Hematologic Disorders

Question 1

Acute Intermittent Porphyria

Answer 1

Gene: HMBS (AD)
Clinical Features: acute attacks of abdominal pain, muscle weakness, No cutaneous findings
Onset: late childhood, after puberty
Clinical tests: urine porphobilinogen (PBG) during attack
Treatment: stop the precipitating event/substance

Question 2

Alpha thalassemia

Answer 2

Gene: HBA1, HBA2 (AR)
Clinical features:
HB Bart: loss of all 4 alpha alleles: hydrops fetalis, severe anemia, neonatal death
HbH: loss of 3 alleles- anemia, jaundice
alpha trait- loss of 2 alleles- low MCV, normal levels of Hgb A2 and F
silent carrier- loss of 1 allele, no or mild effect
Clinical tests: Prenatal screen for at risk pops! MCV, MCH, hemoglobin electrophoresis
Treatment: Hb Bart- no treatment; HbH- transfusions during hemolytic crisis

Question 3

Beta Thalassemia

Answer 3

Gene: HBB (AR)
Clinical features: severe anemia, FTT, early death
clinical test: pheripheral blood smear, MCV, MCH
Mechanism-absence of beta chain> non-assembled alpha chains that precipitate in marror and spleen>deficient erythropoiesis
Treatment: transfusion and chelation therapy

Question 4

Factor V Leiden Thrombophilia

Answer 4

Gene: F5 (AD/AR)
AD a/w moderate risk, AR a/ w high risk
Clinical Features: risk for venous thromboembolism. Not a/w Arterial thrombosis, MI, stroke
Clinical tests: APC
Molecular tests: 100% caused by c.1691G>A missense
Mechanism: missense affects APC cleavage site>resists degradation>inc thrombin generation
Treatment: anticoagulants

Question 5

Hemophilia A

Answer 5

Gene: F8 (XLR)
Clinical Features: intracranial bleed w/o trauma, deep muscle hematomas, prolonged bleeding, excessive bruising
Clinical tests: prolonged PTT, F8 activity
Molecular tests: Severe: mostly intron 22 inversion or LOF
Mild: mostly missense
Mechanism: F8 is a clotting factor, LOF>no clotting
Treatment: IV Factor 8

Question 6

Hemophilia B

Answer 6

Gene: F9 (XLR)
Clinical features: intracranial bleed w/o trauma, deep muscle hematomas, prolonged bleeding, excessive bruising
Clinical tests: prolonged PTT, F8 activity
Molecular tests: mostly LOF
Mechanism: F9 activated FX, which regulates thrombin (clotting) response
Treatment: IV F9