Question | Answer |
Autosomal recessive, pain in extremities after exercise, priapism | Sickle cell disease |
Thalassemia genetics | alpha: 2/2 gene deletion (2 genes on chromosome 16); beta: 2/2 point mutation (1 gene on chromosome 11) |
Microcytosis out of proportion to the anemia = | thalassemia |
Thalassemia: alpha globin chains | 1 chain = Hgb H dz; all 4 chains deleted: hydrops fetalis (stillbirth); silent carrier = 1 gene deleted (nml MCV). Hgb A (trait) |
thalassemia tx | Avoid Fe; Hgb H: folate supp, poss splenectomy; beta: transfusions (deferoxamine vs hemosiderosis); allo BMT |
Cooley anemia AKA: | beta thalassemia major |
beta thalassemia major S/S | sx onset 4-6 mos old; growth probs, abnormal facies, fx's, osteopenia, bone deforms, HSM, jaundice |
Splenectomy: PPx tx includes: | Pneumococcal vaccine |
SCD complications | AVN of femoral head; cholelithiasis, splenomeg, Strep pneumo infxn, stroke, priapism, retinopathies, osteomyelitis |
Due to spectrin protein in cytoskeleton | Hereditary spherocytosis |
Triad: anemia, splenomegaly and jaundice | Hereditary spherocytosis |
Episodic hemolytic anemia related to oxidative stress (hereditary) | G6PD def |
2 RBC conditions w/pigment gallstones | Hereditary spherocytosis, sickle cell |
Degrees of thalassemia disease | Hydrops fetalis = all 4 genes deleted (fatal); Hgb-H dz = 3 deleted (MCV=60-70); A-thal trait = 2 genes (MCV=70-80); silent carrier = 1 gene deleted |
Thalassemia: Hgb-H dz labs | Hgb elect = 10-40% Hgb H; retic is high |
Beta thalassemia types | Major (Cooley's): both beta globin genes mutated, severe anemia, txn dept; intermedia: txn in stress; minor rarely need txn |
Tx for Hgb H disease | Splenectomy? & folic acid |
Tx for beta thalassemia major | Txn, splenectomy, Fe chelation; allogeneic BM trans to cure |
Enzyme disorder: adequate Fe but can't get it into Hgb; Fe accumulates in ? | Sideroblastic anemia; in RBC mitochondria |
Sideroblastic findings | High serum Fe, large spleen/liver; mod anemia, low MCV; BM sideroblasts |
Tx: Sideroblastic anemia | Dept on cause (ETOH, Pb, leukemia, TB Rx); txn/chelation |
Anemia due to spectrin protein in cytoskeleton | Hereditary spherocytosis |
Triad: anemia, splenomegaly and jaundice | Hereditary spherocytosis |
Pigment type gallstones; chronic leg ulcers | Hereditary spherocytosis |
Hereditary spherocytosis findings | Mod micro anemia; reticulocytosis; high indirect bili; Neg coombs |
Hereditary spherocytosis tx | Folic acid 1mg po qd; splenectomy for severe |
G6PD def prevalence | >200M worldwide (usu AA men); X linked recessive; females rare |
Stress triggers of G6PD def | Infxns; toxins/drugs (sulfa/antimalarial); fava beans |
G6PD deficiency findings | N/N anemia. No splenomegaly or chronic hemolytic anemia; bite cells/Heinz bodies; Reticulocytosis and increased bili in crisis. |
G6PD def tx | Splenectomy for severe; (txn rarely); avoid stressors (ASA,sulfa, antimal, fava) |
Autosomal recessive disorder in which abnormal Hgb leads to chronic hemolysis | Sickle cell disorders |
In sickle cell dz, rate of sickling depends on: | Conc of Hgb S, dehydration, presence of other Hgb (F), hypoxemia & acidosis |
Sickle cell prevalence | 8% of AA: Hgb S gene; 1/400 AA have SSA; onset in 1st yr (Hgb F falls); 40-50 yr life exp |
S/S = Pallor, jaundice, splenomegaly, leg ulcers, pigment gallstones, priapism | Sickle cell |
Sickle cell: vascular occlusion leading to infarction | Pulmonary (acute chest syndrome); Retinal (blindness?); Renal (to renal failure ); Stroke, even in kids; Splenic infarcts; aseptic necrosis of femoral head |
Sickle cell tx | Folic acid 1 mg po qd; hydrate, low alt, vax (flu/pneumo/mening) |
Sickle Cell A long-term issues | Splenectomy: infxn probs; narco abuse; Hydroxurea to increase Hgb F |
Total absence of alpha-globin genes = | hydrops fetalis (Hgb Bart's: tetramer of 4 gamma globulin chains). Results in stillbirth |
SCD pathology | Hgb S occurs when valine substitutes for glutamic acid on beta-chain. Decreased Hgb S solubility in hypoxic tissues -> sickling |
Most severe form of thalassemia | Beta thal major (minor is like iron def anemia). FTT, Mediterranean. |