• Integral Proteins (carry the antigen)
• Peripheral Proteins (outside of the membrane)

•  Glycophorin A
• Responsible for the negative charge of red blood cells
• Component a

• Spectrin
• Actin
• Create and protect the skeleton of the red blood cell
• Determine the shape of the red blood cell

• Phospholipids and Cholesterol
• Example of Phospholipids
• Lecithin & Sphingomyelin
• The ratio of Lecithin to Sphingomyelin, in amniotic fluid, is tested to ascertain the lung maturity of a fetus

• Target cells are an indication of Liver disease
• An equal amount of phospholipids and cholesterol in the RBC membrane is necessary, if an imbalance occurs the shape of the RBC membrane will occur
• Spherocytes are indicative of Hemolytic Anemia
• Acanthocytes will show a deficiency in Beta-lipoprotein
• Seen in the lipid profile of electrophoresis

Gas Exchange

(does not require energy)

• Maintenance of intracellular cationic electro-chemical gradients
• Potassium (more inside the RBC than out)
• Sodium (more outside the RBC than in)
• Maintenance of membrane phospholipids
• Maintenance of skeletal protein plasticity
• Maintenance of functional ferrous (Fe ⁺⁺) hemoglobin
• Protection of the cell proteins from oxidative denaturation
• Initiation and maintenance of glycolysis
• Synthesis of Glutathione

• ATP - Adenisontriphosphate-three phosphate groups
• ADP - Adenisondiphosphate - two phosphate groups
• AMP - Adenisonmonophosphate - one phosphate group
• These are obtained when glucose penetrates the RBC membrane, into the cell and glycolysis takes place.  When the glucose enters the cell it will be metabolized anaerobically and aerobically

• 90-95% of the glucose that enters the RBC is metabolized anaerobically
• Embden-Meyerhof Pathway (Phase 1)
• Methemoglobin Reductase Pathway (Phase 2)
• Rapoport-Leubering Pathway (Phase 2)
• The end product of glycolysis is Lactate

• 5-10% of the glucose that enters the RBC is metabolized aerobically
• Hexose Monophosphate Pathway (shunt)
• G-6PD (glucose 6-phosphatedehydrogenase) in the presence of NADP begins the aerobic pathway

• Has the lowest activity of all glycolytic enzymes
• Requires Magnesium (Mg) to function
• Sensitive to pH
• Activity will increase with an increase in the pH
• Deficiency of this enzyme
• Inherited as an autosomal recessive
• Very rare condition to have a deficiency of this enzyme
• Deficiency of this enzyme will cause Hemolytic anemia (very rare)
• Hemolytic Anemia is called Hereditary Non-Spherocytic Hemolytic Anemia (HNSHA)

• Requires Magnesium (Mg) to function
• Sensitive to pH
• Sensitive to inorganic phosphate
• Deficiency of this enzyme is inherited as an autosomal(not sex-linked) recessive trait
• Rare and may lead to severe muscle dysfunction
• Type 7 glycogen
• May also cause mild HNSHA

• X(Sex) linked enzyme
• May be associated with neurological disturbances
• May cause HNSHA

• Inherited as an autosomal recessive trait
• Most common cause of HNSHA

• X-linked recessive trait
• Deficiency leads to oxidative denaturation of the proteins and hemoglobin

•  Four Subunits
• Each subunit consists of a heme molecule and a protein globin chain
• The concentration of hemoglobin in the RBC is 34 g/dL
• Iron in the heme molecule gives the RBC red color

• Consists of Carbon, Hydrogen and Nitrogen atoms
• Called Protoporphyrin IX
• Iron in the Heme molecule is in the Ferrous (Fe⁺⁺) state
• Iron is obtained from diet and is transported by transferrin through the RBC precursor membrane then released into the cell and transferrin returns to plasma
• Each heme molecule is positioned in the pocket of the polypeptide (globin) chain
• The heme components, due to the presence of iron, are able to combine with oxygen and CO₂
• All of the synthesis takes place in the bone marrow in the precursor to the RBC

