Module 1: G6PD deficiency; Sickle Cell and Paroxysmal Nocturnal Hemo Flashcards
What kind of anemia is G6PD deficiency?
Normocytic Anemia with predominant Intravascular hemolysis with also Extravascular hemolysis (only case where its both)
–periodic not chronic
What inheritance pattern is G6PD?
X linked recessive
- -mediterranean, asian and African
- -all men because its x linked
What are the two main type of G6PD deficiency mutation?
G6PD A: African Variant: milder version (only older RBCs are affected)
G6PD B: Mediterranean Variant: More severe ( even younger RBCs are affected)
What is the pathogenesis for G6PD deficiency mutation?
Defect in the hexose monophosphate shunt
G6PD dehydrogenase reduces NAD to NADPH
–NADPH keeps glutathione in the reduced form and therefore keeping glutathione in the reduced form is a protection mechanism from oxidative stress which happens all the time
—In G6DP deficiency there is a decreased half life of G6PD therefore decreased NADPH and decreased reduced glutathione so cells are prone to oxidative stress by H202 (intravascular hemolysis part)
G6PD deficiency is considered episodic not chronic why?
only happens when the cell undergoes oxidative stress
- -Triggers include:
1. Infection (particularly pneumonia)
2. Fava beans (aka diet)
3. Sulfa Drugs - –oxidative stress in intravascular hemolysis
G6PD deficiency is considered intravascular as well as extravascular hemolysis.Explain the two mechanisms
Oxidative stress ——– oxidation of SH groups on globin chains of Hb —- Hb precipitate as Heinz Bodies —- intravascular hemolysis (predominant) — Hemoglobinuria and Hemoglobinemia
—splenic macrophages pick up the Heinz bodies and literally take a bite out of the RBC and eat the Heinz bodies —- extravascular hemolysis
What is the presentation for G6PD deficiency?
Acute hemolysis Fever Jaundice Fatigue Dark Urine (due to free Hb in the intravascular hemolysis)
What are the two stains for G6PD deficiency?
Crystal Violet or Supra Vital Stain (aka green): allows you to see oxidize globin chains aka heinz bodies
Wright-Giemsa Stain: see bite cells directly from the spleen consequence of extravascular hemolysis
What is seen on peripheral blood smear in a patient with G6PD deficiency?
No spherocytes seen on peripheral smear
–do see reticulocytes, heinz bodies and bite cells
What do you see in the bone marrow of a patient with G6PD deficiency?
Erythroid Hyperplasia: bone marrow compensating by forming lots of RBCs
What is the best investigation for G6PD deficiency?
G6PD assay also called enzyme assay
—have to wait a few weeks after hemolytic crisis to do this test because reticulocytes have a normal half life but as they mature into erythrocytes the half life decreases
What do you see as far as lab values in patients with G6PD deficiency?
- Increased LDH
- Unconjugated Bilirubin
- Hyperkalemia
- Hemoglobinemia (due to increased free Hb due to destruction of RBC in the intravascular space)
- Increased Reticulocytes
- Decreased heptoglobin (protein produced by the liver and this protein mops up free hemoglobin in the blood. the levels are reduced because they are getting used up trying to mop up the mess aka free Hb)
- In urine: free Hb —- hemoglobinuria and hemosiderin = hemosiderinuria
What is the complication of patients with G6PD deficiency?
None — self limiting so complete resolution
–note no splenomegaly
If a patient with G6PD gets involved in a car accident and needs his spleen taken out and does not get the needed yearly vaccines and therefore keeps getting infections, what could be a complication?
Acute tubular necrosis (Excess hemoglobin is damaging the renal tubules aka nephrotoxic)
What type of anemia is sickle cell?
Normocytic anemia with predominant extravascular hemolysis
What is the inheritance pattern of sickle cell anemia?
Autosomal recessive point mutation (also called missense mutation) at position 6 of Beta Chain
- -glutamic acid replaced by valine
- -happens in Africans
Explain the bands seen in normal individuals?
HbA2: alpha 2 and delta 2 (Everyone has this no function at all – like 1-2%)
HbF (after 6 months of age expires)
HbA (we all have this in large quanities)
Explain the bands of a carrier/trait (heterozygote carrier)
HbA, HbS (asymptomatic) ---55% HbA --43% HbS ---2% HbA2 RBCs with less than 50% HbS don't sickle in vivo except in renal medulla during extreme hypoxia/hypertonicity of the medulla
Explain the bands of a sickle cell patient (homozygous)
HbS & HbS (again extravascular)
- -90% HbS
- -8% HbF
- -2% HbA2
- –no HbA
A crisis is due to an increase of sickling of the RBC’s, what are these crisis events caused by?
- Hypoxia (long flights)
- Acidosis
- Infection
- Dehydration
- Hypothermia
Explain the 4 different sickle cell crisis’s
- Aplastic crisis: caused by parvo virus B19
- Vaso-occlusive Crisis: bone and joint pain due to ischemia due to sickeled RBC sticking together in the vessels
- Splenic Crisis (splenic sequestration): formation of a white infarction leading to coagulative necrosis of the spleen
- Hemolytic Crisis: Happens in the spleen (Spleen is actually destroying the sickle cells aka splenic macrophages)
What is the pathogenesis for sickle cell anemia?
HbS polymerizes (or crystalizes) when deoxygenated --- polymers aggregate into needle like structures --- sickle cells (note: prone to small vessel thrombosis)
What do you find in the blood of patients with sickle cell?
Increased Reticulocytes Increased LDH Increased unconjugated bilirubin Increased free Hb (dark urine) Decreased haptoglobin (cleaning up all the free Hb, getting used up super fast) Increased potassium
What do you see on a blood smear in patients with sickle cell?
Sickle cells
Target cells (hemoglobin settling in center of RBCs — looks like an actual target)
Reticulocytes
Howell-Jolly Bodies
