The role of heparin and allied compounds in the treatment of sepsis.
The crosstalk between coagulation and inflammation and the propensity for microthromboembolic disease during sepsis calls for anticoagulant measures to prevent tissue hypoxygenation and to attenuate organ damage and dysfunction. Only one anticoagulant, recombinant human activated protein C (aPC, drotrecogin-alpha) has a proven survival benefit when used as an adjunctive therapy for human sepsis, partly because of its anti-inflammatory effect. However, heparin (-like compounds) may exert similar beneficial anti-inflammatory actions as aPC, in spite of the relatively narrow therapeutic window for anticoagulation. This narrative review is based on a Medline search of relevant basic and clinical studies published in English and discusses the potential role of heparin in modulating inflammatory responses in the treatment of animal models and human sepsis and its harmful sequelae. In any case, the results of a meta-analysis based on animal data suggest a potentially life-saving effect of heparin (-like compounds) in the treatment of sepsis. Therefore, a prospective randomized clinical trial is called upon to study effects in human sepsis.
Cornet
Alexander D
AD
Department of Intensive Care, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
Smit
Ellen G M
EG
Beishuizen
Albertus
A
Groeneveld
A B Johan
AB
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects*; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000382:microbiology / Q000517:prevention & control*; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D011486:Protein C / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D018805:Sepsis / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D000925:Anticoagulants; D011486:Protein C; D011994:Recombinant Proteins; D006493:Heparin; C421124:drotrecogin alfa activated