• Consists of two pairs of polypeptide chains
• Each chain consists of 141-146 amino acids
• Variations in the sequence of amino acids produces different chains of hemoglobin (alpha, beta, etc...)
• Each beta chain features 8 helical segments and 7 non-helical segments

Takes place in the mitochondria and in the precursor of Erythrocytes. Mature RBCs can not synthesize heme due to the absence of the nucleus and other organelles

• Occurs in the cytoplasm where the ribosomes are located, at the same time the mitochondria is synthesizing the heme
• Globin chains can not be synthesized in mature RBCs due to the absence of of the nucleus and organelles
• Globin synthesis is due to DNA sending a message, via RNA, that carries the sequence of amino acids to be combined in the formation of the globin chain

• Two Alpha and two Beta Chains
• Modification of Hemoglobin A occurs after DNA/RNA translation and a component will be added to the "N" terminal of the Beta chain.  The modified hemoglobin is called Hemoglobin A1C, the component added to the "N" terminal is glucose.  The normal percentage of A1C is 4%, diabetics are much higher.  Hemoglobin A1C is modified Hemoglobin A where glucose is added to the "N" terminal of Hemoglobin A.
• A2 hemoglobin is two alpha chains and two delta chains

•  Two Alpha Chains and Two Gamma Chains
• Highest concentration from birth to 6 months
• Sickling cells can be treated with Hydroxy Urea, which increases the level of Fetal hemoglobin production

• Two Zeta and Two Epsilon Chains
• Begins production in early embryogenesis; peaks during midgestation and begins rapid decline just before birth

• Two Alpha and two Epsilon chains
• Begins production in early embryogenesis; peaks during midgestation and begins rapid decline just before birth

• Two Delta and two gamma chains
• Begins production in early embryogenesis; peaks during midgestation and begins rapid decline just before birth

• Fetal Hemoglobin (60-90%)
• Two Alpha and two Gamma Chains
• Hemoglobin A (10-40%)
• Two Alpha and two Beta Chains

• Fetal Hemoglobin (
• Two Alpha and Two Gamma Chains
• Hemoglobin A₂ (3-5%)
• Two Alpha and two Delta Chains
• Hemoglobin A (>95%)
• Two Alpha and two Beta Chains

• Alpha - 141 amino acids
• Beta - 146 amino acids
• Gamma A - 146 amino acids (position 136: alanine)
• Gamma G - 146 amino acids (position 136: glycine)
• Delta - 146 amino acids
• Epsilon - Unknown
• Zeta - 141
• Theta - Unknown

• Mononuclear Phagocytic System (MPS)
• Also called the Reticular Endothelial System, occurring mostly in the spleen and considered extra-vascular destruction
• 90% of RBCs are destroyed extra-vascularly
• Usually 1% destroyed daily as they end their life cycle
• Very small percentage destroyed intravascularly due to severe damage
• RBC destruction is also the degradation of hemoglobin

• Hemoglobin is degraded by action of hemeoxygenase in the spleen
• With degradation of hemoglobin the iron and the globin chains will return to plasma, attach to transferrin and go back to bone marrrow to repete the synthesis of heme.  The amino acids will return ot the amino pool to be re-sequenced and used to synthesize globin chains
• With hemoglobin degradation (intravascular) it is released directly into the blood, in the blood it will be dissociated to alpha and beta dimers and will bind to heptablogin, them will be processed and discarded through the liver

• Continuous intravascular destruction
• Hemoglobin dimers will be converted to  hemosidirin or excreted as free hemoglobin or oxidized into methemoglobin. Hemosidirin is a green color crystal occassionally seen in a macrophage
• When hemoglobin in blood is oxidized to methemoglobin, the heme group can dissociate from the dimer group and will sometimes bind to the protein hemopexin.

