Comparison between sepsis-induced coagulopathy and sepsis-associated coagulopathy criteria in identifying sepsis-associated disseminated intravascular coagulation

doi:10.5847/wjem.j.1920-8642.2024.041

Abstract

Abstract:

BACKGROUND: Disseminated intravascular coagulation (DIC) is associated with increased mortality in sepsis patients. In this study, we aimed to assess the clinical ability of sepsis-induced coagulopathy (SIC) and sepsis-associated coagulopathy (SAC) criteria in identifying overt-DIC and pre-DIC status in sepsis patients.
METHODS: Data from 419 sepsis patients were retrospectively collected from July 2018 to December 2022. The performances of the SIC and SAC were assessed to identify overt-DIC on days 1, 3, 7, or 14. The SIC status or SIC score on day 1, the SAC status or SAC score on day 1, and the sum of the SIC or SAC scores on days 1 and 3 were compared in terms of their ability to identify pre-DIC. The SIC or SAC status on day 1 was evaluated as a pre-DIC indicator for anticoagulant initiation.
RESULTS: On day 1, the incidences of coagulopathy according to overt-DIC, SIC and SAC criteria were 11.7%, 22.0% and 31.5%, respectively. The specificity of SIC for identifying overt-DIC was significantly higher than that of the SAC criteria from day 1 to day 14 (P<0.05). On day 1, the SIC score with a cut-off value > 3 had a significantly higher sensitivity (72.00%) and area under the curve (AUC) (0.69) in identifying pre-DIC than did the SIC or SAC status (sensitivity: SIC status 44.00%, SAC status 52.00%; AUC: SIC status 0.62, SAC status 0.61). The sum of the SIC scores on days 1 and 3 had a higher AUC value for identifying the pre-DIC state than that of SAC (0.79 vs. 0.69, P<0.001). Favorable effects of anticoagulant therapy were observed in SIC (adjusted hazard ratio [HR]=0.216, 95% confidence interval [95% CI]: 0.060-0.783, P=0.018) and SAC (adjusted HR=0.146, 95% CI: 0.041-0.513, P=0.003).
CONCLUSION: The SIC and SAC seem to be valuable for predicting overt-DIC. The sum of SIC scores on days 1 and 3 has the potential to help identify pre-DIC.

Key words: Sepsis, Disseminated intravascular coagulation, Sepsis-induced coagulopathy, Sepsis-associated coagulopathy

Huixin Zhao, Yiming Dong, Sijia Wang, Jiayuan Shen, Zhenju Song, Mingming Xue, Mian Shao. Comparison between sepsis-induced coagulopathy and sepsis-associated coagulopathy criteria in identifying sepsis-associated disseminated intravascular coagulation[J]. World Journal of Emergency Medicine, 2024, 15(3): 190-196.

Figures/Tables 6

Table 1.

Table 2.

Figure 1.

Table 3.

Table 4.

Figure 2.

