Sepsis‑induced coagulopathy and its association with mortality in patients with sepsis and septic shock

Abstract

OBJECTIVES: Sepsis induced coagulopathy (SIC) is a common complication in patients with sepsis and septic shock. Early detection of SIC is crucial for timely intervention, as it can significantly impact patient outcomes. This study aims to evaluate the prevalence of SIC and its impact on the 28 day mortality rate in patients with sepsis and septic shock.

METHODS: A single center retrospective observational cohort study was conducted in Vietnam from January 2021 to August 2024. Adult patients diagnosed with sepsis or septic shock who were admitted to the intensive care unit within 24 h of initial presentation were included. Patients with do not resuscitate orders, coagulopathy, malignant blood disorders, incomplete data, or refusal of treatment were excluded. SIC scores were assessed, and 28 day mortality rates were recorded.

RESULTS: A total of 340 patients were included, with 216 (63.5%) exhibiting SIC (SIC score ≥4). The mean age of patients was 69.01 ± 17.04 years, and the majority were male (61.5%). Septic shock accounted for 79.7% of the cases. SIC patients had significantly higher mortality rates at both 4 days (17.6% vs. 4.8%, P = 0.001) and 28 days (40.3% vs. 24.4%, P = 0.005). Nonsurvivors exhibited higher SIC (73.9% vs. 57.9%, P = 0.003) and had worse disease severity scores. Multivariate analysis confirmed that SIC score ≥4 was strongly associated with increased 28 day mortality (odds ratio 1.799, P = 0.033).

CONCLUSIONS: The prevalence of SIC is high in patients with sepsis and septic shock, especially in our cohorts. SIC score ≥4 is also a strong and independent predictor for 28 day mortality.

Introduction

Sepsis is a critical condition defined by life threatening organ dysfunction caused by an aberrant host response to infection. Sepsis can lead to multiorgan dysfunction, with shock and severe coagulopathy being among the most common complications.[1] Coagulation abnormalities encompass a broad spectrum of clinical symptoms, ranging from mild hemostatic abnormalities, such as a slight reduction in platelet amount, to severe conditions like disseminated intravascular coagulation (DIC).[2] The DIC in sepsis is characterized by an acute systemic inflammatory reaction resulting in endothelial dysfunction, coagulation disturbance induced by the infection, and other etiologies. The subsequent inflammatory response significantly influences patient outcomes.[3] For the diagnosis of overt DIC, the International Society on Thrombosis and Hemostasis (ISTH) created the DIC score.[4] However, overt DIC is generally a late stage complication of sepsis, and the ISTH DIC score, based on strict criteria, may delay opportunities for early intervention.[5]

It is crucial for the early detection of patients with sepsis associated coagulopathy before they reach the stage of severe hemostatic derangement. This is the rationale for the Scientific and Standardization Committee on DIC of ISTH proposed a new score, known as the Sepsis induced coagulopathy (SIC) score, which aims to detect DIC early on.[6] The concept of “infection induced organ dysfunction and coagulopathy” facilitates SIC diagnostic criteria, which include platelet count, the Sequential Organ Failure Assessment (SOFA) score, and prothrombin time (PT; international normalized ratio [INR]).[7] A SIC score ≥ 4 indicates significant coagulopathy associated with increased risk of adverse outcomes. Other studies have sought to validate the utility of the recently proposed SIC score in determining the timing of diagnosis, predicting mortality, and guiding the initiation of anticoagulant therapy in the adult population.[6,8] In Japan, the population with SIC score was selected strictly by criteria of severe sepsis and DIC according to the criteria of the Japanese Ministry of Health.[9,10] Furthermore, around one half of patients with suspected DIC were treated with at least one of the antithrombin and thrombomodulin drugs.[6,11] Therefore, it remains uncertain whether the outcomes and incidences vary across different cohorts, particularly within the Asian population, excluding Japanese cohorts. This study aims to evaluate the prevalence of coagulation disorders using the SIC score and its association with 28 day mortality in patients with sepsis and septic shock.

