INTRODUCTION
Sepsis is a serious and potentially fatal complication of infection.[1,2] The causative factors and associated inflammatory responses trigger fibrin formation and deposition by simultaneously upregulating coagulation, downregulating anticoagulation and suppressing fibrinolysis.[3] The interaction between the inflammatory response and the coagulation system affects the microcirculation, leading to tissue damage and coagulation abnormalities, ultimately resulting in disseminated intravascular coagulation (DIC) and even multiple-organ dysfunction.[4] The mortality rate can reach 40% in sepsis patients diagnosed with DIC.[5] Therefore, recognizing and treating DIC at an early stage is essential for improving the prognosis of sepsis patients with DIC.[6] Although the gold standard for DIC diagnosis remains undefined, the overt-DIC criteria developed by the International Society on Thrombosis and Hemostasis (ISTH) are widely recommended for the diagnosis of DIC.[7,8] The ISTH assesses four parameters, namely, platelet count (PLT), prothrombin time (PT), fibrinogen (Fib), and D-dimer.[9] However, Fib is not a reliable indicator because some previous studies have indicated that the level of Fib decreases markedly at the late phase of sepsis.[4,10,11]
In recent years, the sepsis-induced coagulopathy (SIC) and sepsis-associated coagulopathy (SAC) criteria have been proposed by two research teams for the early detection of septic coagulation dysfunction.[12,13] Both criteria include the international normalized ratio (INR) and the PLT, while the SIC uses the Sequential Organ Failure Assessment (SOFA) score (which is the sum of four items: respiratory SOFA, cardiovascular SOFA, hepatic SOFA, and renal SOFA) to reflect sepsis.[12] Iba et al[14] introduced a two‐step process for diagnosing sepsis‐induced DIC (first step, SIC diagnosis; second step, overt‐DIC diagnosis). However, it remains unclear which criterion has greater application value in sepsis patients. This research aimed to compare the clinical ability of the SIC and SAC criteria for detecting overt-DIC and pre-DIC status and identify appropriate candidates for anticoagulant therapy in sepsis patients.
METHODS
Study population
In this single-center retrospective study, data from 419 sepsis patients hospitalized in the Emergency Department of Zhongshan Hospital, Fudan University, from July 2018 to December 2022 were collected according to the sepsis-3 criteria.[15] The team submitted an application form for exemption from signing informed consent, which was approved by the Ethical Committee of Zhongshan Hospital, Fudan University (No: B2021-562).
The inclusion criteria for patients were as follows: (1) ≥ 18 years of age and (2) meeting the sepsis-3 criteria after admission to the emergency department. The exclusion criteria were as follows: (1) existing diseases that affected platelet and coagulation function (heparin-induced thrombocytopenia, drug-associated thrombocytopenia, thrombotic thrombocytopenic purpura, antiphospholipid syndrome, liver cirrhosis classified as Child-Pugh grade C, malignant tumors of the hematologic system, etc.); (2) receiving anticoagulation therapy (heparin, warfarin, dabigatran, rivaroxaban) before entry; (3) pregnancy, trauma, surgery, toxicosis; and (4) length of stay < 3 d.
Criteria and definitions
The criteria for overt-DIC, SIC, and SAC can be found in Tables 1 and 2.[9,12,13] We selected D-dimer as the fibrinogen-related marker in the overt-DIC criteria. A “moderated increase” or “strong increase” in D-dimer was defined as a D-dimer level within ten times the upper limit of normal or ten times the upper limit of normal, respectively.[16] SIC was diagnosed when the total score was 4 or more with a total score of platelet count and INR exceeding 2. For statistical convenience, we assigned 0, 1, 2, and 3 points to represent no SAC, mild SAC, moderate SAC, and severe SAC, respectively. Patients with ISTH-DIC scores ≥ 5 in the first 24 h were diagnosed with overt-DIC; if not, patients who developed overt-DIC within 14 d were diagnosed with pre-DIC.[17] Patients without DIC were diagnosed with non-DIC.
