Evaluation of disseminated intravascular coagulation in critically ill pediatric patients

Won Kyoung Jhang

doi:10.32990/apcc.2023.00080

Arch Pediatr Crit Care > Volume 1(2); 2023 > Article

Jhang: Evaluation of disseminated intravascular coagulation in critically ill pediatric patients

Review Article

Arch Pediatr Crit Care 2023; 1(2): 53-57.

Published online: December 29, 2023

DOI: https://doi.org/10.32990/apcc.2023.00080

Evaluation of disseminated intravascular coagulation in critically ill pediatric patients

Won Kyoung Jhang

Division of Pediatric Critical Care Medicine, Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea

Corresponding author: Won Kyoung Jhang Division of Pediatric Critical Care Medicine, Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea Email: wkjhang@amc.seoul.kr

Received December 11, 2023 Revised December 13, 2023 Accepted December 16, 2023

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

Abstract

Disseminated intravascular coagulation (DIC) is characterized by the extensive activation of the coagulation system, which leads to fibrin deposition within the microcirculation and the consumption of coagulation factors. The pathophysiology of DIC involves three primary pathways: activation of coagulation, suppression of inhibitory systems, and inhibition of fibrinolysis. These pathways can lead to extensive thrombosis and/or bleeding, ultimately resulting in poor clinical outcomes. Therefore, early detection of DIC is of crucial importance. However, no gold standard currently exists for the diagnosis of DIC in critically ill children. While several diagnostic criteria have been established for adults, incorporating coagulation-related laboratory data and associated clinical conditions, they have limitations and their applicability and accuracy in the pediatric population are not well established. Thus, it is necessary to validate the diagnostic criteria previously used in adults through large-scale multicenter studies of pediatric populations and develop an evidence-based, appropriate diagnostic tool for the accurate and early detection of DIC in these patients.

Key Words: Pediatrics; Critical care; Disseminated intravascular coagulation; Multiple organ dysfunction; Mortality

INTRODUCTION

In critically ill pediatric patients, a range of disorders—including severe infections, inflammatory conditions, solid tumors, and hematologic malignancies—can initiate coagulation activation. This activation, coupled with the suppression of natural anticoagulant pathways and fibrinolysis, may result in intravascular fibrin formation and the depletion of platelets and coagulation factors. The most extreme outcome of this dysregulation is disseminated intravascular coagulation (DIC), which carries a high risk of serious complications and poor clinical prognosis [1-4]. This paper aims to provide a review of the pathophysiology and clinical significance of DIC, as well as the currently available diagnostic criteria.

PATHOPHYSIOLOGY

DIC is defined as an acquired disorder characterized by abnormalities in both the coagulation and anticoagulation systems. The pathophysiology of DIC can be explained by three main processes: the activation of coagulation, the suppression of physiological inhibitory anticoagulant pathways, and impaired fibrinolysis (Fig. 1) [5,6]. Activation of coagulation and increased thrombin generation are primarily mediated by the extrinsic pathway (factor VIIa), which is triggered by tissue factors. These tissue factors are initially released into the circulation from damaged vascular endothelial cells. Through the extrinsic pathway, thrombin and fibrin are produced, leading to the formation of diffuse microthrombi.

Depressed antithrombin levels and diminished activity in the protein C pathway are often a consequence of activated inflammatory responses and a deficiency in tissue factor pathway inhibitors. This suppression of the body's natural anticoagulant mechanisms contributes to the enhanced production of thrombin and fibrin. Furthermore, damaged vascular endothelial cells release tissue plasminogen activator (tPA), initiating the fibrinolytic pathway. Both tPA and plasminogen bind to fibrin polymers, with plasmin subsequently breaking down fibrin into D-dimers and other fibrin degradation products. However, this fibrinolytic process is hindered by elevated levels of plasminogen activator inhibitor type 1, which acts to inhibit fibrinolysis.

CLINICAL IMPORTANCE

As DIC can arise from a broad spectrum of clinical scenarios, its impact on morbidity and mortality risk is likely influenced by the underlying disease status (Table 1) [6-8]. Depending on the clinical context and the extent of platelet and/or coagulation factor consumption, DIC may predominantly lead to widespread thrombosis and/or substantial bleeding.

The formation of microthrombi can lead to disturbances in the microcirculation, impairing organ perfusion and resulting in tissue ischemia. This, in turn, contributes to the development of multiple organ dysfunction syndrome [9]. Recent studies have highlighted the significant prognostic value of DIC in critically ill patients, emphasizing its association with poor clinical outcomes [10-16]. Therefore, the early detection and aggressive management of DIC are of paramount importance [5,17].

