5. Haemolytic Anemias: Membranopathies And Enzymopathies Flashcards
List two types of Hereditary Hemolytic anemia that are caused by membrane defects
Hereditary spherocytosis HS
Hereditary elliptocytosis
What is the most common hereditary hemolytic anemia in Northern Europeans
Hereditary spherocytosis HS
List seven steps for the pathogenesis of Hereditary spherocytosis
Deficient or defective membrane proteins Membrane instability Lack of deformability Mature erythrocytes become spherocytic Splenic trapping and phagocytosis Extravascular hemolysis Splenomegaly (Due to this virus it takes shape of these red blood cells they are unable to pass through microvascular spleen vessels and they die prematurely there)
What is the most common inheritance pattern of hereditary spherocytosis
Autosomal dominant
Anemia due to the hereditary spherocytosis presents at which age
At any age from infancy to old age
What are the three main clinical presentations of hereditary spherocytosis
Autosomal dominant inheritance
Splenomegaly
Anemia
Jaundice
(Some presents with pigment call stones)
List five laboratory features of hereditary spherocytosis including relative Reticulocyte, MCV and MCHC values
Variable anemia (severity of anemia is usually similar within families) MCV normal or decreased MCHC normal Blood film shows microspherocytes Reticulocytes I usually 5 to 20%
Read this case and diagnose the patient
A nine year old female jaundiced for several years Is admitted to the hospital at age 18 months and was transfused. Mother has no history of jaundice, father not available. Elder sister died at age 14 after operation for gallstones.
Physical examination shows peel mucosa, moderate jaundice, probable spleen 5 cm below left coastal margin
Results// Hemoglobin 7.5 g/dL MCV 71.0 FL MCHC 36 g/dL Direct Coombes test negative Osmotic fragility increased
Hereditary spherocytosis
What is the osmotic fragility test
It is a test used to measure erythrocyte resistance to hemolysis while being exposed to different levels of dilution of a saline solution
What is the purpose of Osmotic Fragility in testing for Hereditary Spherocytosis
Confirms the presence of HS
What does the Osmotic Fragility test for Hereditary Spherocytosis show
Increased
What is the principle form of treatment for hereditary spherocytosis
Splenectomy (avoided before age 4)
Splenectomy is required for hereditary spherocytosis treatment list three immunizations necessary for this treatment to take place
Haemophilus influenza
Streptococcus pneumoniae
Neisseria meningitidis
True or false most hereditary elliptoCytosis patients are clinically silent
True
What causes hereditary elliptocytosis
Abnormal spectrin
Which enzyme deficiency leads to defective red cell metabolism
Glucose-6-phosphate dehydrogenase deficiency G6PD
What is the function of G6PD
Reduces NADP the while oxidizing Glucose 6 Phosphate
NADP is needed to reduce glutathione (which maintains RBCs cell structure)
What is the result of Glutathione deficiency
Renders the red cell susceptible to oxidant stress
What is the inheritance of Glucose-6-phospate dehydrogenase deficiency
Sex linked, affecting males
And carried by females
Female carriers of G6PD deficiency show what amount of G6PD
1/2
Female G6PD deficiency heterozygotes have an advantage of resistance to which disease
Falciparum Malaria
What are the main races affected by G6PD deficiency
West Africa
Mediterranean
Middle East
South East Asia
What are the clinical features of G6PD deficiency
Usually asymptotic
Acute heamolytic anemia in response to oxidant stress
Neonatal Jaundice
Congenital Non-spherocytic haemolytic anemia (rare)
What are some conditions for ocidant stress that induce Acute Haemolytic Anemia in G6PD deficient patients
Drugs
Fava beans
Infections
What causes acute anemia in G6PD deficient patients
Rapidly developing intravascular haemolysis with haemoglobinuria
What is the blood count of the G6PD deficient patient between crises
Normal
What tests are performed to diagnose G6PD deficiency
Direct enzyme assay on RBCs
What is the presentation of the RBCs of a G6PD deficient patient on a blood film
Contracted or Fragmented cells
‘Bite’ cells/ ‘blister’ cells
((Which have heinz bodies removed by the spleen)
((Heinz bodies are oxidized, denatured Haemoglobein))
What are Heinz Bodies
Heinz bodies are oxidized, denatured Haemoglobein
What is the treatment for G6PD deficiency
- the offending drug (drug/source of oxidant stress)
- ## underlying infection treated
