Krafts' Anemia: Round 2 Flashcards
Warm Autoimmune Hemolytic Anemia
Secondary: Leukemia/lymphoma Other malignancies Autoimmune disorders Infections Drugs
Pathogenesis:
IgG coats red cells
Macrophages either:
wolf red cells down whole (cells disappear)
nibble at red cells (cells become spherocytes)
Clinical: Any age, sex Variable severity Splenomegaly Morphology Spherocytosis
Diagnosis:
DAT (direct antibody test)
Treatment:
Steroids
Splenectomy if necessary
Cold Autoimmune Hemolytic Anemia
Things You Must Know:
IgM, complement
Intravascular hemolysis
Agglutination
Pathogenesis of CAHA: IgM, complement coat red cells IgM falls off in warm body parts IgM bridges red cells (agglutination) Complement lyses red cells
Clinical:
Chronic hemolysis aggravated by cold
Pallor, cyanosis in cold body parts
Morphology:
Red cell agglutinates
Rare spherocytes
Diagnosis:
DAT positive for complement
Treatment:
Keep patient warm
Treat underlying cause
Hemoglobinopathies
Things You Must Know:
Qualitative hemoglobin abnormality
Sickle cell is the most important
Sickle cells hemolysis, vaso-occlusion
Structurally abnormal hemoglobin
Often one amino acid away from normal!
Best lab test: hemoglobin electrophoresis
Most important one: sickle cell anemia
biochem of sickle cell
Point mutation in beta chain gene leads to... abnormal beta chains (substitution of valine for glutamate) leads to... HgbS Aggregates and polymerizes on deoxygenation Red cell becomes sickle shaped Sickles clog up vessels… …plus, they are fragile
Clinical Findings in Sickle Cell Anemia
Blacks (8% are heterozygous) Severity of disease is variable Chronic hemolysis Vaso-occlusive disease increased infections (autosplenectomy)
Morphology of Sickle Cell Anemia
Sickle cells “Post-splenectomy blood picture”: nucleated red blood cells targets Howell-Jolly bodies Pappenheimer bodies increased platelet count
Treatment of Sickle Cell Anemia
Prevent triggers: infection fever dehydration hypoxemia
Vaccinate against encapsulated bugs:
S. pneumoniae
H. influenzae
Blood transfusions
Bone marrow transplantation
Thalassemia
Things You Must Know: Quantitative defect in hemoglobin Can’t make enough α or β chains Variable disease severity Hypochromic, microcytic anemia with increased RBC and target cells
Genes in Thalassemia
Normal globin genes:
4 alpha-chain genes
2 beta-chain genes
Globin genes in thalassemia:
alpha-thal: deletion of alpha-chain gene(s)
beta-thal: defective beta-chain gene(s)
Globin chains in thalassemia
alpha-thal: decreased amount alpha chains
beta-thal: decreased amount beta chains
Problem: defective transcription, translation, or processing of mRNA of -chain gene Severity of defect: beta gene: normal gene beta+ gene: produces some chains beta0 gene: produces no chains
What causes the anemia in thalassemia?
alpha-thalassemia Not enough alpha chains Excess unpaired beta, gamma, or delta chains Newborns: gama4 tetramers (Hb Barts) Adults: B4 tetramers (HbH)
B-thalassemia
Not enough B chains
Excess unpaired a chains
Morphology of Thalassemia
Hypochromic, microcytic anemia Depending on severity: minimal anisocytosis and poikilocytosis marked anisocytosis and poikilocytosis Target cells Basophilic stippling
Clinical Findings in a-Thalassemia
Asians, blacks
Carrier state and thal trait: asymptomatic
HbH disease: moderate to severe disease
Hydrops fetalis: fatal in utero
Clinical Findings in B-Thalassemia
Mediterraneans, Blacks, Asians
Thal minor: usually asymptomatic
Thal major: variable severity, usually presents in infancy
Glucose-6-Phosphate Dehydrogenase Deficiency
Things You Must Know decrease G6PD → increase peroxides → cell lysis Oxidant exposure Bite cells (removal of Heinz bodies) Self-limiting
The highest incidence of G6PD is in areas where malaria is endemic
Why Do G6PD-Deficient Red Cells Die?
They can’t reduce nasties Nasties attack hemoglobin bonds Heme breaks away from globin Globin denatures, sticks to red cell membrane (“Heinz body”) Spleen bites out Heinz bodies
