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Flashcards in RBC Disorders 2 Deck (60):

What are the 4 stages of iron deficiency?

(1) storage iron is depleted (dec. ferritin, inc. TIBC)

(2) serum iron depleted (dec. serum iron, dec. % sat)

(3) normocytic anemia --bone marrow makes fewer, normal-sized RBCs

(4) microcytic, hypochromic anemia --bone marrow makes smaller and fewer RBCs


What syndrome is associated with iron-deficiency anemia?

Plummer-Vinson syndrome


What is Plummer-Vinson syndrome?

iron-deficiency anemia with esophageal webs and atrophic glossitis; presents with anemia, dysphagia, and beefy-red tongue


What is anemia of chronic disease?

Anemia associated with chronic inflammation (e.g., endocarditis or autoimmune conditions) or cancer.


How does chronic disease lead to the production of anemia?

(1) Chronic disease results in the production of acute phase reactants from the liver, including hepcidin

(2) Hepcidin sequesters iron in storage sites

(3) dec available iron --> dec. heme --> dec. Hb --> microcytic anemia


How does hepcidin sequester iron in storage sites?

(1) by limiting iron transfer macrophages to erythroid precursors

(2) by suppressing EPO production

**the aim is to prevent bacteria from accessing iron, which is necessary for their survival


What are the lab findings of anemia of chronic disease?

(1) inc. ferritin

(2) dec. TIBC

(3) dec. serum iron

(4) dec. % sat

(5) inc. free erythrocyte protoporphyrin (FEP)


How do you treat anemia of chronic disease?

(1) Address the underlying cause

(2) exogenous EPO useful in some patients, especially those with cancer

(decreasing inflammation will decrease the amount of hepcidin produced)


What is sideroblastic anemia?

anemia due to defective protoporphyrin synthesis


dec. proto --> dec. heme --> dec. Hb --> microcytic anemia


Breifly sum the reactions involved in the synthesis of protoporphyrin

A image thumb

How does a defect in protoporhyrin synthesis lead to anemia?

Iron is transferred to erythroid precursors and enters the mitochondria to form heme. If protoporphyrin is deficient, iron remains trapped in the mitchondria.

Iron-laden mitochondria form a ring around the nucleus of erythroid precursors; these cells are called ringed sideroblasts.


Sideroblastic anemia can be congenital or acquired. What is the most common congenital defect?

Congenital defect most commonly involves ALAS (aminolevulinic acid synthase), which is the rate-limiting step


Sideroblastic anemia can be congenital or acquired. What are the acquired causes?

(1) alcoholism (EtOH is a mitochondrial poison, and can damage the production of protoporphyrin)

(2) lead poisoning -- inhibits ALAD and ferrochetolase

(3) B6 deficiency --required cofactor for ALAS


Sideroblastic anemia due to B6 deficiency is most commonly due to what?

It is most commonly seen as a side-effect of isoniazid treatment for tuberculosis


What are the laboratory findings in sideroblastic anemia?

(1) inc. ferritin

(2) dec. TIBC

(3) inc. serum iron

(4) inc. % sat.

(iron-overloaded state)


What is thalassemia?

anemia due to decreased synthesis of the globin chains of Hb

dec. globin --> dec. Hb --> microcytic anemia


Carriers of a mutation in the globin gene are protected against what infection?

plasmodium falciparum malaria


What is usually the cause of alpha-thalassemia?

it is usually due to gene deletion

Normally, there are 4 alpha genes present on chromosome 16


In alpha thalassemia, what is the result of one deleted gene?



In alpha-thalassemia, what is the result of 2 genes deleted?

mild anemia with increased RBC count.


What are the two ways in which alpha-thalassemia can genetically manifest when two genes are deleted?

The deletions can be cis (both deletions on the same chromosome) or trans (one deletion on each chromosome)

**cis deletion is associated with an increased risk of severe thalassemia in offspring


In alpha-thalassemia, what is the result of 3 genes deleted?

severe anemia

beta-chains form tetramers (HbH) that damage RBCs

HbH can be seen on electrophoresis


In alpha-thalassemia, what is the result of 4 genes deleted?

lethal in utero (hydrops fetalis)

gamma-chains form tetramers (Hb Barts) that damage RBCs

Hb Barts is seen on electrophoresis


What is Hb Barts?

a tetramer of gamma globin chains.

This is seen in alpha-thalassemia when 4 genes are deleted


What is the genetic cause of Beta-thalassemia?

--usually due to gene mutations (e.g., point mutations)

--two beta genes are present on chromosome 11; mutations result in absent (ß0) or diminished (ß+) production of the ß-globin chain.



What is ß-thalassemia minor?

(ß/ß+) -- the mildest form of the disease

--usually asymptomatic with an increased RBC count


What are the lab findings in ß-thalassemia minor?

(1) microcytic, hypochromic RBCs and target cells seen on blood smear

(2) Hb electrophoresis shows slightly decreased HbA with increased HbA2


What is the key electrophoretic finding in ß-thalassemia minor?

increase in HbA2


What is the genetic manifestation of ß-thalassemia major?

In ß-thalassemia major, both alleles have mutations that result in no ß-globin production.


How does ß-thalassemia major first present?

It first presents a few months after birth. High fetal Hb (HbF) is temporarily protective


How does ß-thalassemia major lead to anemia?

Because there are no ß-globin chains, the a-globin chains aggregate.

This damages the RBCs, resulting in ineffective erythropoiesis and extravascular hemolysis


How does the body compensate for the ineffective erythropoiesis in ß-thalassemia major?

