Reduction of D-dimer levels after therapeutic administration of antithrombin in acquired antithrombin deficiency of severe sepsis

Eight consecutive critically ill medical patients presenting with acute disseminated intravascular coagulation associated with severe sepsis/septic shock received a single bolus infusion of AT over 30 minutes, aiming to achieve physiological AT levels. Haemostatic parameters including D-dimer were assessed prior to, 6 and 24 h after AT administration. An average of 42 ± 9 U/kg body weight was infused.Following AT substitution, elevated levels of D-dimer fell whereas AT levels rose.These observations support the notion that AT can favourably affect fibrin degradation accompanying disseminated intravascular coagulation of severe sepsis.Disseminated intravascular coagulation (DIC) is a systemic process potentially producing both thrombosis and hemorrhage. DIC is characterized by elevated levels of fibrin-related degradation products, prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) as well as reduced levels of endogenous inhibitors of coagulation, such as protein C and antithrombin (AT). In the setting of severe sepsis, persistent high levels of fibrin(ogen) degradation represent a poor prognostic sign in patients with acute DIC [1]. On the other hand, marked reduction of AT levels at the onset of septic shock may be a sensitive marker of unfavorable prognosis, presumably by permitting persistence of the procoagulant state. Smaller phase I and II clinical studies recently demonstrated improvements in coagulation parameters after AT substitution (such as increased prothrombin activity as well as fibrinogen concentration), mediator levels and organ function [2]. A meta-analysis of randomized controlled trials showed significantly better survival rate with AT substitution [3].To assure the effectiveness of AT in the treatment of patients with severe sepsis, the KYBERSept study, a multicenter, double-blind, placebo-controlled trial, was conducted, although it failed to provide definite and conclusive data on this issue [4]. Considering exten