References 25

1	Wang J, Weng L, Xu J, Du B. Blood gas analysis as a surrogate for microhemodynamic monitoring in sepsis. World J Emerg Med. 2023; 14(6):421-7. doi: 10.5847/wjem.j.1920-8642.2023.093 pmid: 37969221
2	Sljivancanin Jakovljevic T, Martic J, Jacimovic J, Nikolic N, Milasin J, Mitrović TL. Association between innate immunity gene polymorphisms and neonatal sepsis development: a systematic review and meta-analysis. World J Pediatr. 2022; 18(10):654-70. doi: 10.1007/s12519-022-00569-7 pmid: 35666457
3	Levi M, van der Poll T. Coagulation and sepsis. Thromb Res. 2017; 149:38-44. doi: S0049-3848(16)30619-3 pmid: 27886531
4	Gando S, Levi M, Toh CH. Disseminated intravascular coagulation. Nat Rev Dis Primers. 2016; 2:16037. doi: 10.1038/nrdp.2016.37 pmid: 27250996
5	Saito S, Uchino S, Hayakawa M, Yamakawa K, Kudo D, Iizuka Y, et al. Epidemiology of disseminated intravascular coagulation in sepsis and validation of scoring systems. J Crit Care. 2019; 50:23-30. doi: S0883-9441(18)30679-8 pmid: 30471557
6	Iba T, Umemura Y, Watanabe E, Wada T, Hayashida K, Kushimoto S, et al. Diagnosis of sepsis-induced disseminated intravascular coagulation and coagulopathy. Acute Med Surg. 2019; 6(3):223-32.
7	Egi M, Ogura H, Yatabe T, Atagi K, Inoue S, Iba T, et al. The Japanese clinical practice guidelines for management of sepsis and septic shock 2020 (J-SSCG 2020). Acute Med Surg. 2021; 8(1):e659.
8	Wada H, Matsumoto T, Yamashita Y. Diagnosis and treatment of disseminated intravascular coagulation (DIC) according to four DIC guidelines. J Intensive Care. 2014; 2(1):15. doi: 10.1186/2052-0492-2-15 pmid: 25520831
9	Taylor FB Jr, Toh CH, Hoots WK, Wada H, Levi M, Scientific Subcommittee on Disseminated Intravascular Coagulation of the International Society on Thrombosis and Haemostasis (ISTH). Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001; 86(5):1327-30.
10	Jackson Chornenki NL, Dwivedi DJ, Kwong AC, Zamir N, Fox-Robichaud AE, Liaw PC, et al. Identification of hemostatic markers that define the pre-DIC state: a multi-center observational study. J Thromb Haemost. 2020; 18(10):2524-31.
11	Ding RY, Wang Z, Lin Y, Liu BY, Zhang ZD, Ma XC. Comparison of a new criteria for sepsis-induced coagulopathy and International Society on Thrombosis and Haemostasis disseminated intravascular coagulation score in critically ill patients with sepsis 3.0: a retrospective study. Blood Coagul Fibrinolysis. 2018; 29(6):551-8.
12	Iba T, Nisio MD, Levy JH, Kitamura N, Thachil J. New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: a retrospective analysis of a nationwide survey. BMJ Open. 2017; 7(9):e017046.
13	Lyons PG, Micek ST, Hampton N, Kollef MH. Sepsis-associated coagulopathy severity predicts hospital mortality. Crit Care Med. 2018; 46(5):736-42. doi: 10.1097/CCM.0000000000002997 pmid: 29373360
14	Iba T, Levy JH, Yamakawa K, Thachil J, Warkentin TE, Levi M, et al. Proposal of a two-step process for the diagnosis of sepsis-induced disseminated intravascular coagulation. J Thromb Haemost. 2019; 17(8):1265-8. doi: 10.1111/jth.14482 pmid: 31099127
15	Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016; 315(8):801-10. doi: 10.1001/jama.2016.0287 pmid: 26903338
16	Bakhtiari K, Meijers JCM, de Jonge E, Levi M. Prospective validation of the International Society of Thrombosis and Haemostasis scoring system for disseminated intravascular coagulation. Crit Care Med. 2004; 32(12):2416-21. doi: 10.1097/01.ccm.0000147769.07699.e3 pmid: 15599145
17	Wada H, Minamikawa K, Wakita Y, Nakase T, Kaneko T, Ohiwa M, et al. Hemostatic study before onset of disseminated intravascular coagulation. Am J Hematol. 1993; 43(3):190-4. doi: 10.1002/ajh.2830430306 pmid: 8352234
18	Peng JC, Nie F, Li YJ, Xu QY, Xing SP, Li W, et al. Favorable outcomes of anticoagulation with unfractioned heparin in sepsis-induced coagulopathy: a retrospective analysis of MIMIC-III database. Front Med. 2022; 8:773339.
19	Yamakawa K, Yoshimura J, Ito T, Hayakawa M, Hamasaki T, Fujimi S. External validation of the two newly proposed criteria for assessing coagulopathy in sepsis. Thromb Haemost. 2019; 119(2):203-12.
20	Iba T, Levy JH, Warkentin TE, Thachil J, van der Poll T, Levi M, et al. Diagnosis and management of sepsis-induced coagulopathy and disseminated intravascular coagulation. J Thromb Haemost. 2019; 17(11):1989-94. doi: 10.1111/jth.14578 pmid: 31410983
21	Iba T, Arakawa M, Di Nisio M, Gando S, Anan H, Sato K, et al. Newly proposed sepsis-induced coagulopathy precedes international society on thrombosis and haemostasis overt-disseminated intravascular coagulation and predicts high mortality. J Intensive Care Med. 2020; 35(7):643-9. doi: 10.1177/0885066618773679 pmid: 29720054
22	Helms J, Severac F, Merdji H, Clere-Jehl R, François B, Mercier E, et al. Performances of disseminated intravascular coagulation scoring systems in septic shock patients. Ann Intensive Care. 2020; 10(1):92. doi: 10.1186/s13613-020-00704-5 pmid: 32651674
23	Okamoto K, Wada H, Hatada T, Uchiyama T, Kawasugi K, Mayumi T, et al. Frequency and hemostatic abnormalities in pre-DIC patients. Thromb Res. 2010; 126(1):74-8. doi: 10.1016/j.thromres.2010.03.017 pmid: 20452653
24	Liao DY, Zhou F, Luo LL, Xu M, Wang HB, Xia JH, et al. Haematological characteristics and risk factors in the classification and prognosis evaluation of COVID-19: a retrospective cohort study. Lancet Haematol. 2020; 7(9):e671-e678. doi: 10.1016/S2352-3026(20)30217-9 pmid: 32659214
25	Papageorgiou C, Jourdi G, Adjambri E, Walborn A, Patel P, Fareed J, et al. Disseminated intravascular coagulation: an update on pathogenesis, diagnosis, and therapeutic strategies. Clin Appl Thromb Hemost. 2018; 24(9_suppl):8S-28S.