• Decreased hemoglobin and hematocrit
• Decrease in hemoglobin causes a decrease in oxygen transportation
• Diagnosis made from physical examination, symptoms and hematological values
• Can be characterized as mild anemia (9 g/dL Hgb), moderate (7-10 g/dL Hgb) or severe (<7 g/dL Hgb) anemia

• Hemoglobin and Hematocrit
• CBC
• RBC Indices
• Smear for Cell Morphology
• Reticulocyte Count (to determin funciton of the bone marrow)
• Bone Marrow aspiration (to check cellularity of the bone marrow)
• Special testing for Anemia
• Plasma Iron Turnover (Confirmatory)
• Red Cell Utilization
• Life Span of the RBC

• Results when iron stores are depleted and insufficient for hemoglobin synthesis
• Normal adult contains 4,000mg (4g) of iron
• 60% iron in circulation
• 40% in store in bone marrow and liver
• 1mL blood features 1mg of iron
• Increased demand for iron in pregnancy and childhool
• Identified by hypochromic, microcytic cells
• Sideroblasts decreased in bone marrow due to lack of iron
• Serum Iron is decreased
• Total Iron Binding Capacity (TIBC) is increased
• Ferritin and Transferrin Saturation is decreased
• RBC count is normal

• Depends on the severity of blood loss, could be from wound, surgery, etc...
• Clinical Symptons depend on the cardiovascular status, the age, physical and emotional health of the patient
• Loss of 25-30% total blood volume
• Hypotension and light headed
• Loss of 30-40%
• Shortness of breath, sweating, loss of consciousness, decrease in blood pressure, rapid and week puls, urine volume decrease
• Loss of 40-50%
• Patient may go into shock, and possible death from hypotension and loss of pressure

• Occurs in loss of small quantities over large periods of time, patient develops Iron Deficient Anemia due to depleted iron storage
• Reticulocyte count decreases
• Polychromataphilia visible
• Due to bone marrow attempting to compensate for chronic blood loss
• Decreased WBCs

• Largely due to erythropoietin production reduced in the kidney of patients experiencing renal failure
• The higher the BUN, the more severe the anemia
• RBCs usually normochromic, normocytic and decrease in the production due to reduced erythropoietin
• May also see hemolysis due to plasma factors
• Occasionally see Burr, Fragmented and Macrocytic cells in dialysis patients due to their loss of folic acid during dialysis
• WBC and Platelet count are normal, but platelet function decreases

• Present in chronic infections, inflammatory diseases and neoplastic diseases, cancer
• Starts as mild to moderate and will usually develop in the 1st or 2ndmonth of disease, due to disease treatment
• Decrease in platelets and RBCs, RBCs usually normochromic and normocytic and can develop into hypochromic, microcytic with treatment of the disease
• May see anisocytosis and poikilocytosis
• Reticulocyte count can be normal or decreased based on severity of the disease
• Iron may be decreased
• TIBC may be normal to decreased
• Life span of RBC may be decreased due to treatment
• Cannot usually be corrected with iron therapy, only if the patients primary disease is corrected

• Hereditary sideroblastic is inherited as a X-linked recessive trait that affects males
• Severe with a hematocrit level of 20%
• RBCs are hypochromic, microcytic w/ moderate anisocytosis and poikilocytosis, target cells and basophilic stippling
• WBC and platelet count is usually normal
• Increase in serum iron (saturation %)
• Ringed sideroblasts in bone marrow
• Defect in heme synthesis (defect in intra-mitochondria)
• Treated with Pyrodixin

• More Common than inherited sideroblastic anemia
• Usually in adults >50 and acquired is moderate anemia not severe
• WBCs and platelet count are normal
• Bone Marrow exam shows the rings of sideroblasts, due to iron not being used for synthesis
• Can be acquired as a secondary to Leukemia, Inflammatory disease, neoplastic disease
• Can be caused by drugs that interfere with heme synthesis; alcoholism, led poisoning, reversible once patients remove the substance from their routine

• Severe Anemia w/ neutopenia (low neutrophil)
• Marrow noted as being yellow(fatty) and hypo-cellular
• Symptoms are genetic and also known as Fanconi Sndrome
• Manifest between infancy and 8 years of age
• An autosomal, chromosomal defect
• Patient has a brown pegment to their skin
• Mental Retardation
• Sexual retardation
• Hypoplasia of spleen and kidney