Material and Methods

Study population

This is a single center, retrospective, observational cohort study conducted at a tertiary hospital in Vietnam from January 1^st, 2021, to August 31^st, 2024. Ethics Committee of the 108 Military Central Hospital approved this study with document reference number 2757/GCN – BV on May 10, 2024. We included adult patients diagnosed with sepsis or septic shock and admitted to the intensive care unit (ICU) within 24 h of onset [Figure 1]. Sepsis and septic shock diagnoses were based on Sepsis 3 definitions.[1] Patients were excluded if they met any of the following criteria: (1) Do Not Resuscitate orders; (2) history of coagulopathy or malignant blood disorders; (3) use of medications that affect coagulation; (4) incomplete clinical or laboratory data; or (5) refusal of treatment.

Figure 1. Study cohort enrollment flowchart

Data collection

Clinical and laboratory data were collected from the hospital’s electronic medical records of patients at hospital admission. These included baseline demographic information, comorbidities, and vital signs at admission. Laboratory data included a complete blood count, comprehensive metabolic panel, and coagulation parameters such as fibrinogen, INR, PT, activated partial thromboplastin time (aPTT), and D dimer.

Illness severity was evaluated within 24 h of ICU admission using the SOFA score,[12] Acute Physiology and Chronic Health Evaluation II score (APACHE II),[13] and Simplified Acute Physiology Score II (SAPS II).[14]

In our study, we completely excluded patients with incomplete data regarding the key parameters needed for SIC scoring (platelet count, PT/INR, and SOFA score). We applied a complete case analysis approach and did not perform imputations for missing data.

Coagulation assessment

SIC was calculated on ICU admission (day 0) using published criteria.[9] The SIC score includes platelet count, SOFA score, and PT/INR. A SIC score ≥4 was considered positive. The ISTH criteria were also used to assess the presence of overt DIC, with D dimer thresholds set at ≥5000 ng/mL for a severe increase and ≥2000 ng/mL for a moderate increase.[15]

Study outcomes

The primary outcome was the prevalence of the SIC score in patients with sepsis and septic shock. The secondary outcome assessed the association between SIC at admission and the 28 day mortality rate.

Statistical analysis

SPSS version 29 (Hearne Scientific Software Pty Ltd, New South Wales, Australia) was used for statistical analyses. We characterized data distribution using standard methods: In normally distributed data, continuous variables were expressed as mean ± standard deviation, while in nonnormal distributions, these variables were presented as median with interquartile range. In contrast, categorical variables were presented as absolute numbers and proportional percentages. Between group comparisons employed Chi squared or Fisher’s exact tests for categorical data. In contrast, independent t tests or Mann–Whitney U tests were used to analyze continuous variables, depending on the data distribution. P <0.05 was statistically significant.

Results

Characteristics of the study group based on sepsis induced coagulopathy score

Baseline characteristics of the study population

A total of 340 patients were included in the study, with 216 patients (63.5%) having a SIC score ≥4. The mean age was 69.01 ± 17.04 years, and the majority were male (61.5%). Septic shock accounted for 79.7% of the cases. No significant differences were observed in baseline characteristics, including the proportion of septic shock, mechanical ventilation, heart rate, mean arterial pressure, norepinephrine dosage, use of continuous renal replacement therapy (CRRT), infection source, or disease severity scores (APACHE II, SOFA, SAPS 2) between the SIC and non SIC groups. However, significant differences were found in gender distribution (males: 57.4% vs. 68.5%, P = 0.042) and the prevalence of coronary artery disease (4.2% vs. 10.5%, P = 0.023). Patients with SIC had significantly higher mortality rates at both 4 days (17.6% vs. 4.8%, P = 0.001) and 28 days (40.3% vs. 24.4%, P = 0.005) [Table 1].

Table 1. Baseline characteristics of the study group according to sepsis‑induced coagulopathy score

Table 1. Contd...

Laboratory findings

Apart from the laboratory results that are components of the SIC score (platelet count, PT, and aPTT), the majority of results did not show statistically significant differences between the groups with and without SIC (SIC ≥4 vs. SIC <4). Serum creatinine, hemoglobin levels, and electrolyte profiles showed no significant differences between the two groups. Procalcitonin (20.1 [3.4–75.8] vs. 8.4 [1.6–52.7] ng/mL, P = 0.009) and lactate level (3.8 [2.2–6.1] vs. 2.9 [1.5 4.6] mmol/L, P = 0.004) were significantly higher in the SIC group. SIC patients exhibited higher total serum bilirubin levels (19 [11–38] vs. 12 [8–20] μmol/L, P < 0.001) and AST levels (66 [22– 113] vs. 34 [19–60] U/L, P = 0.002).

