inherited hematologic disorders

Question 0

Thalassemia

Answer 0

B thal trait: Decreased production of B globin chain, microchip anemia
B thal disease: no production of B globin chain, severe anemia, transfusion dependent
a thal disease: loss of all 4 alleles leads to fetal demise

Question 1

Sickle cell disease

Answer 1

Autosomal recessive
Mutation in the B globin chain
Vasoocclusive crisis: bone pain, splenic sequestration, acute chest, stroke
Hb C and E are less common
Hb SC and SE with more severe disease

Question 2

Hereditary sphere cytosine

Answer 2

Autosomal dominant

Anemia, jaundice, reticulocytosis, gallstones, and splenomegaly

Question 3

Hereditary elliptocytosis

Answer 3

Autosomal dominant
Mild compensated hemolysis
Screen for gallstones

Question 4

Pyruvate kinase deficiency

Answer 4

Glycolysis pathway deficiency
Autosomal recessive
Leads to chronic hemolysis

Question 5

Phosphoglycerate kinase deficiency

Answer 5

X linked
Chronic hemolysis
Failure of glycolysis which RBCs depend on for ATP

Question 6

Glucose 6 phosphate deficiency

Answer 6

X linked
G6PD responsible for production of the reduced form of NADPH which is critical for preventing oxidative damage to RBCs
Anemia progresses when patients are exposed to oxidative stress leading to RBC lysis

Question 7

Hemophilia

Answer 7

A: deficiency in factor VIII
B: deficiency in factor IX
X linked
Bleed into joints, bleed from circumcision

Question 8

Von willebrand disease

Answer 8

Defect in Von willebrand factor
Type I is autosomal dominant with variable penetrance
Nosebleeds, bruising, heavy periods, post op or post partum hemorrhage

Question 9

Glanzmann thrombasthenia

Answer 9

Autosomal recessive
Platelets lack glycoproteins IIbIIIa which binds plts to fibrinogen leading to clot formation
Normal plt counts
Recurrent nosebleeds, GI bleeding, and menorrhagia

Question 10

Bernard soulier syndrome

Answer 10

Autosomal recessive
Deficiency of glycoprotein Ib, which binds plts to VWF and thrombin
Muco cutaneous bleeding
thrombocytopenia
Giant plts

Question 11

TAR Syndrome

Answer 11

Thrombocytopenia absent radii syndrome with presence of the thumbs
Platelet count normalizes by one year
Upper ext abnl: phocomelia, hypoplasia of ulna or humerous, club hand, syndactyly, clinodactyly
Cardiac: septal defects
Facial: micrognathia, tall and broad forehead, low and posteriorly rotated ears
Macrocephaly, short stature
Milk gastroenteritis with diarrhea and FTT
Prevention with soft helmet and prolonged pressure on immunization sites

Question 12

Wiskott Aldrich syndrome

Answer 12

X linked
Small and severely depressed plt counts
Eczema
Impaired immune function

Question 13

Antithrombin deficiency

Answer 13

Autosomal dominant with variable penetrance

Increased risk for thrombosis

Question 14

Factor V Leiden mutation

Answer 14

Leads to factor Va being resistant to degradation by activated protein C
Increased risk of thrombosis in homozygotes

Question 15

Prothrombin G20210a mutation

Answer 15

Increases prothrombin biosynthesis

Predisposition to DVT

Question 16

MTHFR deficiency

Answer 16

Hyperhomocysteinemia

Increased risk for thrombosis