Outcomes of Overt and Non-overt Disseminated Intravascular Coagulation Using the ISTH DIC Scoring System in Children: A Single-Center Study

Jassada Buaboonnam1, Chonthida Wangkittikal1, Nattee Narkbunnam1, Nassawee Vathana1, Chayamon Takpradit1, Kamon Phuakpet1, Phakatip Sinlapamongkolkul2, Kleebsabai Sanpakit1, Khemajira Karaketklang3 and Bunchoo Pongtanakul1.

1 Division of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
2 Department of Pediatrics, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand.
3 Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Correspondence to: Bunchoo Pongtanakul, MD. Associate Professor of Pediatrics. Division of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University 2 Wanglang Road, Bangkok Noi, Bangkok 10700, Thailand. Tel: +66 2 419 5960; Fax: +66 2 411 3010. E-mail: pongtanakul@yahoo.com

Published: January 1, 2023
Received: August 9, 2022
Accepted: December 15, 2022
Mediterr J Hematol Infect Dis 2023, 15(1): e2023004 DOI 10.4084/MJHID.2023.004

This is an Open Access article distributed under the terms of the Creative Commons Attribution License
https://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background: Several disseminated intravascular coagulation (DIC) scoring systems are used for prognosticating the clinical outcomes of patients with DIC. However, research on children is scarce. Therefore, this study compared the clinical outcomes of overt and non-overt DIC using the International Society on Thrombosis and Hemostasis (ISTH) DIC scoring system.
: This retrospective study reviewed data on children aged one month to 15 years diagnosed with DIC between 2003 and 2014.
: Of 244 patients, 179 (73.4%) had overt DIC, and 65 (26.6%) had non-overt DIC. The most common causes were infection (84.8%), tissue injury (7%), and malignancies (2.9%). The 28-day case fatality rate was significantly higher for overt than non-overt DIC (76% vs. 15.6%; 
P < 0.001). DIC scores were significantly associated with mortality (R2 = 0.89). Each clinical parameter (platelet count, prothrombin time, and fibrin degradation products) was associated with mortality (P = 0.01). On multivariable analysis, the factors associated with death were platelet counts ≤ 50 000 cells/mm3 (OR, 2.42; 95% CI, 1.08–5.42; P = 0.031); overt DIC score (OR, 7.62; 95% CI, 2.94–19.75; P < 0.001); renal dysfunction (OR, 2.92; 95% CI, 1.34–6.37; P = 0.007); shock (OR, 39.62; 95% CI, 4.99–314.84; P = 0.001); and acute respiratory distress syndrome (OR, 25.90; 95% CI, 3.12–214.80; P = 0.003).
: The 28-day case-fatality rate was significantly higher for patients with overt than non-overt DIC and concordant with ISTH scores. ISTH DIC scores can be used as a clinical predictor for DIC in children.


Disseminated intravascular coagulation (DIC) is caused by excessive hemostatic system activation. The disease leads to consumptive coagulopathy, microthrombi formation, and severe bleeding. Ultimately, it results in multiorgan dysfunction, manifested in conditions such as trauma, malignancy, and sepsis.[1] DIC is responsible for mortality in such conditions in both child and adult patients.[2,3]
Several scoring systems have demonstrated value in diagnosing DIC. The International Society on Thrombosis and Haemostasis (ISTH) DIC scoring system draws upon prothrombin time, platelet count, fibrinogen, and D-dimer levels, and it has been widely studied in mainly adult patients with DIC.[4] The ISTH DIC system can prognosticate the outcomes of patients in critical condition due to sepsis and non-sepsis etiologies.[5,6] Nevertheless, research on the efficacy of the scoring system for the pediatric population is scarce. Therefore, evaluating ISTH DIC scores in children with DIC may assist physicians in predicting clinical outcomes. This study aimed to evaluate and compare the clinical outcomes of children with overt DIC and non-overt DIC using the ISTH scoring system.

