Chen X, Chen S. ADAMTS13: more than a regulator of thrombosis. Int J Hematol. 2016;104(5):534–9.CrossRef Feng Y, Li X, Xiao J, Li W, Liu J, Zeng X, Chen X, Chen S. ADAMTS13: more than a regulator of thrombosis. Int J Hematol. 2016;104(5):534–9.CrossRef
7.
go back to reference Saha M, McDaniel JK, Zheng XL. Thrombotic thrombocytopenic purpura: pathogenesis, diagnosis and potential novel therapeutics. J Thromb Haemost. 2017;15(10):1889–900.CrossRef Saha M, McDaniel JK, Zheng XL. Thrombotic thrombocytopenic purpura: pathogenesis, diagnosis and potential novel therapeutics. J Thromb Haemost. 2017;15(10):1889–900.CrossRef
8.
go back to reference Masias C, Cataland SR. The role of ADAMTS13 testing in the diagnosis and management of thrombotic microangiopathies and thrombosis. Blood. 2018;132(9):903–10.CrossRef Masias C, Cataland SR. The role of ADAMTS13 testing in the diagnosis and management of thrombotic microangiopathies and thrombosis. Blood. 2018;132(9):903–10.CrossRef
9.
go back to reference Wada H, Matsumoto T, Suzuki K, Imai H, Katayama N, Iba T, Matsumoto M. Differences and similarities between disseminated intravascular coagulation and thrombotic microangiopathy. Thromb J. 2018;16:14.CrossRef Wada H, Matsumoto T, Suzuki K, Imai H, Katayama N, Iba T, Matsumoto M. Differences and similarities between disseminated intravascular coagulation and thrombotic microangiopathy. Thromb J. 2018;16:14.CrossRef
10.
go back to reference Russell RT, McDaniel JK, Cao W, Shroyer M, Wagener BM, Zheng XL, Pittet JF. Low plasma ADAMTS13 activity is associated with coagulopathy, endothelial cell damage and mortality after severe paediatric trauma. Thromb Haemost. 2018;118(4):676–87.CrossRef Russell RT, McDaniel JK, Cao W, Shroyer M, Wagener BM, Zheng XL, Pittet JF. Low plasma ADAMTS13 activity is associated with coagulopathy, endothelial cell damage and mortality after severe paediatric trauma. Thromb Haemost. 2018;118(4):676–87.CrossRef
11.
go back to reference Moore HB, Gando S, Iba T, Kim PY, Yeh CH, Brohi K, Hunt BJ, Levy JH, Draxler DF, Stanworth S, Görlinger K, Neal MD, Schreiber MA, Barrett CD, Medcalf RL, Moore EE, Mutch NJ, Thachil J, Urano T, Thomas S, Scărlătescu E, Walsh M, Subcommittees on Fibrinolysis, Disseminated Intravascular Coagulation, and Perioperative and Critical Care Thrombosis and Hemostasis. Defining trauma-induced coagulopathy with respect to future implications for patient management: Communication from the SSC of the ISTH. J Thromb Haemost. 2020;18(3):740–7.CrossRef Moore HB, Gando S, Iba T, Kim PY, Yeh CH, Brohi K, Hunt BJ, Levy JH, Draxler DF, Stanworth S, Görlinger K, Neal MD, Schreiber MA, Barrett CD, Medcalf RL, Moore EE, Mutch NJ, Thachil J, Urano T, Thomas S, Scărlătescu E, Walsh M, Subcommittees on Fibrinolysis, Disseminated Intravascular Coagulation, and Perioperative and Critical Care Thrombosis and Hemostasis. Defining trauma-induced coagulopathy with respect to future implications for patient management: Communication from the SSC of the ISTH. J Thromb Haemost. 2020;18(3):740–7.CrossRef
12.
