microangiopathic hemolytic anemia & hemolytic uremic syndrome

MICROANGIOPATHIC HEMOLYTIC

ANEMIA

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.

• Types of TMAs assd. with MAHA:–Thrombotic thrombocytopenic purpura.

–Hemolytic uremic syndrome.

–DIC• Other TMA syndromes can

occur with:–Pregnancy–Malignant hypertension–SLE

• 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”.

HEMOLYTIC-UREMIC SYNDROME

PATHOGENESIS1) Endothelial injury and activation.

2) Platelet aggregation

Both cause vascular obstruction and vasoconstriction

=> Precipitate distal ischaemia.

ENDOTHELIAL INJURY & ACTIVATION

• Triggers can be :–Bacterial endotoxins–Cytotoxins–Cytokines–Viruses–Drugs–Antiendothelial antibodies–Abnormal 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.

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(CHILDHOOD) HUS

• ADULT HUS

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.

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.

• Verocytotoxin also binds to platelets and directly activate them.

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.

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

thrombotic microangiopathic disorders.

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.

• 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 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)

• 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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