Patients and Methods

This retrospective study was performed on patients aged 28 days to 15 years who had been diagnosed with DIC during admission at Siriraj Hospital, Mahidol University, Thailand, between January 2005 and December 2014. The clinical parameters of the patients at admission were rated using the ISTH DIC scoring system as follows:[4]
•    Platelet count: > 100 000 cells/mm3 = 0 points; between 50 000 and 100 000 cells/mm
3 = 1 point; and < 50 000 cells/mm3 = 2 points
•    Prolonged prothrombin time: < 3 seconds = 0 points; between 3 and 6 seconds = 1 point; and > 6 seconds = 2 points
•    Fibrinogen level: > 100 mg/dL = 0 points, and < 100 mg/dL = 1 point
•    D-dimer level: no increase = 0 points; moderate increase = 2 points; and strong increase = 3 points
The patients were classified into two groups: (1) “overt DIC”, for those with ISTH DIC scores ≥ 5, and (2) “non-overt DIC”, for patients with ISTH DIC scores < 5.
Patients who were previously diagnosed with DIC were treated with blood components within 24 hours before the diagnosis of DIC or had incomplete laboratory parameters of the ISTH DIC scoring system were excluded. Specific organ dysfunctions were classified according to the international pediatric sepsis consensus conference[7] as follows,
Central nervous system dysfunction was defined as a Glasgow coma score 
11 or decreased Glasgow coma score 3 from baseline.
Respiratory system dysfunction was defined as the ratio of partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2), PaO2/FiO2 < 300 without evidence of cyanotic heart disease and preexisting pulmonary disease or PaCO2 > 65 torr or > 20 mmHg of baseline or requiring oxygen FiO2 > 0.5 to maintain oxygen saturation 
92% or requiring non-elective invasive or non-invasive mechanical ventilator
Renal dysfunction was defined as the serum creatinine
2 times for age or increased serum creatinine > 2 times from baseline.
Hepatic dysfunction was defined as total bilirubin
4 mg/dL or alanine transaminase > 2 times from baseline.
Descriptive statistics were used to detail demographic and clinical characteristic data. Continuous data are presented as medians and ranges, while categorical data are reported as numbers and percentages. Pearson’s chi-squared test was used to compare the proportions of groups with categorical data, and Student’s t-test or the Mann–Whitney U test was used to compare medians for continuous data. Univariable and multivariable predictors of death were evaluated using binary logistic regression analysis (backward method), with results presented as the odds ratio (OR) and 95% confidence interval (CI). A probability (P) value < 0.05 was considered statistically significant. All analyses were performed using PASW Statistics for Windows, version 18.0 (SPSS Inc, Chicago, IL, USA).


Of the 67 992 inpatient cases, 244 patients were diagnosed with DIC, giving a frequency of DIC of 0.35. There were 118 male patients (48.4%) and 126 female patients (51.6%); the age group breakdown of 1 month – 1 year, 1-5 years, 5-10 years, and more than 10 years were 71 (29.1%), 78 (32%), 50 (20.5%) and 45 (18.4%) patients, respectively. Infection was the most common cause of DIC (84.8%), with tissue injury being the second most common cause (7%); other causes are detailed in Table 1. Gram-negative bacterial infection was the most common cause of infection-associated DIC. The other causative organisms are detailed in Table 2. Of the 17 patients with DIC secondary to tissue injury and surgery, open-heart surgery for congenital heart disease (9 patients) was the most common cause. Postorgan transplantation ranked second with 5 patients (liver transplantation, 4 patients; kidney transplantation, 1 patient), followed by intra-abdominal surgery (2 patients) and thermal injury (1 patient). There were 7 patients with malignancies; of these, hematologic malignancies (4 patients) were the most common cause (2 patients with acute lymphoblastic leukemia, 1 patient with acute myeloid leukemia, and 1 patient with non-Hodgkin lymphoma). The other 3 patients had solid tumors: 1 with hepatoblastoma, another with neuroblastoma, and the third with an endodermal sinus tumor. Hemorrhage was the most common manifestation (153 patients; 62.7%), with gastrointestinal hemorrhage being the most common site (41.8%), followed by endotracheal hemorrhage (24.2%) and hematuria (7.8%). Thrombosis was diagnosed in 20 patients (8.1%); venous thrombosis was the most common site (45%), followed by peripheral gangrene (40%).

Table 1 Table 1. Underlying causes of DIC.

Table 2 Table 2. Causative organisms of DIC.

