Hemolytic Uremic Syndrome following O111 Shiga toxin producing ...
Microangiopathic hemolytic Anemia & Hemolytic Uremic Syndrome
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Transcript of Microangiopathic hemolytic Anemia & Hemolytic Uremic Syndrome
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MICROANGIOPATHIC HEMOLYTIC
ANEMIA
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MICROANGIOPATHIC HEMOLYTIC ANEMIA
• Microangiopathic subgroup of hemolytic anemia (loss of red blood cells through destruction) caused by factors in the small blood vessels.
• Occurs when red cells are forced to squeeze through abnormally narrowed small vessels.
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• Types of TMAs assd. with MAHA:–Thrombotic thrombocytopenic purpura.
–Hemolytic uremic syndrome.
–DIC• Other TMA syndromes can
occur with:–Pregnancy–Malignant hypertension–SLE
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• Common Feature:–Microvascular lesion that causes mechanical injury to circulating red cells.
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• Damage evident in peripheral blood smears in the form of red cell fragments- schistocytes, “burr cells”, “helmet cells” and “triangle cells”.
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HEMOLYTIC-UREMIC SYNDROME
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PATHOGENESIS1) Endothelial injury and activation.
2) Platelet aggregation
Both cause vascular obstruction and vasoconstriction
=> Precipitate distal ischaemia.
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ENDOTHELIAL INJURY & ACTIVATION
• Triggers can be :–Bacterial endotoxins–Cytotoxins–Cytokines–Viruses–Drugs–Antiendothelial antibodies–Abnormal multimers or
inhibitors of vWF
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• Endothelial denudation exposes a potentially thrombogenic subendothelial connective tissue.
• Reduced production of PgI2 and nitric oxide enhances platelet aggregation and causes vasoconstriction.
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• Activation of endothelial cells increased adhesivity to leukocytes thrombosis.
• Endothelial cells elaborate multimers of vWF that remain abnormally large platelet aggregation.
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PLATELET AGGREGATION
• With congenital or acquired loss of ADAMTS-13(a vWF cleaving metalloprotease) activity, very large vWF multimers persist in circulation and induce aggregation by activating platelet surface glycoproteins.
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• CLASSIC(CHILDHOOD) HUS
• ADULT HUS
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CLASSIC HUS• 75% in children after intestinal
infection with verocytotoxin-producing E.coli.
• Verocytotoxin similar to Shiga toxin.
• Most frequently assd. with bloody diarrhoea.
• Some traced to ingestion of infected ground meat.
• One of the main causes of acute renal failure in children.
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PATHOGENESIS• Clearly related to Shiga-like
toxin.• Toxin causes:
–Increased adhesion of leukocytes.
–Increased endothelin production.
–Loss of endothelial nitric oxide.
–Endothelial lysis( in presence of cytokines such as TNF).
• Enhancement of both thrombosis and vasoconstriction- microangiopathy.
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• Verocytotoxin also binds to platelets and directly activate them.
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CLINICAL FEATURES• Sudden onset.• Usually after a GI or influenza-
like prodromal episode.• Bleeding
manifestations(hematemesis & malena).
• Severe oliguria.• Hematuria.• Microangiopathic hemolytic
anemia.• Prominent neurological changes
in some patients.
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Fibrin stain showing platelet-fibrin thrombi (red) in the glomerular capillaries, characteristic of
thrombotic microangiopathic disorders.
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ADULT HUS• In association with infection.• In the antiphospholipid
syndrome.• As complications of
pregnancy and contraceptives.
• Assd. with vascular renal diseases.
• In patients treated with chemotherapeutic and immunosuppressive drugs.
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• In typical(epidemic,classic,diarrhoea positive) HUS the trigger for endothelial injury and activation usually is a Shiga toxin.
• In inherited forms of atypical HUS, the cause of endothelial injury appears to be excessive, inappropriate activation of components.
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LAB FINDINGS• CBC
–Anemia–Thrombocytopenia–Peripheral smear checking for schistocytes, burr cells, helmet cells, spherocytes and segmented red blood cells
• LDH (elevated)• Haptoglobin (decreased)• Reticulocyte count
(appropriate)
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• PT/PTT (normal; differentiates from DIC)
• Stool tests–Shiga toxin, E. coli O157:H7 test
• Urine Analysis–Hematuria, casts
• LFT–Increased indirect bilirubin
• Chemistry–Creatinine, hyperkalemia (renal failure)
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