Microangiopathic hemolytic Anemia & Hemolytic Uremic Syndrome

Pathology

1. MICROANGIOPATHIC HEMOLYTIC ANEMIA

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. Types of TMAs assd . with MAHA: Thrombotic thrombocytopenic purpura . Hemolytic uremic syndrome. DIC Other TMA syndromes can occur with: Pregnancy Malignant hypertension SLE

4. Common Feature: Microvascular lesion that causes mechanical injury to circulating red cells.

5. Damage evident in peripheral blood smears in the form of red cell fragments- schistocytes , “burr cells”, “helmet cells” and “triangle cells”.

6. HEMOLYTIC-UREMIC SYNDROME

7. PATHOGENESIS Endothelial injury and activation. Platelet aggregation Both cause vascular obstruction and vasoconstriction => Precipitate distal ischaemia .

8. ENDOTHELIAL INJURY & ACTIVATION Triggers can be : Bacterial endotoxins Cytotoxins Cytokines Viruses Drugs Antiendothelial antibodies Abnormal multimers or inhibitors of vWF

9. Endothelial denudation exposes a potentially thrombogenic subendothelial connective tissue. Reduced production of PgI2 and nitric oxide enhances platelet aggregation and causes vasoconstriction.

10. Activation of endothelial cells increased adhesivity to leukocytes thrombosis. Endothelial cells elaborate multimers of vWF that remain abnormally large platelet aggregation.

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. CLASSIC(CHILDHOOD) HUS ADULT HUS

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. 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. Verocytotoxin also binds to platelets and directly activate them.

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. Fibrin stain showing platelet-fibrin thrombi ( red) in the glomerular capillaries, characteristic of thrombotic microangiopathic disorders.

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. 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. 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. 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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