Unfractioned heparin for treatment of sepsis: A randomized clinical trial (The HETRASE Study)*

Abstract

Our findings suggested that UFH may be a feasible and safe intervention in sepsis. However, this study was not able to demonstrate a beneficial effect on the chosen primary outcomes or in the 28-day mortality rate.

Anticoagulant modulation of inflammation in severe sepsis

“…However, there was no significant difference in the primary endpoint, length of hospital stay. Moreover, the heparin treated patients failed to demonstrate a more rapid improvement in organ failure score or increase in survival [47] . Thus, while heparin is readily available, inexpensive, and widely used for DVT prophylaxis in septic patients, its role in the treatment of sepsis remains undetermined.…”

“…There were no severe adverse events in either group. These findings suggests that plasma derived APC as a remarkably reduced dose compared to rhAPC can improve DIC, without increasing bleeding and its effects should be evaluated in future [27] (Kybersept) Gando et al [29] 2013 Tagami et al [30] 2014 Sepsis-associated DIC in severe pneumonia [33] (Prowess trial) Vincent et al [35] (Enhance trial) [36] (Address trial) Ranieri et al [37] (Prowess shock) Rimmer et al [38] 2012 [47] (HETRASE study) Abraham et al [50] (OPTIMIST trial) [52] (CAPTIVATE trial) Allen KS et al . Anticoagulant modulation of inflammation in severe sepsis trials.…”

Nonanticoagulant heparin prevents histone-mediated cytotoxicity in vitro and improves survival in sepsis

“…Low dose unfractionated heparin (UFH) has been tested in a clinical trial as a complementary treatment of sepsis. 7 The study rationale linked infection, inflammation, and coagulation in sepsis and sought to inhibit the coagulation part with low doses of heparin so as not to increase the risk of bleeding in a patient who is already at risk due to sepsis-associated consumption coagulopathy. 7,8 Nevertheless, although this study failed to demonstrate a significant benefit on 28-day mortality rate, we hypothesize that the minor beneficial effects of heparin observed might be attributed to a mechanism independent of the anticoagulant properties of heparin.…”

“…7 The study rationale linked infection, inflammation, and coagulation in sepsis and sought to inhibit the coagulation part with low doses of heparin so as not to increase the risk of bleeding in a patient who is already at risk due to sepsis-associated consumption coagulopathy. 7,8 Nevertheless, although this study failed to demonstrate a significant benefit on 28-day mortality rate, we hypothesize that the minor beneficial effects of heparin observed might be attributed to a mechanism independent of the anticoagulant properties of heparin. We reasoned that removing the anticoagulant fraction from UFH would yield an antithrombin affinity-depleted heparin (AADH) that neutralizes histone-mediated cytotoxicity and effectively treats sepsis without increasing risk of bleeding.…”

Ronda clínica y epidemiológica. Análisis de datos longitudinales

“…En Medellín se llevó a cabo un ensayo clínico aleatorio para determinar el efecto de la heparina a bajas dosis y en infusión continua en el tiempo de estancia hospitalaria y el cambio en el puntaje de disfunción de órganos (MOD) durante el manejo hospitalario de pacientes con sepsis (28). El análisis realizado por medio de un modelo de efectos mixtos demostró que tanto el grupo de placebo como el grupo de heparina tuvieron una reducción diaria estadísticamente significativa en el puntaje MOD (-0,13; IC 95% = -0,159; -0,105 y -0,11; IC 95% = -0,137; -0,080, respectivamente), pero la diferencia entre esas dos velocidades de declive no fue estadísticamente significativa (p = 0,24).…”