The laboratory parameters of the patients with overt and non-overt DIC are compared in Table 3. Of the 244 patients with DIC, 179 (73.3%) were diagnosed with overt DIC, and the remaining 65 (26.7%) had non-overt DIC. The 28-day case fatality rate for overt DIC (76%) was significantly higher than that for non-overt DIC (15.4%; P < 0.001). The median time from the diagnosis of DIC to death was 7.1 days (0–37 days), while the median time from diagnosis of DIC to recovery was 14 days (2–61 days). The correlation between mortality and the ISTH DIC scores is illustrated in Figure 1 (R2 = 0.89).

Table 3 Table 3. Comparison of laboratory parameters of patients with overt and non-overt DIC.

Figure 1 Figure 1. Correlation between the DIC scores and the 28-day case fatality rate.

In terms of admission, 209 patients (85.7%) were admitted to the intensive care unit (ICU), whereas the other 35 patients (14.3%) were not. The rates of ICU admission of the patients with overt and non-overt DIC were not significantly different (P = 0.129). Anticoagulant was prescribed for 9 patients; the most commonly used anticoagulant was unfractionated heparin (4 patients), followed by low molecular weight heparin (3 patients) and warfarin (2 patients). Of the 9 patients requiring anticoagulant therapy, 4 had venous thrombosis, 4 had arterial thrombosis, and one prophylactically received an anticoagulant to prevent clotting after cardiac surgery. Recombinant factor VIIa was prescribed for 9 patients. Neither treatment-associated hemorrhage nor thrombosis was observed. The most typical indication was dengue hemorrhagic fever with severe hemorrhage (6 patients). The other indications were cancer with severe hemorrhage (2 patients) and chronic liver disease requiring a postsurgery bleeding prophylactic (1 patient). The factors associated with the death of DIC patients are presented in Table 4, and the laboratory parameters of the decedents and survivors are compared in Table 5. Univariable and multivariable factors associated with death in DIC are detailed in Table 6.

Table 4 Table 4. Factors associated with death of DIC patients.

Table 5 Table 5. Comparison of laboratory parameters of decedents and survivors.

Table 6 Table 6. Univariable and multivariable factors associated with death.


