Metabolic Modulation of Inflammation-Induced Activation of Coagulation

ABSTRACT

The bidirectional interaction between coagulation and inflammation, which is relevant in various disease states that are dominated by systemic inflammatory responses, such as severe infection or chronic vascular disease, is modulated by metabolic factors. Changes in lipoprotein metabolism affect the inflammation-induced activation of coagulation, which may have impact on downstream effects, including organ dysfunction and survival. Likewise, glucose and insulin seem to influence inflammation-induced effects on coagulation and fibrinolysis. Hyperglycemia affects inflammation-induced and tissue factor-driven activation of coagulation, whereas hyperinsulinemia modulates the fibrinolytic response. There are indications that this modulatory role of metabolic factors in inflammation and coagulation may also have an impact on clinical outcome in various disease states.

Coagulation - fibrinolysis - inflammation - cytokines - lipoproteins - cholesterol - triglycerides - glucose - insulin

REFERENCES

• 1 Levi M, van der Poll T, Buller H R. Bidirectional relation between inflammation and coagulation.  Circulation. 2004;  109 2698-2704
• 2 Levi M, Opal S M. Coagulation abnormalities in critically ill patients.  Crit Care. 2006;  10 222-232
• 3 Levi M. Disseminated intravascular coagulation.  Crit Care Med. 2007;  35 2191-2195
• 4 Levi M, ten Cate H. Disseminated intravascular coagulation.  N Engl J Med. 1999;  341 586-592
• 5 Shimamura K, Oka K, Nakazawa M, Kojima M. Distribution patterns of microthrombi in disseminated intravascular coagulation.  Arch Pathol Lab Med. 1983;  107 543-547
• 6 Levi M, Schultz M J, Rijneveld A W, van der Poll T. Bronchoalveolar coagulation and fibrinolysis in endotoxemia and pneumonia.  Crit Care Med. 2003;  31 S238-S242
• 7 Kessler C M, Tang Z, Jacobs H M, Szymanski L M. The suprapharmacologic dosing of antithrombin concentrate for Staphylococcus aureus-induced disseminated intravascular coagulation in guinea pigs: substantial reduction in mortality and morbidity.  Blood. 1997;  89 4393-4401
• 8 Taylor F BJ, Chang A, Ruf W et al.. Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody.  Circ Shock. 1991;  33 127-134
• 9 Welty-Wolf K E, Carraway M S, Miller D L et al.. Coagulation blockade prevents sepsis-induced respiratory and renal failure in baboons.  Am J Respir Crit Care Med. 2001;  164 1988-1996
• 10 Miller D L, Welty-Wolf K, Carraway M S et al.. Extrinsic coagulation blockade attenuates lung injury and proinflammatory cytokine release after intratracheal lipopolysaccharide.  Am J Respir Cell Mol Biol. 2002;  26 650-658
• 11 Dhainaut J F, Yan S B, Joyce D E et al.. Treatment effects of drotrecogin alfa (activated) in patients with severe sepsis with or without overt disseminated intravascular coagulation.  J Thromb Haemost. 2004;  2 1924-1933
• 12 Bakhtiari K, Meijers J C, de Jonge E, Levi M. Prospective validation of the international society of thrombosis and maemostasis scoring system for disseminated intravascular coagulation.  Crit Care Med. 2004;  32 2416-2421
• 13 Gando S. Tissue factor in trauma and organ dysfunction.  Semin Thromb Hemost. 2006;  32 48-53
• 14 Levi M, van der Poll T, ten Cate H. Tissue factor in infection and severe inflammation.  Semin Thromb Hemost. 2006;  32 33-39
