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Microangiopathic hemolytic Anemia & Hemolytic Uremic Syndrome

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Pathology

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Microangiopathic hemolytic Anemia & Hemolytic Uremic Syndrome

  1. 1. MICROANGIOPATHIC HEMOLYTIC ANEMIA
  2. 2. 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.
  3. 3. • Types of TMAs assd. with MAHA: – Thrombotic thrombocytopenic purpura. – Hemolytic uremic syndrome. – DIC • Other TMA syndromes can occur with: – Pregnancy – Malignant hypertension – SLE
  4. 4. • Common Feature: – Microvascular lesion that causes mechanical injury to circulating red cells.
  5. 5. • Damage evident in peripheral blood smears in the form of red cell fragments- schistocytes, “burr cells”, “helmet cells” and “triangle cells”.
  6. 6. HEMOLYTIC-UREMIC SYNDROME
  7. 7. PATHOGENESIS 1) Endothelial injury and activation. 2) Platelet aggregation Both cause vascular obstruction and vasoconstriction => Precipitate distal ischaemia.
  8. 8. ENDOTHELIAL INJURY & ACTIVATION • Triggers can be : – Bacterial endotoxins – Cytotoxins – Cytokines – Viruses – Drugs – Antiendothelial antibodies – Abnormal multimers or inhibitors of vWF
  9. 9. • Endothelial denudation exposes a potentially thrombogenic subendothelial connective tissue. • Reduced production of PgI2 and nitric oxide enhances platelet aggregation and causes vasoconstriction.
  10. 10. • Activation of endothelial cells increased adhesivity to leukocytes thrombosis. • Endothelial cells elaborate multimers of vWF that remain abnormally large platelet aggregation.
  11. 11. 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.
  12. 12. • CLASSIC(CHILDHOOD) HUS • ADULT HUS
  13. 13. 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.
  14. 14. 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.
  15. 15. • Verocytotoxin also binds to platelets and directly activate them.
  16. 16. 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.
  17. 17. Fibrin stain showing platelet-fibrin thrombi (red) in the glomerular capillaries, characteristic of thrombotic microangiopathic disorders.
  18. 18. 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.
  19. 19. • 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.
  20. 20. 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)
  21. 21. • 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)
  22. 22. THANK YOU

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