Heme Flashcards
Hematopoiesis
Stem cells from mesoderm
Active sites hematopoiesis:
1. Yolk sac 2.5-10 wga early active site with blood cells as early as 16-19 days gestation declining hematopoiesis at 8 weeks
2. Fetal liver 5-6 weeks begins, primary 6-22
3. Bone marrow starts 8-19 weeks and primary at 22
Globin chain trends (alpha, beta, gamma, delta, epsilon
Epsilon: highest early gestatuon gone by 10 weeks
Alpha: starts around 5 weeks peeks 12+ weeks and plateaus
Beta: low starting just before 10 weeks slow increase and peaks after birth
Gamma: starts around alpha lower levels plateaus st lower amount snd then drops off slowly after birth
Delta: starts low level after birth - slight rise but stays low
Hb Gower 1 and 2
- Zeta2 epsilon2 embryonic by yolk
2. Alpha2 epsilon2 embryonic by yolk
Hb Portland
Zeta2gamma2 embryonic yolk sac
Hb F, HbA2, hBA
HbF alpha2 gamma2 fetal liver
HbA2 alpha2 delta2 adult bone marr
HbA alpha2 beta2 adult bone marr
Hb Barts, Hb H
Hb barts gamma4 fetal liver and bone marrow - seen increasing amts in alpha thalassemia
HbH beta 4 adult bone marrow - alpha thalassemia absence of 3 genes
Alpha thalassemia general
Defect of 1-4 alpha globin genes (chrom16)
Prevalent chinese, malaysia, indochina, Africa
May be detected ay birth
Beta thalassemia general
Defect in 1 or both beta globin genes chromosome 11
Prevalent mediterranean, Africa, Pakistan, India, Middle east
Usually
Not dx until after 6 mknths hen anemia persists beyond expected physiologic nadir
Alpha thal characteristics by number genes absent
1 gene = silent carrier normal Hb and clinical
2 genes = alpha thal trait - normal to increased Hb barts (4-6%) - mild microcytosis, hypochromia, erythrocytosis, may be asx
3 genes = hb H (4 beta chains) - infant 20-30% Barts and child 4-20% Hb H - moderatley severe hemolytic anemia, heinz bodies, may require splenectomy
No genes: 80-90% Barts (gamma4) no Hb A or F - rare very severe hydrops fetalis P50 «_space;P50 adult
Beta thal types
Trait (beta 0 or beta + mutation) mild increased A2 (alpha2 gamma2) and Hg F
Mild Microcytic, hypochromic anemia with tsrget cells
Beta thal disease - beta 0 or beta plus only - increased HbF (90%), increased A2.
Beta + 20-40% hb A, 60-80% F
Beta 0
Severe anemia first year with splenomegaly, poor growth, thalassemia bony changes, chrinic transfusions
Beta+ moderate anemia may not need transfusions
Hemoglobin E
Most common hemoglobinopathy in the world
Abnl transcription in beta globin genes ( glu for lys protein due to nucleotide substitution) leads to decreased beta chains resulting in mild chronic anemia
High in southeast asia (Laos, Cambodia, Thailand)
Can still form tetramer with alpha2 with potentially normal function
More severe anemia if inherit HbE allele with beta thal allele
KB vs Apt test
KB - done on maternal blood detects HbF - treat with citric acid-phosphate buffer adult Hb sipluble snd dissolved out - 1% = 50 mL fetal blood. False positive if maternal hemoglobinopathy with increased HbF
Apt - fone in fetal sample to detect maternal blood - add NaOH to sample fetal Hb is resistant to alkali densturation so appears pink and adult is yellow brown
Diamond Blackfan Anemia
“Congenital erythroid aplasia”
4-7/1,000,000 AD or AR (12-25% inherited)
Labs: pure red cell aplasia though some May have low plts and neutropenia; elevated HbF; elevated i vs I antigen present marker of fetal erythropoiesis
Sxs: by 4 months. Macrocytic anemia with reticulocytopenia in first year. No erythrocyte precursors in BM, increased serum erythropoietin, inc RBC adenosine deaminase levels
LBW, short stature, abnl facies, abnl musculature and triphalangeal thumbs, cardiac and renal anomalies possible (40% congenital anomalies)
Mgmt: chronic transfusions, steroids, BM tx if unresponsive to steroids
Prog: 1/3 enter remission, remaining need above. Inc risk appastic anemia, myelodysplastic syndrome, acute leukemia
Fanconi Anemia
“Constituitional aplastic anemia”
Rare 2.5/1,000,000. AR - chromosome instability with BREAKS common
Clinical: msk abnl (triphalangeal thumbs, radial hypoplasia, short stature, small cranium); hyperpigmentation, microcephaly, DD, strabismus, malformed ears, renal anomalies, marrow hypoplasia (eventually pancytopenia) progressive after 5 yrs (median 7 years), macrocytosis increased HbF and i antigen
Dx: test chromosomes with mitomycin C = increased chromosomal breaks
Mgmt: 50-75% respond to androgens, hematopoietic growth factors - BM tx definitive treatment
Prog: predisposed to malignancy esp acute myelogenous leukemia, Lymphoma
Transient erythroblastopenia if childhood
Common unknown rtiology
Usually second year of life (0.5-4yrs)
Normocytic anemia low retic count, absent fetal hg and i antigen no assoc anomalies
Mgmt - no specific tx - transient
Prognosis - resolves in several months
Basophilic stippling ddx
Fe def
Lead poisoning
Hemolytic anemia
Thalassemia
Blister cells ddx
G6PD def
Heinz bodies ddx
= precipitated denatured Hb in RBC, usually occurs when Hb unstable but can be normal neonate
Hemolytic anemias, enzymatic defects
Erythropoietin fetus and neonate
Main source fetal liver, switch kidneys 3rd trimester (liver source still greater than kidney)
Detected at 17 weeks
Hepatic EPO allows liver to be insensitive to tissue hypoxia avoiding marked erythrocytosis
Neonates: plasma epo drops rapidly post exogenous admin, increased volume of distribution, increased metabolism and clearance
Epo increased by Fe supplementation