Comparison of clinical characteristics between 28 day survivors and nonsurvivors patient characteristics

Among 340 patients, 221 (65%) survived, and 119 (35%) died at 28 days. Nonsurvivors demonstrated higher rates of mechanical ventilation (93.3% vs. 65.2%, P < 0.001). The duration of mechanical ventilation was significantly longer in nonsurvivors (6.7 [5.5–7.8] vs 5.7 [4.5–6.8] days, P < 0.001). CRRT was more frequently required in nonsurvivors (70.6% vs. 56.7%, P < 0.001), with higher norepinephrine requirements (0.33 [0.10–0.75] vs. 0.16 [0.07–0.35] μg/kg/min, P < 0.001).

Regarding comorbidities, chronic kidney disease (17.6% vs. 10.0%, P = 0.042) and cardiac arrest (8.4% vs. 2.7%, P = 0.018) were more prevalent in nonsurvivors. The primary source of infection differed significantly between groups, with higher rates of pulmonary (58.8% vs. 47.1%, P = 0.038) and urinary tract infections (2.5% vs. 15.8%, P < 0.001) in nonsurvivors [Table 2].

Table 2. Comparison of clinical characteristics between 28‑day survivors and nonsurvivors in patients with sepsis and septic shock

Table 2. Contd...

Laboratory findings and disease severity

Laboratory parameters showed distinct patterns between groups. Nonsurvivors had lower red blood cell counts (3.8 [3.1–4.3] vs. 4.1 [3.5–4.6] ×10¹²/L, P = 0.026) and prolonged aPTT (36.4 [30.0–43.2] vs. 34.2 [29.7–38.9] s, P = 0.039). Disease severity scores were consistently higher in nonsurvivors, including SOFA (12 [9–15] vs. 9 [7–11]), SAPS II (48 [38–60] vs. 40 [28–49]), APACHE II (22 [19–28] vs. 18 [14–24]), and mNUTRIC scores (6 [4–7] vs. 5 [3–6]), P < 0.001 [Table 2].

Clinical outcomes

SIC scores≥4 were more prevalent in nonsurvivors (73.9% vs. 57.9%, P = 0.003). In our cohort, 63.5% of patients (216/340) had a SIC score ≥4, and the overall 28 day mortality rate was 34.5% (117/340). Univariate analysis revealed several predictors of increased mortality risk. Mechanical ventilation was the most significant, with a 7.41 fold increase in mortality risk (95% confidence interval [CI]: 3.450–16.670, P < 0.001), followed by the need for noradrenaline (2.84 fold, 95% CI 2.088–7.129, P < 0.001) and CRRT (4.15 fold, 95% CI: 2.360–6.670, P < 0.001). Cardiac arrest and pulmonary infection also significantly raised the risk of death, with odds ratios (OR) of 3.35 fold (95% CI: 1.180–9.434, P = 0.023) and 1.66 fold (95% CI: 1.053–2.597, P = 0.004), respectively. A SIC score of 4 or more was another predictor, with a 2.06 fold increase in mortality risk (95% CI: 1.260–3.360, P = 0.004).

In the multivariate analysis, after adjusting for potential confounders, mechanical ventilation remained the strongest independent predictor (OR 5.085, 95% CI: 2.140–13.698, P < 0.001), followed by noradrenaline requirements (OR 2.280, 95% CI: 1.231–4.223, P = 0.009). Among clinical factors, a urinary source of infection was protective, reducing mortality risk (OR 0.230, 95% CI: 0.087–0.764, P = 0.029). In addition, a SIC score ≥4 nearly doubled the risk of death (OR 1.799, 95% CI 1.384–2.242, P = 0.033), and each point increase in the SOFA score was associated with a higher risk of mortality (OR 1.086, 95% CI: 1.014–1.165, P = 0.019) [Table 3].

