A Pathological Clarification of Sepsis-Associated Disseminated Intravascular Coagulation Based on Comprehensive Coagulation and Fibrinolysis FunctionFunding 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.
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.
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.
Received: 27 February 2020
Accepted: 26 May 2020
17 July 2020 (online)
© 2020. Thieme. All rights reserved.
Georg Thieme Verlag KG
Stuttgart · New York
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