Review. Anticoagulant Therapy in Sepsis. The Importance of Timing

Abstract

Sepsis associated coagulopathy is due to the inflammation-induced activation of coagulation pathways concomitant with dysfunction of anticoagulant and fibrinolytic systems, leading to different degrees of haemostasis dysregulation. This response is initially beneficial, contributing to antimicrobial defence, but when control is lost coagulation activation leads to widespread microvascular thrombosis and subsequent organ failure. Large clinical trials of sepsis-related anticoagulant therapies failed to show survival benefits, but posthoc analysis of databases and several smaller studies showed beneficial effects of anticoagulants in subgroups of patients with early sepsis-induced disseminated intravascular coagulation. A reasonable explanation could be the difference in timing of anticoagulant therapy and patient heterogeneity associated with large trials. Proper selection of patients and adequate timing are required for treatment to be successful. The time when coagulation activation changes from advantageous to detrimental represents the right moment for the administration of coagulation-targeted therapy. In this way, the defence function of the haemostatic system is preserved, and the harmful effects of overwhelming coagulation activation are avoided.

Common anti-haemostatic medications increase the severity of systemic infection by uropathogenicEscherichia coli

“…Clinical trials of anticoagulants to treat sepsis-induced coagulopathy have delivered inconsistent results, however an emerging theme is that early coagulation is host protective while late coagulation drives pathology [13]. Subsequently, administration of anticoagulants at early stage can be detrimental to the clearance of pathogen by the native immune system [14]. Additionally, there is little evidence on the beneficial effect of anticoagulants on the overall population, however, is beneficial for critically ill subgroups such as sepsis-induced disseminated intravascular coagulation [13, 15].…”

Clinical characteristics of critically ill patients with COVID-19 infection: A retrospective single-centre study on 88 patients in the ICU

“…Acute respiratory distress syndrome (ARDS), acute kidney injury, sepsis, shock, acute liver injury, and acute cardiac injury were defined according to the interim guidance of WHO for SARS-CoV-2 7 . All patients received standard intensive medical treatment in the ICU.…”

Hypocoagulable Tendency on Thromboelastometry Associated With Severity and Anticoagulation Timing in Pediatric Septic Shock: A Prospective Observational Study

“…Sepsis-induced coagulopathy (SIC) is initially triggered by the combination of procoagulant upregulation, endogenous anticoagulant downregulation, and fibrinolytic impairment. These mechanisms are beneficial host responses that contribute to a hypercoagulable state, which is termed "immunothrombosis"-a defense against the spread of pathogens into the nearby tissues or systemic circulation at an early stage of sepsis (1)(2)(3). However, its dysregulation leads to overwhelming activation of coagulation that induces microthrombosis, particularly disseminated intravascular coagulation (DIC) and multiple organ dysfunction syndrome (MODS).…”

“…However, its dysregulation leads to overwhelming activation of coagulation that induces microthrombosis, particularly disseminated intravascular coagulation (DIC) and multiple organ dysfunction syndrome (MODS). The ongoing excessive consumption of coagulation factors ultimately results in a hypocoagulable state with a high risk of severe hemorrhagic complications (2,4,5). Previous studies have reported that the early phase of sepsis is characterized by hypercoagulability, whereas the later stages (severe sepsis or septic shock) trend toward hypocoagulability and are associated with increased morbidity and mortality (1,(6)(7)(8)(9)(10)(11)(12).…”

“…Hypocoagulable Tendency on Thromboelastometry Associated With Severity and Anticoagulation Timing in Pediatric Septic Shock: A Prospective Observational Study Ta Anh Tuan 1,2 † , Nguyen Thi Thu Ha 1 * † , Tran Dang Xoay 1 , Tran Thi Kieu My 3 , Luong Thi Nghiem 4 and Tran Minh Dien 2,5 Hypocoagulable tendency on thromboelastometry had a higher hazard at a PT > 16.1 s [area under the curve (AUC) = 0.747, odds ratio (OR) = 10.5, p = 0.002], INR > 1.4 (AUC = 0.754, OR = 6.9, p = 0.001), fibrinogen < 3.3 g/L (AUC = 0.728, OR = 9.9, p = 0.004), and D-dimer > 3,863 ng/mL (AUC = 0.728, OR = 6.7, p = 0.004).…”