Table 3. Univariate and multivariate logistic regression analysis of clinical factors associated with 28‑day mortality in sepsis and septic shock

Discussion

SIC is a critical factor in the pathophysiology of sepsis and septic shock, representing an early stage of coagulation dysfunction before overt DIC manifests. This study highlights the prevalence of SIC and its association with 28 day mortality in patients with sepsis and septic shock, emphasizing the utility of the SIC score as an early diagnostic tool. In this study, 63.5% of patients with sepsis and septic shock had a SIC score ≥ 4, reflecting a high burden of coagulopathy in this critically ill population.

The clinical profiles in Table 2, including higher use of organ support (mechanical ventilation, CRRT, and vasopressors) and worse severity scores (SOFA, SAPS II, and APACHE II) among nonsurvivors, confirm that SIC ≥4 aligns closely with overall clinical deterioration. This supports its utility as a prognostic marker, complementing traditional severity scoring systems. Moreover, the length of hospital stay was longer in survivors compared to nonsurvivors (14 vs. 8 days, P < 0.001). This can be explained by the fact that hospitalization for nonsurvivors ends at the time of death, whereas survivors tend to require a longer stay for the recovery process. It is important to distinguish SIC from the ISTH DIC score. While both share platelet count and PT/INR as components, the SIC score excludes fibrinogen and D dimer, focusing instead on early detection by incorporating the SOFA score to reflect concurrent organ dysfunction. This design enhances its utility for identifying coagulopathy earlier in the sepsis continuum. In our multivariate analysis, SIC score ≥4 remained an independent predictor of 28 day mortality (OR 1.799, P = 0.033), even after adjusting for SOFA and other clinical variables.

Sepsis is a dysregulated host response to infection characterized by an inflammatory process. The inflammatory response is triggered by recognizing pathogen associated molecular patterns in immune cells.[16] Robust platelet activation contributes to the high incidence of thrombocytopenia observed in sepsis, ranging from 37.5% to 83.5%.[17,18] Tissue factor released from damaged epithelium can activate the coagulation cascades. The tissue factor has long been proven to be a key factor in initiating the extrinsic coagulation cascade and the subsequent formation of thrombosis.[19] Neutrophil extracellular traps, released by activated neutrophils, have vigorously promoted hypercoagulability in inflammation and significantly contributed to the incidence and mortality of SIC.[3,11,20,21] In summary, in sepsis, the body’s immune response triggers a state of hypercoagulation, leading to the formation of thrombi and inhibition of thrombolysis factors contributing to the pathogenesis of sepsis, such as the nature and degree of pathogen invasion and the host immune response, are also central to determining the pathogenesis and severity of coagulopathy.

When compared with findings from current data from previous studies, our result revealed both areas of agreement and divergence, offering a deeper understanding of coagulopathy in sepsis patients. Among recent high quality research addressing this topic, the HYPRESS trial was a double blind randomized controlled trial conducted across 34 centers in Germany, involving prospective data from 380 sepsis patients.[22] Newly published in June 2024, a retrospective observational cohort study by Tullo collected 357 cases of sepsis diagnosed in the ED to evaluate the predictive value of the SIC score in sepsis outcomes.[23] We observed a significantly higher prevalence of coagulopathy, defined as SIC ≥4, in our sepsis patients (63.5%) compared to the HYPRESS trial (22.1%) and study by Tullo et al. (15.4%).[8,22,23] Meanwhile, compared to the classical report on SIC first introduced by Iba et al., the prevalence of SIC among patients diagnosed with sepsis in our study is comparable (63.5% vs. 60.2%).[9]

