***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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    ***EXAMPLES*** 
    Input: The present study aim ed to investigate whether low-dose heparin improves the condition of patients suffering from early disseminated intravascular coagulation ( pre-DIC ) during sepsis . In total , 37 patients were r and omly divided into low-dose heparin intervention and control groups . The heparin group received a low-dose of heparin for 5–7 days , while the other group received only saline . The two groups were treated for sepsis . Blood sample s were collected at various times and acute physiology and chronic health evaluation (APACHE)-II scores were recorded at day 1 and 7 . In addition , the number of days applying mechanical ventilation and in the intensive care unit ( ICU ) were recorded , as well as the 28-day mortality rate . APACHE-II scores in the two groups decreased following treatment , however , scores in the heparin group decreased more significantly . Prothrombin fragment and thrombin-antithrombin complex levels in the heparin group were significantly decreased . In addition , the number of days applying a ventilator was fewer and the total stay in ICU was significantly shorter compared with the control group . Significantly fewer complications were observed in the heparin group , however , there was no significant difference in the 28-day mortality rate . In conclusion , low-dose heparin improves the hypercoagulable state of sepsis , which subsequently reduces the incidence of DIC or multiple organ dysfunction syndrome , decreasing the number of days of mechanical ventilation and hospitalization Background : Sepsis and septic shock represent a systemic inflammatory state with substantial pro-coagulant elements . Unfractionated heparin is a known anticoagulant , which also possesses anti-inflammatory properties . Unfractionated heparin has been shown to increase survival in experimental models of septic shock . Objective : To evaluate the impact of intravenous therapeutic dose unfractionated heparin in a cohort of patients diagnosed with septic shock . Design : Retrospective , propensity matched , multicenter , cohort study . Setting : Regional intensive care units in Winnipeg , Canada between 1989 and 2005 . Patients : Two thous and three hundred fifty-six patients diagnosed with septic shock , of which 722 received intravenous therapeutic dose heparin .  Measurements and Main Results : The primary outcome of study was 28-day mortality , and mortality stratified by severity of illness ( Acute Physiologic and Chronic Health Evaluation II quartile ) . Safety was assessed by comparing rates of gastrointestinal hemorrhage , intracranial hemorrhage , and the need for transfusion . By using a Cox proportional hazards model , systemic heparin therapy was associated with decreased 28-day mortality ( 307 of 695 [ 44.2 % ] vs. 279 of 695 [ 40.1 % ] ; hazard ratio 0.85 [ confidence interval ( CI ) 95 % 0.73–1.00 ] ; p = 0.05 ) . In the highest quartile of severity of illness ( Acute Physiologic and Chronic Health Evaluation II score 29–53 ) , heparin administration was associated with a clinical ly and statistically significant reduction in 28-day mortality [ 127 of 184 ( 69.0 % ) vs. 94 of 168 ( 56.0 % ) ; hazard ratio 0.70 ( CI 95 % 0.54–0.92 ) ; p = 0.01 ] . The use of intravenous unfractionated heparin was associated with successful liberation from mechanical ventilation [ odds ratio of 1.42 ( CI 95 % 1.13–1.80 ) ; p = 0.003 ] , and successful discontinuation of vasopressor/inotropic support [ odds ratio of 1.34 ( CI 95 % 1.06–1.71 ) ; p = 0.01 ] . No significant differences in the rates of major hemorrhage or need for transfusion were identified . Conclusion : Early administration of intravenous therapeutic dose unfractionated heparin may be associated with decreased mortality when administered to patients diagnosed with septic shock , especially in patients with higher severity of illness . Prospect i ve r and omized trials are needed to further define the role of this agent in sepsis and septic shock Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Purpose The safety of using heparin concomitantly with drotrecogin alfa ( activated ) { DrotAA } was explored in the XPRESS study . No heparin effect on mortality was observed . Safety results from that study are explored in more detail . Methods A r and omized , double-blind trial of prophylactic heparin versus placebo in severe sepsis patients treated with DrotAA ( 24 μg/(kg h ) for 96 h ) was conducted at 224 sites in 20 countries . Patients were r and omized 1:1:2 to receive unfractionated heparin ( UFH ) ( 5,000 Units twice daily ) ( n = 511 ) , low-molecular-weight heparin ( LMWH ) ( enoxaparin , 40 mg per day ) ( n = 493 ) , or placebo ( n = 990 ) every 12 h during the DrotAA infusion . Results Bleeding events during the DrotAA infusion period ( Days 0–6 ) were higher in the heparin than placebo groups ( 10.8 vs. 8.1 % ; p = 0.049 ) , but serious bleeding events were similar ( heparin 2.3 % vs. placebo 2.5 % ; p = 0.72 ) and central nervous system ( CNS ) bleeds were rare in both groups ( 0.3 vs. 0.3 % ) . Fewer heparin patients experienced an ischemic stroke during infusion ( 0.3 vs. 1.3 % ; p = 0.018 ) and 28-day period ( 0.5 vs. 1.8 % ; p = 0.009 ) . Conclusions Coadministration of DrotAA with low-dose heparin in severe sepsis patients did not increase incidence of serious bleeding . Fewer ischemic strokes in the heparin group suggest heparin cessation should be avoided during DrotAA infusion To investigate treatment effects of thrombomodulin alfa ( TM-&agr ; ) in patients with disseminated intravascular coagulation ( DIC ) having infection as the underlying disease , retrospective sub analysis of a double-blind , r and omized controlled phase 3 trial was conducted . In the phase 3 