Table 1. The scoring system of the ISTH overt-DIC and SIC criteria
| 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 | - |
| 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 |
ISTH: International Society of Thrombosis and Hemostasis; DIC: disseminated intravascular coagulation; SIC: sepsis-induced coagulopathy; PT: prothrombin time; INR: international normalized ratio; SOFA: Sequential Organ Failure Assessment. a: “moderated increase” and “strong increase” were defined as D-dimer levels within ten times the upper limit of normal, and ten times the upper limit of normal, respectively; b: SOFA score: total score of respiratory SOFA, cardiovascular SOFA, hepatic SOFA, and renal SOFA; c: SIC: 4 points or more with total score of platelet and INR exceeding 2.
Table 2. The scoring system of sepsis-associated coagulopathy (SAC)
| INR | PLT (×109/L) | |||
|---|---|---|---|---|
| ≥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 |
INR: international normalized ratio; PLT: platelet. For statistical convenience, 0 point represents no SAC; 1 point represents mild SAC; 2 points represents moderate SAC; 3 points represents severe SAC.
The heparin treatment group was defined as patients who received unfractionated heparin, low-molecular-weight heparin or heparin derivatives at preventive or therapeutic doses for 5 d or longer after admission. The control group included patients who received no anticoagulant therapy or for < 5 d.[18] We evaluated the associations between 28-day mortality and anticoagulant therapy according to the SIC or SAC to clarify the value of the criteria as a pre-DIC indicator.
Data collection
The following information was collected through the electronic medical record system: age, sex, preexisting conditions, primary source of infection, laboratory tests, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, SOFA score, anticoagulant therapy and 28-day outcome. The SIC, SAC and overt-DIC scores were calculated according to the PLT, PT, INR, D-dimer, and Fib results on days 1, 3, 7, and 14.
Statistical analysis
We used SPSS 26.0 software and MedCalc 20.01 software to analyze the final dataset. The numerical data are expressed as the median and interquartile, and categorical data are expressed as the frequency (percentage). The Mann-Whitney U test or the Kruskal-Wallis test was used to compare the numerical data between the different groups. The Chi-square test or McNemar’s test was used to compare the categorical data, and Fisher’s exact probability test was used when necessary. To evaluate the diagnostic and prognostic value of these scoring systems, receiver operating characteristic (ROC) curves were drawn, and the optimal cut-off value, sensitivity and specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Propensity score matching (PSM) was applied between the heparin treatment group and the control group to reduce possible bias before survival analysis. The Cox regression method was used to evaluate the association between heparin therapy and 28-day mortality in the SIC/SAC positive or negative groups. A two-tailed P-value of less than 0.05 was considered to indicate statistical significance.
RESULTS
Baseline characteristics of the study population
The patient flowchart is shown in supplementary Figure 1. Of the 419 sepsis patients, 49 were diagnosed with overt-DIC, 25 with pre-DIC, and 345 with non-DIC (supplementary Table 1). There were no significant differences in gender among the three groups. Compared to those in the non-DIC group, the pre-DIC and overt-DIC groups had lower Fib and platelet counts and significantly higher PT, INR and D-dimer levels (P<0.05). The severity of the illness, as determined by the SOFA and APACHE II scores, was significantly different between the non-DIC group and the other two groups. The pre-DIC group had the highest mortality rate (48.0%), while the non-DIC group had the lowest (6.1%). Lung infection was the most common cause of sepsis in the study population (57.0%) and in the pre-DIC group (72.0%).
Comparison of the SIC and SAC criteria for detecting overt-DIC
On the first day, 49 (11.7%), 92 (22.0%), and 132 (31.5%) of the 419 patients were diagnosed with overt-DIC, SIC, or SAC, respectively (Figure 1). The incidence of SAC was significantly higher than that of SIC from day 1 to day 14. On days 1, 3, 7 and 14, of the patients with DIC, the percentages who fulfilled the SIC criteria or the SAC criteria were comparable, nearly 70%-90%.