The high SIC prevalence in our study (63.5%) compared to Western cohorts (15.4%–22.1%) can be explained by several key factors. As noted, the first two studies mainly collected data from patients in emergency departments or intermediate care units, whereas our study and that of Iba et al. primarily focused on patients in the ICU, where conditions are typically more critical. This discrepancy underscores the significantly high prevalence of coagulopathy in patients with sepsis admitted to the ICU. Furthermore, as a tertiary referral center in Vietnam, our hospital receives the most severe cases from lower level facilities, resulting in a concentration of advanced sepsis patients. The delayed healthcare presentation, common in our setting, allows unchecked progression of sepsis before intervention. Our assessment of SIC within 24 h of ICU admission likely captures peak coagulation derangements. In addition, the predominance of pulmonary infections (51.2%) in our cohort may contribute to different coagulation patterns compared to other populations. Furthermore, due to differences in the selection of study populations, the mortality rates in patients with sepsis and SIC vary significantly. The 28 day mortality in patients admitted to the ICU is markedly higher (40.3% in our study and 38.4% in Iba research) compared to other studies, which report mortality rates ranging from 17.2% to 26.8%.[9,22,23] The similarity across all listed studies is that SIC ≥4 is a positive prognostic factor for 28 day mortality in the study populations. A significantly higher mortality rate over 28 days was observed in patients with SIC in our study and in the re analysis of the HYPRESS trial and the study by Schmoch or Iba et al. [8,9] Highlighted in Tullo’s study, SIC ≥4 is an independent predictor of 28 day mortality with an OR of 2.28 (1.16–4.48) and a P = 0.017. Prolonged aPTT is significantly more common in nonsurviving patients across the studies.[23] Other research reveals that SIC typically occurs during diagnosis or within the first 4 days.[9,22,24] Tullo et al. also reported a significant correlation between SIC ≥4 and the development of DIC, new organ damage, bleeding, thrombosis, and the need for transfusion.[23]

Based on our findings, we propose four key clinical applications for SIC scoring: First, as an initial screening tool in emergency departments using readily available parameters to quickly identify high risk patients, particularly in resource limited settings. Second, for risk stratification and ICU admission decisions, patients with SIC ≥4 showed significantly higher mortality rates (40.3% vs. 24.4% at 28 days). Third, for guiding monitoring frequency – daily assessments for SIC <4 and for SIC ≥4 during the first 72 h. Fourth, to identify patients who may benefit from targeted interventions, including closer monitoring for thrombotic/bleeding complications, more aggressive source control, and cautious transfusion strategies. Given the strong association between SIC and mortality (OR 1.799), implementing SIC guided algorithms could improve outcomes, though further validation studies are needed.

Limitations

We acknowledge several limitations in our study. This study’s retrospective, single center design may introduce biases and limit generalizability. The relatively small sample size further constrains the applicability of our findings. We recognize that our exclusion criteria may have introduced selection bias, particularly excluding patients with preexisting coagulopathy and those on anticoagulation therapy. While these exclusions were necessary to evaluate SIC specifically attributable to sepsis without confounding factors, they limit our ability to generalize findings to all septic patients, especially those with complex comorbidities. This could potentially lead to an underestimation of the overall coagulopathy burden in the general sepsis population, as patients with baseline coagulation disorders might experience more severe derangements during sepsis. In addition, we did not differentiate between SIC present at sepsis onset and SIC developing later, which could influence its prognostic value. Future prospective, multicenter studies are needed to validate these findings and provide comprehensive insights into SIC in diverse sepsis populations.

Conclusion

The prevalence of SIC is higher in our population than in other cohorts, and a SIC score ≥4 serves as an independent predictor for 28 day mortality. These findings have important clinical implications. First, the SIC score should be utilized as an early prognostic tool to identify high risk septic patients who may require more aggressive management. Second, early monitoring and targeted intervention strategies for patients with SIC, including more frequent reassessment of coagulation parameters and organ function, may improve treatment outcomes. Third, SIC scoring could potentially guide anticoagulant therapy decisions in septic patients, though specific protocols require further validation. Early detection and management of coagulopathy using the easily calculated SIC score may significantly improve sepsis outcomes, particularly in critical care settings. Further prospective, multicenter studies are needed to clarify SIC’s value across different patient populations and healthcare systems.

How to cite this article: Quy HP, Thoi NT, Thanh NH, Hai PD. Sepsis‑induced coagulopathy and its association with mortality in patients with sepsis and septic shock. Turk J Emerg Med 2026;26:28-36.

Ethics Committee of the 108 Military Central Hospital approved this study with document reference number 2757/GCN – BV on May 10, 2024.

HPQ: Conceptualization (lead); writing – original draft (lead); formal analysis (lead). NHT: writing – original draft (equal); writing – review and editing (equal); formal analysis (equal). NTT: writing – original draft (equal); PDH: Conceptualization (equal); Writing – review and editing (lead); formal analysis (equal).

None Declared.

None.

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