***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Patients with fulminant hepatic failure have severe circulatory disturbances which may be due to fibrin and cellular plugs in micro-vessels which are a consequence of intravascular coagulation and which can lead to multiorgan failure . Since antithrombin III supplementation has been shown to be beneficial in animal models of septic shock with disseminated intravascular coagulation , a controlled study was performed to investigate the effect of antithrombin III supplementation in fulminant hepatic failure .  Twenty-five patients in grade III or IV coma were selected on the basis of evidence of sepsis , intravascular coagulation and a high risk of developing multiorgan failure . Thirteen patients received 3000 units of antithrombin III ( Kybernin P ; Behringwerke ) , followed by a further 1000 units every 6 h.  Antithrombin III activity increased from 0.26 + /- 0.04 SE U/ml to 0.82 + /- 0.07 U/ml at 3 h post infusion ( normal range 0.80 - 1.20 U/ml ) and remained greater than 0.80 U/ml throughout the study without any apparent increase in the frequency of bleeding . However , survival was not improved and markers of intravascular coagulation remained similar between the two groups . Thus , although the antithrombin III deficiency in fulminant hepatic failure can be corrected by supplementation with antithrombin III concentrate , its use in the prevention of intravascular coagulation and to avoid microvessel plugging needs to be studied at an earlier stage in the disease Introduction Treatment of sepsis is aim ed at increasing both the duration and quality of survival . A long-term focus on quality of life ( QoL ) in clinical trial evaluations of sepsis care should be a priority . Method QoL data were used to evaluate the effects of intravenous antithrombin III treatment for severe sepsis measured for up to 90 days during the follow-up phase of the KyberSept phase III clinical trial . A visual analog scale and a Karnofsky scale were used to measure physical , psychologic , and social QoL at regular intervals . Changes from baseline between placebo and antithrombin III groups were assessed using  Wilcoxon statistical tests  , with additional analyses by severity of illness and admitting diagnosis . Results Among all sepsis survivors in the trial , there was a significant advantage on some attributes of QoL in the antithrombin III subgroup of patients who did not receive heparin as compared with the corresponding placebo group . Discussion The present study represents the first attempt to evaluate patient QoL over a relatively long period in a large , r and omized , placebo-controlled sepsis trial . Over a 90-day period , survivors of severe sepsis receiving antithrombin III experienced significant improvements as compared with placebo on several attributes of QoL. In conclusion , the present study demonstrated that clinical improvements over an extended time period with antithrombin III were complemented by improvements in QoL , particularly in social and psychologic functioning , in many patients BACKGROUND ATIII is decreased in sepsis and /or shock and its baseline value correlates with mortality . The efficacy of ATIII therapy on mortality was assessed in a selected group of patients admitted to the intensive care unit ( ICU ) in a double-blind , r and omized , multicenter study . METHODS 120 patients admitted to the ICU with an ATIII concentration < 70 % were r and omized to receive ATIII ( total dose 24000 units ) or placebo treatment for 5 days ; 56 patients had septic shock . RESULTS ATIII concentrations in the treated group remained constant throughout the treatment period ( range 97 - 102 % ) . The Kaplan-Meier analysis showed no difference in overall survival between the two groups : 50 and 46 % for ATIII and placebo , respectively . Septic shock and hemodynamic support were unbalanced in the two groups at admission . Therefore the Cox analysis was carried out after adjusting for these two variables . Treatment with ATIII decreases the risk of death with an odds ratio ( OR ) of 0.56 . Of the covariates analyzed , septic shock and the baseline multiple organ failure score were negatively associated with survival and plasma activity level was positively associated with survival with an OR of 0.97 for each 1 % increase in the ATIII plasma concentration at baseline . CONCLUSIONS The results of ATIII treatment in this population of patients suggests that replacement therapy reduces mortality in the subgroup of septic shock patients only A double-blind , r and omized , placebo-controlled trial was conducted to evaluate whether treatment with Antithrombin ( AT ) concentrates improved the clinical and perinatal outcome in patients