Disseminated intravascular coagulation: cause, molecular mechanism, diagnosis, and therapy

Abstract

Disseminated intravascular coagulation (DIC) is a complex and serious condition characterized by widespread activation of the coagulation cascade, resulting in both thrombosis and bleeding. This review aims to provide a comprehensive overview of DIC, emphasizing its clinical significance and the need for improved management strategies. We explore the primary causes of DIC, including sepsis, trauma, malignancies, and obstetric complications, which trigger an overactive coagulation response. At the molecular level, DIC is marked by excessive thrombin generation, leading to platelet and fibrinogen activation while simultaneously depleting clotting factors, creating a paradoxical bleeding tendency. Diagnosing DIC is challenging and relies on a combination of existing diagnostic criteria and laboratory tests. Treatment strategies focus on addressing the underlying causes and may involve supportive care, anticoagulation therapy, and other supportive measures. Recent advances in understanding the pathophysiology of DIC are paving the way for more targeted therapeutic approaches. This review highlights the critical need for ongoing research to enhance diagnostic accuracy and treatment efficacy, ultimately improving patient outcomes in those affected by DIC.

Keywords: coagulation; disseminated intravascular coagulation; fibrinolysis; sepsis; trauma.

FIGURE 1

Cell‐based model of coagulation. The cell‐based model of DIC emphasizes the role of cellular interactions in coagulation. Initiation occurs on TF‐bearing cells via the extrinsic pathway, leading to thrombin generation. This thrombin activates more coagulation factors and platelets, amplifying the response. The propagation phase, primarily on platelet surfaces, generates a large burst of thrombin necessary for fibrin clot formation, a key step in the coagulation process.

FIGURE 2

DIC course: imbalance of coagulative system, anticoagulant activity, and fibrinolysis system. Two phenotypes of DIC: thrombotic and fibrinolytic. The thrombotic phenotype includes coagulation activation, insufficient anticoagulation, and hypofibrinolysis, indicating a proclivity for clot formation. Conversely, the fibrinolytic phenotype is characterized by hyperfibrinolysis, which suggests an increased risk of bleeding due to excessive clot breakdown.

FIGURE 3

Crosstalk between inflammation and DIC. Schematic representation of the interplay between trauma, pathogen‐associated molecular patterns (PAMPs), damage‐associated molecular patterns (DAMPs), immune response, and coagulation pathways leading to thrombus formation. Trauma and pathogens trigger neutrophil activation, resulting in the release of NETs and monocyte activation. The activated monocytes express TF, further amplifying the coagulation cascade. Intracellular immune sensors, such as DAMP‐induced inflammasomes, also stimulate TF release through pyroptosis. Complement components C3a and C5a also contribute to platelet aggregation, which together with the coagulation cascade, leads to thrombus formation.

FIGURE 4

The causes and treatments of DIC. Treatment is divided into addressing the underlying condition and specific management for asymptomatic patients, thromboembolism, and bleeding, with recommendations for LMWH prophylaxis, antithrombin, platelet concentrates, and other supportive therapies based on clinical presentation.