• 15 Laterre P F, Wittebole X, Collienne C. Pharmacological inhibition of tissue factor.  Semin Thromb Hemost. 2006;  32 71-76
• 16 Osterud B, Bjorklid E. Sources of tissue factor.  Semin Thromb Hemost. 2006;  32 11-23
• 17 Levi M, de Jonge E, van der Poll T. Rationale for restoration of physiological anticoagulant pathways in patients with sepsis and disseminated intravascular coagulation.  Crit Care Med. 2001;  29 S90-S94
• 18 Esmon C T. Role of coagulation inhibitors in inflammation.  Thromb Haemost. 2001;  86 51-56
• 19 Levi M. The imbalance between tissue factor and tissue factor pathway inhibitor in sepsis.  Crit Care Med. 2002;  30 1914-1915
• 20 Levi M, van der Poll T, ten Cate H, van Deventer S J. The cytokine-mediated imbalance between coagulant and anticoagulant mechanisms in sepsis and endotoxaemia.  Eur J Clin Invest. 1997;  27 3-9
• 21 Levels J H, Pajkrt D, Schultz M et al.. Alterations in lipoprotein homeostasis during human experimental endotoxemia and clinical sepsis.  Biochim Biophys Acta. 2007;  1771 1429-1438
• 22 Feingold K R, Staprans I, Memon R A et al.. Endotoxin rapidly induces changes in lipid metabolism that produce hypertriglyceridemia: low doses stimulate hepatic triglyceride production while high doses inhibit clearance.  J Lipid Res. 1992;  33 1765-1776
• 23 Hudgins L C, Parker T S, Levine D M et al.. A single intravenous dose of endotoxin rapidly alters serum lipoproteins and lipid transfer proteins in normal volunteers.  J Lipid Res. 2003;  44 1489-1498
• 24 van Leeuwen H J, Heezius E C, Dallinga G M et al.. Lipoprotein metabolism in patients with severe sepsis.  Crit Care Med. 2003;  31 1359-1366
• 25 Chien J Y, Jerng J S, Yu C J, Yang P C. Low serum level of high-density lipoprotein cholesterol is a poor prognostic factor for severe sepsis.  Crit Care Med. 2005;  33 1688-1693
• 26 Read T E, Grunfeld C, Kumwenda Z L et al.. Triglyceride-rich lipoproteins prevent septic death in rats.  J Exp Med. 1995;  182 267-272
• 27 Pajkrt D, Doran J E, Koster F et al.. Antiinflammatory effects of reconstituted high-density lipoprotein during human endotoxemia.  J Exp Med. 1996;  184 1601-1608
• 28 Kjalke M, Silveira A, Hamsten A, Hedner U, Ezban M. Plasma lipoproteins enhance tissue factor-independent factor VII activation.  Arterioscler Thromb Vasc Biol. 2000;  20 1835-1841
• 29 van der Poll T, Coyle S M, Levi M et al.. Fat emulsion infusion potentiates coagulation activation during human endotoxemia.  Thromb Haemost. 1996;  75 83-86
• 30 Pajkrt D, Lerch P G, van der Poll T et al.. Differential effects of reconstituted high-density lipoprotein on coagulation, fibrinolysis and platelet activation during human endotoxemia.  Thromb Haemost. 1997;  77 303-307
• 31 Buga G M, Frank J S, Mottino G A et al.. D-4F Reduces EO6 immunoreactivity, SREBP-1c mRNA levels, and renal inflammation in LDL receptor null mice fed a Western diet.  J Lipid Res. 2008;  49 192-205
• 32 Birjmohun R S, van Leuven S I, Levels J H et al.. High-density lipoprotein attenuates inflammation and coagulation response on endotoxin challenge in humans.  Arterioscler Thromb Vasc Biol. 2007;  27 1153-1158
• 33 Bisoendial R J, Kastelein J J, Peters S L et al.. Effects of CRP infusion on endothelial function and coagulation in normocholesterolemic and hypercholesterolemic subjects.  J Lipid Res. 2007;  48 952-960
