Heme Review Flashcards
Lab values for iron def anemia?
Ferritin down, iron down, TIBC up, percent saturation
MCV of iron deficiency anemia?
Normocytic, then microcytic.
Alpha thalassemia
Decrease in alpha globin chains due to deletions. 4 genes. 1 or 2 deletions is fine. Cis deletion is worse. 3 Deletions causes severe anemia. Beta tetramers HBH form which are toxic to RBCs and cause RBC death. 4 deletions is incompatible with life and causes hydrops fetalis.
Beta thalassemia
Due to mutations of the beta globin genes. Prevalent in mediterranean populations. Thalassemia minor has slight increase in HBA2. Thalassemia major has massive erythroid hyperplasia in skull in facial bones. A2A2 is formed which is toxic and leads to extravascular hemolysis.
Lead poisoning
Destroys ferrochelatase and ALAD. Prevents rRNA degeneration which causes basophilic stippling. Abdominal colic and sideroblastic anemia.
How to treat lead poisoning
Dimercaprol and EDTA. Succimer in kids.
Sideroblastic anemia
due to a genetic mutation in ALAS. No protoporphyrin so free iron in mitochondria. Can be caused by b6 deficiency isoniazid and MDS. Iron up, tibc normal, increased ferritin. b6 for treatment.
Things that cause nonmegaloblastic microcytic anemias
Liver disease, alcoholism, 5FU, zidovudine, hydroxyurea.
Orotic aciduria
Due to a lack of UMP synthase that causes orotate to build up in cells. This causes a megaloblastic anemia in kids that cannot be cured with folate or B12. This doesn’t have hyperammonemia like ornithine transcarbamylase deficiency does.
Orotic aciduria
Due to a lack of UMP synthase that causes orotate to build up in cells. This causes a megaloblastic anemia in kids that cannot be cured with folate or B12. This doesn’t have hyperammonemia like ornithine transcarbamylase deficiency does.
Consequences of extravascular hemolysis
Anemia, increased unconjugated bilirubin in blood, splenomegaly due to work hypertrophy of macrophages. Can cause jaundice or bilirubin gallstones
What diseases are characterized by extravascular hemolysis?
Hereditary spherocytosis Sickle Cell Anemia G6PD deficiency Pyruvate Kinase Deficiency IgG autoimmune hemolytic anemia (SLE, CLL, methyldopa)
Defect in hereditary spherocytosis
Ankyrin spectrin missing, autosomal dominant. Loss of central pallor can’t pass through sinusoids – extravascular hemolysis
Defect in sickle cell
Glutamate to valine at position 6, causes sickling in hypoxic conditions and eventually irreversible sickling. Some intravascular hemolysis as well causing decreased haptoglobin.
Metabisulfate screen
Will cause sickling of RBCs even with sickle cell trait.
What diseases are characterized by extravascular hemolysis?
Hereditary spherocytosis
Sickle Cell Anemia
Pyruvate Kinase Deficiency
IgG autoimmune hemolytic anemia (SLE, CLL, methyldopa)
G6PD Deficiency
Mostly intravascular hemolysis causing hemoglobinuria and back pain. Most common deficiency where halflife is markedly reduced. African variant and mediterranian variant. Mediterranian is worse. No NADPH can be generated so glutathione can’t be reduced back to GSH to help get rid of H2O2. Free radical damage causes aggregates of hemoglobin called heinz bodies. Bite cells.
Free radicals from fava beans, sulfa drugs, antimalarials,
Pyruvate kinase deficiency
Disease of the newborn where RBCs cannot generate ATP and become very rigid.
Pyruvate kinase deficiency
Disease of the newborn where RBCs cannot generate ATP and become very rigid.
Diseases with predominantly intravascular hemolysis
G6PD deficiency
IgM mediated hemolysis
PNH
TTP/HUS
What happens with intravascular hemolysis?
Increased serum hemoglobin, decreased serum haptoglobin, hemoglobinuria, hemosiderinuria days later.
PNH and treatment
No gpi anchor, complement mediated lysis treat with eculizumab (terminates complement).
IgM autoimmune hemolytic anemia
Cold agglutinins cause hemolytic anemia intravascularly also happens with mycoplasma and mono.
TTP
Defect in ADAMTS13 that breaks vWF down. Platelet aggregation everywhere causes schistocytes.
