Chapter 129: Hemolytic Uremic Syndrome

SUMMARY

Hemolytic uremic syndrome (HUS) refers to thrombotic microangiopathy (TMA) that usually causes oliguric or anuric renal failure in addition to thrombocytopenia and microangiopathic hemolytic anemia. Ingestion of Shiga toxin–producing Escherichia coli (STEC) can cause the most common form of HUS referred to as STEC-HUS, which is usually preceded by bloody diarrhea. Inherited or acquired defects in the regulation of complements in the alternative pathway cause a rare form of HUS referred to as complement-mediated or atypical HUS (aHUS) because it often occurs without a prodrome of bloody diarrhea. HUS must be differentiated from another thrombotic microangiopathy known as thrombotic thrombocytopenic purpura, which is primarily caused by autoantibodies against a disintegrin and metalloprotease with a thrombospondin type 1 motif member 13 (ADAMTS13) or rarely caused by inherited mutations in ADAMTS13. Diagnosis of HUS relies on a distinct clinical feature and laboratory assessment, including the assays for stool Shiga toxins, plasma ADAMTS13 activity, and mutations in the genes related to complement activation and regulatory proteins in the alternative complement pathway. Supportive therapy is usually sufficient for patients with STEC-HUS. Inhibition of terminal complement activation complexes such as the use of eculizumab is required for aHUS. Secondary TMA may occur in association with disseminated malignancy, infections, bone marrow or solid organ transplantation, and certain drugs. These variants of TMA differ in pathogenesis and prognosis but can be difficult to distinguish because their clinical features often overlap.

Acronyms and Abbreviations

ADAMTS, a disintegrin and metalloprotease with thrombospondin repeats; ADAMTS13, a disintegrin and metalloprotease with a thrombospondin type 1 motif member 13; aHUS, atypical hemolytic uremic syndrome; ANA, antinuclear antibody; APS, antiphospholipid syndrome; aPTT, activated partial thromboplastin time; CFH, complement factor H; CFHR, complement factor H-related protein; DGKE, diacylglycerol kinase ε; D+HUS, diarrhea plus HUS; Gb3, globotriaosylceramide 3; HELLP, hemolysis, elevated liver enzymes, low platelet count; HIT, heparin-induced thrombocytopenia; HUS, hemolytic uremic syndrome; LDH, lactate dehydrogenase; MMACHC (methylmalonic aciduria and homocystinuria type C protein); MCP, membrane cofactor protein; PT, prothrombin time; SLE, systemic lupus erythematosus; STEC, Shiga toxin–producing Escherichia coli; Stx, Shiga toxin; TM, thrombomodulin (gene name THBD); TTP, thrombotic thrombocytopenic purpura; VEGF, vascular endothelial growth factor; VWF, von Willebrand factor.