go back to reference Gando S, Wada H, Kim HK, Kurosawa S, Nielsen JD, Thachil J, Toh CH, Scientific and Standardization Committee on DIC of the ISTH. Comparison of disseminated intravascular coagulation in trauma with coagulopathy of trauma/acute coagulopathy of trauma-shock. J Thromb Haemost. 2012;10(12):2593–5.CrossRef Gando S, Wada H, Kim HK, Kurosawa S, Nielsen JD, Thachil J, Toh CH, Scientific and Standardization Committee on DIC of the ISTH. Comparison of disseminated intravascular coagulation in trauma with coagulopathy of trauma/acute coagulopathy of trauma-shock. J Thromb Haemost. 2012;10(12):2593–5.CrossRef
13.
go back to reference Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101(6):1644–55.CrossRef Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;101(6):1644–55.CrossRef
14.
go back to reference Gando S, Saitoh D, Ogura H, Mayumi T, Koseki K, Ikeda T, Ishikura H, Iba T, Ueyama M, Eguchi Y, Ohtomo Y, Okamoto K, Kushimoto S, Endo S, Shimazaki S, Japanese Association for Acute Medicine Disseminated Intravascular Coagulation (JAAM DIC) Study Group. 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.CrossRef Gando S, Saitoh D, Ogura H, Mayumi T, Koseki K, Ikeda T, Ishikura H, Iba T, Ueyama M, Eguchi Y, Ohtomo Y, Okamoto K, Kushimoto S, Endo S, Shimazaki S, Japanese Association for Acute Medicine Disseminated Intravascular Coagulation (JAAM DIC) Study Group. 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.CrossRef
15.
go back to reference Kato S, Matsumoto M, Matsuyama T, Isonishi A, Hiura H, Fujimura Y. Novel monoclonal antibody-based enzyme immunoassay for determining plasma levels of ADAMTS13 activity. Transfusion. 2006;46(8):1444–52.CrossRef Kato S, Matsumoto M, Matsuyama T, Isonishi A, Hiura H, Fujimura Y. Novel monoclonal antibody-based enzyme immunoassay for determining plasma levels of ADAMTS13 activity. Transfusion. 2006;46(8):1444–52.CrossRef
16.
go back to reference Fujimura Y, Matsumoto M. Registry of 919 patients with thrombotic microangiopathies across Japan: database of Nara Medical University during 1998-2008. Intern Med. 2010;49(1):7–15.CrossRef Fujimura Y, Matsumoto M. Registry of 919 patients with thrombotic microangiopathies across Japan: database of Nara Medical University during 1998-2008. Intern Med. 2010;49(1):7–15.CrossRef
17.
go back to reference Masias C, Vasu S, Cataland SR. None of the above: thrombotic microangiopathy beyond TTP and HUS. Blood. 2017;129(21):2857–63.CrossRef Masias C, Vasu S, Cataland SR. None of the above: thrombotic microangiopathy beyond TTP and HUS. Blood. 2017;129(21):2857–63.CrossRef
18.
go back to reference Farkas P, Csuka D, Mikes B, Sinkovits G, Réti M, Németh E, Rácz K, Madách K, Gergely M, Demeter J, Prohászka Z. Complement activation, inflammation and relative ADAMTS13 deficiency in secondary thrombotic microangiopathies. Immunobiology. 2017;222(2):119–27.CrossRef Farkas P, Csuka D, Mikes B, Sinkovits G, Réti M, Németh E, Rácz K, Madách K, Gergely M, Demeter J, Prohászka Z. Complement activation, inflammation and relative ADAMTS13 deficiency in secondary thrombotic microangiopathies. Immunobiology. 2017;222(2):119–27.CrossRef
19.
go back to reference Martin K, Borgel D, Lerolle N, Feys HB, Trinquart L, Vanhoorelbeke K, Deckmyn H, Legendre P, Diehl JL, Baruch D. 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.CrossRef Martin K, Borgel D, Lerolle N, Feys HB, Trinquart L, Vanhoorelbeke K, Deckmyn H, Legendre P, Diehl JL, Baruch D. 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.CrossRef
20.
go back to reference Ono T, Mimuro J, Madoiwa S, Soejima K, Kashiwakura Y, Ishiwata A, Takano K, Ohmori T, Sakata Y. 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.CrossRef Ono T, Mimuro J, Madoiwa S, Soejima K, Kashiwakura Y, Ishiwata A, Takano K, Ohmori T, Sakata Y. 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.CrossRef
21.