trial , 227 DIC patients ( full- analysis set ) having infection and /or hematologic malignancy as the underlying disease received either TM-&agr ; ( 0.06 mg·kg−1 for 30 min once daily ) or heparin ( 8 U·kg−1·h−1 for 24 h ) for 6 days using the double-dummy method . Among these patients , 147 patients with noninfectious comorbidity leading to severe thrombocytopenia ( e.g. , hematologic malignancy , or aplastic anemia ) were excluded from the present analysis , and 80 patients with infectious disease and DIC were extracted and subjected to the present retrospective sub analysis . Disseminated intravascular coagulation resolution rates were determined using the DIC diagnostic criteria for critically ill patients at 7 days , and mortality rates were evaluated at 28 days . In the TM-&agr ; and heparin  groups , DIC resolution rates were 67.5 % ( 27/40 ) and 55.6 % ( 20/36 ) , and 28-day mortality rates were 21.4 % ( 9/42 ) and 31.6 % ( 12/38 ) , respectively . Mortality rates of patients who recovered from DIC were 3.7 % ( 1/27 ) in the TM-&agr ; group and 15 % ( 3/20 ) in the heparin group . These results suggest TM-&agr ; may be valuable in the treatment of DIC associated with infection BACKGROUND There have been conflicting reports on the efficacy of recombinant human activated protein C , or drotrecogin alfa ( activated ) ( DrotAA ) , for the treatment of patients with septic shock . METHODS In this r and omized , double-blind , placebo-controlled , multicenter trial , we assigned 1697 patients with infection , systemic inflammation , and shock who were receiving fluids and vasopressors above a threshold dose for 4 hours to receive either DrotAA  ( at a dose of 24 μg per kilogram of body weight per hour ) or placebo for 96 hours . The primary outcome was death from any cause 28 days after r and omization . RESULTS At 28 days , 223 of 846 patients ( 26.4 % ) in the DrotAA group and 202 of 834 ( 24.2 % ) in the placebo group had died ( relative risk in the DrotAA group , 1.09 ; 95 % confidence interval [ CI ] , 0.92 to 1.28 ; P=0.31 ) . At 90 days , 287 of 842 patients ( 34.1 % ) in the DrotAA group and 269 of 822 ( 32.7 % ) in the placebo group had died ( relative risk , 1.04 ; 95 % CI , 0.90 to 1.19 ; P=0.56 ) . Among patients with severe protein C deficiency at baseline , 98 of 342 ( 28.7 % ) in the DrotAA group had died at 28 days , as compared with 102 of 331 ( 30.8 % ) in the placebo group ( risk ratio , 0.93 ; 95 % CI , 0.74 to 1.17 ; P=0.54 ) . Similarly , rates of death at 28 and 90 days were not significantly different in other predefined subgroups , including patients at increased risk for death . Serious bleeding during the treatment period occurred in 10 patients in the DrotAA group and 8 in the placebo group ( P=0.81 ) . CONCLUSIONS DrotAA did not significantly reduce mortality at 28 or 90 days , as compared with placebo , in patients with septic shock . ( Funded by Eli Lilly ; PROWESS-SHOCK Clinical Trials.gov number , NCT00604214 . ) Heparin has been given intravenously , as part of a prospect i ve study , to 11 of 26 infants and children with severe meningococcal septicemia . This therapy was started as early as possible following admission to hospital , and continued for two days . The age and sex distributions were roughly similar for the two treatment groups , but the prognostic signs on admission were somewhat less favourable for the group that did not receive heparin . Two boys who received heparin and two girls who did not , died . The clinical courses of the surviving patients in the two groups were also roughly similar , except that the tendency to cutaneous necroses was slightly more prominent in those who had not received heparin . We have thus no evidence that heparin has any great influence on the final outcome of meningococcal septicemia , even when given so early that shock had not developed RATIONALE Patients with severe sepsis frequently receive prophylactic heparin during drotrecogin alfa ( activated ) ( DrotAA ) treatment due to risk of venous thromboembolic events ( VTEs ) . Biological plausibility exists for heparin to reduce DrotAA efficacy and /or increase bleeding . OBJECTIVES Primary : demonstrate in adult patients with severe sepsis receiving DrotAA treatment  that 28-day mortality was equivalent for patients treated with concomitant prophylactic heparin compared with placebo ; secondary : safety and VTE incidence . METHODS International , r and omized , double-blind , phase 4 , equivalence- design trial ( n = 1994 ) . Patients were eligible if indicated for and receiving DrotAA treatment under the country 's approved label . Study drug ( low molecular weight/unfractionated heparin ) or placebo ( saline ) was administered every 12 hours during DrotAA infusion ( 24 ug/kg/hr for 96 hr ) . In patients on baseline heparin and r and omized to placebo , heparin was stopped . MEASUREMENTS AND MAIN RESULTS Twenty-eight-day mortality was not equivalent between treatment groups . Heparin mortality was numerically lower ( 28.3 vs. 31.9 % ; p = 0.08 ) . In the prospect ively defined subgroup of patients exposed to heparin at baseline , patients receiving placebo experienced higher mortality ( 35.6 vs. 26.9 % ; p = 0.005 ) . For safety , significant differences were observed during Days 0 - 6 for any bleeding event ( placebo , n = 78 ; heparin , n = 105 ; p = 0.049 ) and ischemic stroke during Days 0 - 6 ( placebo , n = 12 ; heparin , n = 3 ; p = 0.02 ) and Days 0 - 28 ( placebo , n = 17 ; heparin , n = 5 ; p = 0.009 ) . The VTE rate was low , with no statistical difference between groups ( 0 - 6 d , p = 0.60 ; 0 - 28 d , p = 0. 
    Output:
    
CONCLUSIONS Heparin in patients with sepsis , septic shock , and disseminated intravascular coagulation associated with infection may be associated with decreased mortality ; however , the overall impact remains uncertain .