heme/onc Flashcards
What are the sites of erythropoiesis
embryo –> yolk sac fetus during first trimester through birth –> liver fetus during second trimester through adulthood –> bone marrow
Describe chronology of hemoglobin switching
Embryonic Hb during 1st trimester from yolk sac: includes HbGower 1 [z2e2], [a2e2], and Hb Portland [z2g2].
Fetal Hb (HbF) is a2g2, predominant Hb during fetal life and newborn (75% at birth). Doesn’t bind to 2,3 dbg which makes it have higher affinity for O2.
Adult Hb (HbA) is a2b2 and minor form HbA2 a2d2 increase after birth. Majority is HbA by 6m.
How are fetal RBCs different than adult RBCs
- larger MCV
- shorter life span 60-80d instead of 120
describe erythropoises in neonate
Epo production starts in liver initially and switches to kidney near birth. Erythropoeisis under control of neonate b/c epo doesn’t cross placenta. Higher production than adults because of relative hypoxia.
When does physiologic anemia of infancy happen and how is it different from anemia of prematurity
Anemia of infancy happens at about 8-12w in term infants, at an average of Hb 11.
Anemia of prematurity is multifactorial and usually at 6w with Hb 7-10.
Describe hemolytic disease of the newborn
HDN is usually due to maternal IgG against D Ag on RBC crossing placenta. This is clinically significant usually only after 2nd pregnancy. It can also be against C, E, anti-Kell and anti-Duffy antigents.
Anti-Kell also impacts reticulocytes.
In contrast, it is not usually severe with ABO incompatibility, although ABO hemolytic anemia can happen during first pregnancy and is not more severe with subsequent pregnancies.
how does RhoGAM work
RhoGAM is anti-D Ab. It is given to Rh- moms at 28w and 7w after delivery. It clears Rh+ fetal cells from maternal circulation before mother can make her own anti-D Ab.
Describe the different a thalassemias
There are four copies of a-globin gene on chr. 16.
more commonly in aa:
Deletion of 1 gene: silent carrier.
Deletion of 2 genes: a-thal trait. Mild anemia.
more commonly in asian:
Deletion of 3 genes: majority Hb B, and later in infancy HbH (b4)
Deletion of 4 genes: homozygous a-thal. mostly Hb Barts (g4)
HbH and HbBarts usually results in severe fetal anemia and hydrops.
Describe the types of B-Thallesemia
We have two copies of B-globin gene on Chr. 11. Gamma-globin in fetus prevents B-thal babies from being symptomatic as a fetus, usually mild symptoms at most in neonate.
Deletion of B-globin gene can results in silent carrier, B-thal trait, B- thal intermedia and B-thal major.
What is the genetic mutation that causes HbS
point mutation at position 6 in B chain replacing valine with glutamic acid
What is appropriate follow up for NBS for hemoglobinopathies?
Initial NBS is done using isoelectric focusing and high-performance liquid chromatography.
Anormal tests should be confirmed with Hb electrophoresis at 6 months.
HbS infants can benefit from PCN ppx, immunization against h. flu and s. pneumoniae.
What are two major intrinsic RBC defects that cause non-immune mediated hemolysis?
1) Glucose 6 Phosphate Dehydrogenase (G6PD) Deficiency: G6PD supplies NADPH to reduce glutathione in RBC via hexose monophospate shunt/pentose phosphate pathway. Without this, during oxidative stress hemolysis occurs. X-linked recessive. More common in AA and Medidterranean descent. Difficult to diagnose during crisis because immature RBCs have higher levels of G6PD.
2) Pyruvate Kinase (PK) deficiency: PK is enzyme in glycolysis, if deficient RBC cannot produce enough energy –> hemolysis. Autosomal recessive.
What are membrane protein defects causing non-immune hemolysis?
1) Spherocytosis: AD defect in ankyrin. Dx: Spherocytes on smear, osmotic fragility test.
2) Elliptocytosis: AD mutation in a/b spectrin. Dx: ovalocytes. Milder anemia than spherocytosis.
3) Pyropoikilcytosis: mutations of a or b spectrin.
What is Diamond - Blackfan Anemia
DBA is an AD bone marrow syndrome causing impaired erythropoises –> paucity of erythrocyte precursors, non-megaloblastic (vs b12/folate def) macrocytic anemia, reticulocytopenia, and assc with short stature, abnormal facies, abnormal (triphalangeal) thumbs and skeletal abnormalities. Mutations in genes that code ribosomal units.
pneumonics: diamond ring (finger — tri phalyngeal thumb), ‘black’fan - bone marrow is dark without any rbcs, ‘non-mega’loblastic –> congenital
What is Fanconis Anemia
Bone marrow syndrome, anemia +/- thrombocytopenia/leukopenia. Usually presents in late childhood. Due to BRCA2 mutation –> defect in DNA repair enzymes. Higher incidence of cancer. Inherited aplastic anemia, AR. Hypoplastic or absent thumb, radius bone abnormalities.
pneumonic: ‘fan’ –> brrr –> BRCA mutation / fan cuts off your thumb
What is Shwachman-Bodian-Diamond Syndrome?
Bone marrow failure syndrome. Neutropenia +/- anemia/thrombocytopenia. Assc with exocrine pancreatic insufficiency and skeletal abnormalities. Due to SBDS gene mutation on chr. 7.
What is Pearson Syndrome?
Mitochondrial disease with anemia, exocrine pancreatic insufficicency, renal and hepatic failure.
What is appropriate iron supplemenation to avoid iron deficiency anemia.
Term infants : On formula, no additional Fe needed. If >50% breast milk, 1mg/kg Fe starting at 4 months.
Preterm infants: 2mg/kg Fe starting at 1m.
Wait to give cow’s milk until 1 y/o –> not enough Fe.
what are symptoms of chronic kernicterus
dental dysplasia, hearing loss, choreoatheosis
what are sypmtoms of acute bilirubin encephalopathy
hypertonia (opisthotonis/retrocollis), high pitched cry, fever, poor feeding. Preterm infants will have abornmal BAER.
In hematopoiseis, what do lymphoid progenitors and myeloid progenitors become?
lymphoid: all lymphocytes including B cells, T cells and NK cells
myeloid: RBCs, platelets, and other WBCs including granulocytes, monocytes and macrophages
In NAIT, what is the most common platelet antigen involved
HPA-a1 (75%)
how low do platelets get in NAIT and what is the typical course and treatment?
Can have severe thrombocytopenia (<50k), usually recovers after 3d b/c Ab wear off. 10% can have intercranial bleed.
Treat with anti-antigen platelets, or maternal washed platelets. Normal pooled platelets are fine too. Steroids and IVIG are optional.
There is a high recurrence rate in moms, treating prenatally with IVIG and steroids can help.
What are characteristic features of TAR?
Thrombocytopenia that resolves in a year, due to maturation defect in megakaryocyte progenitors. Unlike fanconis, thumbs are normal. Radii are absent. High risk of ICH.
