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Antithrombin, heparin, and heparan sulfate
Steven M Opal1, Craig M Kessler, Juergen Roemisch
1Infectious Disease Division, Brown Medical School, Providence, RI 02860, USA. Steven_Opal@brown.edu
Critical Care Medicine
|May 11, 2002
Summary
Antithrombin (AT) has anticoagulant and anti-inflammatory effects, interacting with heparin and cell surfaces. Its role in sepsis is complex, with potential benefits observed when heparin is not co-administered.
Area of Science:
- Biochemistry
- Immunology
- Pharmacology
Background:
- Antithrombin is the primary endogenous anticoagulant in human plasma.
- It regulates clotting in physiological and pathological conditions, including sepsis.
- Reduced antithrombin activity in sepsis exacerbates procoagulant states and immune responses.
Purpose of the Study:
- To review evidence on antithrombin's anticoagulant and anti-inflammatory mechanisms.
- To examine antithrombin's interactions with heparin and proteoglycans.
- To explore antithrombin's role and therapeutic potential in sepsis.
Main Methods:
- Literature review of antithrombin research over the past 25 years.
- Analysis of experimental and clinical data.
- Examination of molecular interactions and cellular effects.
Main Results:
- Antithrombin binds to specific oligosaccharides on heparin and proteoglycans.
- It modulates neutrophil, monocyte, and endothelial cell functions.
- Antithrombin exhibits both prostacyclin-dependent and independent anti-inflammatory actions.
- Heparin can interfere with antithrombin's anti-inflammatory properties.
- Clinical trials suggest benefits of high-dose antithrombin in sepsis, particularly without concurrent heparin.
Conclusions:
- Antithrombin's interactions with coagulation and inflammation in sepsis are intricate.
- Further research is needed to clarify the therapeutic implications of antithrombin and heparin in critically ill patients.