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Published in: Thrombosis Journal 1/2018

Open Access 01-12-2018 | Research

Decreased antithrombin activity in the early phase of trauma is strongly associated with extravascular leakage, but not with antithrombin consumption: 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 1/2018

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Abstract

Background

We conducted a prospective observational study for investigating coagulofibrinolytic changes and mechanisms of antithrombin (AT) alternations in trauma.

Methods

Trauma patients hospitalized for more than seven days were analyzed for coagulofibrinolytic biomarkers. The patients were stratified into two groups according to AT activity level on admission (day 0), comprising normal AT and low AT patients.

Results

Thirty-nine patients (median Injury Severity Score 20) exhibited initial coagulatory activation and triphasic fibrinolytic changes. AT activity did not show a negative linear correlation with levels of thrombin-antithrombin complex (TAT), a marker of coagulation activity and AT consumption, but was strongly correlated with levels of albumin (Alb), an index of vascular permeability, on day 0 (r = 0.702, p <  0.001). Furthermore, Alb was one of the independent predictors for AT on day 0. IL-6 on day 0 and thrombomodulin (TM) levels during the study period, reflecting systemic inflammation and endothelial cell injury, respectively, were significantly higher in the lower AT group (n = 10) than in the normal group (n = 29) (IL-6, p = 0.004; TM, p = 0.017). On days 2 and 4, TAT levels in the lower AT group were significantly higher than in the normal group.