Erythroid hyperplasia ensues, resutling in:

(1) expansion of hematopoises to the skull and facial bones (chipmunk facies)

(2) extramedullary hematopoiesis with hepatosplenomegaly

(3) risk of aplastic crisis with parvovirus B19 infection of erythroid precursors 


What is seen on blood smear in ß-thalassemia major?

(1) microcytic, hypochromic RBCs

(2) target cells

(3) nucleated RBCs


What would you see on electrophoresis with ß-thalassemia major?

--little or no HbA

--increased HbA2 and HbF


Why do you see nucleated RBCs on PBS in ß-thalassemia major?

Normally, RBCs don't have nuclei, which are removed before they enter the blood. However, if RBCs are produced extramedullary (in the spleen, for example), some of the nucleated RBCs can escape into the blood.


If 90% of the Hb in a patient with sickle cell disease is HbS, what comprises the other 10%?

HbA2 and HbF


Genetically, what is the difference between sickle cell disease and sickle cell trait?

In sickle cell disease, 2 mutated ß-globin genes are present

In sickle cell trait, one ß-globin gene is mutated, and one is normal


How does the body compensate for the anemia produced in sickle cell disease?

Erythroid hyperplasia ensues, resutling in:

(1) expansion of hematopoises to the skull and facial bones (chipmunk facies)

(2) extramedullary hematopoiesis with hepatosplenomegaly

(3) risk of aplastic crisis with parvovirus B19 infection of erythroid precursors 


What is found on peripheral blood smear in sickle cell disease? Are these findings seen in sickle cell trait?

Sickle cells and target cells are seen on PBS in sickle cell disease, but not in sickle cell trait.


What test can be used to screen for both sickle cell disease and trait?

Metabisulfite screen

metabisulfite is a chemical that can induce any cell to sickle that has any amount of HbS. It can therefore be used to screen for sickle cell disease and trait


What are the clinical manifestations of sickle cell trait?

sickle cell trait is generally asymptomatic with no anemia.

**RBCs wtih <50% HbS don't sickle in vivo except in the renal medulla


Why would RBCs with <50% HbS sickle in the renal medulla?

Extreme hypoxia and hypertonicity of the medulla (dehydrates the RBCs) can cause sickling


What are the clinical consequences of sickling RBCs in the renal medulla?

Sickle cells result in vaso-occlusion and microinfarctions, leading to microscopic hematuria.

Eventually, this leads to a decreased ability to concentrate urine.


How does sickling of RBCs lead to anemia?

Cells continuously sickle and de-sickle while passing through the microcirculation, resulting in complications related to membrane damage.

These RBCs are then removed via intravascular and extravascular hemolysis.


Describe extravascular hemolysis as it relates to sickle cell anemia.

In sickle cell anemia, the reticuloendothelial system (splenic macrophages) remove RBCs with damaged membranes, leading to:


--jaundice with unconjugated hyperbilirubinemia

--increased risk for bilirubin gallstones


Describe intravascular hemolysis as it relates to sickle cell anemia.

RBCs with damaged membranes dehydrate, leading to:

--hemolysis with decreased haptoglobin

--target cells on blood smear


What are the clinical consequences of irreversible sickling of RBCs?

Irreversible sickling leads to complications of vaso-occlusion.

(1) Dactylitis--swollen feet and hands due to vaso-occlusive infarcts in bones

(2) Autosplenectomy

(3) Acute chest syndrome

(4) Pain crisis

(5) Renal papillary necrosis


Dactylitis is classically a presenting sign in which group of sickle cell patients?

Infants, classically around 6 months of age


In a sickle cell patient that experiences auto-splenectomy, what are the consequences of autosplenectomy?

(1) increased risk of infection with encapsulated bacteria (h. flu, s. pneumoniae

(2) increased risk of salmonella paratyphi osteomyelitis

(3)Howell-Jolly bodies on PBS


What is acute chest syndrom as it relates to sickle cell anemia?

sickle cells --> vaso-occlusion of pulmonary microcirculation

(1) presents with chest pain, SOB, and lung infiltrates

(2) often precipitated by pneumonia

(3) is the most common cause of death in adult patients


What disease is indicated by this PBS?

Q image thumb

Hemoglobin C -- an autosomal recessive mutation in the ß-chain of hemoglobin

normal glutamic acid at position 6 is replaced by lysine


How does hemoglobin C (HbC) typically present?

presents with mild anemia due to extravascular hemolysis


What is the hematologic consequence of Malaria?

RBCs rupture as part of the Plasmodium life cycle, resulting in predominantly intravascular hemolysis and cyclical fever.

The spleen also consumes some infected RBCs, which results in mild extravascular hemolysis with splenomegaly.


What is the vector for Plasmodium?

the female Anopheles mosquito


How do the cyclical fevers of P falciparum, P vivax, and P ovale compare?

P falciparum -- daily fever

P vivax and P ovale -- fever every other day


What are the general etiologies of anemias due to underproduction? (3)

(1) causes of microcytic and macrocytic anemias

(2) Renal failure -- decreased production of EPO by peritubular cells

(3) Damage to bone marrow precursor cells (may result in anemia or pancytopenia)


How is the reticulocyte count affected in anemias of underproduction?

It is lower than normal


What is a myelophthisic process?

A pathologic process that replaces bone marrow (e.g., metastatic cancer)

hematopoiesis is impaired, resulting in pancytopenia


What is immune hemolytic anemia (IHA)?

Antibody-mediated (IgG or IgM) destruction of RBCs


What type of hemolysis is involved in immune hemolytic anemia that is mediated by IgG and IgM?

IgG-mediated usually involved extravascular hemolysis

IgM-mediated usually involves intravascular hemolysis