Figure 1.
Figure 1.
Distribution and mortality of patients according to the overt-DIC, SIC and SAC criteria. The numbers represent the number of cases in each category. The numbers in parentheses are the non-survivors and mortality rate. DIC: disseminated intravascular coagulation; SIC: sepsis-induced coagulopathy; SAC: sepsis-associated coagulopathy.
The diagnostic value of SIC and SAC for overt-DIC was evaluated using ROC curve (Table 3). The sensitivity and area under the curve (AUC) values of the SIC and SAC criteria for diagnosing DIC were comparable from day 1 to day 14. The specificity of the SIC was significantly higher than that of the SAC criterion from day 1 to day 14 (P<0.05).
Table 3. Comparison of SIC and SAC criteria for detecting overt-DIC in sepsis patients
| Time | SIC | SAC | P-value |
|---|---|---|---|
| Day1 | |||
| 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 |
| Day3 | |||
| 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 |
| Day7 | |||
| 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 |
| Day14 | |||
| 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 |
DIC: disseminated intravascular coagulation; SIC: sepsis-induced coagulopathy; SAC: sepsis-associated coagulopathy; AUC: area under the curve; 95% CI: 95% confidence interval; PPV: positive predictive value; NPV: negative predictive value.
Comparison of SIC and SAC criteria for detecting pre-DIC
After admission, 25 (6.0%) patients developed pre-DIC within 14 d. Of these patients, 11 (44.0%) were diagnosed with SIC and 13 (52.0%) with SAC on day 1. The incidence of pre-DIC was higher in SIC patients (11.9%, 11/92) than in SAC patients (9.8%, 13/132) on day 1, without significant difference (P>0.05). The specificity of the SIC on day 1 for predicting pre-DIC was significantly higher than that of the SAC (79.44% vs. 69.80%, P<0.001). The AUC, sensitivity, PPV, and NPV were similar for both criteria. The SIC score on day 1 (cut-off value >3) had a significantly higher sensitivity for identifying pre-DIC (from 44.00% to 72.00%). Additionally, the AUC increased from 0.62 to 0.69, but the specificity decreased from 79.44% to 62.94% (Table 4).
Table 4. Comparison of SIC and SAC criteria for detecting pre-DIC in sepsis patients
| 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% |
SIC: sepsis-induced coagulopathy; SAC: sepsis-associated coagulopathy; DIC: disseminated intravascular coagulation; AUC: area under the curve; 95% CI: 95% confidence interval; PPV: positive predictive value; NPV: negative predictive value. *P<0.05.
Comparison of cumulative SIC and SAC scores for detecting pre-DIC
The sum of the SIC or SAC scores on days 1 and 3 was used to determine the dynamic trend of coagulopathy and evaluate the ability to identify pre-DIC. After plotting the ROC curves, a cut-off value of >7 was set for the SIC cumulative score, and >1 was set for the SAC cumulative score. The AUC for diagnosing pre-DIC according to the sum of the SIC score was significantly higher than that of the SAC score (0.79 vs. 0.69, P<0.001). There were no other significant differences between the cumulative scores of SIC and SAC. However, the SIC demonstrated a slightly higher sensitivity (72.00% vs. 64.00%) and specificity (75.63% vs. 74.87%) in detecting pre-DIC (Figure 2).
Figure 2.
Figure 2.
ROC curve of cumulative SIC and SAC scores on days 1 and 3 for the detection of pre-DIC. ROC curve: receiver operating characteristic curve; SIC: sepsis-induced coagulopathy; SAC: sepsis-associated coagulopathy; DIC: disseminated intravascular coagulation; AUC: area under the curve; 95% CI: 95% confidence interval; PPV: positive predictive value; NPV: negative predictive value.
Association between heparin treatment and mortality according to the first day of coagulopathy
After performing PSM (supplementary Table 2), 136 patient pairs were fully matched. Survival curves for both the anticoagulant and control groups, based on coagulopathy status on day 1, are illustrated in supplementary Figure 2. Favorable effects of anticoagulant therapy were observed in patients with 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).
