Hemolytic Anemia

Question 1

what is released upon RBC hemolysis?

Answer 1

lactate dehydrogenase (LDH) & hemoglobin

Question 2

haptoglobin

Answer 2

binds to free hemoglobin in circulation. decreased free levels in intravascular hemolysis.

Question 3

bilirubin conjugated vs unconjugated

Answer 3

breakdown of heme. conjugated form when released from liver, **unconjugated when released by hemolysis

Question 4

clinical manifestations specific to hemolysis

Answer 4

jaundice, hemoglobinuria (specifically intravascular hemolysis), pigmented gallstone disease

Question 5

notable causes of intravascular hemolysis

Answer 5

microangiopathy (MAHA), paroxysmal nocturnal hemoglobinuria (PNH), infections

Question 6

causes of extravascular hemolysis

Answer 6

herediatry spherocytosis, G6PD deficiency, autoimmune, drug induced, infections

Question 7

proteins defective in hereditary spherocytosis

Answer 7

band 3, spectrin, or ankyrin

Question 8

diagnostic test for HS?

Answer 8

osmotic fragility test (HS cells lyse earlier)

Question 9

treatment for HS?

Answer 9

splenectomy

Question 10

G6PD deficiency

Answer 10

renders RBCs more susceptible to free radical damage due to inability to synthesize glutathione

Question 11

morphological consequence of G6PD deficiency?

Answer 11

Heinz bodies (denatured hemoglobin aggregates in these within RBCs) with bite cells (macrophages nibble on the cells)

Question 12

G6PD A-

Answer 12

decreased G6PD activity in aged RBCs (African Americans)

Question 13

G6PD B

Answer 13

decreased G6PD activity in all RBCs (Mediterranean & Asians)

Question 14

clinical manifestations of G6PD deficiency

Answer 14

precipitated by oxidative stress (acute illness, drugs, fava beans)

Question 15

diagnosis of G6PD deficiency

Answer 15

G6PD biochemical assay (months after event)

Question 16

treatment of G6PD deficiency

Answer 16

avoid triggers, RBC transfusion

Question 17

AutoImmune Hemolytic Anemia (AIHA) types

Answer 17

IgG mediated (warm) & IgM mediated (cold)

Question 18

Warm AIHA

Answer 18

IgG binds to RBC at body temp, splenic macrophages activated by Fc receptor binding. Nibbling results in microspherocytes

Question 19

where is clearance of warm AIHA cells?

Answer 19

spleen

Question 20

Cold AIHA

Answer 20

IgM binds to antigens below body temp, attracts and binds complement to RBC, after which the cells are cleared by Kuppfer cells.

Question 21

where is clearance of cold AIHA cells?

Answer 21

liver

Question 22

what happens to cold AIHA RBCs at room temp?

Answer 22

agglutination

Question 23

diagnostic test for AIHA

Answer 23

Direct Coombs test (incubate RBCs with reagent that binds complement or IgG)

Question 24

common causes of warm AIHA

Answer 24

autoimmune disorders, lymphoproliferative diseases

Question 25

common causes of cold AIHA

Answer 25

infection (EBV), lymphoproliferative diseases

Question 26

treatment for warm AIHA

Answer 26

corticosteroids (downregulate Fc receptors on macrophages), splenectomy

Question 27

treatment for cold AIHA

Answer 27

avoid cold, treat underlying infection, rituximab, plasma exchange

Question 28

drug induced immune hemolytic anemia

Answer 28

clinical presentation like warm AIHA but history of drug exposure. treat via drug withdrawal

Question 29

three potential mechanisms of drug induced hemolytic anemia

Answer 29

hapten mediated (drug serves as bound antigen), neo-antigen mediated (drug causes conformational change in cell that become antigenic), alteration of antigen without binding

Question 30

microangiopathy (MAHA)

Answer 30

some sort of issue in vessel that causes destruction of RBCs.

Question 31

hallmark finding of microangiopathy

Answer 31

schistocytes in blood smear

Question 32

causes of microangiopathy

Answer 32

TTP, HUS, super hypertension, vasculitis, DIC

Question 33

paroxysmal nocturnal hemoglobinuria (PNH)

Answer 33

acquired somatic mutation in PIG-A, which causes deficiency of CD55 & CD59 GPI anchoring proteins. RBC becomes very susceptible to complement mediated intravascular hemolysis

Question 34

diagnosis of PNH

Answer 34

flow cytometry of CD55/59 in neutrophils or monocytes (NOT IN RBCs)

Question 35

treatment of PNH

Answer 35

iron/folate supplementation, blood transfusion, eculizumab (C5 inhibitor)

Question 36

clinical manifestations of PNH

Answer 36

increased risk of venous thrombosis and aplastic anemia

Question 37

hemolysis due to infection

Answer 37

toxins destroy membrane, infestation causes RES clearance, antigen mimicry