DIAGNOSIS

Despite the clinical significance of DIC, no single diagnostic test can definitively confirm or rule out its presence. DIC is typically diagnosed through a combination of coagulation-related laboratory tests and clinical findings [7]. However, since the Japanese Ministry of Health, Labor and Welfare proposed diagnostic criteria for DIC, numerous research studies and trials have aimed to establish more accurate definitions and diagnostic approaches for this condition [18-26]. Consequently, several diagnostic scoring systems have emerged, primarily integrating coagulation-related factors such as platelet count, fibrinogen level, prothrombin time, and fibrin degradation products. These factors are used either individually or in conjunction with clinical parameters (Table 2). Additionally, these criteria have been adapted to suit specific clinical scenarios, and validation studies have been conducted [11,12,27-31].

These scoring systems offer certain advantages as they are relatively straightforward and can be easily calculated at the bedside. They provide quantified guidance for the diagnosis of DIC, which can aid in its detection, management, and prognostic evaluation. However, there are certain limitations to consider. The transition from an activated hemostatic system to a clearly defined overt state of DIC may not always be distinct, and the borderline between normal and abnormal values can be challenging to discern. Additionally, these laboratory parameters can be influenced by various clinical conditions, such as hematologic malignancies, severe hepatic dysfunction, or acute inflammatory states. Furthermore, although a few reports have applied and validated these scoring systems in critically ill children, the limited number and heterogeneity of the study populations necessitate further large-scale multicenter validation studies and the establishment of evidence-based diagnostic criteria for DIC in critically ill pediatric patients [32-36].

CONCLUSIONS

DIC is a complex and potentially life-threatening condition characterized by the dysregulation of coagulation and fibrinolysis. In critically ill pediatric patients, DIC can have serious implications and lead to poor clinical outcomes. Although diagnostic criteria exist for DIC in adults, their applicability to pediatric patients remains uncertain. Future research should concentrate on creating evidence-based diagnostic tools tailored to critically ill children. This would facilitate the early and accurate detection of DIC, thereby improving patient outcomes.

ARTICLE INFORMATION

CONFLICT OF INTEREST

Won Kyoung Jhang is an Editor-in-Chief of the journal but was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.

Fig. 1.

Pathophysiology of disseminated intravascular coagulation. TFPI, tissue factor pathway inhibitor; tPA, tissue plasminogen activator; PAI, plasminogen activator inhibitor, FDP, fibrinogen degradation product.

Table 1.

Common clinical conditions associated with disseminated intravascular coagulation in critically ill pediatric patients

Clinical conditions
Infectious diseases
Sepsis
Oncologic disorders
Leukemia
Solid tumors
Vascular disorders
Giant hemangioma (Kasabach-Merritt syndrome)
Vascular aneurysm
Microangiopathic hemolytic anemia
Immunologic disorders
Severe allergic reaction
Hemolytic transfusion reaction
Transplant rejection
Reactions to toxins
Severe trauma
Burns
Anaphylaxis
Acute pancreatitis

Table 2.

Comparison of various DIC scoring systems

Parameter	Score	ISTH overt	JAAM	JMHW	KSTH	SIC
Platelets (×10³/µL)	0	>100	≥120	≥120	>100	>150
	1	≥50 to ≤100	≥80 to <120 or 30% decrease within 24 hr	≥80 to <120	≤100	≥100 to ≤150
	2	<50		>50 to <80		<100
	3		<80 or 50% decrease within 24 hr	≤50
PT (sec)	0	<3	<1.2 (PT ratio)	<1.25 (PT ratio)	<3	<1.2
	1	≥3 to <6		≥1.25 to <1.67	≥3 (or aPTT ≥5 sec)	≥1.2 to ≤ 1.4
	2	≥6		≥1.67		>1.4
	3		≥1.2
Fibrin-related marker (mg/L)	0	D-dimer <1.0	FDP <10	FDP <10	D-dimer <1.0
	1		≥10 to <25	≥10 to <20	≥1.0
	2	≥1 to ≤ 5		≥20 to <40
	3	>5	≥25	≥40
Fibrinogen (g/L)	0	>1.0	>3.5	>1.5	>1.5
	1	≤1.0	≤3.5	>1.0 to <1.5	≤1.5
	2			≤1.0
SIRS score	0		0–2
	1		≥3
SOFA score	0
	1					1
	2					≥2
Underlying disease			Present	Present
Bleeding				Present
Organ failure				Present
Overt DIC		≥5	≥5	≥7	≥3	≥4

DIC, disseminated intravascular coagulation; ISTH, International Society on Thrombosis and Haemostasis; JAAM, Japanese Association for Acute Medicine; JMHW, Japanese Ministry of Health and Welfare; KSTH, Korean Society on Thrombosis and Hemostasis; SIC, sepsis-induced coagulopathy; PT, prothrombin time; aPTT, activated partial thromboplastic time; FDP, fibrin/fibrinogen degradation product; SIRS, systemic inflammatory response syndrome; SOFA, Sequential Organ Failure Assessment.

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