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Published in: Thrombosis Journal 1/2020

01-12-2020 | Acute Promyelocytic Leukemia | Research

Analysis of the association between resolution of disseminated intravascular coagulation (DIC) and treatment outcomes in post-marketing surveillance of thrombomodulin alpha for DIC with infectious disease and with hematological malignancy by organ failure

Authors: Noriaki Kawano, Hideo Wada, Toshimasa Uchiyama, Kazuo Kawasugi, Seiji Madoiwa, Naoki Takezako, Kei Suzuki, Yoshinobu Seki, Takayuki Ikezoe, Tsuyoshi Hattori, Kohji Okamoto

Published in: Thrombosis Journal | Issue 1/2020

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Abstract

Background

Although disseminated intravascular coagulation (DIC) is life-threatening, any organ failure associated with DIC resolution and outcomes have been unclear.

Patients and methods

A total of 2795 DIC patients (infection: 1990, hematological malignancy: 805) were analyzed in the post-marketing surveillance of thrombomodulin alpha (TM-α). The background factors of sequential organ failure assessment (SOFA) and antithrombin (AT) were investigated in DIC with infectious disease for their association with DIC resolution and outcome using κ statistics, indicating DIC resolution and survival or DIC non-resolution and non-survival. The same analyses were performed for total bilirubin, creatinine, lactate dehydrogenase, and underlying disease in DIC with hematological malignancy.

Results

In DIC with infectious disease, higher SOFA score severity was closely correlated with lower overall survival in both the DIC resolution and non-resolution groups, but AT activity was not. κ coefficients were 0.234, 0.295, and 0.311 for the SOFA score 0–6, 7–12, and 13–24 groups, respectively. In DIC with hematological malignancy, κ coefficients of total bilirubin were 0.251 and 0.434, and those of creatinine were 0.283 and 0.437 in the normal and abnormal groups, respectively, showing better concordance in the abnormal group than in the normal. Other factors had poor concordance.

Conclusion

In DIC with infectious disease, DIC resolution is an important therapeutic target in patients who have higher SOFA score severity. In DIC with hematological malignancy, DIC resolution is similarly important in patients with abnormality of bilirubin and/or creatinine.