Conclusions

Trauma caused clear triphasic coagulofibrinolytic changes. Decreased AT in the later phase might lead to a prolonged hypercoagulation. AT reduction in the initial phase of trauma is strongly associated with extravascular leakage as suggested by the association of Alb depletion with IL-6 and TM elevation, but not with AT consumption.
Literature
1.
2.
go back to reference Macleod JB, Lynn M, McKenney MG, Cohn SM, Murtha M. Early coagulopathy predicts mortality in trauma. J Trauma. 2003;55:39–44.CrossRefPubMed Macleod JB, Lynn M, McKenney MG, Cohn SM, Murtha M. Early coagulopathy predicts mortality in trauma. J Trauma. 2003;55:39–44.CrossRefPubMed
3.
go back to reference Gando S, Otomo Y. Local hemostasis, immunothrombosis, and systemic disseminated intravascular coagulation in trauma and traumatic shock. Crit Care. 2015;19:72.CrossRefPubMedPubMedCentral Gando S, Otomo Y. Local hemostasis, immunothrombosis, and systemic disseminated intravascular coagulation in trauma and traumatic shock. Crit Care. 2015;19:72.CrossRefPubMedPubMedCentral
4.
go back to reference Hess JR, Brohi K, Dutton RP, Hauser CJ, Holcomb JB, Kluger Y, et al. The coagulopathy of trauma: a review of mechanisms. J Trauma. 2008;65:748–54.CrossRefPubMed Hess JR, Brohi K, Dutton RP, Hauser CJ, Holcomb JB, Kluger Y, et al. The coagulopathy of trauma: a review of mechanisms. J Trauma. 2008;65:748–54.CrossRefPubMed
5.
go back to reference Brohi K, Cohen MJ, Ganter MT, Matthay MA, Mackersie RC, Pittet JF. Acute traumatic coagulopathy: initiated by hypoperfusion: modulated through the protein C pathway? Ann Surg. 2007;245:812–8.CrossRefPubMedPubMedCentral Brohi K, Cohen MJ, Ganter MT, Matthay MA, Mackersie RC, Pittet JF. Acute traumatic coagulopathy: initiated by hypoperfusion: modulated through the protein C pathway? Ann Surg. 2007;245:812–8.CrossRefPubMedPubMedCentral
6.
go back to reference Oshiro A, Yanagida Y, Gando S, Henzan N, Takahashi I, Makise H. Hemostasis during the early stages of trauma: comparison with disseminated intravascular coagulation. Crit Care. 2014;18:R61.CrossRefPubMedPubMedCentral Oshiro A, Yanagida Y, Gando S, Henzan N, Takahashi I, Makise H. Hemostasis during the early stages of trauma: comparison with disseminated intravascular coagulation. Crit Care. 2014;18:R61.CrossRefPubMedPubMedCentral
7.
go back to reference Yanagida Y, Gando S, Sawamura A, Hayakawa M, Uegaki S, Kubota N, et al. Normal prothrombinase activity, increased systemic thrombin activity, and lower antithrombin levels in patients with disseminated intravascular coagulation at an early phase of trauma: comparison with acute coagulopathy of trauma-shock. Surgery. 2013;154:48–57.CrossRefPubMed Yanagida Y, Gando S, Sawamura A, Hayakawa M, Uegaki S, Kubota N, et al. Normal prothrombinase activity, increased systemic thrombin activity, and lower antithrombin levels in patients with disseminated intravascular coagulation at an early phase of trauma: comparison with acute coagulopathy of trauma-shock. Surgery. 2013;154:48–57.CrossRefPubMed
8.
go back to reference Liener UC, Brückner UB, Strecker W, Steinbach G, Kinzl L, Gebhard F. Trauma severity-dependent changes in AT III activity. Shock. 2001;15:344–7.CrossRefPubMed Liener UC, Brückner UB, Strecker W, Steinbach G, Kinzl L, Gebhard F. Trauma severity-dependent changes in AT III activity. Shock. 2001;15:344–7.CrossRefPubMed
9.
go back to reference Hayakawa M, Sawamura A, Gando S, Kubota N, Uegaki S, Shimojima H, et al. Disseminated intravascular coagulation at an early phase of trauma is associated with consumption coagulopathy and excessive fibrinolysis both by plasmin and neutrophil elastase. Surgery. 2011;149:221–30.CrossRefPubMed Hayakawa M, Sawamura A, Gando S, Kubota N, Uegaki S, Shimojima H, et al. Disseminated intravascular coagulation at an early phase of trauma is associated with consumption coagulopathy and excessive fibrinolysis both by plasmin and neutrophil elastase. Surgery. 2011;149:221–30.CrossRefPubMed
10.
11.
go back to reference Owings JT, Bagley M, Gosselin R, Romac D, Disbrow E. Effect of critical injury on plasma antithrombin activity: low antithrombin levels are associated with thromboembolic complications. J Trauma. 1996;41:396–406.CrossRefPubMed Owings JT, Bagley M, Gosselin R, Romac D, Disbrow E. Effect of critical injury on plasma antithrombin activity: low antithrombin levels are associated with thromboembolic complications. J Trauma. 1996;41:396–406.CrossRefPubMed
12.
13.
go back to reference Ilias W, List W, Decruyenaere J, Lignian H, Knaub S, Schindel F, et al. Antithrombin III in patients with severe sepsis: a pharmacokinetic study. Intensive Care Med. 2000;26:704–15.CrossRefPubMed Ilias W, List W, Decruyenaere J, Lignian H, Knaub S, Schindel F, et al. Antithrombin III in patients with severe sepsis: a pharmacokinetic study. Intensive Care Med. 2000;26:704–15.CrossRefPubMed
14.
go back to reference Asakura H, Ontachi Y, Mizutani T, Kato M, Ito T, Saito M, et al. 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;67:170–5.CrossRefPubMed Asakura H, Ontachi Y, Mizutani T, Kato M, Ito T, Saito M, et al. 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;67:170–5.CrossRefPubMed
15.
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;27:139–44.CrossRefPubMed 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;27:139–44.CrossRefPubMed
