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.

Highlights

  • These differences in the aforementioned clinical courses can be explained by the individual disease pathogeneses: kidney injury in thrombocytopenic purpura (TTP) is primarily caused by platelet aggregation in the vasculature, whereas kidney injury in hemolytic uremic syndrome (HUS) arises from damage to the glomerular endothelial cells and the resident renal cells [12]

  • Sepsis-associated disseminated intravascular coagulation DIC is a common complication in sepsis, and its diagnosis is typically made based on some combination of basic coagulation markers [13, 14]

  • DIC disseminated intravascular coagulation, Thrombotic microangiopathy (TMA) thrombotic microangiopathy, TTP thrombotic thrombocytopenic purpura, ADAMTS13 a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13, MAHA microangiopathic hemolytic anemia, STEC Shiga toxin-producing Escherichia coli, HUS hemolytic uremic syndrome, aHUS atypical HUS, HELLP hemolysis, elevated liver enzymes low platelets, Antiphospholipid syndrome (APS) antiphospholipid syndrome, Catastrophic antiphospholipid syndrome (CAPS) catastrophic antiphospholipid syndrome, IVIg intravenous immunoglobulin, Heparin-induced thrombocytopenia (HIT) heparin-induced thrombocytopenia, Immune thrombocytopenic purpura (ITP) immune thrombocytopenia purpura, Hemophagocytic syndromes (HPSs) hemophagocytic syndromes, Acute infectious purpura fulminans (AIPF) acute infectious purpura fulminans, Severe fever and thrombocytopenia syndrome (SFTS) fever and thrombocytopenia syndrome follow: 68 cases out of 500 patients who were diagnosed as having DIC (Japanese Association for Acute Medicine [JAAM] criteria) (13.6%) showed FDP level of less than 10 mg/mL, and 91 cases out of 500 JAAM-DIC patients (18.2%) showed prothrombin time (PT) ratio of less than 1.2

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Summary

Background

Sepsis is currently defined as “dysregulated host immune response to infection leading to organ failure” [1], and the severity of organ dysfunction has been recognized as a significant prognostic factor. Society for Thrombosis and Hemostasis (ISTH) released guidelines for the differentiation of sepsis-associated DIC from other thrombocytopenic conditions in 2018 [9]. In conjunction with those guidelines, the Working Group for DIC of the Japanese Surviving Sepsis Campaign Guideline 2020 has highlighted the most important thrombocytopenic diseases. 30% to 40% of patients with renal failure and HUS require renal support [10, 11], whereas severe renal failure and chronic renal insufficiency are rare in TTP These differences in the aforementioned clinical courses can be explained by the individual disease pathogeneses: kidney injury in TTP is primarily caused by platelet aggregation in the vasculature, whereas kidney injury in HUS arises from damage to the glomerular endothelial cells and the resident renal cells [12]. We will discuss the pathophysiology of various thrombocytopenic conditions

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