When investigating mortality linked to anticoagulant therapy in patients without coagulopathy, significant differences were observed between the SIC-negative subgroups (adjusted HR=0.306, 95% CI: 0.106-0.883, P=0.029). In contrast, no such differences were found between the SAC-negative subgroups (adjusted HR=0.430, 95% CI: 0.140-1.320, P=0.140). These data suggest that a minority of patients might benefit from anticoagulant therapy despite not fulfilling the SIC criteria.
DISCUSSION
In the present study, we retrospectively evaluated the SIC and SAC criteria in sepsis patients to identify overt-DIC and pre-DIC. The results showed that most patients with overt-DIC met the SIC criteria (84%) or SAC criteria (90%), indicating that both criteria could be used in identifying overt-DIC. Furthermore, both the SIC score on day 1 (with a cut-off value >3) and the sum of SIC scores on days 1 and 3 (with a cut-off value >7) displayed higher sensitivity and AUC values for identifying pre-DIC than did the SIC or SAC status on day 1. Patients with SIC or SAC would benefit from anticoagulation therapy by reducing the risk of death.
It is crucial to use quick and simple techniques to screen DIC in sepsis patients. To simplify the assessment of coagulopathy in sepsis patients, the ISTH members proposed the SIC criteria, and another group released the SAC criteria. Both criteria mainly used the PLT and PT/INR.[12,13] An external validation study showed that 554 sepsis patients were diagnosed with ISTH-DIC at the time of ICU admission.[19] All the overt-DIC patients met the SIC criteria, but only 86.5% met the SAC criteria. In our study, 84% of the overt-DIC patients met the SIC criteria, and 90% met the SAC criteria. Additionally, our results demonstrated that the SIC criteria had higher specificity in identifying overt-DIC when compared with SAC. Iba et al[20,21] highlighted the efficacy of the SIC score and recommended using a combination of the SIC and ISTH-DIC scores to screen overt-DIC. However, the findings of Helm et al[22] did not provide any evidence supporting the recommendation of Iba et al.[20,21] In our study, only 18.4% of the patients might have had septic shock, and the incidence of SIC on day 1 was 22.0%. Therefore, SIC remains an effective screening tool for overt-DIC. For this reason, we recommend that SIC or SAC be used depending on the severity of the patient’s condition.
Although some researchers believe that SIC and SAC are early DIC, diagnostic criteria for the pre-DIC state have not yet been established.[23] Given that there is no gold standard for diagnosing DIC, we chose the ISTH-DIC score for diagnosing overt-DIC. When using the SIC or SAC status on day 1 to identify pre-DIC, the AUC values were only 0.62 and 0.61, respectively. However, when the SIC score on day 1 with a cut-off value >3 was used, the sensitivity (72.00%) and AUC (0.69) increased for identifying pre-DIC. These findings support the previous explanation that SIC gradually develops into pre-DIC, which can be considered early DIC.[14,22,24] Furthermore, we found that the sum of the SIC scores on days 1 and 3 was more effective than the SIC score on day 1 or the sum of the SAC scores in identifying pre-DIC status. Several factors could explain this observation. First, the predictive value of PLT and INR for overt-DIC can be amplified by the sum of SIC scores. Second, the SOFA score (the sum of four items) is a component of the SIC score and is strongly associated with organ dysfunction. It can indirectly reflect the severity of microthrombi, as organ dysfunction in sepsis is usually caused by disseminated microthrombi within the microvascular and small vessel systems.[25] Finally, it is important to note that the maximum SOFA score for SIC was no more than 2. Therefore, the sum of SIC scores could serve as a reliable indicator of pre-DIC status in patients with moderate organ dysfunction. However, for those with severe organ dysfunction, this may not be the case, as their SOFA scores no longer increase and provide additional predictive value. This difference and potential should be investigated in future research.
