Coagulopathy of sepsis

Abstract

Disseminated intravascular coagulation (DIC) is a common phenomenon in patients with sepsis, but the clinical implications of this condition are not clear. Clinical trials with coagulation inhibitors have failed to show a significant benefit concerning survival. DIC is primarily a laboratory diagnosis, based on the combination of elevated fibrin-related markers (FRM), with decreased procoagulant factors and platelets. Non-overt DIC is observed in most patients with sepsis, whereas overt DIC is less frequent. Patients with overt DIC may display consumption coagulopathy and purpura fulminans. Consumption coagulopathy is a bleeding disorder caused by low levels of platelets and procoagulant factors associated with massive coagulation activation. Purpura fulminans is caused by widespread microvascular thrombosis, resulting in tissue necrosis. Treatment with drotrecogin alfa (activated) improves survival and other outcome parameters in severe sepsis, including a subgroup of patients fulfilling the laboratory criteria of overt DIC. No randomized trials demonstrating effective therapies in consumption coagulopathy have been published. Bleeding patients with consumption coagulopathy are most frequently treated with platelet transfusions and various plasma products including fresh frozen plasma and coagulation factor concentrates. Based on case reports, treatment with drotrecogin alfa (activated) or substitution of protein C have been recommended for adjuvant treatment of sepsis-related purpura fulminans.

Infection-Stimulated Fibrin Deposition Controls Hemorrhage and Limits Hepatic Bacterial Growth during Listeriosis

“…These opposing conclusions caused significant controversy; some clinicians considered fibrin sufficiently harmful to warrant its surgical removal (24,34,39), while others believed fibrin sufficiently protective to warrant spraying fibrin-promoting solutions into the peritoneal cavity during abdominal surgery (16). In recent years, researchers have focused largely upon the deleterious functions of infection-stimulated fibrin deposition, which are clearly evident during advanced septic infections (13,30).…”

“…In fact, therapeutic administration of activated protein C, a natural anticoagulant protein, was recently shown to reduce septic mortality in humans (4), suggesting that some aspect of coagulation functions pathologically during sepsis (14). However, several robust anticoagulant therapies have failed to improve septic morbidity in humans (13,30), and a gene polymorphism that increases coagulant activity (factor V Leiden) actually confers a significant survival advantage during severe sepsis (26). These apparent inconsistencies can be reconciled by hypothesizing that coagulation plays both protective and pathological roles during sepsis.…”

Trombocytopenia: One of the Markers of Disseminated Intravascular Coagulation

“…This phase can be considered as non-overt DIC and can only be traced in patients by careful follow-up of laboratory tests including sensitive tests for thrombin and fibrin generation. It appears that detection of this state may be clinically relevant because non-overt DIC indicated increased mortality in intensive care patients (partly reviewed in [9]). …”

“…During this stage of overt DIC diminishing concentrations of coagulation proteins and platelets can become clinically relevant in relation with an increased bleeding risk or overt bleeding. This type of "consumption coagulopathy" is associated typically with bleeding from puncture sites and mucous membranes, while the picture known as purpura fulminans is typically associated with massive cutaneous bleeding [9]. Another distinct type of overt DIC is the so-called defibrination syndrome which is marked by low fibrinogen levels and high turnover of fibrin due to increased fibrinolytic activity.…”

Adrenal apoplexy caused by fulminant sepsis in 20-year-old healthy male?: case report

“…Frequent laboratory features include a significant drop in the hemoglobin and electrolyte changes of adrenal insufficiency that often take several days to develop [6][7][8]. Death can occur within a few hours or after many days [1].…”