Sepsis-associated disseminated intravascular coagulation and its differential diagnoses

Abstract

Disseminated intravascular coagulation (DIC) is a common complication in sepsis. Since DIC not only promotes organ dysfunction but also is a strong prognostic factor, its diagnosis at the earliest possible timing is important. Thrombocytopenia is often present in patients with DIC but can also occur in a number of other critical conditions. Of note, many of the rare thrombocytopenic diseases require prompt diagnoses and specific treatments. To differentiate these diseases correctly, the phenotypic expressions must be considered and the different disease pathophysiologies must be understood. There are three major players in the background characteristics of thrombocytopenia: platelets, the coagulation system, and vascular endothelial cells. For example, the activation of coagulation is at the core of the pathogenesis of sepsis-associated DIC, while platelet aggregation is the essential mechanism in thrombotic thrombocytopenic purpura and endothelial damage is the hallmark of hemolytic uremic syndrome. Though each of the three players is important in all thrombocytopenic diseases, one of the three dominant players typically establishes the individual features of each disease. In this review, we introduce the pathogeneses, symptoms, diagnostic measures, and recent therapeutic advances for the major diseases that should be immediately differentiated from DIC in sepsis.

Keywords: Disseminated intravascular coagulation; Hemolytic uremic syndrome; Heparin-induced thrombocytopenia; Sepsis; Thrombotic thrombocytopenic purpura.

Fig. 1

An algorithm to differentiate sepsis-associated DIC from other diseases with thrombocytopenia. Both the prothrombin time (PT) ratio and the level of fibrin/fibrinogen degradation products are elevated in sepsis-associated DIC (disseminated intravascular coagulation). If either marker is within the normal range, other diseases can be suspected. If microangiopathic hemolytic anemia (MAHA) is recognized, Escherichia coli (STEC)-hemolytic uremic syndrome (HUS) will be discriminated by performing a stool culture or polymerase chain reaction (PCR) assay first. If it is not, thrombotic thrombocytopenic purpura (TTP), atypical HUS (aHUS), or secondary thrombotic microangiopathy are suspicious, and the early initiation of plasma exchange is recommended unless a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) level is confirmed. TTP is diagnosed by the identification of a low ADAMTS13 activity (< 10%). If plasma exchange is ineffective, refractory TTP, aHUS, or other disease is suspicious and the use of either rituximab or eculizumab will be considered. In those cases, the laboratory findings and clinical symptoms such as acute kidney injury and gastrointestinal or neurological damage will be carefully examined; if these findings suggest aHUS, the patient’s age and medical and family histories can be helpful for a diagnosis. Similarly, the possibility of secondary TMAs can be considered. If the presence of MAHA is not recognized, the possibility of other diseases such as heparin-induced thrombocytopenia (HIT), immune thrombocytopenia purpura (ITP), hemophagocytic syndrome (HPS), acute infectious purpura fulminans (AIPF), severe fever and thrombocytopenia syndrome (SFTS), and thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO) syndrome would be considered

Fig. 2

Check sheet for the secondary thrombotic microangiopathic diseases. For the discrimination in secondary TMA, each item in the check sheet will be confirmed