Trial registration

The clinical characteristics and treatment outcomes of patients with DIC treated with TM-α between May 2008 and April 2010 were retrospectively analyzed by subgroup analysis of the post-marketing surveillance data.
Literature
1.
go back to reference Levi M, Ten Cate H. Disseminated intravascular coagulation. N Engl J Med. 1999;341:586–92.CrossRef Levi M, Ten Cate H. Disseminated intravascular coagulation. N Engl J Med. 1999;341:586–92.CrossRef
2.
go back to reference Bick RL. Disseminated intravascular coagulation current concepts of etiology, pathophysiology, diagnosis and treatment. Hematol Oncol Clin North Am. 2003;17:149–76.CrossRef Bick RL. Disseminated intravascular coagulation current concepts of etiology, pathophysiology, diagnosis and treatment. Hematol Oncol Clin North Am. 2003;17:149–76.CrossRef
6.
go back to reference Wada H, Thachil J, Di Nisio M, Kurosawa S, Gando S, Toh CH. The scientific standardization committee on DIC of the international society on thrombosis Haemostasis. Guidance for diagnosis and treatment of DIC from harmonization of the recommendations from three guidelines. J Thromb Haemost. 2013;11:2078–9. https://doi.org/10.1111/jth.12366.CrossRefPubMed Wada H, Thachil J, Di Nisio M, Kurosawa S, Gando S, Toh CH. The scientific standardization committee on DIC of the international society on thrombosis Haemostasis. Guidance for diagnosis and treatment of DIC from harmonization of the recommendations from three guidelines. J Thromb Haemost. 2013;11:2078–9. https://​doi.​org/​10.​1111/​jth.​12366.CrossRefPubMed
7.
go back to reference Wada H, Asakura H, Okamoto K, et al. Japanese Society of Thrombosis Hemostasis/DIC subcommittee.Expert consensus for the treatment of disseminated intravascular coagulation in Japan. Thromb Res. 2010;125:6–11.CrossRef Wada H, Asakura H, Okamoto K, et al. Japanese Society of Thrombosis Hemostasis/DIC subcommittee.Expert consensus for the treatment of disseminated intravascular coagulation in Japan. Thromb Res. 2010;125:6–11.CrossRef
8.
go back to reference 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;145:24–33.CrossRef 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;145:24–33.CrossRef
9.
go back to reference 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;5:31–41.CrossRef 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;5:31–41.CrossRef
10.
go back to reference Mimuro J, Takahashi H, Kitajima I, et al. Impact of recombinant soluble thrombomodulin (thrombomodulin alfa) on disseminated intravascular coagulation. Thromb Res. 2013;131:436–43.CrossRef Mimuro J, Takahashi H, Kitajima I, et al. Impact of recombinant soluble thrombomodulin (thrombomodulin alfa) on disseminated intravascular coagulation. Thromb Res. 2013;131:436–43.CrossRef
11.
go back to reference Asakura H, Takahashi H, Tsuji H, et al. Post-marketing surveillance of thrombomodulin alfa, a novel treatment of disseminated intravascular coagulation - safety and efficacy in 1,032 patients with hematologic malignancy. Thromb Res. 2014;133:364–70.CrossRef Asakura H, Takahashi H, Tsuji H, et al. Post-marketing surveillance of thrombomodulin alfa, a novel treatment of disseminated intravascular coagulation - safety and efficacy in 1,032 patients with hematologic malignancy. Thromb Res. 2014;133:364–70.CrossRef
12.
go back to reference Eguchi Y, Gando S, Ishikura H, et al. Post-marketing surveillance data of thrombomodulin alfa: sub-analysis in patients with sepsis-induced disseminated intravascular coagulation. J Intensive Care. 2014;2:30.CrossRef Eguchi Y, Gando S, Ishikura H, et al. Post-marketing surveillance data of thrombomodulin alfa: sub-analysis in patients with sepsis-induced disseminated intravascular coagulation. J Intensive Care. 2014;2:30.CrossRef
19.
go back to reference Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33:159–74.CrossRef Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33:159–74.CrossRef
20.
go back to reference Dempfle CE, Wurst M, Smolinski M, et al. Use of soluble fibrin antigen instead of D-dimer as fibrin-related marker may enhance the prognostic power of the ISTH overt DIC score. Thromb Haemost. 2004;91:812–8.CrossRef Dempfle CE, Wurst M, Smolinski M, et al. Use of soluble fibrin antigen instead of D-dimer as fibrin-related marker may enhance the prognostic power of the ISTH overt DIC score. Thromb Haemost. 2004;91:812–8.CrossRef
21.
go back to reference Hatada T, Wada H, Nobori T, et al. Plasma concentrations and importance of high mobility group box protein in the prognosis of organ failure in patients with disseminated intravascular coagulation. Thromb Haemost. 2005;94:975–9.CrossRef Hatada T, Wada H, Nobori T, et al. Plasma concentrations and importance of high mobility group box protein in the prognosis of organ failure in patients with disseminated intravascular coagulation. Thromb Haemost. 2005;94:975–9.CrossRef
22.
