Heme Aplastic Anemias and Lead Poisoning Case Study Tutorial

What type of anemia is typically seen in chronic lead poisoning?

normocytic/normochromic or slightly hypochromic/microcytic

What heme synthesis enzyme is most sensitive to inhibition by lead?

ALA dehydratase

Which heme synthesis enzyme is the second most sensitive to inhibition by lead?

Ferrochelatase

How does lead affect iron incorporation into heme?

impedes intracellular iron delivery and causes zinc to be inserted into the protoporphyrin ring instead of iron 

Besides heme synthesis, what other major processes in erythropoiesis does lead interfere with?

globin synthesis

What hematologic effect can occur with prolonged lead exposure?

erythroid hypoplasia

How does lead poisoning promote hemolysis?

increased red cell destruction due to membrane protein derangement leading to potassium loss 

At what blood lead level does pyrimidine 5’- nucleotidase inhibition occur and what does this cause?

>200 ug/dL, causes nucleotide accumulation that inhibits the hexose monophosphate shunt→ promotes hemolysis

What is the characteristic peripheral blood smear finding in lead poisoning?

basophilic stipiling

What causes basophilic stippling in lead poisoning?

RNA precipitation due to inhibition of pyrimidine 5’-nucleotidase

What is pancytopenia?

reduced circulating leukocytes, erythrocytes and platelets due to impaired bone marrow function

What causes hypoproliferative anemias?

depletion, damage or inhibition of hematopoietic stem or progenitor cells 

Why is bone marrow evaluation essential in hypoproliferative anemias?

these disorders cause bone marrow failure and pancytopenia

How is aplastic anemia defined?

pancytopenia with a hypocellular bone marrow, no abnormal infiltrate and no increase in reticulum

What are the diagnostic criteria for aplastic anemia?

at least 2: hemoglobin < 100 g/L, PLTs< 50 ×10^9/L, neutrophils <1.5 × 10^9/L 

What are common presenting symptoms of aplastic anemia?

anemia, mucosal/skin hemmorrhage, infections less common

What is the initial treatment for aplastic anemia?

remove underlying cause, supportive care (RBC transfusion, PLTS, infection management)

What is the only curative therapy for aplastic anemia?

allogenic hematopoietic stem cell transplantation 

What is the most common congenital aplastic anemia?

Fanconi anemia

What are the major physical abnormalities in Fanconi anemia?

growth retardation, skeletal defects, renal abnormalities, microcephaly, hypogonadism, skin pigmentation abnormalities

When does pancytopenia typically develop in Fanconi anemia?

between ages 5-10

What is the diagnostic test for Fanconi anemia?

elevated chromosomal breakage with diepoxybutane or mitomycin C

What is the only curative treatment for Fanconi bone marrow failure?

hematopoietic stem cell transplantation

What characterizes pure red cell aplasia?

selective decrease in erythroid progenitors, normal WBC and PLTs

What is the most common congenital PRCA?

diamond blackfan anemia

What age does diamon blackfan anemia typically present?

early infancy (pallor, failure to thrive)

What is the RBC morphology in Diamond blackfan anemia?

normochromic/ microcytic anemia (can be normocytic)

What is the first line of therapy for diamond blackfan anemia?

corticosteroids

What are common causes of secondary aplastic anemia?

radiation, drugs, viruses, autoimmune disorders (T cell mediated suppression)

What is idiopathic aplastic anemia?

bone marrow aplasia without an identifiable cause (not drug/toxin/infection related)

What causes myelophthisic anemia?

marrow replacement by tumor or metastatic cancer

What is the characteristic blood film finding in myelophthisic anemia?

leukoerythroblastosis and increased poikilocytes