develops from inadequate levels of iron

usually occurs in:

infancy

pregnancy

women in childbearing years

chronic blood loss

inadequate intake of iron: develops as rbcs are slowly deprived of iron

rbcs become unable to produce Hgb

increased iron need: pregnancy, infancy, childhood

chronic loss of Hgb: occurs with slow hemorrhage or hemolysis

- gastrointestinal bleeding from ulcers

-heavy menstrual bleeding

-kidney stones or tumors

- hook worms

CBC- microcytic, hypochromic anemia, low: rbc ct, Hgb, Hct, MCV, MCH, MCHC

Rbc morphology- target cells/ elliptocytes

iron overload conditions

body has adequate amount but unable to incorporate it into heme synthesis

accumulation leads to prescence of iron depositws arond the nucleus of normoblasts

prussian blue stain of bone marrow will show ringed sideroblasts

hereditary sideroblastic anemia: sex-linked reccesive trait, seen mostly in men

secondary sideroblastic anemia: typically caused by toxins or drugs; lead poisining

idiopathic acquired sideroblastic anemia: cause unknown

dimorphic: microcytes and some normal cells; hypochromic and some normochromic cells

anisopoikilocytosis

target cells

pappenheimer bodies

Basophilic stippling

excess accumulation of iron

iron excess is toxic to the liver

maybe acquired or hereditary

result of mutations that affect proteins directly related to iron metabolism

may lead to iron overload

patient develops excess iron due to repeated transfusion of rbcs

iron in the donor rbcs overloads the patients liver

elevated transferrin saturation: Common screening test

elevated liver function test

elevated serum ferritin: assesses degree of iron overload

directly affects DNA synthesis

results in anemia when ineffective heamtopoiesis develops and developing cells die within the bone marrow

indirectly affects DNA synthess

takes years to manifest as anemia

anemias characterized by a structural defect in the Hgb

caused by a.a. substitutions in the polypeptide chains

amindo acid substitution in the polypeptide chain:

Hgb S: sickle cell anemia and sickle cell trait

Hgb C

Hgb SC

Hgb E

impaired production of the globin chain

beta thalassemia

alpha thalassemia

sickledex tube test

solubility method for Sickle Cell Screening

Hemoglobin Electrophoresis

a serouos inhereited disease in which the body makes HGb S

an abnormal hgb caused by a substitution of one a.a. in the beta chain

red cells possessing hgb S as the majority of hgb become sicked in areas of low oxygen concentration

sickle shaped cells dont move easily through your blood vessels

blocked blood vessels can cause pain serious infection and organ damage

inherited disease: person ineherits two copies of the sicke cell gene-  one from each parent

causes the body to make abnormal hgb

person who inherits only one copy of the sickle cell gene has sickle trait

chroic hemolytc anemia

vaso-occlusion episodes and complications

infectious crises primary cause of death

asymptomatic inder normal conditions

sickling can be caused by:

acidosis

extreme hypoxic conditions

sever respiratory infection

unpressurized flight conditions

under anesthesia in which pH and oxygen levels are greatly reduced

Lab findings for sickle cell anemia/ trait

rbc morphology:

 anemia- few to moderated slc, few target cells, hjb, nrbcs, polychromasia, retics

trait- normal cbc, no slc in peripheral smear unless in sickle crisis

lab findings in slc anemia/ trait:

Hb electrophoresis in alkaline pH

anemia: no Hb A 80% or more Hb S

1-20% hgb f

trait 60% hb a

40%hb s

a.a. substitution of lysine for glutamic acid in the 6th position in te beta chain

homozygous: disease

heterozygous: trait

lab findings hgb c anemia/ trait:

rbc morphology

anemia

50-90% target cells

spherocytes maybe present

polychromasia

increased retic count

may see hgb c crystals

trait: clinically asymptomatic

caused by two abnormal betac chains hgb s and c

high incidence in the black race

clinical symptoms lke sickle cell anemia but less severe

Lab findings of hgb sc:

rbc morphology

high number of target cells

few sickled and folded cells

may have hgb c crystals: looks like the washington monument  "bar of gold"

lab findings hgb sc:

hb electrophoresis in alkaline pH

50% hgb s

50% hgb c

results from a.a. substitution of lusie for glutamic acid at the 26th position

seen in ppl from southeast asia

secod most hgb variant world-wide

lab findings hgb e:

rbc morphology

anemia: microcytes and target cells

triat: microcytic cells few target cells

lab finding hgb e:

electrophoresis

95-97% hgb e

3-5% hgb f

defective globin synthesis results in:

defective hgb production

damage to rbcs

inherited disorders caused by genetic alterations: reduce or disable the ability to synthesize one or more of the globin chains of the hgb tetramer

beta thalassemia

alpha thalassemia

caused by defect in the rate of beta chain synthesis: beta cains maybe completely absent or reduced in number

alpha chains are synthesized in normal amounts

excess alpha chains precipitate and induce hemolysis

homozygous state and more severe

also known as cooley's disease

heterozygous state

also known as cooley's trait

severe anemia:

detected btwn 6mths and 2 yrs, as the gamma chain to beta chain switch takes place

hepatomegaly and splenomegaly

retarded growth and mongoloid facial features

increased retic count

severe microcytic, hypochromic abnormally shaped rbcs, many target cells, high number of nrbcs, marked polychromasia, basophillic stippling, hjb, pappenheimer bodies