• 50-75% Idiopathic, could be caused by exposure to radiation, some benzene compounds, chloramphenicol, mustard compound and can lead to bone marrow failure. 
• Lab studies show pancytopenia (decrease in cells in peripheral blood)
• RBCs would be normochromic, normocytic, slight anisocytosis, poikilocytosis
• Decrease in WBCs, platelets and reticulocytes
• Bone Marrow is hyper-cellular (increase in fat)
• Can be idiopathic or congenital (Fanconi Syndrome)

• Found mostly in 60 years or older, rare in young people
• Caused by deficiency of Vitamin B 12
• Usually caused by gastric mucosa of stomach, which can't secrete the Intrinsic Factor, necessary for absorption of B 12
• Inherited as an autoimmune disease
• Patients experience weakness, shortness of breath, yellow skin, tongue is sore/red and pale, GI symptoms (pain, diarrhea, nauseous, vomiting), problems w/ central nervous system, degeneration of CNS, numbness and tingling of extremities, muscle weakness
• Peripheral blood-macrocytic, ovalocytes, tear drops, anisocytosis, poikilocytosis, stippling basophilia, howell jolly bodies, hypersegmentation of neutrophils
• Bone marrow is all megaloblastic erythroid precursors
• B12 and Folic Acid level is decreased
• MCV is increased
• LDH elevated, rapid cell turn over caused by premature death of megaloblastic cells in bone marrow
• Megaloblastic anemia means the precursors are very large, variety of different cell types, Vitamin B 12 deficiency, Intrinsic Factor is produced by parietal cells of the stomach, can be an autoimmune creating antibodies against either the IF or parietal cells
• Schilling Test-usually positive in pernicious anemia, patient received labeled vitamin B 12, collect 24 hour urine and measure the radioactivity of the urine to see how much is bein excreted.

• A hereditary disease found in people from Africa, Asia and Mediterranean, impaired production of one of the polypeptide chains of hemoglobin.
• Structure formation of the chain is normal, bu the rate of formation is decreased
• Impaired synthesis of the Beta chain is more common than the Alpha Chain
• B₀ is the absence of Beta chains, or there could be beta chains, but not enough to be functional.
• Two Types
• Thalassemia Major
• Thalassemia Minor

• There is a reduction in beta chain synthesis, an imbalance in teh alpha and beta chain and will result in precipitation of excess alpha chain and RBC and there will be damage in teh membrane of the cell leading to hemolysis
• Cooley's Anemia/Homozygous Beta Thalassemia
• Usually starts in infancy, patient is very pale due to poorly synthesized hemoglobin, spleenomegaly, enlarged liver, retarded growth, mongoloids
• Rarely live beyond 20 years
• Usually hav esevere hemolytic anemia
• Peripheral blood usually hypochromic, microcytic due to decreased globin chain synthesis
• Markedly anisocytosis, poikilocytosis, basophilic stippling, polychromatia, target cells, howel jolly bodies, increase in NRBCs, increase in reticulocytes, WBCs are usually normal or slightly increased, platelets slightly increased, osmotic fragility test is usually decreased, bone marrow shows erythroid-hyperplasia, iron is increased due to not being used in hemoglobin synthesis, heptaglobinis decreased
• Hemoglobin electrophoresis shows 40-60% fetal hemoglobin, some cases hemoglobin A2 is increased

• Heterozygous (Cooley's Trait)
• Not as severe as Thalassemia Major, symptoms not as severe
• Usually lives a normal life
• Hemoglobin F is usually between 2-6%, Hemoglobin A2 3-7% and the remaining percentage is Hemoglobin A

