[200x2] Unit 2 Homework: Flash Cards - Microcytic, Macrocytic, and Normochromic anemias.

MICROCYTIC ANEMIA Factors Affecting Iron Levels

- Only ~ 10% of ingested Iron is absorbed: Fe3+ converts to Fe2+; Fe2+ transports to bone marrow by transferrin. - Recycled hemoglobin (Hgb) components: iron from heme returned to storage pool on bone marrow and tissues; amino acids from globin returned to storage pool. Iron stores: Ferritin, Hemosiderin. Blood loss = Iron loss.

List the Normochromic anemias

------MEMBRANE DEFECTS-------- 1. Hereditary spherocytosis 2. Hereditary elliptocytosis - Common hereidtary elliptocytosis (Mild/Severe) - SE Asian hereditary elliptocytosis - Spherocytic Hereditary elliptocytosis - Hereditary propoikilocytosis 3. Hereditary stomatocytosis 4. Hereditary xerocytosis --------ENZYME/METABOLIC DISORDERS---------- 5. G6PD disorders - Drug-induced acute hemolytic anemia - Favism - Neonatal jaundice - Congenital nonspherocytic anemia 6. Pyruvate Kinase Deficiency ------MISC. RBC DISORDERS------- 7. Aplastic anemia 8. Fanconi's anemia 9. Diamond-Blackfan anemia 10. Paroxysmal nocturnal hemoglobinuria (PNH) 11. Cold agglutinin syndrome 12. Paroxysmal Cold Hemoglobinura

MICROCYTIC ANEMIA THALASSEMIC SYNDROMES: 4 ALPHAS (Major) Bart's hydrops fetalis

--/-- Total absence of alpha chain synthesis: No Hgb A, only Hgb Bart's; high affinity for oxygen ⇨ Severe anemia, stillbirth/spontaneous abortion.

MICROCYTIC ANEMIA THALASSEMIC SYNDROMES: 4 ALPHAS (Intermedia) Hgb H disease

--/-α Only 1 functional alpha gene, other 3 are deleted. Hgb < 10g/dl, retic 5%-10%, Hgh H inclusions seen (pitted golf ball), microcytosis, hypochromia, RBC fragments ⇨ Life long anemia with variable splenomegaly and bone changes.

MICROCYTIC ANEMIA THALASSEMIC SYNDROMES: 4 ALPHAS (Minor) Alpha thalassemia trait

-α/-α, --/αα Two gene deletion, two functional. Mild anemia, some Hgb Barts. Not clinical yet is detectable.

MICROCYTIC ANEMIA THALASSEMIC SYNDROMES: 4 ALPHAS (Minima) "The Silent Carrier"

-α/αα One gene deletion, three functional alpha chains. Hematologically normal.

MICROCYTIC ANEMIA List the 4 Alpha Thalassemic syndromes

1. (Major) Bart's hydrops fetalis 2. (Intermedia) Hgb H disease 3. (Minor) Alpha thalassemia trait 4. (Minima) "The Silent Carrier" High incidence in the Asian, Saudi Arabian and Filipino populations.

Microcytic anemias: List the 3 Beta Thalassemic syndromes

1. (Major) Cooley's anemia or Mediterranean anemia 2. Beta Thalassemia Intermedia 3. (Minor) Beta Thalassemia Trait

NORMOCHROMIC ANEMIAS List the 6 Hypoproliferative Disorders

1. Aplastic anemia 2. Fanconi's anemia 3. Diamond Blackfan anemia 4. Paroxysmal nocturnal hemoglobinuria (PNH) 5. Cold agglutinin syndrome (CAS) 6. Paroxysmal Cold Hemoglobinura

NORMOCHROMIC ANEMIAS HEMOGLOBINOPATHIES List the haplotypes of HbsS Sickle Cell Anemias

1. Asian 2. Benin 3. Bantu 4. Senegal Differ in amount of Hgb F present; ⇧ Hgb F = less severe presentation.

NORMOCHROMIC ANEMIAS List the 4 Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD) disorders.

1. Drug-induced acute hemolytic anemia. 2. Favism. 3. Neonatal jaundice: 4. Congenital nonspherocytic anemia:

List the microcytic anemias

1. Iron deficiency anemia (IDA) 2. Anemia of chronic disorders/anemia of inflammation (AOC/AOI) 3. Sideroblastic anemias/Iron overload - HH 4. Thalassemias Alpha: - (Major) Bart's hydrops fetalis - (Intermedia) Hgb H disease - (Minor) Trait - (Minima) "Silent Carrier" Beta: - (Major) Cooley's/Mediterranean anemia - Beta Thalassemia Intermedia - (Minor) Beta Thalassemia Trait

List the macrocytic anemias.

1. Megaloblastic anemia - Pernicious Anemia 2. Non-megaloblastic anemia

List of the normochromic anemias due to hemoglobinopathy.

1. Sickle cell anemia - Asian - Benin - Bantu - Senegal 2. Sickle cell trait 3. Hgb C disease 4. Hgb C trait 5. Hgb SC 6. Hgb S-beta thalassemia 7. Hgb E 8. Hgb D Punjab 9. Hgb G Phila 10. Hgb P Arab

MICROCYTIC ANEMIA The 3 Stages of IDA

1: Continuum of iron depletion from marrow. Prussian blue stain will show absence of iron. II: Iron deficient erythropoiesis. III: Frank case of IDA in the peripheral circulation.

NORMOCHROMIC ANEMIAS G6PD DISORDERS Neonatal jaundice

2-3 days after birth: More jaundice than anemia. management of jaundice required to prevent neurological complications. Treatment: Phototherapy

List all of the disorders covered in this unit.