with severe preeclampsia . Severe preeclamptic patients ( 24 to 35 weeks of gestation . Gestosis Index ( GI ) > or = 6 points ) were r and omized into two groups : 66 received AT and 67 received placebo . There were no statistical differences in the clinical profiles of the two groups . Study drugs were given intravenously once daily for 7 consecutive days . Maternal symptoms were evaluated from the difference of GI between before and after treatment , and fetal findings were evaluated from the changes of the biophysical profile score and the estimated fetal weight gain . Improvement was significantly greater in the AT group for both the GI ( p = 0.020 ) and the estimated fetal weight gain ( p = 0.029 ) . The improvement of coagulation parameters was also evaluated . The D-dimer levels increased significantly in the placebo group ( p = 0.026 ) , but did not change in the AT group . Gestation was significantly prolonged ( p = 0.007 ) , and the number of low-birth weight infants was significantly smaller ( p = 0.011 ) in the AT group . No adverse events related to AT were observed . It is revealed that AT concentrate therapy for preeclampsia is effective and safe , leading to an improved perinatal outcome Objective To determine the incidence , cost , and outcome of severe sepsis in the United States . Design Observational cohort study . Setting All nonfederal hospitals ( n = 847 ) in seven U.S. states . Patients All patients ( n = 192,980 ) meeting criteria for severe sepsis based on the International Classification of Diseases , Ninth Revision , Clinical Modification . Interventions None . Measurements and Main Results We linked all 1995 state hospital discharge records ( n = 6,621,559 ) from seven large states with population and hospital data from the U.S. Census , the Centers for Disease Control , the Health Care Financing Administration , and the American Hospital Association . We defined severe sepsis as documented infection and acute organ dysfunction using criteria based on the International Classification of Diseases , Ninth Revision , Clinical Modification . We vali date d these criteria against prospect i ve clinical and physiologic criteria in a subset of five hospitals . We generated national age- and gender-adjusted estimates of incidence , cost , and outcome . We identified 192,980 cases , yielding national estimates of 751,000 cases ( 3.0 cases per 1,000 population and 2.26 cases per 100 hospital discharges ) , of whom 383,000 ( 51.1 % ) received intensive care and an additional 130,000 ( 17.3 % ) were ventilated in an intermediate care unit or cared for in a coronary care unit . Incidence increased > 100-fold with age ( 0.2/1,000 in children to 26.2/1,000 in those > 85 yrs old ) . Mortality was 28.6 % , or 215,000 deaths nationally , and also increased with age , from 10 % in children to 38.4 % in those > 85 yrs old . Women had lower  age-specific incidence and mortality , but the difference in mortality was explained by differences in underlying disease and the site of infection . The average costs per case were $ 22,100 , with annual total costs of $ 16.7 billion nationally . Costs were higher in infants , nonsurvivors , intensive care unit patients , surgical patients , and patients with more organ failure . The incidence was projected to increase by 1.5 % per annum . Conclusions Severe sepsis is a common , expensive , and frequently fatal condition , with as many deaths annually as those from acute myocardial infa rct ion . It is especially common in the elderly and is likely to increase substantially as the U.S. population ages Activation of thrombin and of the coagulation system plays an important role in the pathophysiology of sepsis-associated organ dysfunction . Antithrombin III ( AT III ) is a natural inhibitor of thrombin , a central procoagulatory factor with pleiotropic activities . Experimental supplementation of AT III improved coagulation parameters and ameliorated organ dysfunction . To determine whether long-term AT III supplementation has beneficial effects on organ function , we conducted a r and omized , prospect i ve study in surgical patients with severe sepsis . The study evaluated the long-term effect of AT III supplementation ( duration of treatment : 14 days ) . After r and omization ( AT III vs. control group ) , AT III was infused continuously over 14 days to obtain plasma AT III activities > 120 % . Forty consecutive patients were recruited ( 20 AT III/20 control group ) . Eleven patients had a rapid fatal course and did not met the criterion of a 14 day treatment period . From these 11 patients , 8 patients ( 5 AT III/3 control group )  died within 72 h due to septic shock . The remaining 14 AT III patients and 15 controls survived 14 days and showed no differences in baseline parameters of organ function .  