• Reduced synthesis of alpha globin chain or completely absent
• Usually two pairs of genes (one on each chromosome)
• Severity depends on the number of genes effected and how much of the chain is synthesized
• Capacity to synthesize the alpha globin chain is reduced, leading to the accumulation of excess gamma chain in fetal life , this creates Bart's hemoglobin with only four gamma chains.  Fetal hemoglobin features alpha and gamma chains, with no alpha there are four gamma chains. In adults there would be no alpha chains and four beta chains.
• With the deletion of one (alpha) gene the anemia is slight or slightly microcytic anemia
• The deletion of two genes, there will be moderate microcytic anemia
• Asian people usually have a deletion of two genes on the same chromosome
• African population usually have a deletion of one gene from each of two chromosomes
• A deletion of three genes will lead to hemoglobin H disease
• MCV < 70, hypochromic, mild to severe hemolytic anemia, caused by hemoglobin H denaturation and RBC destruction
• Peripheral smear is hypochromic, microcytic, anisocytosis, poikilocytosis, target cells, basophilic stippling, reticulocyte increase from 5-10%, spleenomegaly, hemoglobin in excess beta chain synthesis, usually precipitate as H bodies (seen only with Brilliant Cresol Blue Stain)
• With alpha chain production is completely absent, there is no A hemoglobin or F hemoglobin production, no oxygen transportation and leads to fetal death in-utero (hydrops fatalis)

• Also called Congenital Hemolytic Jaundice
• Ingerited as Non-sex linked (autosomal), dominant trait
• Symptoms more severe in early life (childhood), usually diagnosed a spherocytosis in children
• Caused by a defect in the RBC membrane peripheral protein, Spectrin
• The quantity of the protein is correlated with the severity of the disease
• Cell Membrane is more permeable to sodium due to the weakened membrane structure
• In the case of spherocytic cells, the osmotic balance is maintained with sufficient glucose and ATP, this is needed to expel the sodium and the rate of influx to maintain equilibrium in the cell
• Glucose is consumed at a rapid rate, causing an increase in the destruction of RBCs
• Physical findings are the enlargement of the spleen, jaundice, enlarged liver and extra-vascular hemolysis
• Peripheral smear shows spherocytosis, polychromataphilia, increase in reticulocytes, increase in NRBCs, platelets and WBCs are normal, osmotic fragility is increased, increased bilirubin, increased urobilinogen in urine and stool, heptaglobin is decreased
• Bone marrow is hyper cellular with an increase in erythroid precursor cells
• DAT is negative, due to the RBC not being coated with antibodies
• Most effective treatment is Splenectomy, transfusion may provide temporary relief
• Anemia will continue and thing will return to normal until another episode occurs

• Autosomal dominant trait
• Peripheral smear shows excessive ovalocytes/elliptocytes
• Lives a normal life span
• Reticulocytes are normal, 90% of patients have no clinical symptoms
• < 10% have hemolytic problems
• Usually osmotic fragility is increased in the smaller percentage of the population

• Inherited as a sex linked, recessive disease
• X chromosome diseases effect males more than females
• Homozygous(both parents) in female, Hemizygous (only mother carries) in males
• Most common RBC enzyme abnormality
• Effects 10% African American Males
• Plays important role in the Hexose Monophosphate shunt (aerobic pathway)
• Important for regeneration of NADPH
• Absence of enzyme usually harmless unless RBC is exposed to Redux compound
• Anti-Malaria drugs will denature the hemoglobin and Heinz bodies will form
• With deficiency patient will not be able to produce NADPH, hemoglobin will be denature/oxidized when the RBC is exposed to these drugs
• When hemoglobin is deoxidized it will form methemoglobin
• Heinz bodies will lead to hemolysis of RBCs due to membrane rigidity
• Deficiency can be qualitative or quantitative
• Individuals may have a sensitivity to fava beans and result in hemolysis of RBCs
• Continuous ingestion of Redux compound medications, with this deficiency, will cause hemolytic episodes, usually divided into three phases
• Hemolytic phase 30-50% of RBCs, formation of Heinz bodies, basophilic stippling, polychromataphilia, increased bilirubin, increase in reticulocytes
• During the recovery phase, usually 50th to 40th day of episode, retic count usually reaches a peak of 8-12%, macrocytes are seen, hemoglobin and hematocrit will increase, heptaglobin is absent, increased hemoglobin in plasma due to hemolysis
• Resistant phase, begins when anemia disappears adn until another Redux compound is introduced the patient will be normal

