NOTES

NOTES
CONGENITAL ANEMIA

GENERALLY, WHAT IS IT?

PATHOLOGY & CAUSES SIGNS & SYMPTOMS
▪ Inherited macrocytic-normochromic ▪ See individual disorders
anemias
▫ Diamond–Blackfan anemia
DIAGNOSIS
▫ Fanconi anemia
▪ See individual disorders
COMPLICATIONS
▪ Congenital anomalies, ↑ blood malignancy
risk, solid tumor cancers TREATMENT
▪ See individual disorders

368 OSMOSIS.ORG
 Chapter 44 Congenital Anemia

DIAMOND–BLACKFAN ANEMIA
(DBA)
osms.it/diamond-blackfan-anemia
anemia
PATHOLOGY & CAUSES ▫ No other significant cytopathies evident
▫ Sporadic, unpredictable penetrance →
▪ Autosomal dominant ribosomopathy
high degree of genotypic heterogeneity
resulting in inherited bone-marrow failure
→ variety of possible congenital
syndrome, macrocytic-normochromic
anomalies
anemia, associated congenital anomalies
▪ Genetic mutation → ribosomopathy →
impaired hematopoiesis → red blood
cell aplasia → macrocytic-normochromic

OSMOSIS.ORG 369
 COMPLICATIONS no erythroid precursors
▪ Genetic predisposition to malignancies like ▪ Serum erythropoietin, fetal hemoglobin
myelogenous leukemia, myelodysplastic (HbF) increased secondary to stress
syndrome, solid tumors hematopoiesis
▪ Congenital anomalies increase complication ▪ Elevated erythrocyte adenosine deaminase
risk (eADA)

SIGNS & SYMPTOMS OTHER DIAGNOSTICS

▪ Classical physical congenital anomalies
▪ Anemia often present at birth → signs and associated with DBA
symptoms of impaired oxygen-carrying ▪ Genetic testing, family history
capacity (e.g. pallor, tachycardia, apnea,
lethargy)
▪ Low birth weight, evidence of growth
restriction usually present TREATMENT
Congenital anomalies ▪ 25% chance of spontaneous remission
▫ Craniofacial: low-set ears, micrognathia,
high-arched/cleft palate, broad nasal MEDICATIONS
bridge
▫ Neck: short, may be webbed Corticosteroids
▫ Ophthalmological: congenital glaucoma, ▪ Hemoglobin ↑ observed after steroid
cataracts, strabismus therapy initiation
▫ Thumbs: duplex/bifid; flat thenar ▪ Weigh dose, duration of steroid treatment
eminence against adverse effects (e.g. growth
▫ Urogenital: absent/horseshoe kidney disturbances, adrenal suppression,
▫ Cardiac: ventricular/atrial septal defect, immunosuppression, pathological fractures)
coarctation of the aorta
SURGERY
DIAGNOSIS Curative
▪ Allogeneic hematopoietic stem cell
▪ DBA usually diagnosed within first month transplant
of life
OTHER INTERVENTIONS
DIAGNOSTIC IMAGING ▪ Monitor for development of malignancies
▪ Specialist care (e.g. cardiology, nephrology,
Renal imaging/echocardiography
urology)
▪ Find internal congenital anomalies
▪ Family support, genetic counseling

LAB RESULTS Transfusions

▪ Complete blood cell count (CBC) with red ▪ Packed red blood cells
blood cell indices ▫ Maintain Hgb ≥ 8g/dL
▫ ↓ red blood cell count, hemoglobin, ▫ Must be leukocyte poor to decrease
hematocrit transmission of cytomegalovirus
▫ Reticulocytopenia ▫ Monitor for iron overload, hemosiderosis
▫ ↑ mean corpuscular volume (MCV)
▫ Normal mean corpuscular hemoglobin
(MCH), white blood cell, platelet counts
▪ Bone marrow aspirate normal, except few/

370 OSMOSIS.ORG
 Chapter 44 Congenital Anemia

FANCONI ANEMIA (FA)

osms.it/fanconi-anemia

PATHOLOGY & CAUSES SIGNS & SYMPTOMS

▪ Autosomal recessive/X-linked disorder of ▪ Cytopenias develop → clinical
chromosome fragility causing inherited manifestations → increased bruising/
bone marrow failure syndrome, macrocytic- bleeding, frequent infections
normochromic anemia, pancytopenia ▪ Symptomatic anemia related to impaired
oxygen-carrying capacity develops late in
Physical abnormalities disease
▪ Short stature, malformations associated
with the VACTERL-H (vertebral, anal,
cardiac, tracheoesophageal, renal, limb and DIAGNOSIS
hydrocephalus) association
▫ Microcephaly, congenital heart disease, ▪ History, physical examination
imperforate anus, conductive deafness,
hypogenitalia, cafe-au-lait spots
LAB RESULTS
▪ CBC assessment, bone marrow
CAUSES examination
▪ Mutation of several genes responsible for
DNA repair FA testing indicators
▫ Impaired cellular repair of DNA cross- ▪ Evidence of single-/multilineage cytopenias
links → impaired regulation of cell cycle, with no other identified cause
genomic instability → hematopoietic ▫ ↓ absolute neutrophil count, platelet
stem cell loss → macrocytic- count, absolute reticulocyte count,
normochromic anemia → bone marrow hemoglobin
aplasia → pancytopenia ▪ Hypocellular bone marrow (without
▫ Predisposition for development of blood/ evidence of malignancy/other known cause)
solid tumor malignancies ▪ Congenital anomalies
▪ Bone marrow biopsy usually normocellular ▪ Family history: people of Ashkenazi Jewish
at birth descent have ↑ carrier frequency
▪ Macrocytic-normochromic anemia and
other cytopenias develop gradually → FA-specific testing
usually diagnosed within first eight years ▪ Chromosome DEB assay
of life ▫ Laboratory test for chromosomal
breakage performed on leukocytes
COMPLICATIONS (indicates chromosome instability
syndrome; not FA-specific)
▪ Neutropenia: life-threatening infections
▪ Cytometric flow analysis
▪ Thrombocytopenia: bleeding tendencies
▫ Examines cellular growth, division;
▪ Malignancies: e.g. myelogenous leukemia,
cytometry following DNA crosslinking
myelodysplastic syndrome, solid tumors
shows cells unable to repair DNA
▪ Endocrine derangements: hypothalamic- damage, cellular arrest in cell cycle G2
pituitary axis disruption during fetal phase
development
▪ Chromosomal breakage test positive → FA
▪ Congenital anomalies gene sequencing recommended

OSMOSIS.ORG 371
 TREATMENT
MEDICATIONS OTHER INTERVENTIONS
▪ Screen, monitor for malignancies
Growth factors
▪ Specialist care (e.g. cardiology, nephrology,
▪ Granulocyte colony-stimulating factor (G-
endocrinology)
CSF)
▪ Family support, genetic counselling
▪ Granulocyte-macrophage-stimulating
factor (GM-CSF) Transfusions
▪ Thrombopoietin mimetics (e.g. romiplostim) ▪ Leukoreduced, irradiated packed red blood
cells
Androgen therapy
▫ Symptomatic anemia
▪ (e.g. oxymetholone) sometimes ↑ blood cell
count ▫ Hemodynamic instability
▪ Platelet transfusions
▫ Platelet count < 10,000/microL
SURGERY
▫ Evidence of severe bruising, bleeding
Bone marrow failure
▪ Allogeneic hematopoietic stem cell
transplant

372 OSMOSIS.ORG