Sepsis, Coagulation and Anticoagulants

Department of Anesthesiology, Pain and Critical Care - Federal University of Sao Paulo, Sao Paulo, SP, Brazil.
Endocrine, metabolic & immune disorders drug targets 09/2010; 10(3):204-13. DOI: 10.2174/187153010791936892
Source: PubMed


Sepsis is one of the major health problems all over the word. Its pathophysiological mechanisms are not completely understood, but coagulation alterations are a hallmark of this syndrome. There is a clear exacerbation of coagulation and a suppression of control mechanisms of this process, including a reduction in fibrinolysis with consequent impairment of fibrin removal. The leading cause of these alterations is the proinflammatory state of those patients, characterized by high cytokine levels, increase in adhesion molecules expression, endothelial and platelets activation, release of microparticles and other related phenomena. Moreover, coagulation and inflammation are linked in a variety of pathways with mutual activation that ultimately contributes for its maintenance. The components of this process will be herein discussed as well as therapeutical alternatives that have excessive coagulation as a target.

1 Follower
41 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Sepsis, the systemic inflammatory response to infection, represents the major cause of death in critically ill veterinary patients. Whereas important advances in our understanding of the pathophysiology of this syndrome have been made, much remains to be elucidated. There is general agreement on the key interaction between pathogen-associated molecular patterns and cells of the innate immune system, and the amplification of the host response generated by pro-inflammatory cytokines. More recently, the concept of immunoparalysis in sepsis has also been advanced, together with an increasing recognition of the interplay between regulatory T cells and the innate immune response. However, the heterogeneous nature of this syndrome and the difficulty of modeling it in vitro or in vivo has both frustrated the advancement of new therapies and emphasized the continuing importance of patient-based clinical research in this area of human and veterinary medicine.
    Journal of Veterinary Internal Medicine 03/2012; 26(3):457-82. DOI:10.1111/j.1939-1676.2012.00905.x · 1.88 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The coagulation system is considered part of the defense machinery, but its excessive activation can lead to additional damage. We studied the effects of oral administration of Lactobacillus casei CRL 431--a probiotic bacterium--on the activation of coagulation and the relationship with inflammatory parameters during a respiratory infection in malnourished mice. Malnourished Swiss albino mice were nourished with a balanced commercial diet (BCD) for 7 days or BCD with L. casei for the last 2 days (BCD + Lc). BCD, BCD + Lc, malnourished (MNC) and well-nourished controls (WNC) were infected with Streptococcus pneumoniae. Blood and bronchoalveolar lavage samples were obtained at different times post-infection. Malnutrition altered most of the evaluated parameters before and after infection. The repletion diet with supplemental L. casei was the most effective in limiting coagulation activation and normalizing coagulation inhibition mechanisms. These findings will help develop further strategies to reduce the damaging effects of clotting and enhance its beneficial contribution to immune reactions.
    Agents and Actions 04/2012; 61(7):775-85. DOI:10.1007/s00011-012-0472-4 · 2.35 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pediatric septic shock continues to be an important public health problem. Several investigative groups have applied genetic and genomic approaches as a means of identifying novel pathways and therapeutic targets, discovery of sepsis-related biomarkers, and identification of septic shock subclasses. This review will highlight studies in pediatric sepsis with a focus on gene association studies and genome-wide expression profiling. A summary of published literature involving gene association and expression profiling studies specifically involving pediatric sepsis and septic shock. Several polymorphisms of genes broadly involved in inflammation, immunity, and coagulation have been linked with susceptibility to sepsis, or outcome of sepsis in children. Many of these studies involve meningococcemia, and the strongest association involves a functional polymorphism of the plasminogen activator inhibitor-1 promoter region and meningococcal sepsis. Expression profiling studies in pediatric septic shock have identified zinc supplementation and inhibition of matrix metalloproteinase-8 activity as potential, novel therapeutic approaches in sepsis. Studies focused on discovery of sepsis-related biomarkers have identified interleukin-8 as a robust outcome biomarker in pediatric septic shock. Additional studies have demonstrated the feasibility and clinical relevance of gene expression-based subclassification of pediatric septic shock. Pediatric sepsis and septic shock are increasingly being studied by genetic and genomic approaches and the accumulating data hold the promise of enhancing our future approach to this ongoing clinical problem.
    Critical care medicine 05/2012; 40(5):1618-26. DOI:10.1097/CCM.0b013e318246b546 · 6.31 Impact Factor
Show more