Anemia: Blood Loss - PNH & Immunohemolytic

Question 1

What is the only hemolytic anemia caused by an ACQUIRED gene defect?

Answer 1

Paroxysmal nocturnal hemoglobinuria (PNH)

Question 2

PNH is an acquired defect in myeloid stem cells resulting in absent ______; making cells susceptible to destruction by complement.

Answer 2

glycosylphosphatidylinositol (GPI)

(auto-immune ab are made against GPI antigens)

Question 3

PNH is due to a _______ mutation

Answer 3

PIGA gene

Question 4

What does PIGA gene encode for?

Answer 4

Complement regulatory (inhibitory) proteins: CD55 & CD59

Question 5

CD55 function? CD59?

Answer 5

CD55: prevents formation of C3 convertase

CD59: blocks binding of C9, blocking “MAC attack”

Question 6

Why does the absence of GPI (Paroxysmal nocturnal hemoglobinuria) make RBCs susceptible to destruction by complement?

Answer 6

1. Decay accelerating factor (DAF or CD55) on the surface of RBCs inhibits C3 convertase.
2. DAF is secured to the cell membrane by GPI (an anchoring glycolipid).

Question 7

Intravascular hemolysis occurs episodically, often at night during sleep in PNH. ________ develops with shallow breathing during sleep and activates complement → _______ are lysed.

Answer 7

• Mild respiratory acidosis
• RBCs, WBCs, and platelets

Question 8

Intravascular hemolysis occurs episodically, often at night during sleep in PNH → leads to ______ (2) (especially in the morning); _____ is seen days after hemolysis.

Answer 8

• hemoglobinemia and hemoglobinuria
• hemosiderinuria

Question 9

_______ test is used to screen for PNH; confirmatory test is the ______ test or ______.

Answer 9

• Sucrose
• acidified serum
• flow cytometry to detect lack of CDSS (DAF) on RBCs

Question 10

Main cause of death in PNH is ______.

Answer 10

thrombosis of the hepatic, portal, or cerebral veins

(Destroyed platelets release cytoplasmic contents into circulation, inducing thrombosis.)

Question 11

Complications of PNH include _______ and ____, which develops in 10% of patients.

Answer 11

• iron deficiency anemia (due to chronic loss of hemoglobin in the urine)
• acute myeloid leukemia (AML)

Question 12

PNH: tx

Answer 12

Eculizumab

Question 13

Eculizumab MOA

Answer 13

inhibits C5 → C5a

Question 14

Immune Hemolytic Anemia (IHA) is due to _______.

Answer 14

antibody-mediated destruction of RBCs

Question 15

In immune hemolytic anemia, IgG-mediated disease usually involves ______ hemolysis, while IgM-mediated disease usually involves _______ hemolysis.

Answer 15

• extravascular
• intravascular

Question 16

IgG-mediated (IHA) may be triggered by ______ (3).

Answer 16

1. SLE (most common cause)
   CLL
2. Rx: penicillin & cephalosporins

Question 17

How can drugs lead to IHA?

Answer 17

1. Drug attaches to RBC membrane (e.g., penicillin) → Ab binds to drug-membrane complex
2. Drug-induced autoantibodies (e.g., a-methyldopa) that bind self antigens on RBCs

Question 18

IHA tx (4)

Answer 18

1. cessation of the offending drug
2. steroids
3. IVIG
4. splenectomy

Question 19

How does IgM-mediated IHA lead to intravascular hemolysis?

Answer 19

RBCs inactivate complement, but residual C3b = opsonin for splenic MFs → spherocytes; extreme activation of complement → intravascular hemolysis

Question 20

IgM-mediated IHA is associated with _______ (2 infections).

Answer 20

1. Mycoplasma pneumoniae
2. infectious mononucleosis

Question 21

_____ is the most important test for IHA.

Answer 21

Direct Coombs test

Question 22

_______ confirms the presence of antibodies in patient serum (IHA).

Answer 22

Indirect Coombs test

(Anti-IgG and test RBCs are mixed with the patient serum; agglutination occurs if serum Ab are present)