• Most common cause for Hereditary Non-Spherocytic Hemolytic Anemia (HNSHA)
• Inherited as autosomal recessive trait
• Homozygous, patient has the disease, Heterozygous exhibits no symptoms
• Detected at birth, genetic
• Newborn is jaundice, may require transfusion or exchange transfusion
• Characteristic also include splenomegaly, anemia and dark urine due to hemolysis
• Lab results usually show mild to severe anemia with hematocrit concentration 18036%.
• RBCs usually normochromic and slightly macrocytic, retic is moderately to markedly increased, polychromataphilia, increased NRBCs, WBC and platelet counts are normal
• Bone Marrow shows erythroid hyperplasia heptaglobin is absent
• No exact treatment for PK deficiency, usually splenectomy or transfusion
• Deficiency in PK will lead to decrease in life span of the RBC

• Usually consists of polypeptide chains with the normal number of amino acids, but the sequence of amino acids is different
• In The normal beta chain glutamic acid is at position 6
• In sickle cell patients glutamic acid is replaced by valene in position 6
• With Bart's Hemoglobin there are four gamma chains
• In Hemoglobin H there are four beta chains

• In position 6 the glutamic acid is replaced with lysene

• Position 121 is replaced by glysene

• Position 26 is replaced by lysene

Morphologic Classification of Anemias

• Macrocytic, normochromic red blood cells

• Vitamin B₁₂ and Folic Acid Deficiency
• Pernicious Anemia
• Sprue
• Following Gastrectomy
• Disease of the Liver

Morphologic Classification of Anemias

• Normocytic, Normochromic Red Blood Cells

• Defective formation of blood cells, or presence of tumor cells in bone marrow
• Aplastic Anemia
• Leukemia
• Hodkin's Disease
• Multiple Myeloma
• Leukoerythroblastosis
• Metastatic Cancer
• Anemia associated with renal disease
• Anemia associated with inflammatory disease
• Abnormal hemoglobin, increased destruction of red blood cells
• Certain acquired hemolytic anemias
• Paroxysmal nocturnal hemoglobinuria
• Sickle Cell anemia
• Hemolytic disease of the newborn

Morphologic Classification of Anemias

• Microcytic, hypochromic red blood cells

• Iron-deficiency anemia
• Thalassemia
• Sideroblastic anemia

Classification of Anemias According to Cause

• Decreased production of red blood cells (hypoproliferative)

• Bone Marrow damage
• Leukemia
• Leukoerythroblastosis
• Aplastic Anemia
• Decreased erythropoietin
• Inflammatory process
• Renal disease
• Hypothyroidism
• Iron-deficiency

Classification of Anemias According to Cause

• Nuclear maturation abnormality

• Vitamin B12 deficiency
• Pernicious Anemia
• Folic Acid deficiency
• Refractory macrocytic anemia
• Di Guglielmo's anemia

Classification of Anemias According to Cause

• Cytoplasmic Maturation Abnormality

• Severe iron deficiency
• Defect in globin production
• Thalassemia
• Defect in heme synthesis
• Sideroblastic anemia

Classification of Anemia According to Cause

• Hemolytic Anemia

• Acute
• Hemorrhage
• Chronic
• Congenital
• Red Cell Membrane Defect
• Hereditary Spherocytosis
• Hemoglobinopathies
• Hemoglobin C
• Hemoglobin S
• Enzyme Defect
• G-6PD deficiency
• Acquired
• Overactivity of the reticuloendothelial system
• Heinz body anemia
• Autoimmune hemolytic anemia
• Hereditary Elliptocytosis

Microcytic Anemias

• MCV < 80

• Sideroblastic Anemia
• Iron-deficiency Anemia
• Anemia of Chronic Inflammation
• Globin Deficiency
• Thalassemia

Macrocytic Anemias

• MCV >100 ↑

• Non-Megaloblastic
• Alcoholism
• Chronic Liver Disease
• Aplastic Anemia
• Megaloblastic
• Vitamin B12 deficiency
• Absorption problems
• Loss intrinsic factor
• Fish tapeworm
• Diseased ileum
• Folic Acid deficiency
• Neither
• Malignant Growth