Studies regarding DIC in children are scarce. Oren et al. reported that the frequency of DIC in the pediatric population was 1.12 hospitalized in a Turkey University Hospital,[8] similar to the present study’s finding of 0.35. However, the frequency in children is lower than in adults (34.4).[9] Additionally, the present investigation found that infections were the most common etiology of DIC, which is consistent with previous studies on adults and children.[8,9] On the other hand, the proportion of children in the current study with infection (approximately 80%) is markedly higher than the corresponding levels previously reported for adults (30%–40%).[10] Furthermore, the rate of malignancy-related DIC seems lower in children than adults, which may indicate differences in the etiologies of the disease in children and adults. Prevalent in tropical regions, dengue hemorrhagic fever can cause thrombocytopenia, plasma leakage, and decreased coagulation factors secondary to hepatic derangement, the combined effects of which lead to DIC.[11] Dengue hemorrhagic fever was the most common cause of viral-associated DIC in the present study; however, this phenomenon might be uncommon in countries where dengue is not endemic. Similarly, our investigation determined that tropical diseases such as disseminated tuberculosis and strongyloidiasis also caused DIC. Therefore, physicians in tropical regions caring for patients with such diseases should be aware of DIC as a peculiar clinical manifestation.
The hemostasis in infants, especially neonates, differs from that in adults. The decreased coagulation factors and natural anticoagulants gradually reach the normal level at approximately six months of age, leading to the counterbalance of hemostasis.[12] The prolonged prothrombin time in such patients might not reflect the proper hemostasis. Therefore, in this cohort, neonates with DIC were excluded from the study.
The clinical severity of hemorrhage and organ failure might be related to the etiologies of DIC in adults. Research on adults showed that multiorgan failure was prevalent in infection-associated DI; in contrast, hemorrhage was common in noninfectious-associated DIC.[13,14] Furthermore, the bleeding tendency in these adult studies appeared to be lower than that of the present pediatric study. The different populations and DIC etiologies of the adult and pediatric investigations may account for the variations in the observed clinical manifestations. The present work identified a thrombosis incidence of 8.1%, comparable with other studies on adult and pediatric populations, and neither arterial nor venous sites predominated.[8,15] Consequently, clinical vigilance of thromboembolic complications is needed in both pediatric and adult patients with DIC. In terms of treatment-associated both hemorrhagic and thrombotic complications, such complications were not observed in this cohort; this may result from the scarcity of patients treated with recombinant factor VIIa, tranexamic acid, and anticoagulant.
Concordant with other studies,[16,17] the 28-day case fatality rate of children with overt DIC or those with organ dysfunction requiring advanced organ support was significantly higher than that for children with non-overt DIC. Additionally, mortality was significantly correlated with the ISTH DIC score and the clinical parameters platelet number, prothrombin time, and D-dimer. Similarly, our multivariable analysis revealed that overt DIC and thrombocytopenia below 50 000/mm3 were associated with death. These results substantiate the role of the ISTH DIC scoring system in predicting the clinical outcomes of DIC in the pediatric population, with platelet number possibly being a pivotal clinical factor in prognosticating the risk of death in DIC. Although other factors (underlying diseases and age at diagnosis) were not significantly associated with mortality, preexisting cancer tended to be correlated with mortality. Therefore, patients with a high ISTH DIC score, especially those with preexisting cancer, should be closely monitored, and treatment interventions for underlying diseases should be delivered promptly.
Compared to the score of 5, the ISTH score of 3 demonstrated a better mortality prediction in sepsis-associated DIC.[18] Furthermore, other DIC scoring systems, namely Texas Children’s Hospital criteria[19] and Japanese Association for Acute Medicine criteria[20] were previously described and demonstrated a good prediction of clinical outcome. However, the former system required sequential evaluation by specialists while the latter required the anti-thrombin level, which was somewhat not performed; these scoring systems might not be applicable in our institute. Taken together, the heterogeneity of results and scoring system substantiated the warrant of further investigation of scoring systems in the pediatric population.
This study had some limitations. First, since this was a retrospective study, there is the possibility of missing or incomplete data. Second, given that the population was drawn from a national tertiary referral hospital, where some tropical diseases appeared to be prevalent, the data may not be generalized to other populations or clinical settings; therefore, the prevalence and causation of DIC may vary from other studies.


Infection was the most common cause of DIC. The children with overt DIC had a higher mortality rate than those with non-overt DIC. The ISTH scoring system can predict the clinical outcomes of children with DIC.


The authors are indebted to Mr David Park and Mrs. Sam Ormond for the English-language editing of this paper.

Author Contributions

BP designed the study; CW, JB, NN, NV, CT, KP, KK, PS, and KS collected and analyzed data; JB and BP wrote the manuscript; all authors read and approved the final manuscript. 


