[Therapeutic modulation of coagulation in sepsis].
Based on the increasing knowledge of defects in haemostasis in patients with sepsis as well as on the non-conclusive results of studies which tried to increase the prognosis by modulating cytokine response of the patients, in the last years the impact of therapeutic modulation of coagulation in sepsis has been investigated. In contrast to the results of phase III studies with the coagulation inhibitors antithrombin and tissue factor pathway inhibitor recombinant human activated protein C (rhAPC) resulted in a significant reduction in mortality for the whole study population. Data analyses showed, that treatment with rhAPC was clinically beneficial especially in patient groups who showed a high mortality in the placebo arm. Inhibition of thrombus formation due to the therapy with natural coagulation inhibitors resulted in an increase of sepsis-imminent haemorrhage, which became significant in some studies. Treatment with antithrombin and heparin resulted in a considerable increase in bleeding complications and on the other hand, may have antagonized the expected effect of antithrombin on the patient's prognosis. Some results suggesting beneficial effects of heparin on patient prognosis in the placebo arms and on the other hand negative effects of heparin in the verum arms -- especially with antithrombin or tissue factor pathway inhibitor -- let to a controversial discussion of the risk/benefit relation of heparin, given in prophylactic doses to patients with severe sepsis. Whereas the impact and optimal application of heparin to patients with severe sepsis needs to be clarified study results with rhAPC resulted in the approval of this therapy and the implementation in the guidelines of the treatment of patients with severe sepsis.
Loew
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A
Charité Campus Virchow-Klinikum, Medizinische Klinik und Poliklinik, Augustenburger Platz 1, 13353 Berlin.
Riess
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H
D000925:Anticoagulants / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects; D001778:Blood Coagulation Disorders / Q000209:etiology / Q000628:therapy*; D006801:Humans; D018046:Protein C Inhibitor / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D018805:Sepsis / Q000150:complications*
D000925:Anticoagulants; D018046:Protein C Inhibitor; D011994:Recombinant Proteins