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Microangiopathic hemolytic Anemia & Hemolytic Uremic Syndrome

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Microangiopathicsubgroup ofhemolytic 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.

Types of TMAs assd. with MAHA:Thrombotic thrombocytopenic purpura.Hemolytic uremic syndrome.DICOther TMA syndromes can occur with:PregnancyMalignant hypertensionSLE

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.


PATHOGENESISEndothelial injury and activation.

Platelet aggregationBoth cause vascular obstruction and vasoconstriction

=> Precipitate distal ischaemia.

ENDOTHELIAL INJURY & ACTIVATIONTriggers can be :Bacterial endotoxinsCytotoxinsCytokinesVirusesDrugsAntiendothelial antibodiesAbnormal multimers or inhibitors of vWF

Endothelial denudation exposes a potentially thrombogenic subendothelial connective tissue.

Reduced production of PgI2 and nitric oxide enhances platelet aggregation and causes vasoconstriction.

Activation of endothelial cells increased adhesivity to leukocytes thrombosis.

Endothelial cells elaborate multimers of vWF that remain abnormally large 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.



CLASSIC HUS75% 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.

PATHOGENESISClearly 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.

Verocytotoxin also binds to platelets and directly activate them.

CLINICAL FEATURESSudden 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.

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

ADULT HUSIn 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.

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.

LAB FINDINGSCBCAnemiaThrombocytopeniaPeripheral smear checking for schistocytes, burr cells, helmet cells, spherocytes and segmented red blood cellsLDH (elevated)Haptoglobin (decreased)Reticulocyte count (appropriate)

PT/PTT (normal; differentiates fromDIC)Stool testsShiga toxin, E. coli O157:H7 testUrine AnalysisHematuria, castsLFTIncreased indirect bilirubinChemistryCreatinine, hyperkalemia (renal failure)