Hemolytic Anemia Flashcards
what is released upon RBC hemolysis?
lactate dehydrogenase (LDH) & hemoglobin
haptoglobin
binds to free hemoglobin in circulation. decreased free levels in intravascular hemolysis.
bilirubin conjugated vs unconjugated
breakdown of heme. conjugated form when released from liver, **unconjugated when released by hemolysis
clinical manifestations specific to hemolysis
jaundice, hemoglobinuria (specifically intravascular hemolysis), pigmented gallstone disease
notable causes of intravascular hemolysis
microangiopathy (MAHA), paroxysmal nocturnal hemoglobinuria (PNH), infections
causes of extravascular hemolysis
herediatry spherocytosis, G6PD deficiency, autoimmune, drug induced, infections
proteins defective in hereditary spherocytosis
band 3, spectrin, or ankyrin
diagnostic test for HS?
osmotic fragility test (HS cells lyse earlier)
treatment for HS?
splenectomy
G6PD deficiency
renders RBCs more susceptible to free radical damage due to inability to synthesize glutathione
morphological consequence of G6PD deficiency?
Heinz bodies (denatured hemoglobin aggregates in these within RBCs) with bite cells (macrophages nibble on the cells)
G6PD A-
decreased G6PD activity in aged RBCs (African Americans)
G6PD B
decreased G6PD activity in all RBCs (Mediterranean & Asians)
clinical manifestations of G6PD deficiency
precipitated by oxidative stress (acute illness, drugs, fava beans)
diagnosis of G6PD deficiency
G6PD biochemical assay (months after event)
treatment of G6PD deficiency
avoid triggers, RBC transfusion
AutoImmune Hemolytic Anemia (AIHA) types
IgG mediated (warm) & IgM mediated (cold)
Warm AIHA
IgG binds to RBC at body temp, splenic macrophages activated by Fc receptor binding. Nibbling results in microspherocytes
where is clearance of warm AIHA cells?
spleen
Cold AIHA
IgM binds to antigens below body temp, attracts and binds complement to RBC, after which the cells are cleared by Kuppfer cells.
where is clearance of cold AIHA cells?
liver
what happens to cold AIHA RBCs at room temp?
agglutination
diagnostic test for AIHA
Direct Coombs test (incubate RBCs with reagent that binds complement or IgG)
common causes of warm AIHA
autoimmune disorders, lymphoproliferative diseases
common causes of cold AIHA
infection (EBV), lymphoproliferative diseases
treatment for warm AIHA
corticosteroids (downregulate Fc receptors on macrophages), splenectomy
treatment for cold AIHA
avoid cold, treat underlying infection, rituximab, plasma exchange
drug induced immune hemolytic anemia
clinical presentation like warm AIHA but history of drug exposure. treat via drug withdrawal
three potential mechanisms of drug induced hemolytic anemia
hapten mediated (drug serves as bound antigen), neo-antigen mediated (drug causes conformational change in cell that become antigenic), alteration of antigen without binding
microangiopathy (MAHA)
some sort of issue in vessel that causes destruction of RBCs.
hallmark finding of microangiopathy
schistocytes in blood smear
causes of microangiopathy
TTP, HUS, super hypertension, vasculitis, DIC
paroxysmal nocturnal hemoglobinuria (PNH)
acquired somatic mutation in PIG-A, which causes deficiency of CD55 & CD59 GPI anchoring proteins. RBC becomes very susceptible to complement mediated intravascular hemolysis
diagnosis of PNH
flow cytometry of CD55/59 in neutrophils or monocytes (NOT IN RBCs)
treatment of PNH
iron/folate supplementation, blood transfusion, eculizumab (C5 inhibitor)
clinical manifestations of PNH
increased risk of venous thrombosis and aplastic anemia
hemolysis due to infection
toxins destroy membrane, infestation causes RES clearance, antigen mimicry