go back to reference Kotajima N, Kanda T, Fukumura Y, et al. Serum thrombomodulin as a prognostic marker of disseminated intravascular coagulation. J Med. 1999;30:19–29.PubMed Kotajima N, Kanda T, Fukumura Y, et al. Serum thrombomodulin as a prognostic marker of disseminated intravascular coagulation. J Med. 1999;30:19–29.PubMed
23.
go back to reference Gando S, Saitoh D, Ogura H, et al. Japanese Association for Acute Medicine Disseminated Intravascular Coagulation (JAAMDIC) 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.CrossRef Gando S, Saitoh D, Ogura H, et al. Japanese Association for Acute Medicine Disseminated Intravascular Coagulation (JAAMDIC) 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.CrossRef
24.
go back to reference Seki Y, Wada H, Kawasugi K, et al. Japanese Society of Thrombosis Hemostasis/DIC subcommittee: a prospective analysis of disseminated intravascular coagulation in patients with infections. Intern Med. 2013;52:1893–8.CrossRef Seki Y, Wada H, Kawasugi K, et al. Japanese Society of Thrombosis Hemostasis/DIC subcommittee: a prospective analysis of disseminated intravascular coagulation in patients with infections. Intern Med. 2013;52:1893–8.CrossRef
25.
go back to reference Kawano N, Tasaki A, Kawano S, et al. Sequential organ failure assessment (SOFA) score as a prognostic factor for disseminated intravascular coagulation patients with infectious disease treated with recombinant human soluble thrombomodulin (rhTM) in clinical practice. Japanese J Transfus Cell Ther. 2017;63:763–79.CrossRef Kawano N, Tasaki A, Kawano S, et al. Sequential organ failure assessment (SOFA) score as a prognostic factor for disseminated intravascular coagulation patients with infectious disease treated with recombinant human soluble thrombomodulin (rhTM) in clinical practice. Japanese J Transfus Cell Ther. 2017;63:763–79.CrossRef
26.
go back to reference 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;87:116–9.CrossRef 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;87:116–9.CrossRef
27.
go back to reference Yamakawa K, Umemura Y, Hayakawa M, et al. Benefit profile of anticoagulant therapy in sepsis: a nationwide multicentre registry in Japan. Crit Care. 2016;20:229.CrossRef Yamakawa K, Umemura Y, Hayakawa M, et al. Benefit profile of anticoagulant therapy in sepsis: a nationwide multicentre registry in Japan. Crit Care. 2016;20:229.CrossRef
29.
go back to reference Bird GT, Farquhar-Smith P, Wigmore T, Potter M, Gruber PC. Outcomes and prognostic factors in patients with haematological malignancy admitted to a specialist cancer intensive care unit: a 5 yr study. Br J Anaesth. 2012;108:452–9.CrossRef Bird GT, Farquhar-Smith P, Wigmore T, Potter M, Gruber PC. Outcomes and prognostic factors in patients with haematological malignancy admitted to a specialist cancer intensive care unit: a 5 yr study. Br J Anaesth. 2012;108:452–9.CrossRef
30.
go back to reference Benoit DD, Vandewoude KH, Decruyenaere JM, Hoste EA, Colardyn FA. Outcome and early prognostic indicators in patients with a hematologic malignancy admitted to the intensive care unit for a life-threatening complication. Crit Care Med. 2003;31:104–12.CrossRef Benoit DD, Vandewoude KH, Decruyenaere JM, Hoste EA, Colardyn FA. Outcome and early prognostic indicators in patients with a hematologic malignancy admitted to the intensive care unit for a life-threatening complication. Crit Care Med. 2003;31:104–12.CrossRef
31.
32.
go back to reference Cuthbertson BH, Rajalingham Y, Harrison S, McKirdy F. The outcome of haematological malignancy in Scottish intensive care units. J Intensive Care Soc. 2008;9:135–40.CrossRef Cuthbertson BH, Rajalingham Y, Harrison S, McKirdy F. The outcome of haematological malignancy in Scottish intensive care units. J Intensive Care Soc. 2008;9:135–40.CrossRef
34.
go back to reference Radojevic-Skodric S, Bogdanovic L, Jovanovic M, Baralic I, Dzamic Z, Gordon R, Ognjanovic S, Basta-Jovanovic G. Acute renal failure in different malignant tumors. Curr Med Chem. 2016;23:2041–6.CrossRef Radojevic-Skodric S, Bogdanovic L, Jovanovic M, Baralic I, Dzamic Z, Gordon R, Ognjanovic S, Basta-Jovanovic G. Acute renal failure in different malignant tumors. Curr Med Chem. 2016;23:2041–6.CrossRef
Metadata
Title
Analysis of the association between resolution of disseminated intravascular coagulation (DIC) and treatment outcomes in post-marketing surveillance of thrombomodulin alpha for DIC with infectious disease and with hematological malignancy by organ failure
Authors
Noriaki Kawano
Hideo Wada
Toshimasa Uchiyama
Kazuo Kawasugi
Seiji Madoiwa
Naoki Takezako
Kei Suzuki
Yoshinobu Seki
Takayuki Ikezoe
Tsuyoshi Hattori
Kohji Okamoto
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Thrombosis Journal / Issue 1/2020
Electronic ISSN: 1477-9560
DOI
https://doi.org/10.1186/s12959-020-0216-6

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