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• Microangiopathic subgroup of hemolytic
anemia (loss of red blood cells through
destruction) caused by factors in the small
• Occurs when red cells are forced to squeeze
through abnormally narrowed small vessels.
• Types of TMAs assd. with MAHA:
– Thrombotic thrombocytopenic purpura.
– Hemolytic uremic syndrome.
• Other TMA syndromes can occur with:
– Malignant hypertension
• Common Feature:
– Microvascular lesion that causes
mechanical injury to circulating red cells.
• Damage evident in peripheral blood
smears in the form of red cell
fragments- schistocytes, “burr cells”,
“helmet cells” and “triangle cells”.
1) Endothelial injury and activation.
2) Platelet aggregation
Both cause vascular obstruction and vasoconstriction
=> Precipitate distal ischaemia.
ENDOTHELIAL INJURY &
• Triggers can be :
– Bacterial endotoxins
– Antiendothelial antibodies
– Abnormal multimers or inhibitors of vWF
• Endothelial denudation exposes a
potentially thrombogenic subendothelial
• Reduced production of PgI2 and nitric
oxide enhances platelet aggregation and
• Activation of endothelial cells increased
adhesivity to leukocytes thrombosis.
• Endothelial cells elaborate multimers of
vWF that remain abnormally large
• 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
• 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
• 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
• Verocytotoxin also binds to platelets and
directly activate them.
• Sudden onset.
• Usually after a GI or influenza-like prodromal
• Bleeding manifestations(hematemesis & malena).
• Severe oliguria.
• Microangiopathic hemolytic anemia.
• Prominent neurological changes in some patients.
Fibrin stain showing platelet-fibrin thrombi (red) in
the glomerular capillaries, characteristic of
thrombotic microangiopathic disorders.
• In association with infection.
• In the antiphospholipid syndrome.
• As complications of pregnancy and
• Assd. with vascular renal diseases.
• In patients treated with chemotherapeutic and
• 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.