• 34 Almog Y, Novack V, Eisinger M et al.. The effect of statin therapy on infection-related mortality in patients with atherosclerotic diseases.  Crit Care Med. 2007;  35 372-378
• 35 Drage S M, Barber V S, Young J D. Statins and sepsis: panacea or Pandora's box?.  Lancet Infect Dis. 2007;  7 80-81
• 36 Grant P J. Diabetes mellitus as a prothrombotic condition.  J Intern Med. 2007;  262 157-172
• 37 Meigs J B, Mittleman M A, Nathan D M et al.. Hyperinsulinemia, hyperglycemia, and impaired hemostasis: the Framingham Offspring Study.  JAMA. 2000;  283 221-228
• 38 Juhan-Vague I, Roul C, Alessi M C et al.. Increased plasminogen activator inhibitor activity in non insulin dependent diabetic patients-relationship with plasma insulin.  Thromb Haemost. 1989;  61 370-373
• 39 Mansfield M W, Stickland M H, Grant P J. PAI-1 concentrations in first-degree relatives of patients with non-insulin-dependent diabetes: metabolic and genetic associations.  Thromb Haemost. 1997;  77 357-361
• 40 Mansfield M W, Heywood D M, Grant P J. Circulating levels of factor VII, fibrinogen, and von Willebrand factor and features of insulin resistance in first-degree relatives of patients with NIDDM.  Circulation. 1996;  94 2171-2176
• 41 Alessi M C, Peiretti F, Morange P et al.. Production of plasminogen activator inhibitor 1 by human adipose tissue: possible link between visceral fat accumulation and vascular disease.  Diabetes. 1997;  46 860-867
• 42 Pinsky D J, Liao H, Lawson C A et al.. Coordinated induction of plasminogen activator inhibitor-1 (PAI-1) and inhibition of plasminogen activator gene expression by hypoxia promotes pulmonary vascular fibrin deposition.  J Clin Invest. 1998;  102 919-928
• 43 Folsom A R, Wu K K, Davis C E et al.. Population correlates of plasma fibrinogen and factor VII, putative cardiovascular risk factors.  Atherosclerosis. 1991;  91 191-205
• 44 Heywood D M, Mansfield M W, Grant P J. Factor VII gene polymorphisms, factor VII:C levels and features of insulin resistance in non-insulin-dependent diabetes mellitus.  Thromb Haemost. 1996;  75 401-406
• 45 Stegenga M E, van der Crabben S N, Levi M et al.. Hyperglycemia stimulates coagulation, whereas hyperinsulinemia impairs fibrinolysis in healthy humans.  Diabetes. 2006;  55 1807-1812
• 46 Rana J S, Nieuwdorp M, Jukema J W, Kastelein J J. Cardiovascular metabolic syndrome - an interplay of obesity, inflammation, diabetes and coronary heart disease.  Diabetes Obes Metab. 2007;  9 218-232
• 47 Ahmad R, Cherry R A, Lendel I et al.. Increased hospital morbidity among trauma patients with diabetes mellitus compared with age- and injury severity score-matched control subjects.  Arch Surg. 2007;  142 613-618
• 48 Kornum J B, Thomsen R W, Riis A et al.. Type 2 diabetes and pneumonia outcomes: a population-based cohort study.  Diabetes Care. 2007;  30 2251-2257
• 49 Levi M, Levy M, Williams M D et al.. Prophylactic heparin in patients with severe sepsis treated with drotrecogin alfa (activated).  Am J Respir Crit Care Med. 2007;  176 483-490
• 50 Singer G, Granger D N. Inflammatory responses underlying the microvascular dysfunction associated with obesity and insulin resistance.  Microcirculation. 2007;  14 375-387
• 51 Samad F, Pandey M, Loskutoff D J. Regulation of tissue factor gene expression in obesity.  Blood. 2001;  98 3353-3358
• 52 van den Berghe G, Wouters P, Weekers F et al.. Intensive insulin therapy in the critically ill patients.  N Engl J Med. 2001;  345 1359-1367