Anticoagulation therapy is crucial in the treatment of coagulation disorders in sepsis. Due to the lack of gold standards, it is difficult to accurately identify overt-DIC. Therefore, the ability of the SIC and SAC criteria to predict overt-DIC cannot be truly compared. In this study, we found that anticoagulation therapy significantly reduced the mortality rate of SIC- or SAC-positive patients. This finding was consistent with previous research showing that heparin may be beneficial for SIC patients. In addition, our study indicated that heparin also provided significant benefits for patients without SIC but not for patients without SAC. Therefore, SAC may be a more effective indicator for guiding anticoagulant treatment than SIC in sepsis patients.
Limitations
This study has several limitations. First, the sample size was limited, and retrospective information did not allow us to control the anticoagulation treatment plan. Second, most patients were respiratory infections, and other infections were relatively few. Finally, we used the PSM method to balance some confounding factors in that lost a certain sample size.
CONCLUSIONS
The SIC and SAC criteria seem to be valuable for identifying overt-DIC. The sum of SIC scores on days 1 and 3 has the potential to help identify pre-DIC. SAC may be a more effective indicator for guiding anticoagulant treatment in sepsis patients.
Funding: This work was supported by the National Key Research and Development Program of China (2021YFC2501800), Shanghai Committee of Science and Technology (20Y11900100, 21MC1930400, and 20DZ2261200), Clinical Research Plan of Shanghai Hospital Development Center (SHDC2020CR4059).
Ethical approval: This study was approved by the Ethical Committee of Zhongshan Hospital, Fudan University (B2021-562).
Conflicts of interest: The authors declared there are no conflicts of interest.
Contributors: ZJS, MS, and MMX: conception and design; ZJS: administrative support; MS and MMX: provision of study materials or patients; HXZ, YMD, SJW, and JYS: collection and assembly of data; HXZ and MS: data analysis and interpretation; all authors: manuscript writing and final approval of manuscript.
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PMID:29373360
[Cited within: 3]
To assess whether sepsis-associated coagulopathy predicts hospital mortality.Retrospective cohort study.One-thousand three-hundred beds urban academic medical center.Six-thousand one-hundred forty-eight consecutive patients hospitalized between January 1, 2010, and December 31, 2015.Mild sepsis-associated coagulopathy was defined as an international normalized ratio greater than or equal to 1.2 and less than 1.4 plus platelet count less than or equal to 150,000/µL but greater than 100,000/µL; moderate sepsis-associated coagulopathy was defined with either an international normalized ratio greater than or equal to 1.4 but less than 1.6 or platelets less than or equal to 100,000/µL but greater than 80,000/µL; severe sepsis-associated coagulopathy was defined as an international normalized ratio greater than or equal to 1.6 and platelets less than or equal to 80,000/µL.Hospital mortality increased progressively from 25.4% in patients without sepsis-associated coagulopathy to 56.1% in patients with severe sepsis-associated coagulopathy. Similarly, duration of hospitalization and ICU care increased progressively as sepsis-associated coagulopathy severity increased. Multivariable analyses showed that the presence of sepsis-associated coagulopathy, as well as sepsis-associated coagulopathy severity, was independently associated with hospital mortality regardless of adjustments made for baseline patient characteristics, hospitalization variables, and the sepsis-associated coagulopathy-cancer interaction. Odds ratios ranged from 1.33 to 2.14 for the presence of sepsis-associated coagulopathy and from 1.18 to 1.51 for sepsis-associated coagulopathy severity for predicting hospital mortality (p < 0.001 for all comparisons).The presence of sepsis-associated coagulopathy identifies a group of patients with sepsis at higher risk for mortality. Furthermore, there is an incremental risk of mortality as the severity of sepsis-associated coagulopathy increases.
Proposal of a two-step process for the diagnosis of sepsis-induced disseminated intravascular coagulation
DOI:10.1111/jth.14482 PMID:31099127 [Cited within: 2]
The third international consensus definitions for sepsis and septic shock (Sepsis-3)
DOI:10.1001/jama.2016.0287
PMID:26903338
[Cited within: 1]
Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.To evaluate and, as needed, update definitions for sepsis and septic shock.A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment).Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant.Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less.These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.
