Sickle Cell DIsease, G6PD Deficiency & Other Hemolytic Anemias

Question 1

Disease that gives inherent resistance to Falciparum malariae

Answer 1

Sickle Cell Disease

Question 2

What causes the formation of HbS in SCD?

Answer 2

Replacement of Glutamate with Valine at Beta-6 position

Question 3

What makes the RBC sticky in SCD? What are it’s consequences?

Answer 3

HbS polymerization makes the RBC sticky and it results in micro-occlusions in blood vessels, leading to organ infarction.

Question 4

Do the px. w/ SCD present with pathological jaundice? Why?

Answer 4

Nope. Cuz for the 1st 6 months after birth, HbF plays a protective role and the damaged HbS doesn’t show symptoms.

Question 5

Till what age is SCD asymptomatic?

Answer 5

Till 6 months of age. Beyond which HbF decreases and the patient starts showing symptoms of SCD.

Question 6

Most common presentation of SCD? Other symptoms?

Answer 6

Most common: Fever>Pain (d/t vaso-occlusive crisis)

Question 7

Age of presentation of Hand Foot Syndrome?

Answer 7

HFS presents in >5yrs old children.

Question 8

Hand foot syndrome vs Osteomyelitis

Answer 8

HFS can be confused with osteomyelitis but the difference is that OM mostly has infective etiology and mostly affects the long bones, U.L HFS.

Question 9

Hand foot syndrome also seen in?

Answer 9

A.S.I px. undergoing chemotherapy with Capecitabane or 5-Fluorouracil. Known as Palmer-Planter Acrodysthesia.

Symptoms include: Redness, desquamation & pain over palm and sole of foot

Question 10

DOC for pulmonary artery HTN

Answer 10

Bosentan

Question 11

Autosplenectomy predisposes px. to what organisms? Mgmt.?

Answer 11

Capsulated organisms (Pneumococcus, Meningiococcus, H. inlfuenza)

Managed by vaccination

Question 12

Acute chest syndrome vs Acute coronary syndrome

Answer 12

• Acute chest syndrome occurs due to occlusion of small coronary vessels by the sticky HbS, leading to coronary infarction.
• Acute coronary syndrome is due to atherosclerosis.

Question 13

Homozygous vs heterozygous SCD

Answer 13

HOMOZYGOUS

 - early & more severe manifestation (~3yrs of age)
 - A.K.A Sickle cell DISEASE
 - Lack HbA (HbS,  HbF, HbA2 present)

HETEROZYGOUS

 - late presentation cuz px. already has enough HbA to avoid symptoms but will develop symptoms oof SCD with some triggers like dehydration & hypoxia which causes HbS polymerization leading to sickling episodes.
 - A.K.A Sickle cell TRAIT
 - Has all 4 types of Hb (HbS, HbF, HbA & HbA2) present

Question 14

IOC for SCD

Answer 14

High Performance Liquid Chromatography > Hb Electrophoresis

Question 16

Workup of a SCD px.

Answer 16

1) Peripheral smear: i) Dec. Hb d/t extravascular hemolysis
d/t rigid RBCs stuck in splenic
capillaries —— J.L Hered. Sphero.)
ii) Sickle cell
2) Reticulocyte count: Increased (J.L other hemolytic anemias)
3) IOC: HPLC>Hb electrophoresis (High Performance Liq. Chromatog.)
4) USG abdomen: to evaluate spleen size and kidney status
5) Echo T.T.E: to evaluate ischemic/dilated cardiomyopathy
6) X-Ray Hand/Foot: to look for dactylitis and to R/O osteomyelitis

Question 17

Management of SCD

Answer 17

1) Hydroxyurea (decreases sickling episodes)
2) Fentanyl/Morphine/Codeine (for bone pain)
3) Bosentan if PAH present
4) During sickling episodes: i) Analgesics mentioned in (2)
ii) Whole blood transfusion

• Packed RBCs not given as it will increase the viscosity of blood leading to increased incidence of sickling episodes.
• No TOC for SCD

Question 18

Peripheral smear findings in splenectomy patients

Answer 18

1) Cabot Ring

2) Howell Jolly Bodies

Question 19

Symptoms of SCD

Answer 19

1) Fever and pain
2) Hand Foot Syndrome (Dactylitis) caused by occlusion of nutrient artery by HbS.
3) Avascular necrosis of bone (MRI)
4) Autosplenectomy (~3yr) d/t splenic infarction
5) Coronary infarction leading to dilated cardiomyopathy (— causing acute chest syndrome)
6) Pulmonary vaso-occlusive episodes (PAH)
7) Kidney - Papillary necrosis/isostheuria (inability to conc. & dilute urine d/t damage to the collecting duct present at the renal papilla)
8) Hemolytic gall stones
9) Non-healing ulcers on medial malleolus (J.L: Hered. Sphero.)
10) Aplastic Crisis (Human Parvo virus B19)

Question 21

Triggers of G6PD def.

Answer 21

1) Fava beans
2) Antimalarial drugs (Primaquine)
3) Aspirin
4) Nitrofurantoin etc.

