Pathoma Ch 5-RBC Disorders

Question 1

pathogenesis:

Hereditary Spherocytosis

Answer 1

Inherited defect of RBC cytoskeleton-membrane tethering proteins

Most commonly involves spectrin, ankyrin, or band 3.1

membrane blebs are formed.

RBCs eventually consumed by splenic macrophages.

Question 2

Clinical/Lab findings of

Hereditary Spherocytosis

Answer 2

Spherocytes with loss of central pallor (Fig. 5.7)

Increased RDW and increased mean corpuscular hemoglobin concentration (MCHC)

Splenomegaly, jaundice with unconjugated bilirubin, and increased risk for bilirubin gallstones (extravascular hemolysis)

Increased risk for aplastic crisis with parvovirus Bl9 infection of erythroid
precursors

Question 3

How to diagnose Hereditary Spherocytosis?

treat?

Answer 3

osmotic fragility test

Tx: splenectomy

Question 4

pathogenesis:

SICKLE CELL ANEMIA

Answer 4

AR mutation in Beta chain of Hb.

Carried by 10% of Africans

DISEASE arises when TWO abnomral Beta genes are present; resulting in > 90% HbS.

Question 5

What kind of hemolysis will you see with Sickle cell anemia?

Answer 5

Extravascular hemolysis-Reticuloendothelial system

Intravascular hemolysis

Question 6

Characteristic finding of Sickle Cell Anemia on X-ray?

Answer 6

Massive Erythroid hyperplasia.
Expansion of hematopoiesis into skull
in liver: hepatomegaly

Question 7

Complications of Sickle Cell Anemia?

Answer 7

Irreversible sickling leads to complications of vaso-occlusion.

Dactylitis- swollen hands and feet. common in infants (African)

Autosplenectomy-shrunken spleen

Acute chest syndrome

Pain crisis

Question 8

Consequence of autosplenectomy in Sickle cell?

Answer 8

Increased risk of infection with encapsulated organisms such as S. pneumoniea and H. influenzae.

Increased risk of Salmonella paratyphi

Question 9

How to Dx Sickle Cell Anemia?

Answer 9

Hb electrophoresis to confirm the presence of HbS!!

Question 10

MCC of death in children with Sickle cell?

Answer 10

Infections due to H. influenzae (autosplenectomy)

Question 11

How does someone get Sickle Cell Trait and NOT Sickle cell disease?

Answer 11

If only one beta chain is mutated then less than 50% of RBCs have HbS.

Question 12

Pathogenesis of PNH?

Answer 12

DAF is anchored onto RBC cell membrane by GPI which protects RBC from the complement system.

Acquired defect in MYELOID STEM cells resulting in absent GPI :

susceptible to destruction by complement.

Question 13

PNH intravascular or extravascular? So signs of PNH?

Answer 13

Intravascular: hemoglobinemia, hemoglobinuria, hemoglobinsideruria.

Question 14

So what cell(s) is (are) destroyed in PNH?

Answer 14

RBC
WBC
Platelets

defect is in myeloid stem cell!

Question 15

How do you diagnose PNH?

Answer 15

flow cytometry to detect lack of DAF

Question 16

MCC of death in in PNH?

Answer 16

Thrombosis because of platelet rupture.

Question 17

Pathogenesis of G6PD?

Answer 17

X-Linked Recessive disorder resulting in a reduced half life of G6PD = cells more susceptible to oxidative stress

G6PH makes NADPH, NADPH is needed to regenerated reduced glutathione so it can neutralize H202.

No G6PD, No NADH, no reduced form of glutathoine to neutralize H202 –> intravascular hemolysis.

Question 18

Are there types of G6PD?

Answer 18

Yes, African- mildy reduced half life
Mediterranean- markeldy reduced half life

Both likely due to protective role against falciparum malaria.

Question 19

How do you screen for G6PD?

Answer 19

Oxidative stress causes precipitation of Hb to Heinz bodies.

These Heinz bodies are removed from RBCs by splenic macrophages: BITE CELLS.

Heinz preparation is used to screen with Heinz stain.

Question 20

Pathogenesis of Immune Hemolytic Anemia

Answer 20

antibody mediated (IgM/IgG) destruction of RBC’s.

IgG usually extravascular hemolysis.
Associated with SLE, CLL and certain drugs

IgM usually intravascular hemolysis
Associated with M. pneumoniae and infectious mononucleosis

Question 21

How do you dx Immune Hemolytic Anemia

Answer 21

Coombs Test!

Direct- Get pt’s RBC’s and add anti-IgG. Agglutination will occur if there were RBCs were coated with IgG.

Indirect- Get patients serum and add test RBCs. If there are Ab, they will bind the test RBCs and then add your anti-IgG. Agglutination will occur if serum antibodies were present.