Prospective validation of the International Society of Thrombosis and Haemostasis scoring system for disseminated intravascular coagulation
DOI:10.1097/01.ccm.0000147769.07699.e3
PMID:15599145
[Cited within: 1]
A diagnosis of disseminated intravascular coagulation (DIC) is hampered by the lack of an accurate diagnostic test. Based on the retrospective analysis of studies in patients with DIC, a scoring system (0-8 points) using simple and readily available routine laboratory tests has been proposed. The aim of this study was to prospectively validate this scoring system and assess its feasibility, sensitivity, and specificity in a consecutive series of intensive care patients.Prospective cohort of intensive care patients.Adult intensive care unit in a tertiary academic center.Consecutive patients with a clinical suspicion of disseminated intravascular coagulation.Patients were followed during their admission to the intensive care unit, and the DIC score was calculated every 48 hrs and compared with a "gold standard" based on expert opinion. In addition, an activated partial thromboplastin time (aPTT) waveform analysis, which has been reported to be a good predictor for the absence or presence of DIC, was performed.We analyzed 660 samples from 217 consecutive patients. The prevalence of DIC was 34%. There was a strong correlation between an increasing DIC score and 28-day mortality (for each 1-point increment in the DIC score, the odds ratio for mortality was 1.25). The sensitivity of the DIC score was 91% and the specificity 97%. An abnormal aPTT waveform was seen in 32% of patients and correlated well with the presence of DIC (sensitivity 88%, specificity 97%). In 19% of patients, the aPTT waveform-based diagnosis of DIC preceded the diagnosis based on the scoring system.A diagnosis of DIC based on a simple scoring system, using widely available routine coagulation tests, is sufficiently accurate to make or reject a diagnosis of DIC in intensive care patients with a clinical suspicion of this condition. An aPTT waveform analysis is an interesting and promising tool to assist in the diagnostic management of DIC.
Hemostatic study before onset of disseminated intravascular coagulation
DOI:10.1002/ajh.2830430306
PMID:8352234
[Cited within: 1]
Early diagnosis is necessary for the treatment of disseminated intravascular coagulation (DIC), but criteria for the stage preceding the diagnosis of DIC (pre-DIC) have not yet been established. To clarify hemostatic abnormalities that occur before the onset of DIC, we performed hemostatic studies in 117 patients within at least a week before the onset of DIC (pre-DIC), in 237 patients with DIC, and in 50 patients without DIC or pre-DIC (non-DIC). Levels of FDP, PT, and fibrinogen, and platelet counts were significantly abnormal after the onset of DIC, but not before. Thrombin-antithrombin III complex (TAT), plasmin-alpha 2 plasmin inhibitor complex (PIC), and FDP-D-dimer levels were significantly higher before the onset of DIC compared to the non-DIC patients. Hemostatic abnormalities were observed within a week before the onset of DIC. Monitoring the plasma levels of TAT, PIC, and FDP-D-dimer might be useful for the diagnosis of a pre-DIC condition.
