Animal models of DIC and their relevance to human DIC: A systematic review

被引:28
|
作者
Berthelsen, Line Olrik [1 ]
Kristensen, Annemarie T. [2 ]
Tranholm, Mikael [1 ]
机构
[1] Novo Nordisk AS, Malov, Denmark
[2] Univ Copenhagen, Fac Life Sci, Dept Small Anim Clin Sci, DK-1168 Copenhagen, Denmark
关键词
Disseminated intravascular coagulation; Animal models; Scoring system; DISSEMINATED INTRAVASCULAR COAGULATION; FACTOR PATHWAY INHIBITOR; MOLECULAR-WEIGHT HEPARIN; ACTIVATED PROTEIN-C; HUMAN SOLUBLE THROMBOMODULIN; TISSUE-PLASMINOGEN-ACTIVATOR; TUMOR-NECROSIS-FACTOR; SYNTHETIC THROMBIN INHIBITOR; MULTIPLE ORGAN FAILURE; PULMONARY VASCULAR INJURY;
D O I
10.1016/j.thromres.2010.12.002
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:103 / 116
页数:14
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