16.
go back to reference Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. 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;101:1644–55.CrossRefPubMed Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. 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;101:1644–55.CrossRefPubMed
17.
go back to reference Gando S, Saitoh D, Ogura H, Mayumi T, Koseki K, Ikeda T, et al. 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;36:145–50.CrossRefPubMed Gando S, Saitoh D, Ogura H, Mayumi T, Koseki K, Ikeda T, et al. 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;36:145–50.CrossRefPubMed
18.
go back to reference Rodgers GM. Role of antithrombin concentrate in treatment of hereditary antithrombin deficiency. An update Thromb Haemost. 2009;101:806–12.CrossRefPubMed Rodgers GM. Role of antithrombin concentrate in treatment of hereditary antithrombin deficiency. An update Thromb Haemost. 2009;101:806–12.CrossRefPubMed
19.
go back to reference Levy JH, Sniecinski RM, Welsby IJ, Levi M. Antithrombin: anti-inflammatory properties and clinical applications. Thromb Haemost. 2016;115:712–28.CrossRefPubMed Levy JH, Sniecinski RM, Welsby IJ, Levi M. Antithrombin: anti-inflammatory properties and clinical applications. Thromb Haemost. 2016;115:712–28.CrossRefPubMed
20.
go back to reference Gando S. Disseminated intravascular coagulation in trauma patients. Semin Thromb Hemost. 2001;27:585–92.CrossRefPubMed Gando S. Disseminated intravascular coagulation in trauma patients. Semin Thromb Hemost. 2001;27:585–92.CrossRefPubMed
21.
23.
go back to reference Miller RS, Weatherford DA, Stein D, Crane MM, Stein M. Antithrombin III and trauma patients: factors that determine low levels. J Trauma. 1994;37:442–5.CrossRefPubMed Miller RS, Weatherford DA, Stein D, Crane MM, Stein M. Antithrombin III and trauma patients: factors that determine low levels. J Trauma. 1994;37:442–5.CrossRefPubMed
24.
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;160:688–93.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;160:688–93.CrossRef
25.
go back to reference Egawa G, Nakamizo S, Natsuaki Y, Doi H, Miyachi Y, Kabashima K. Intravital analysis of vascular permeability in mice using two-photon microscopy. Sci Rep. 2013;3:1932.CrossRefPubMedPubMedCentral Egawa G, Nakamizo S, Natsuaki Y, Doi H, Miyachi Y, Kabashima K. Intravital analysis of vascular permeability in mice using two-photon microscopy. Sci Rep. 2013;3:1932.CrossRefPubMedPubMedCentral
26.
go back to reference Weinbaum S, Tarbell JM, Damiano ER. The structure and function of the endothelial glycocalyx layer. Annu Rev Biomed Eng. 2007;9:121–67.CrossRefPubMed Weinbaum S, Tarbell JM, Damiano ER. The structure and function of the endothelial glycocalyx layer. Annu Rev Biomed Eng. 2007;9:121–67.CrossRefPubMed
28.
go back to reference Levick JR, Michel CC. Microvascular fluid exchange and the revised Starling principle. Cardiovasc Res. 2010;87:198–210.CrossRefPubMed Levick JR, Michel CC. Microvascular fluid exchange and the revised Starling principle. Cardiovasc Res. 2010;87:198–210.CrossRefPubMed
29.
30.
go back to reference Di Battista AP, Rizoli SB, Lejnieks B, Min A, Shiu MY, Peng HT, et al. Sympathoadrenal activation is associated with acute traumatic coagulopathy and Endotheliopathy in isolated brain injury. Shock. 2016;46:96–103.CrossRefPubMedPubMedCentral Di Battista AP, Rizoli SB, Lejnieks B, Min A, Shiu MY, Peng HT, et al. Sympathoadrenal activation is associated with acute traumatic coagulopathy and Endotheliopathy in isolated brain injury. Shock. 2016;46:96–103.CrossRefPubMedPubMedCentral
32.
go back to reference Ornaghi S, Barnhart KT, Frieling J, Streisand J, Paidas MJ. Clinical syndromes associated with acquired antithrombin deficiency via microvascular leakage and the related risk of thrombosis. Thromb Res. 2014;133:972–84.CrossRefPubMed Ornaghi S, Barnhart KT, Frieling J, Streisand J, Paidas MJ. Clinical syndromes associated with acquired antithrombin deficiency via microvascular leakage and the related risk of thrombosis. Thromb Res. 2014;133:972–84.CrossRefPubMed
33.
go back to reference Bauer KA, Rosenberg RD. The pathophysiology of the prethrombotic state in humans: insights gained from studies using markers of hemostatic system activation. Blood. 1987;70:343–50.PubMed Bauer KA, Rosenberg RD. The pathophysiology of the prethrombotic state in humans: insights gained from studies using markers of hemostatic system activation. Blood. 1987;70:343–50.PubMed
34.
go back to reference Di Minno MN, Dentali F, Lupoli R, Ageno W. Mild antithrombin deficiency and risk of recurrent venous thromboembolism: a prospective cohort study. Circulation. 2014;129:497–503.CrossRefPubMed Di Minno MN, Dentali F, Lupoli R, Ageno W. Mild antithrombin deficiency and risk of recurrent venous thromboembolism: a prospective cohort study. Circulation. 2014;129:497–503.CrossRefPubMed
Metadata
Title
Decreased antithrombin activity in the early phase of trauma is strongly associated with extravascular leakage, but not with antithrombin consumption: 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
01-12-2018
Publisher
BioMed Central
Published in
Thrombosis Journal / Issue 1/2018
Electronic ISSN: 1477-9560
DOI
https://doi.org/10.1186/s12959-018-0171-7

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