Favorable outcomes of anticoagulation with unfractioned heparin in sepsis-induced coagulopathy: a retrospective analysis of MIMIC-III database
External validation of the two newly proposed criteria for assessing coagulopathy in sepsis
Diagnosis and management of sepsis-induced coagulopathy and disseminated intravascular coagulation
DOI:10.1111/jth.14578 PMID:31410983 [Cited within: 2]
Newly proposed sepsis-induced coagulopathy precedes international society on thrombosis and haemostasis overt-disseminated intravascular coagulation and predicts high mortality
DOI:10.1177/0885066618773679
PMID:29720054
[Cited within: 2]
Disseminated intravascular coagulation (DIC) has been recognized as an urgent and critical condition in patients with sepsis. Therefore, unfamiliar and time-consuming tests or a complex scoring system are not suitable for diagnosis. Sepsis-induced coagulopathy (SIC), a newly proposed category delineated by a few global coagulation tests, has been established as an early warning sign for DIC. The purpose of this study was to elucidate the characteristics of SIC, especially in relation to the score of the International Society on Thrombosis and Haemostasis (ISTH) for overt DIC.A data set for 332 patients with sepsis who were suspected to have DIC, antithrombin activity <70%, and treated with antithrombin substitution was utilized to examine the relationship between SIC and overt DIC. The performance of SIC calculated at baseline (ie, before treatment) as well as on days 2, 4, or 7 was analyzed in terms of its ability to predict 28-day mortality and overt DIC.At baseline, 149 (98.7%) of 151 patients with overt DIC according to the ISTH definition were diagnosed as having SIC. Of the 49, 46 (93.9%) patients who developed overt DIC between days 2 and 4 had received a prior diagnosis of SIC. The sensitivity of baseline SIC for the prediction of death was significantly higher than that of overt DIC (86.8% vs 64.5%, <.001). The sensitivity of SIC on days 2, 4, and 7 was significantly higher than those of overt DIC (96.1%, 92.3%, and 84.4% vs 67.1%, 57.7%, and 50.0%, <.001,.001, and.001, respectively), although the specificity of SIC was lower at all time points.
Performances of disseminated intravascular coagulation scoring systems in septic shock patients
DOI:10.1186/s13613-020-00704-5
PMID:32651674
[Cited within: 2]
There is no gold standard to diagnose septic shock-induced disseminated intravascular coagulation (DIC). The objective of our multicenter prospective study was to assess the performances of the different major scoring systems in terms of mortality prediction and DIC diagnosis. The JAAM-DIC 2016 score, the ISTH overt-DIC 2001 score, the associations of sepsis-induced coagulopathy (SIC) score with JAAM-DIC 2016 or ISTH overt-DIC scores were tested in patients within 12 h of their admission in ICU for septic shock (day 1) and at day 2.582 patients were enrolled in the study. 182/567 (32.1%) were diagnosed with DIC according to ISTH overt-DIC score, and 193/561 (34.4%) according to JAAM-DIC score; 486/577 patients (84.2%) were diagnosed with a coagulopathy according to SIC score. A moderate concordance was observed between ISTH overt-DIC and JAAM-DIC [κ = 0.67 (0.60, 0.73), p < 0.001]. The delay of positivity of the scores for early DIC patients was not different between JAAM-DIC and ISTH overt-DIC scores. Although it was positive earlier, SIC score had worse diagnosis specificity, as 84.2% of the patients with septic shock were diagnosed with "coagulopathy". The specificity of SIC score alone to predict mortality was very low [0.18 (0.15; 0.22)], compared to the ones of JAAM-DIC score [0.71 (0.67; 0.75)], and of ISTH overt-DIC score [0.76 (0.72; 0.80)], p < 0.001. The sensitivity of SIC score to predict mortality was 0.95 [0.89; 0.98], and the ones of JAAM-DIC score and ISTH overt-DIC score were 0.61 [0.50; 0.70] and 0.68 [0.58; 0.77], respectively. There was no benefit in sensitivity and specificity in combining SIC score to JAAM-DIC score or to ISTH overt-DIC score, compared to JAAM-DIC score or ISTH overt-DIC score alone.Our data suggest that the added value of SIC score alone or combined with other scores is limited, and that both JAAM-DIC score and ISTH overt-DIC score can be used in septic shock patients. Trial registration clinicaltrial; Trial registration number: NCT02391792; Date of registration: 18/03/2015; URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT02391792?term=meziani&draw=4&rank=1.