go back to reference Levi M, Scully M, Singer M. The role of ADAMTS-13 in the coagulopathy of sepsis. J Thromb Haemost. 2018;16(4):646–51.CrossRef Levi M, Scully M, Singer M. The role of ADAMTS-13 in the coagulopathy of sepsis. J Thromb Haemost. 2018;16(4):646–51.CrossRef
22.
go back to reference Aibar J, Castro P, Espinosa G, Fernández S, Hernández C, Rinaudo M, Butjosa M, Tàssies D, Reverter JC, Nicolás JM. ADAMTS-13 in critically ill patients with septic syndromes and noninfectious systemic inflammatory response syndrome. Shock. 2015;43(6):556–62.CrossRef Aibar J, Castro P, Espinosa G, Fernández S, Hernández C, Rinaudo M, Butjosa M, Tàssies D, Reverter JC, Nicolás JM. ADAMTS-13 in critically ill patients with septic syndromes and noninfectious systemic inflammatory response syndrome. Shock. 2015;43(6):556–62.CrossRef
23.
go back to reference Lin JJ, Chan OW, Hsiao HJ, Wang Y, Hsia SH, Chiu CH. Decreased ADAMTS 13 activity is associated with disease severity and outcome in pediatric severe sepsis. Medicine (Baltimore). 2016;95(16):e3374.CrossRef Lin JJ, Chan OW, Hsiao HJ, Wang Y, Hsia SH, Chiu CH. Decreased ADAMTS 13 activity is associated with disease severity and outcome in pediatric severe sepsis. Medicine (Baltimore). 2016;95(16):e3374.CrossRef
24.
go back to reference Uemura M, Tatsumi K, Matsumoto M, Fujimoto M, Matsuyama T, Ishikawa M, Iwamoto TA, Mori T, Wanaka A, Fukui H, Fujimura Y. Localization of ADAMTS13 to the stellate cells of human liver. Blood. 2005;106(3):922–4.CrossRef Uemura M, Tatsumi K, Matsumoto M, Fujimoto M, Matsuyama T, Ishikawa M, Iwamoto TA, Mori T, Wanaka A, Fukui H, Fujimura Y. Localization of ADAMTS13 to the stellate cells of human liver. Blood. 2005;106(3):922–4.CrossRef
25.
go back to reference Dong JF, Moake JL, Bernardo A, Fujikawa K, Ball C, Nolasco L, López JA, Cruz MA. ADAMTS-13 metalloprotease interacts with the endothelial cell-derived ultra-large von Willebrand factor. J Biol Chem. 2003;278(32):29633–9.CrossRef Dong JF, Moake JL, Bernardo A, Fujikawa K, Ball C, Nolasco L, López JA, Cruz MA. ADAMTS-13 metalloprotease interacts with the endothelial cell-derived ultra-large von Willebrand factor. J Biol Chem. 2003;278(32):29633–9.CrossRef
26.
go back to reference 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.CrossRef 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.CrossRef
27.
go back to reference Hiura H, Matsui T, Matsumoto M, Hori Y, Isonishi A, Kato S, Iwamoto T, Mori T, Fujimura Y. Proteolytic fragmentation and sugar chains of plasma ADAMTS13 purified by a conformation-dependent monoclonal antibody. J Biochem. 2010;148(4):403–11.PubMed Hiura H, Matsui T, Matsumoto M, Hori Y, Isonishi A, Kato S, Iwamoto T, Mori T, Fujimura Y. Proteolytic fragmentation and sugar chains of plasma ADAMTS13 purified by a conformation-dependent monoclonal antibody. J Biochem. 2010;148(4):403–11.PubMed
28.
go back to reference 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.CrossRef 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.CrossRef
29.
go back to reference Aibiki M, Fukuoka N, Umakoshi K, Ohtsubo S, Kikuchi S. Serum albumin levels anticipate antithrombin III activities before and after antithrombin III agent in critical patients with disseminated intravascular coagulation. Shock. 2007;27(2):139–44.CrossRef Aibiki M, Fukuoka N, Umakoshi K, Ohtsubo S, Kikuchi S. Serum albumin levels anticipate antithrombin III activities before and after antithrombin III agent in critical patients with disseminated intravascular coagulation. Shock. 2007;27(2):139–44.CrossRef
30.