Normocytic Anemia

• MCV 80-100

• Increased Retic
• Hemolytic Anemia
• Normal or decreased Retic
• Bone Marrow
• Acellular
• Aplastic Anemia
• Hypercellular
• Myeloma
• Myelofibrosis
• 1 degree refractory anemia
• Normocellular
• Neoplasm
• Uremia

Erythrocyte Inclusions

• Basophilic Stippling

• Precipitate of Ribosomes and Polyribosomes
• Punctate Blue Granules
• Seen in
• Thalassemias
• Lead Poisoning
• Myelodysplasias
• Sideroblastic anemias
• Congenital dyserythropoietic anemias

Erythrocyte Inclusions

• Howell Jolly Body

• Nuclear Fragment (DNA)
• Round blue granules, 1 µm diameter, at periphery of cell, usually single but may be multiple (megaloblastic anemia)
• Hyposplenic conditions
• Absent spleen
• Severe Hemolytic anemia
• Megaloblastic anemia

Erythrocyte Inclusions

• Pappenheimer Body

• Iron containing autophagosomes
• Blue-purple granules at periphery of cell; <1 µm, sometimes <0.5 µm; may form doublets; DNA stain (Feulgen) negative, Iron stain positive
• Absent spleen
• Megaloblastic anemia
• Sideroblastic anemia
• Thalassemias
• Hemolytic anemias
• Congenital dyserythropoietic anemias

Erythrocyte Inclusions

• Siderosome

• Iron
• Usually invisible; designated Pappenheimer body if visible by Wright-Giemsa stain
• Normal finding in bone marrow
• Absent spleen,
• Megaloblastic anemia
• Sideroblastic anemias
• Thalassemias
• Hemolytic anemias
• Congenital dyserythropoietic anemias

Erythrocyte Inclusions

• Heinz Body

• Denatured Hemoglobin
• Invisible (visible with Supravital stains only)
• Unstable hemoglobinopathies
• Oxidant Drugs
• Severe alcoholic
• Liver disease

Erythrocyte Inclusions

• H Bodies

• Denatured hemoglobin (excess beta chains)
• Invisible (visible with supravital stains only)
• Alpha Thalassemia (triple alpha gene deletion)

Erythrocyte Inclusions

• Alpha Chain Inclusion Bodies

• Denatured Hemoglobin (excess alpha chains)
• Invisible (visible with supravital stains only)
• Beta Thalassemia Major

Erythrocyte Inclusion

• Cabot Rings

• Remnants of mitotic spindle
• Red-purple thread like rings
• Megaloblastic anemia
• Severe anemia
• Leukemia
• Lead poisoning
• Other causes of dyserythropoiesis

Erythrocyte Inclusions

• Crystals

• Hemoglobin C
• Dark pink to red rods; hexagagonal or pointed crystalloid structures
• Hemoglobin C
• Hemoglobin SC

Erythrocyte Inclusions

• Bacteria

• Bacteria
• Artifactual inclusion; bacteria adhere to surface of cell, but appear to be inside
• Sepsis
• Adherence to red cell membrane most pronounced in Baronellosis

Erythrocyte Inclusions

• Parasites

• Variable
• See specific descriptions of malaria and babesia organisms
• Malaria
• Babesiosis

Erythrocyte Inclusions

• Mauer's Dots

• Malarial Pigment
• Course violet granules that vary greatly in size
• Plasmodium flaciparum infections

Erythrocyte Inclusions

• Schuffner's Dots

• Malarial Pigment
• Fine-reddish granules
• Plasmodium Vivax infection

Erythrocyte Inclusions

• Nucleus

• DNA
• Round or lobated, sometimes fragmented; rosette forms suggest dysplasia
• Stress erythrocytosis
• Myelodysplasias
• Myeloproliferative disorders
• Leukoerythroblastic conditions especially bone marrow fibrosis

Erythrocyte Inclusions

• Artifacts

• Variable (organisms, bubles, dirt, stain, platelets, etc.)
• Variable; structures overlay red cells and mimic intracellular inclusions
• No specific disease states
• Due to poorly made blood smears or improper air drying