mild anemia

slight splenomegaly

increased retic count

microcytic, hypochromic abnormally shaped rbcs, few target cells, polychromasia

genetic abnormality in which there are large deletions in alpha globin genes

degree of severity varies in proportion to the number of genes affected

two different types: hgb h disease, barts hydrops fetalis

charaterized by the presence of only one gene producing alpha chains

typically diagnosed when an individual experiences a hemolytic crises, otherwise those with the disease lead normal lives

characterized by the absence or deletion of all alpha chain synthesis (INCOMPATIBLE WITH LIFE)

hemogloblin Bart predominant hgb

has a high oxygen affinity

cannot transport oxygen to the tissues

severe anemia results and usually leads to stillbirth or spontaneous abortion

offspring that inherits the double deletion from one parent and the single from the other will have hgb h disease

the offspring who inherits no alpha genes from the parents dies in utero due to the development of hydrops fatalis

microcytic, hypochromic anemia

decreased hgb and hct

elevated rdw ( untreated thalassemia major)

normal rdw ( thalassemia minor)

very low mcv

increased HgbA2 (3.5-8%)- diagnostic

increased HgbF (1-5%) in 50% of patients

develops as a result of poor diet

good sources include green leafy vegetables, dried beans, liver, beef, and oranges

develops as result of a vitamin b12 deficient diet

good sources obtained from liver, milk, and eggs

increased need

impaired absorption

excessive loss/ use

lab findings for megablastic anemia:

cbc

decreased wbc, rbc, and plts

decreased hgb and hct

increased mch, mcv, and rdw

normal mchc

low absolute retic ct

lab findings for megablastic anemia:

rbc morphology

oval macrocytes, slight tear drops, moderate to marked anisocytosis/poikilocytosis,

rbc inclusions: basophillic stippling, cabot rings, hjb

lab findings of megablastic anemia:

neutrophil lobe counts

hyper-segmented neutrophils

five 5 lobed 1 6lobed neutrophil per 100 wbc

lab findings for megablastic anemia:

blood serum

aplastic anemia: codition in which the body stops producing bew blood cells (rbcs, wbcs, and plts)

red cell aplasia:rare disorder marked by a severe decrease in rbc precursors in otherwise normal bone marrow

hereditary spherocytosis: deffect in rbc membrane protein ( spectrin) composition; most commonly reported hereditary hemolytic anemia

hereditary elliptocytosis: caused by defective cytoskeleton in rbc membrane: around 90% have no symptoms

hereditary stomatocytosis: deficiency in rbc protein stomatin

G6PD deficiency: individuals lack the G6PD enzyme

Pyruvate Kinase Deficiency: rare enzyme disorder of the Embden-Meyerhoff pathway

genetic sex-linked disorder: gene for g6pd is located on the x chromosome

harmless unless rbcs are exposed to oxidative stress

most common rbc enzyme disorder: gen. seen in blacks

normochromic/normocytic anemia

increased retics

rbc morph: basophillic stippling, heinz bodies, bite cells, polychromasia

hemoglobinuria: urine turns black or brown

causes reduced atp production: rbcs have a decreased lifes span due to lack of atp

increased retics

marked polychromasia, few nrbcs

drug-induced hemolytic anemia

paroxysmal nocturnal hemo-globinuria: rare, chronic, acquired, hemolytic anemia

acquired non-immune hemolytic anemia

can be caused by drugs that lead to: immune complex formation; autoimmunity, drug absorption into rbc, membrane modification

results in lysis of rbcs

termination of drug is preferred treatment

rare, chronic, acquried, hemolytic disease

abnormal rbc membrane becomes highly susceptible to hemolytic action of complement

clasically, red cells destroyed while patient sleeps

results in chronic anemia

normocytic/ normochromic anemia

hematuria (blood in urine)

leukopenia and thrombocytopenia

slight marocytosis and polychromasia reticulocytosis

warm agglutinin syndrome: involves antibodies whose serological activity is optimal at 37C

very rare

cold agglutinin syndrome: rare disorder caused by an IgM antibody in which rbcs hemolyze at cold temps 10-30C; primary CAS onset by cold environments

secondary CAS onset following infections

Paroyxsmal Cold

non-immune hemolytic anemia:

infectious organisms

characteristics

malaria: parasites

babesia: transmitted by deer mice

clostridium perfingens: sepsis leads to destruction of RBCs  and lysis

cardiac replacement valve: anemia caused by rbc injury and fragmentation

hemolytic uremic syndrome: usually in infants and children

burns: thermal injuries cause rbc fragmentation and membrane loss leading to hemolytic anemia; schistocytes often seen in peripheral smear

fatigue

skin pallor, jaundice and petechiae

headaches and low blood pressure

tachycardia

acute or chronic blood loss

decreased or impaired rbc production

increased rbc destruction or loss

cbc/ rbc indices: rbc ct, hgb, hct, rbc indices, wbc, and plt ct

red cell distribution width (Rdw): indicates the degree of anisocytosis

retic ct: indicates shortened rbc survival

blood smear: serves as q.c.

exams of bone marrow smear: performed when the cause cant be determined or the differential diagnosis remains broad

osmotic fragility test: measures the ability of the rbcs to take up fluid without lysing

sugar water screening test/ hams test: PNH

Sickle Cell testing and hgb electrophoresis

acute blood loss: normocytic/normochromic anemia; fluid from the extravascular spaces enters the blood circulation dilutes remaining cells and produces subsequent anemia

chronic blood loss: beigns normocytic/normochromic develops into microcytic/hypochromic anemia

rbc values- decreased hct and retics; increased rdw

iron studies- increased serum iron; decreased tbic

decreased serum iron

increased tbic

decreased serum ferritin