Hematopoietic Disorders

Aplastic anemia is characterized by:

Pancytopenia on peripheral smear, hypocellular marrow, delayed plasma iron clearance

What happens to granulocytes with aplastic anemia

disappear within days

what happens to platelets with aplastic anemia

decline by half in about a week

what happens to erythrocytes with aplastic anemia

decline over weeks in the absence of bleeding or hemolysis

aplastic anemia can be

inborn or acquired

what is inborn anemia called?

fanconi anemia

the majority of cases of so-called idiosyncratic aplastic anemias are caused by

autoimmune attack on CD34+ hematopoietic stem cells

as with other autoimmune disease certain HLA patterns are associated with a genetic predisposition for the condition, namly

HLA DR2

following exposure to ionizing radiation, a pancytopenia ensues as a result of

injury to stem and progenitor cells

How is hemoglobin composed

4 protein globin chains each attached to a prosthetic group called heme

how are globin chains held together

by noncovalent electrostatic attraction into a tetrahedral array

until _______ of intrauterine life epsilon, zeta, gamma, and alpha chains are produced and assembled in various combinations in yolk sac-derived erythrocytes

8 weeks

The predominant adult hemoglobin is termed ___________

Hemoglobin A

Approximately what % of normal adult hemoglobin is in the form of hemoglobin A2

2.5

__________ therefore represents oxidation of the hemoglobin molecule at the iron atom

methemoglobin

who is more susceptible to methemoglobinemia than the adult

fetus and neonate

why are fetuses and neonates more susceptible to oxidation

because HbF is more susceptible than adult hemoglobin

what is the hallmark of hereditary hemochromatosis

excess absorption relative to body stores

what plays a central role in iron control

hepcidin produced by the liver

erythrocytes deficient in G6PD activity are less able to

resist oxidant attack

Ethnic population from tropical and subtropical countries have a much higher prevalence of

G6PD deficiency possible because the phenotype protects against malaria

Normal G6PD has a half like of about

60 days

because the erythrocyte cannot synthesize new protein, the activity of G6PD normally declines by

approx 75% over its 12--day life span

in all cases older erythrocytes are less like to recover following

exposure to an oxidant and will hemolyze first

phenotypic testing for G6PD deficiency is best done _______ after a hemolytic crisis

2-3 months

Both class 1 and class 2 patients are severely deficient, with

less than 10% of normal g6PD activity

a normal bone marrow can compensate for ongoing _______ and can return the hemoglobin concentration to normal

hemolysis

_________ are essential for one carbon metabolism in mammals

vitamin b12 and folate

the hematologic manifestation of vitamin b12 or folate deficiency is a characteristic _____ termed _______

panmyelosis, megaloblastic anemia

A functional vitamin B12 deficiency is induced by chronic exposure to

nitrous oxide, biguanides, colchicine, neomycin, and PPI

What does hydroxyurea and cytarabine inibit

ribonucleoride reductase

Hydroxyurea and cytarabine can delay nuclear maturation and function and frequently cause

megaloblastosis

condition in which erythrocyte precursors are absent from an otherwise normal bone marrow

pure red call aplasia

what is the difference between pure red cell aplasia and aplastic aneima

other blood cells lines are unaffected in pure red cell aplasia unlike aplastic anemia

denotes an increase in the red cell mass

erythrocytosis

reduction in circulating neutrophils at least 2 standard deviations below the norm

neutropenia

severe neutropenia is termed

agranulocytosis

neutropenia results from

decrease production, increased destruction, or retention of neutrophils

who has a very high risk for agranulocytosis

cocaine users

although leukemia is monoclonal in origin, they affect all cell lines derived from the

progenitor cell

what are the most common leukemias associated with xenobiotics

acute myeloid leukemia and myelodysplastic

what is the hallmark of thrombotic thrombocytopenic purpura

presence of platelet aggregates throughout the microvasculature without a fibrin clot