Frequency and hemostatic abnormalities in pre-DIC patients
DOI:10.1016/j.thromres.2010.03.017
PMID:20452653
[Cited within: 1]
Disseminated intravascular coagulation (DIC) sometimes has a poor outcome, and therefore early diagnosis and treatment are required. This study prospectively evaluated the hemostatic abnormalities and the onset of DIC in 613 patients with underlying diseases to identify a useful marker for diagnosing Pre-DIC. Pre-DIC was defined as the condition of patients within a week before the onset of DIC. Initially, 34.4% of patients were diagnosed with DIC, and about 8.5% of the patients without DIC were diagnosed as DIC within a week after registration (pre-DIC). The mortality of DIC, Pre-DIC and "without DIC" was 35.3%, 32.4% and 17.2%, respectively. All hemostatic parameters were significantly worse in "DIC" than "without DIC" and the values of the prothrombin time ratio, platelet count and fibrin monomer complex could classify the three groups; "DIC", "pre-DIC" and "without DIC". No useful marker was identified that provided an adequate cutoff value to differentiate "pre-DIC" from "without DIC". A multivariate analysis identified clinical symptoms that were related to poor outcome. DIC must be treated immediately; there is no specific marker to identify pre-DIC.Copyright (c) 2010 Elsevier Ltd. All rights reserved.
Haematological characteristics and risk factors in the classification and prognosis evaluation of COVID-19: a retrospective cohort study
DOI:10.1016/S2352-3026(20)30217-9
PMID:32659214
[Cited within: 1]
COVID-19 is an ongoing global pandemic. Changes in haematological characteristics in patients with COVID-19 are emerging as important features of the disease. We aimed to explore the haematological characteristics and related risk factors in patients with COVID-19.This retrospective cohort study included patients with COVID-19 admitted to three designated sites of Wuhan Union Hospital (Wuhan, China). Demographic, clinical, laboratory, treatment, and outcome data were extracted from electronic medical records and compared between patients with moderate, severe, and critical disease (defined according to the diagnosis and treatment protocol for novel coronavirus pneumonia, trial version 7, published by the National Health Commission of China). We assessed the risk factors associated with critical illness and poor prognosis. Dynamic haematological and coagulation parameters were investigated with a linear mixed model, and coagulopathy screening with sepsis-induced coagulopathy and International Society of Thrombosis and Hemostasis overt disseminated intravascular coagulation scoring systems was applied.Of 466 patients admitted to hospital from Jan 23 to Feb 23, 2020, 380 patients with COVID-19 were included in our study. The incidence of thrombocytopenia (platelet count <100 × 10 cells per L) in patients with critical disease (42 [49%] of 86) was significantly higher than in those with severe (20 [14%] of 145) or moderate (nine [6%] of 149) disease (p<0·0001). The numbers of lymphocytes and eosinophils were significantly lower in patients with critical disease than those with severe or moderate disease (p<0·0001), and prothrombin time, D-dimer, and fibrin degradation products significantly increased with increasing disease severity (p<0·0001). In multivariate analyses, death was associated with increased neutrophil to lymphocyte ratio (≥9·13; odds ratio [OR] 5·39 [95% CI 1·70-17·13], p=0·0042), thrombocytopenia (platelet count <100 × 10 per L; OR 8·33 [2·56-27·15], p=0·00045), prolonged prothrombin time (>16 s; OR 4·94 [1·50-16·25], p=0·0094), and increased D-dimer (>2 mg/L; OR 4·41 [1·06-18·30], p=0·041). Thrombotic and haemorrhagic events were common complications in patients who died (19 [35%] of 55). Sepsis-induced coagulopathy and International Society of Thrombosis and Hemostasis overt disseminated intravascular coagulation scores (assessed in 12 patients who survived and eight patients who died) increased over time in patients who died. The onset of sepsis-induced coagulopathy was typically before overt disseminated intravascular coagulation.Rapid blood tests, including platelet count, prothrombin time, D-dimer, and neutrophil to lymphocyte ratio can help clinicians to assess severity and prognosis of patients with COVID-19. The sepsis-induced coagulopathy scoring system can be used for early assessment and management of patients with critical disease.National Key Research and Development Program of China.Copyright © 2020 Elsevier Ltd. All rights reserved.
Disseminated intravascular coagulation: an update on pathogenesis, diagnosis, and therapeutic strategies