Question 22

Function of G6PD? What happens in G6PDD?

Answer 22

Neutralizes the free radical induced damage inside RBC

In G6PDD, unopposed oxidative stress leads to complement mediated intravascular hemolysis, resulting in hemoglobinemia (Free Hb in blood) which in turn leads to hemoglobinuria (black urine). Hemoglobinuria may lead to acute tubular necrosis [d/t blockage of tubules by hemoglobin (high molecular wt.)], causing death.

Question 23

M.C.C of death in px. w/ G6PDD

Answer 23

Acute tubular necrosis

Question 24

Kind of hemolysis in G6PDD

Answer 24

G6PDD is an example of INTRAVASCULAR as well as EXTRAVASCULAR hemolysis.

• If the question mentions a trigger (like fava beans intake or administration of anti-malarial drugs), then it’s INTRAvascular hemolysis.

Question 25

Drugs to be avoided in G6PDD

Answer 25

“PCM NA”

P: Primaquine
C: Chloroquine
M: Mefloquine

N: Nitrofurantoin
A: Aspirin, sulfa drugs (Sulfonamide)

Question 26

Anti-malarial drugs that can be given to G6PDD px.

Answer 26

1) Artesunate

2) Artemisinin

Question 27

Two major classes of antibodies causing Auto-Immune Hemolytic anemias

Answer 27

1) Warm antibodies (IgG class) | 2) Cold Antibodies (IgG & IgM)

Question 28

Examples of warm antibodies

Answer 28

1) SLE 2) CLL (m.c adult blood cancer) 3) . NHL 4) Alpha-Methldopa

Question 29

Types and features of Cold Antibodies mediated AIHA

Answer 29

Two types: 1) Paroxysmal Cold Hemoglobinuria (IgG mediated) - Mycoplasma pneumoniae inf. leads to production of DONATH LANDSTEINER ANTIBODIES which attacks self RBCs at low body temp. leading to hemoglobinemia and then to hemoglobinuria. 2) Cold-agglutinin syndrome (IgM mediated) - Molting of the acral parts (tip of nose, earlobes, fingertips) - BLACK URINE

Question 30

How does Donath Landsteiner Ab cause AIHA?

Answer 30

DONATH LANDSTEINER ANTIBODIES, which normally attacks the bacteria (Mycoplasma pneumoniae) may end up accidentally attacking self RBCs. This happens because DLA usually attacks the “M Protein” on the surface of the bacteria and RBCs also have a protein structurally similar to the M proteins on the bacteria.

Question 31

Presentation of px. w/ AIHA

Answer 31

- Pallor, body malaise/chest pain | - Palpitations/Pedal edema

Question 32

Work up of AIHA

Answer 32

- Peripheral smear: i) Dec. Hb ii) Spherocytes (A.S.I Hered. Sphero.) - IOC: Direct Coomb’s Test

Question 33

Management of AIHA

Answer 33

Cause specific but usually steroids

Question 34

Peripheral smear characteristics of Microangiopathic Hemolytic Anemia

Answer 34

- Schistocytes/HELMET CELLS - Echinoctes/BURR CELLS * MAHA: Complement mediated damage to RBC

Question 35

Causes of MAHA

Answer 35

1) Hemolytic Uremic Syndrome (caused by E.coli 0157 H7 which is an enterohemorrhagic E. coli and releases shiga toxin causes activation of complement system and in turn MAHA) 2) Thrombotic Thrombocytopenic Purpura (Variant of HUS) PENTAD - i) Fever ii) Acute Ischemic Stroke iii) Hemolysis iv) Uremia/Renal variety AKI v) Purpura (Palpable bleed) 3) Metallic Prosthetic Heart Valves

Question 36

Work up of px. w/ MAHA

Answer 36

1) Direct Coombs Test: NEGATIVE (HA are always positive for coombs test. So, MAHA is a.k.a Cooombs negative hemolytic anemia) 2) Peripheral smear: Helmet cells and Burr cells

Question 37

Management of MAHA

Answer 37

Cause specific (Usually conservative. If HUS: Dialysis)

Question 38

Investigations/work up in G6PDD px.

Answer 38

1) G6PD Assay (IOC) 2) Peripheral smear: i) Dec. Hb ii) BITE CELLS iii) HEINZ BODIES [on Supravital (Crystal violet) stain] * Heinz bodies: Denatured Hb d/t oxidative stress

Question 39

IOC for G6PDD

Answer 39

G6PD assay

Question 40

Blood smear results: 1) Flower cells 2) Sezary cells 3) Mott cells 4) Spurr cell/Acanthocytes 5) Schistocyte/Helmet cells 6) Howel Jolly Bodies and Calot rings

Answer 40

1) Flower cells: Adult T cell leukemia by HTLV-1 2) Sezary Cells: T cell Non-Hodgkin’s Lmphoma 3) Mott cells: Multiple Myeloma (Russel bodies) 4) Spurr cell/Acanthocytes: Abetalipoproteinemia (caused by Vit. E def.) 5) Schistocytes/Helmet cells: HUS/TTP 6) Howel jolly bodies and Calot rings: Asplenia