Items	Point	Overt-DIC	SIC
Platelet, ×10⁹/L	0	>100	≥150
	1	50-100	≥100, < 150
	2	<50	<100
Prolonged PT/INR, s	0	<3	≤1.2
	1	3-6	>1.2, ≤ 1.4
	2	>6	>1.4
Fibrinogen, g/mL	0	≥100	-
Fibrinogen, g/mL	1	<100	-
D-dimer ^a	0	Normal	-
	2	Moderate increase	-
	3	Severe increase	-
SOFA score ^b	0	-	0
	1	-	1
	2	-	≥2
Diagnosis		≥5 points	≥4 points ^c

INR	PLT (×10⁹/L)
INR	≥150	100-149	80-99	<80
<1.2	No SAC	No SAC	No SAC	No SAC
≥1.2, <1.4	No SAC	Mild SAC	Moderate SAC	Moderate SAC
≥1.4, <1.6	No SAC	Moderate SAC	Moderate SAC	Moderate SAC
≥1.6	No SAC	Moderate SAC	Moderate SAC	Severe SAC

Time	SIC	SAC	P-value
Day 1
Prevalence, %	22.0 (92/419)	31.5 (132/419)	<0.001
AUC (95% CI)	0.85 (0.81-0.88)	0.83 (0.79-0.87)	0.307
Sensitivity, %	83.67	89.80	0.250
Specificity, %	86.22	76.22	<0.001
PPV, %	44.6	33.3	0.088
NPV, %	97.6	98.3	0.545
Day 3
Prevalence, %	14.1 (59/419)	20.8 (87/419)	<0.001
AUC (95% CI)	0.84 (0.80-0.87)	0.81 (0.77-0.85)	0.097
Sensitivity, %	75.00	77.50	1.000
Specificity, %	92.16	84.86	<0.001
PPV, %	50.8	35.6	0.067
NPV, %	97.2	97.2	0.957
Day 7
Prevalence, %	10.3 (42/409)	14.4 (59/409)	<0.001
AUC (95% CI)	0.86 (0.82-0.90)	0.89 (0.85-0.92)	0.422
Sensitivity, %	80.00	90.00	0.500
Specificity, %	92.40	88.18	<0.001
PPV, %	38.1	30.5	0.426
NPV, %	98.7	99.4	0.725
Day 14
Prevalence, %	5.7 (22/389)	7.5 (29/389)	0.016
AUC (95% CI)	0.93 (0.89-0.96)	0.91 (0.87-0.95)	0.007
Sensitivity, %	90.91	90.91	1.000
Specificity, %	94.69	91.59	0.016
PPV, %	45.5	34.5	0.128
NPV, %	99.5	99.5	0.539

Criteria	AUC	95% CI	Cut-off value	Sensitivity	Specificity	PPV	NPV
SIC criteria	0.62^*	0.57-0.66	-	44.00%	79.44%	12.0%	95.7%
SAC criteria	0.61^*	0.56-0.67	-	52.00%	69.80%	9.8%	95.8%
SIC score on day 1	0.69^*	0.65-0.74	>3	72.00%	62.94%	11.0%	97.3%
SAC rating	0.61^*	0.57-0.66	> 0	52.00%	69.80%	9.8%	95.8%

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