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”.

7. HEMOLYTIC-UREMIC
SYNDROME

8. PATHOGENESIS
1) Endothelial injury and activation.
2) Platelet aggregation
Both cause vascular obstruction and vasoconstriction
=> Precipitate distal ischaemia.

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

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

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

12. 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.

13. • CLASSIC(CHILDHOOD) HUS
• ADULT HUS

14. 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.

15. 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.

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

17. 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.

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

19. 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.

20. • 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.

21. 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)

22. • 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)

23. THANK YOU