• Thrombotic Microangiopathies
    • Include
      • Thrombotic Thrombocytopenic Purpura (TTP)
      • Hemolytic-Uremic Syndrome (HUS)
    • TTP was defined as the pentad of (MCQ)
      • Fever
      • Thrombocytopenia
      • microangiopathic hemolytic anemia
      • transient neurologic deficits
      • renal failure.
    • HUS is also associated with microangiopathic hemolytic anemia and thrombocytopenia but is distinguished by the (MCQ)
      • absence of neurologic symptoms
      • prominence of acute renal failure
      • frequent occurrence in children.
    • HUS and TTP are both caused by insults that lead to the excessive activation of platelets, which deposit as thrombi in microcirculatory beds. (MCQ)
    • These intravascular thrombi cause a microangiopathic hemolytic anemia and widespread organ dysfunction(MCQ)
    • the attendant consumption of platelets leads to thrombocytopenia
    • TTP (MCQ)
      • usually associated with a deficiency in a plasma enzyme called ADAMTS13
      • ADAMTS13 (MCQ)
        • designated as “vWF metalloprotease.”
        • deficiency of ADAMTS13 can be inherited or acquired.
        • normally degrades very high-molecular-weight multimers of von Willebrand factor (vWF)
        • In its absence, these multimers accumulate in plasma and tend to promote platelet activation and aggregation.
      • Superimposition of endothelial cell injury (caused by some other condition) may further promote the formation of platelet microaggregates, thus initiating or exacerbating clinically evident TTP(MCQ)
      • Plasma exchange
        • removes autoantibodies
        • provides functional ADAMTS13,
      • TTP
        • treated successfully in more than 80% of patients.
    • HUS
      • In contrast, HUS is associated with normal levels of ADAMTS13
      • Epidemic, “typical” HUS (MCQ)
        • strongly associated with infectious gastroenteritis caused by Escherichia coli strain O157:H7, which elaborates a Shiga-like toxin(MCQ)
        • This toxin is absorbed from the inflamed gastrointestinal mucosa into the circulation
        • it alters endothelial cell function in some manner that results in platelet activation and aggregation. (MCQ)
        • Children and the elderly are at highest risk.
        • Those affected present with bloody diarrhea, and a few days later HUS makes its appearance.
        • With appropriate supportive care complete recovery is possible
        • irreversible renal damage and death can occur in more severe cases. (MCQ)
      • Nonepidemic, “atypical” HUS (MCQ)
        • often associated with defects in three proteins that normally act to prevent excessive activation of the alternative complement pathway
          • complement factor H
          • membrane cofactor protein (CD46)
          • factor I,
        • Deficiencies of these proteins can be caused by inherited defects or acquired inhibitory autoantibodies
        • It is associated with a remitting, relapsing course
      • DIC  vs thrombotic microangiopathies(MCQ)
        • In TTP and HUS (unlike in DIC), activation of the coagulation cascade is not of primary importance
        • hence laboratory tests of coagulation, such as the PT and PTT, are usually normal.
    • Thrombotic Microangiopathies: Causes and Associations
      • Thrombotic thrombocytopenic purpura
        • Deficiency of ADAMTS13
          • Inherited
          • Acquired (autoantibodies)
      • Hemolytic uremic syndrome
        • Epidemic:
          • Escherichia coli strain O157 : H7 infection(MCQ)
          • Endothelial damage by Shiga-like toxin(MCQ)
        • Nonepidemic:
          • alternative complement pathway inhibitor deficiencies (complement factor H, membrane cofactor protein (CD46), or factor I)
            • Inherited
            • Acquired (autoantibodies)
        • Miscellaneous associations
          • Drugs
            • Cyclosporine(MCQ)
            • chemotherapeutic agents
            • Radiation
            • bone marrow transplantation
          • Other infections
            • HIV(MCQ)
            • pneumococcal sepsis(MCQ)
        • Conditions associated with autoimmunity
        • systemic lupus erythematosus
        • HIV infection
        • lymphoid neoplasms

    Hemolytic Uremic Syndrome
    Instructional Tutorial Video
    Hemolytic Uremic Syndrome
    Haemolytic Uremic Syndrome- E.coli.wmv
    Hemolytic Uremic Syndrome (HUS)
    TTP-HUS Overview
    A brief, basic and animated overview of the mechanism and treatment of TTP-HUS.