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Animal models of DIC and their relevance to human DIC: a systematic review
Line Olrik Berthelsen1, Annemarie T Kristensen, Mikael Tranholm
1Novo Nordisk A/S, Måløv, Denmark. lineberthelsen@yahoo.dk
Insights
Standardizing animal models for disseminated intravascular coagulation (DIC) is crucial. Current models lack consistency, hindering research translation, but implementing scoring systems can improve comparability and treatment efficacy.
Area of Science:
- Hematology
- Translational Medicine
- Preclinical Research
Background:
- Disseminated intravascular coagulation (DIC) is a critical condition marked by widespread coagulation and fibrinolysis.
- Diagnosis relies on the International Society of Thrombosis and Haemostasis (ISTH) scoring system.
- Existing animal models for DIC lack standardization, impeding research comparability and clinical translation.
Purpose of the Study:
- To review and analyze existing animal models of DIC.
- To assess the standardization of diagnostic approaches and treatment administration in these models.
- To identify strategies for improving the translational relevance of DIC research.
Main Methods:
- Systematic review of animal models used for DIC research.
- Analysis of species, inducers, dosing regimens, and diagnostic parameters.
- Comparison of diagnostic methods with the ISTH DIC score criteria.
- Summary of therapeutic interventions tested in animal models.
Main Results:
- Rats are the most common species, and lipopolysaccharides (LPS) the most frequent inducer.
- Only approximately 25% of studies report all four ISTH DIC score parameters.
- Most treatments are administered prophylactically, not therapeutically, limiting clinical relevance.
Conclusions:
- Standardizing animal models through consistent scoring systems is essential for DIC research.
- Improved model standardization will enhance inter-model comparability.
- Adopting more clinically relevant treatment paradigms in animal models is necessary for successful therapeutic translation.
Abstract:
Disseminated intravascular coagulation (DIC) is a severe clinical condition with activation of coagulation and fibrinolysis. Its diagnosis is based on the International Society of Thrombosis and Haemostasis (ISTH) scoring system of DIC. Animal models of DIC, used to investigate pathophysiology and evaluate treatments, have not been developed in a standardized way, which impedes comparison between models and translation to the human setting. In the current review of animal models of DIC an overview of species, inducers, and dosing regimens is provided. Diagnostic approaches are compared in the light of the ISTH score and treatments tested in animal models of DIC are summarized. Systematic analysis revealed that the rat is by far the preferred species amongst animal models of DIC and lipopolysaccharides (LPS) the preferred inducer of DIC. An overview of the reporting of ISTH DIC score parameters elucidated that only about 25% of the studies measure all of the four parameters necessary for the implementation the ISTH scoring system. Furthermore, most therapeutic interventions tested in animal models of DIC are administered prophylactically, which may be irrelevant to the clinical setting and could explain why compounds effective in preclinical animal models often fail in clinical trials. It is concluded that Implementation of a scoring system in animal models of DIC may increase the ability to compare DIC amongst animal models and improve the translational aspect of treatment effect.