Modulators of coagulation. A critical appraisal of their role in sepsis

R. C. Bone
Department of Internal Medicine, Rush-Presbyterian-St Luke's Medical Center, Chicago, Ill 60612.

Widespread intravascular coagulation is common in patients with sepsis. Coagulation abnormalities may result from exposure to endotoxin, from tumor necrosis factor alpha or interleukin 1 release, or from the actions of a more specific mediator, such as vascular permeability factor. The result is marked activation of the contact and coagulation systems; simultaneously, there is decreased fibrinolysis and depressed levels of the inhibitors of the contact and coagulation systems. Multiple agents are being studied to correct these abnormalities. Antithrombin III holds promise because it inhibits a number of factors important in contact and coagulation activation, not just thrombin. Plasminogen activators may prove helpful in increasing fibrinolysis during sepsis; because they have been associated with rebound thrombin generation, however, plasminogen activators may be most effective if used in conjunction with hirudin or a synthetic hirudin analogue. Bradykinin may offset hypotension in sepsis. Protein C may inhibit thrombin formation and also complex with plasminogen activator inhibitor 1, thereby promoting fibrinolysis. Other agents that may prove effective include alpha 1-antitrypsin Pittsburgh, C1-esterase inhibitor, monoclonal antibodies to contact factors, soybean trypsin inhibitors, thrombomodulin, prostaglandin I2, and aprotinin. There are no data to support the use of heparin or fibronectin, except in limited circumstances.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

The Coagulation System Contributes to Synergistic Liver Injury from Exposure to Monocrotaline and Bacterial Lipopolysaccharide
Yee et al.
Toxicol Sci 2003;74:457-469.
ABSTRACT | FULL TEXT  

Low Levels of Protein C Are Associated With Poor Outcome in Severe Sepsis
Yan et al.
Chest 2001;120:915-922.
ABSTRACT | FULL TEXT  

Tumor Necrosis Factor-Dependent Adhesions as a Major Protective Mechanism Early in Septic Peritonitis in Mice
Echtenacher et al.
Infect. Immun. 2001;69:3550-3555.
ABSTRACT | FULL TEXT  

Antithrombin reduces leukocyte adhesion during chronic endotoxemia by modulation of the cyclooxygenase pathway
Hoffmann et al.
Am. J. Physiol. Cell Physiol. 2000;279:C98-C107.
ABSTRACT | FULL TEXT  

Consequences of Interaction of a Lipophilic Endotoxin Antagonist with Plasma Lipoproteins
Rose et al.
Antimicrob. Agents Chemother. 2000;44:504-510.
ABSTRACT | FULL TEXT  

Lepirudin blunts endotoxin-induced coagulation activation
Pernerstorfer et al.
Blood 2000;95:1729-1734.
ABSTRACT | FULL TEXT  

Disseminated Intravascular Coagulation
Levi and ten Cate
NEJM 1999;341:586-592.
FULL TEXT  

Effect of urokinase on disseminated intravascular coagulation
Vasquez et al.
J. Appl. Physiol. 1998;85:1421-1428.
ABSTRACT | FULL TEXT  

Potential Mechanisms for a Proinflammatory Vascular Cytokine Response to Coagulation Activation
Johnson et al.
J. Immunol. 1998;160:5130-5135.
ABSTRACT | FULL TEXT  

Potent and Selective Kunitz Domain Inhibitors of Plasma Kallikrein Designed by Phage Display
Dennis et al.
J. Biol. Chem. 1995;270:25411-25417.
ABSTRACT | FULL TEXT