  1. Gando S, Levi M, Toh C-H. Disseminated intravascular coagulation. Nat Rev Dis Primers 2016; 2: 16037. https://doi.org/10.1038/nrdp.2016.37 PMid:27250996
  2. Kongstad C, Mikkelsen TS, Hvas AM. Disseminated intravascular coagulation in children with cancer: A systematic review. Pediatr Hematol Oncol 2020; 37: 390-411. https://doi.org/10.1080/08880018.2020.1733717 PMid:32202958
  3. Niederwanger C, Bachler M, Hell T, et al. Inflammatory and coagulatory parameters linked to survival in critically ill children with sepsis. Ann Intensive Care 2018; 8: 111.  https://doi.org/10.1186/s13613-018-0457-8 PMid:30446841 PMCid:PMC6240023
  4. Taylor FB, Jr., Toh CH, Hoots WK, Wada H, Levi M. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost 2001; 86: 1327-1330. https://doi.org/10.1055/s-0037-1616068 PMid:11816725
  5. Helms J, Severac F, Merdji H, et al. Performances of disseminated intravascular coagulation scoring systems in septic shock patients. Ann Intensive Care 2020; 10: 92. https://doi.org/10.1186/s13613-020-00704-5 PMid:32651674 PMCid:PMC7352012
  6. Grafeneder J, Krychtiuk KA, Buchtele N, et al. The ISTH DIC score predicts outcome in non-septic patients admitted to a cardiovascular intensive care unit. Eur J Intern Med 2020; 79: 37-42. https://www.sciencedirect.com/science/article/pii/S0953620520302557 https://doi.org/10.1016/j.ejim.2020.06.017 PMid:32622514
  7. Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005; 6: 2-8. https://doi.org/10.1097/01.PCC.0000149131.72248.E6 PMid:15636651
  8. Ören H, Cingöz I, Duman M, Yılmaz S, Irken G. Dsseminated intravascular coagulation in pediatric patients: Clinical and laboratory features and prognostic factors influencing the survival. Pediatr Hematol Oncol 2005; 22: 679-688. https://doi.org/10.1080/08880010500278749 PMid:16251173
  9. Okamoto K, Wada H, Hatada T, et al. Frequency and hemostatic abnormalities in pre-DIC patients. Thromb Res 2010; 126: 74-78. https://doi.org/10.1016/j.thromres.2010.03.017 PMid:20452653
  10. Wu Y, Luo L, Niu T, et al. Evaluation of the new Chinese disseminated intravascular coagulation scoring system in critically ill patients: A multicenter prospective study. Sci Rep 2017; 7: 9057. https://doi.org/10.1038/s41598-017-09190-5 PMid:28831134 PMCid:PMC5567287
  11. Nurnaningsih, Sunbanu SE, Rusmawatiningtyas D, Arguni E, Makrufardi F, Kumara IF. Disseminated intravascular coagulation initial score as a predictor of mortality in children with dengue shock syndrome: A retrospective cohort study. Ann Med Surg 2022; 79: 103890. https://doi.org/10.1016/j.amsu.2022.103890 PMid:35860092 PMCid:PMC9289251  
  12. Davenport P, Sola-Visner M. Hemostatic challenges in neonates. Front Pediatr 2021; 9: 627715. https://doi.org/10.3389/fped.2021.627715 PMid:33738269 PMCid:PMC7960661  
  13. Okajima K, Sakamoto Y, Uchiba M. Heterogeneity in the incidence and clinical manifestations of disseminated intravascular coagulation: a study of 204 cases. Am J Hematol 2000; 65: 215-222. https://doi.org/10.1002/1096-8652(200011)65:3<215::AID-AJH7>3.0.CO;2-7 PMid:11074538
  14. Ohbe H, Yamakawa K, Taniguchi K, et al. Underlying disorders, clinical Phenotypes, and treatment diversity among patients with disseminated intravascular coagulation. Jma J 2020; 3: 321-329. https://doi.org/10.31662/jmaj.2020-0023
  15. Mahanupap P, Angchaisuksiri P, Rattanasiri S. Disseminated intravascular coagulation in Ramathibodi hospital. J Hem Transfus Med 2010; 20: 27-38.
  16. Khemani RG, Bart RD, Alonzo TA, Hatzakis G, Hallam D, Newth CJL. Disseminated intravascular coagulation score is associated with mortality for children with shock. Intensive Care Med 2009; 35: 327-333. https://doi.org/10.1007/s00134-008-1280-8 PMid:18802683
  17. Kunwar S, Alam M, Ezekwueme F, et al. Diagnostic scores and treatment options for acute disseminated intravascular coagulation in children. Cureus 2021; 13: e17682. https://doi.org/10.7759/cureus.17682
  18. Slatnick LR, Thornhill D, Deakyne Davies SJ, et al. Disseminated intravascular coagulation is an independent predictor of adverse outcomes in children in the emergency department with suspected sepsis. J Pediatr 2020; 225: 198-206.e192. https://doi.org/10.1016/j.jpeds.2020.06.022 PMid:32553867 PMCid:PMC7529972
  19. Soundar EP, Jariwala P, Nguyen TC, Eldin KW, Teruya J. Evaluation of the international society on thrombosis and haemostasis and institutional diagnostic criteria of disseminated intravascular coagulation in pediatric patients. Am J Clin Pathol 2013; 139: 812-816. https://doi.org/10.1309/AJCPO64IWNLYCVVB PMid:23690126 PMCid:PMC5281061
  20. Jhang WK, Ha EJ, Park SJ. Evaluation of disseminated intravascular coagulation scores in critically ill pediatric patients. Pediatr Crit Care Med 2016; 17. https://doi.org/10.1097/PCC.0000000000000705  PMid:27028791