AT III caused a disappearance of disseminated intravascular coagulation ( DIC ) in all patients with DIC , whereas in control patients , the frequency of DIC remained constant ( p < .05 ) . In AT III patients a progressive increase in oxygenation index ( Pao2/Fio2 ratio ) and a continuous decrease in pulmonary hypertension index ( mean pulmonary artery pressure/mean arterial pressure ( PAP/MAP ) ratio ) indicated an improvement of lung function ( p < .05 vs. control ) . AT III prevented the continuous rise in total serum bilirubin concentration observed in control patients and diminished the frequency of artificial renal support therapy ( p < .05 ) . Long-term supplementation with AT III may improve lung function and prevent the development of septic liver and kidney failure in patients with severe sepsis This study will determine if early administration of antithrombin concentrate to patients with traumatic brain injury ( TBI ) can inhibit or significantly shorten the time of coagulopathy . The progress of brain injury monitored by computed tomographic scan ( CT ) was also assessed , as was the time needed for intensive care and outcome related to Glasgow outcome scale ( GOS ) . Twenty-eight patients with isolated brain trauma verified with CT were included in either of two parallel groups . The Glasgow coma score ( GCS ) was mean 7.5 , and median 7.0 ; signifying a moderate to severe traumatic brain injury but with a mortality of only 3.5 % . The patients r and omized to antithrombin treatment  received a total of 100 U/kg BW during 24 hours . To measure hypercoagulability , soluble fibrin ( SF ) , D-dimer ( D-d ) , and thrombin-antithrombin complex ( TAT ) were assessed together with antithrombin ( AT ) and routine coagulation tests . Before treatment , SF , D-d , and TAT were markedly increased in both groups . Soluble fibrin and D-dimer ( measured after treatment began ) appeared to decrease faster in the AT group , and there was a statistically significant difference between the groups at 36 hours for SF and at 36 hours , 48 hours , and at Day 3 for D-d . Thrombin-antithrombin complex levels were very high in both groups but , surprisingly , showed no significant difference between the groups . The authors conclude that antithrombin concentrate administered to patients with severe TBI result ed in a marginal reduction of hypercoagulation . We could not detect any obvious influence by antithrombin on brain injury progress , on CT , or on outcome or time needed for intensive care A prospect i ve , r and omized , controlled trial to examine the effects of antithrombin supplementation on mortality , coagulation and renal function has been carried out on 132 intensive care patients .  Antithrombin activity was measured in all patients on admission to the intensive care unit ( ICU ) . Patients with an antithrombin activity of less than 70 % were r and omized to either receive antithrombin replacement or to act as controls . Antithrombin activity was maintained above 70 % in the treated patients throughout their stay on ICU . Ninety-three patients had an antithrombin activity of less than 70 % and 35 received replacement therapy . Patients with antithrombin activity below 70 % remained on the ICU significantly longer and had a significantly higher mortality rate than patients with antithrombin activity above 70 % . Antithrombin supplementation neither reduced mortality nor shortened the intensive care stay . Fifty patients with reduced antithrombin activity remained on the ICU for at least 4 days , 25 received antithrombin and 25 acted as controls ; coagulation parameters and renal function have been monitored in these patients . Fibrinogen concentration and platelet count were unaffected by antithrombin replacement . Antithrombin supplementation did not appear to reduce the incidence of impaired renal function in sepsis , trauma and postoperative patients . The creatinine clearance fell below 20 ml/min in eight patients in the no-treatment arm while by comparison only three patients in the treatment arm developed impaired renal function . Our study does not demonstrate a clear role for the use of antithrombin supplementation in intensive care , however the finding that antithrombin reduced renal impairment is encouraging and a larger study to confirm this finding is at present underway CONTEXT Activation of the coag 
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Conclusions There is insufficient evidence to support AT III substitution in any category of critically ill participants including those with sepsis and DIC .
AT III did not show an impact on mortality , but increased the risk of bleeding