Disseminated intravascular coagulation and its immune mechanisms

Abstract

Disseminated intravascular coagulation (DIC) is a syndrome triggered by infectious and non-infectious pathologies characterized by excessive generation of thrombin within the vasculature and widespread proteolytic conversion of fibrinogen. Despite diverse clinical manifestations ranging from thrombo-occlusive damage to bleeding diathesis, DIC etiology commonly involves excessive activation of blood coagulation and overlapping dysregulation of anticoagulants and fibrinolysis. Initiation of blood coagulation follows intravascular expression of tissue factor or activation of contact pathway in response to pathogen-associated or host derived damage-associated molecular patterns. The process is further amplified through inflammatory and immuno-thrombotic mechanisms. Consumption of anticoagulants and disruption of endothelial homeostasis lower the regulatory control and disseminate microvascular thrombosis. Clinical DIC development in patients associates with worsening morbidities and increased mortality regardless of the underlying pathology, therefore timely recognition of DIC is critical to reduce the pathologic burden. Due to diversity of triggers and pathogenic mechanisms leading to DIC, diagnosis is based on algorithms that quantify hemostatic imbalance, thrombocytopenia and fibrin/ogen conversion. Since current diagnosis primarily assesses overt consumptive coagulopathies, there is a critical need for better recognition of non-overt DIC and/or pre-DIC states. Therapeutic strategies for DIC patients involve resolution of the eliciting triggers and supportive care for the hemostatic imbalance. Despite medical care, mortality in DIC patients remains high and new strategies, tailored to the underlying pathologic mechanisms, are needed.

Serum concentration as a predictor of tigecycline-induced hypofibrinogenemia in critically ill patients: A retrospective cohort study

“…The ISTH diagnostic score for overt DIC is calculated based on platelet count (< 100×10 9 / L but > 50 × 10 9 / L score 1; < 50 × 10 9 / L score 2 ), PT (Prolonged > 3s but < 6s score 1; > 6s score 2), fibrinogen level (FIB < 1 g/L score 1), and fibrinogen/fibrin degradation peptides (D-dimer) (Moderate increase score 2; Strong increase score 3) in conjunction with clinical considerations. If score ≥ 5, compatible with overt DIC (Popescu et al, 2022). For all patients, the tigecycline-induced HF was defined by the following conditions based on the WHO-Uppsala Monitoring Centre (UMC) causality assessment criteria (The Uppsala Monitoring Centre), (i) FIB < 2 g/L occurred at least 48h after commencement of tigecycline therapy.…”

Platelets as a Gauge of Liver Disease Kinetics?

“…In CLD, increased platelet destruction may be due to cirrhosis-related hypersplenism with sequestration and destruction of platelets, immune-mediated platelet destruction such as with hepatitis C virus infection, and intrahepatic and extrahepatic intravascular platelet consumption [ 31 ] as occurs in DIC [ 32 ].…”

“…Endothelial injury can initiate DIC by releasing tissue factor and promoting platelet aggregation to exposed collagen. The causes of endothelial injury may include vasculitis due to the deposition of antigen–antibody complexes (lupus erythematosus and feline infectious peritonitis), temperature extremes (heat stroke and burns), and direct damage by trauma, toxins, rickettsiae, bacteria or their toxins, and viruses [ 32 ]. One more underlying feature to exclude (or include in the decision algorithms) is HIT in relation to the mandatory use of unfractionated and low-molecular-weight heparin in clinical practice, including anticoagulation for extracorporeal membrane oxygenator circuits, and dialysis.…”

The miracle of Maglavit (1935) and the Romanian psychology of religion

“…While both are the result of a neurotic dysfunctionality, they could still be distinguished by their effect: visions had a positive effect upon the life of the visionary and upon society, whereas hallucinations were destructive to both. Petrache's visions had had a positive effect on him: he could now speak and hear perfectly fine and there was every indication that his preaching was having a positive effect on the Romanian population as well (Popescu‐Sibiu, 1935). Despite the reference to syphilis and neurosis, Popescu‐Sibiu's description could be—and was—interpreted as tantamount to giving the shepherd a clean bill of health.…”