Thromb Haemost 2020; 120(09): 1257-1269
DOI: 10.1055/s-0040-1713890
Coagulation and Fibrinolysis

A Pathological Clarification of Sepsis-Associated Disseminated Intravascular Coagulation Based on Comprehensive Coagulation and Fibrinolysis Function

Tomoko Onishi
1  Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan
,
Keiji Nogami
1  Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan
,
Takashi Ishihara
1  Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan
,
Satoki Inoue
2  Department of Anesthesiology, Nara Medical University, Kashihara, Nara, Japan
,
Masahiko Kawaguchi
2  Department of Anesthesiology, Nara Medical University, Kashihara, Nara, Japan
,
Kenji Nishio
3  Department of General Medicine, Nara Medical University, Kashihara, Nara, Japan
,
Hidetada Fukushima
4  Department of Emergency and Critical Care Medicine, Nara Medical University, Kashihara, Nara, Japan
,
Hiroshi Kobayashi
5  Department of Obstetrics and Gynecology, Nara Medical University, Kashihara, Nara, Japan
,
Itsuto Amano
6  Second Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan
,
Toshiya Nishikubo
7  Neonatal Intensive Care Unit, Nara Medical University, Kashihara, Nara, Japan
,
Masaharu Yamasaki
8  Division of Clinical Laboratory, Nara Medical University, Kashihara, Nara, Japan
,
Masato Kasahara
9  Clinical Research Center, Nara Medical University, Kashihara, Nara, Japan
,
Midori Shima
1  Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan
› Author Affiliations
Funding This work was supported in part by a Grant-in-Aid for Scientific Research (KAKENHI) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) provided to T.O. (Grant No. 18K15726) and K.N. (Grant No. 18K07885) and a Special Project Grant at Nara Medical University.

Abstract

Background The functional dynamics of coagulation and fibrinolysis in patients with disseminated intravascular coagulation (DIC) vary due to the pathology and severity of various underlying diseases. Conventional measurements of hemostasis such as thrombin–antithrombin complex, plasmin-α2-plasmin-inhibitor complex, and fibrinogen-fibrin degradation products may not always reflect critical pathophysiologic mechanisms in DIC. This article aims to clarify the pathology of sepsis-associated DIC using assessment of comprehensive coagulation and fibrinolysis.

Methods Plasma samples were obtained from 57 patients with sepsis-associated DIC at the time of initial diagnosis. Hemostasis parameters were quantified by clot-fibrinolysis waveform analysis (CFWA) and thrombin/plasmin generation assays (T/P-GA). The results were expressed as ratios relative to normal plasma.

Results CFWA demonstrated that the maximum coagulation velocity (|min1|) ratio modestly increased to median 1.40 (min − max: 0.10 − 2.60) but the maximum fibrinolytic velocity (|FL-min1|) ratio decreased to 0.61 (0 − 1.19). T/P-GA indicated that the peak thrombin (Th-Peak) ratio moderately decreased to 0.71 (0.22 − 1.20), whereas the peak plasmin (Plm-Peak) ratio substantially decreased to 0.35 (0.02 − 1.43). Statistical comparisons identified a correlation between |min1| and Th-Peak ratios (ρ = 0.55, p < 0.001), together with a strong correlation between |FL-min1| and Plm-Peak ratios (ρ = 0.71, p < 0.001), suggesting that CFWA reflected the balance between thrombin and plasmin generation. With |min1| and |FL-min1| ratios, DIC was classified as follows: coagulation-predominant, coagulation/fibrinolysis-balanced, fibrinolysis-predominant, and consumption-impaired coagulation. The majority of patients in our cohort (80.7%) were coagulation-predominant.

Conclusion A pathological clarification of sepsis-associated DIC based on the assessment of coagulation and fibrinolysis dynamics may be useful for the hemostatic monitoring and management of optimal treatment in these individuals.

Authors' Contributions

T.O. designed the research, collected the samples, performed experiments, interpreted the data, and drafted the manuscript; K.N. designed the research, interpreted the data, drafted the manuscript, edited the manuscript, and approved the final version for publication; T.I. designed the research, interpreted the data, and supported the experimental studies; M.K., K.N., H.F., H.K., I.A., and N.T. all provided clinical support for this study; M.Y. performed the laboratory examinations; and M.K. and M.S. supervised the study.


Supplementary Material



Publication History

Received: 27 February 2020

Accepted: 26 May 2020

Publication Date:
17 July 2020 (online)

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