go back to reference Asakura H, Ontachi Y, Mizutani T, Kato M, Ito T, Saito M, Morishita E, Yamazaki M, Aoshima K, Takami A, Yoshida T, Suga Y, Miyamoto K, Nakao S. Decreased plasma activity of antithrombin or protein C is not due to consumption coagulopathy in septic patients with disseminated intravascular coagulation. Eur J Haematol. 2001;67(3):170–5.CrossRef Asakura H, Ontachi Y, Mizutani T, Kato M, Ito T, Saito M, Morishita E, Yamazaki M, Aoshima K, Takami A, Yoshida T, Suga Y, Miyamoto K, Nakao S. Decreased plasma activity of antithrombin or protein C is not due to consumption coagulopathy in septic patients with disseminated intravascular coagulation. Eur J Haematol. 2001;67(3):170–5.CrossRef
31.
go back to reference Kobayashi A, Matsuda Y, Mitani M, Makino Y, Ohta H. Assessment of the usefulness of antithrombin-III in the management of disseminated intravascular coagulation in obstetrically ill patients. Clin Appl Thromb Hemost. 2010;16(6):688–93.CrossRef Kobayashi A, Matsuda Y, Mitani M, Makino Y, Ohta H. Assessment of the usefulness of antithrombin-III in the management of disseminated intravascular coagulation in obstetrically ill patients. Clin Appl Thromb Hemost. 2010;16(6):688–93.CrossRef
32.
go back to reference Matsumoto H, Takeba J, Umakoshi K, Kikuchi S, Ohshita M, Annen S, Moriyama N, Nakabayashi Y, Sato N, Aibiki M. Decreased antithrombin activity in the early phase of trauma is strongly associated with extravascular leakage, but not with antithrombin consumption: a prospective observational study. Thromb J. 2018;16:17.CrossRef Matsumoto H, Takeba J, Umakoshi K, Kikuchi S, Ohshita M, Annen S, Moriyama N, Nakabayashi Y, Sato N, Aibiki M. Decreased antithrombin activity in the early phase of trauma is strongly associated with extravascular leakage, but not with antithrombin consumption: a prospective observational study. Thromb J. 2018;16:17.CrossRef
33.
go back to reference Margarson MP, Soni N. Serum albumin: touchstone or totem? Anaesthesia. 1998;53(8):789–803.CrossRef Margarson MP, Soni N. Serum albumin: touchstone or totem? Anaesthesia. 1998;53(8):789–803.CrossRef
34.
35.
go back to reference Chauhan AK, Kisucka J, Brill A, Walsh MT, Scheiflinger F, Wagner DD. ADAMTS13: a new link between thrombosis and inflammation. J Exp Med. 2008;205(9):2065–74.CrossRef Chauhan AK, Kisucka J, Brill A, Walsh MT, Scheiflinger F, Wagner DD. ADAMTS13: a new link between thrombosis and inflammation. J Exp Med. 2008;205(9):2065–74.CrossRef
36.
go back to reference Straat M, Müller MC, Meijers JC, Arbous MS, Spoelstra-de Man AM, Beurskens CJ, Vroom MB, Juffermans NP. 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.CrossRef Straat M, Müller MC, Meijers JC, Arbous MS, Spoelstra-de Man AM, Beurskens CJ, Vroom MB, Juffermans NP. 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.CrossRef
Metadata
Title
ADAMTS13 activity decreases in the early phase of trauma associated with coagulopathy and systemic inflammation: a prospective observational study
Authors
Hironori Matsumoto
Jun Takeba
Kensuke Umakoshi
Satoshi Kikuchi
Muneaki Ohshita
Suguru Annen
Naoki Moriyama
Yuki Nakabayashi
Norio Sato
Mayuki Aibiki
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Thrombosis Journal / Issue 1/2021
Electronic ISSN: 1477-9560
DOI
https://doi.org/10.1186/s12959-021-00270-1

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