>>>>>>>>>>>>>>>>>>>>>>>>MICROCYTIC<<<<<<<<<<<<<<<<<<<<<< 1. Iron deficiency anemia (IDA) 2. Anemia of chronic disorders/anemia of inflammation (AOC/AOI) 3. Sideroblastic anemias/Iron overload - HH 4. Thalassemias Alpha: - (Major) Bart's hydrops fetalis - (Intermedia) Hgb H disease - (Minor) Trait - (Minima) "Silent Carrier" Beta: - (Major) Cooley's/Mediterranean anemia - Beta Thalassemia Intermedia - (Minor) Beta Thalassemia Trait >>>>>>>>>>>>>>>>>>>>>>>MACROCYTIC<<<<<<<<<<<<<<<<<<<<<<<< 1. Megaloblastic anemia - Pernicious Anemia 2. Non-megaloblastic anemia >>>>>>>>>>>>>>>>>>>>NORMOCHROMIC<<<<<<<<<<<<<<<<<<<<<< ....................MEMBRANE DEFECTS.................................... 1. Hereditary spherocytosis 2. Hereditary elliptocytosis - Common hereidtary elliptocytosis (Mild/Severe) - SE Asian hereditary elliptocytosis - Spherocytic Hereditary elliptocytosis - Hereditary propoikilocytosis 3. Hereditary stomatocytosis 4. Hereditary xerocytosis ..................ENZYME/METABOLIC DISORDERS.......... 5. G6PD disorders - Drug-induced acute hemolytic anemia - Favism - Neonatal jaundice - Congenital nonspherocytic anemia 6. Pyruvate Kinase Deficiency .................MISC. RBC DISORDERS.................................... 7. Aplastic anemia 8. Fanconi's anemia 9. Diamond-Blackfan anemia 10. Paroxysmal nocturnal hemoglobinuria (PNH) 11. Cold agglutinin syndrome 12. Paroxysmal Cold Hemoglobinura ................HEMOGLOBINOPATHIES................................. 1. Sickle cell anemia - Asian - Benin - Bantu - Senegal 2. Sickle cell trait 3. Hgb C disease 4. Hgb C trait 5. Hgb SC .............VARIANT HEMOGLOBINS................................... 6. Hgb S-beta thalassemia 7. Hgb E 8. Hgb D Punjab 9. Hgb G Phila 10. Hgb P Arab

Leukopenia

A reduction in the number of white cells in the blood, typical of various diseases.

Normochromic anemias discussion.

Abnormal RBC membrane. The spleen surveys RBCs for imperfections. its' filtration is crucial to RBC membrane defects: RBC passes through the spleen & inspected for imperfections (inclusions, parasites, abnormal hemoglobin products), or an abnormal membrane. If a RBC has abnormal hemoglobin or abnormal membrane components, RBC elasticity and deformability are harmed and some degree of hemolysis usually results. Exterior RBC membranes may be shaved off to leave smaller, compact spherocyte.

MICROCYTIC ANEMIA THALASSEMIC SYNDROMES: 3 BETAS Beta Thalassemia Intermedia

B+/B+, Bx/B+, or Bx/B develop problems later in life. splenomegaly. no need for transfusions. mild bone changes.

MACROCYTIC ANEMIAS Megaloblastic anemia

B12 and Folic Acid Deficiencies ⇨ thymidine cannot be incorporated into DNA ⇨ impaired cell division & nuclear maturation. Intrinsic factor is necessary for B12 to be absorbed, else gastric abnormalities: competition, tropical sprue. Megaloblastic Erythropoiesis: Asynchrony between the nuclear structure and the cytoplasm; the nuclear age appears to be out of sync with the cytoplasm development ⇨ production of megaloblasts in bone marrow, oval-macrocytes found in peripheral blood. Symptoms: shortness of breath. light-headedness. extreme weakness. pallor. glossitis. dyspepsia. diarrhea. jaundice. numbness. vibratory loss: paresthesias. difficulty walking/balance. demyelinization ⇨ neurological problems. ⇧ LDH, bilirubin, RDW, initial MCV 100-140 fL, MCHC ⇩ retics, RBC life span ~ 75 days, M:E ratio pancytopenia. macrocytosis. bone marrow hyperplasia. hypersegmented neutrophils. macro-ovalocytes. possible: basophilic stippling, howell-jolly bodies, schistocytes, target cells, teardrop cells. Diagnosed by: ⇩ Serum B12 and/or Folic Acid, methylmalonic acid (MMA) ⇨ metabolite; ⇨ If B12 is ⇩ then MMA is ⇧; ⇨ ⇧ Homocysteine if B12/FA cannot be metabolized. Treatment depends on cause: modify diet as needed. daily intramuscular injections of B12 ⇨ elicits a rapid reticulocyte response with fast patient improvement. oral ingestion of folic acid. treat gastric conditions

MACROCYTIC ANEMIAS MEGALOBLASTIC ANEMIA Pernicious Anemia

B12 deficiency due to lack of functional intrinsic factor. Antibodies against IF factor may be produced. Symptoms similar to megaloblastic anemia-but greater tendency for neurological symptoms = "megaloblastic madness" Treat with B12 injections.

NORMOCHROMIC ANEMIAS HEREDITARY ELLIPTOCYTOSIS (HE) Southeast Asian ovalocytosis

Band 3 molecular defect. Melanesia/Malaysian population. ± Hemolysis: Provides mild protection against malaria. Cells strongly resistant to heat and rigid. spoon shaped, 2 bars across their center.

Mediterranean

Beta Thalassemia: Cooley's/Mediterranean anemia. G6PD Mediterranean type Sickle cell anemia (Hgb S)

NORMOCHROMIC ANEMIAS HYPOPROLIFERATIVE DISORDERS Diamond-Blackfan anemia

Bone marrow lacking in red cell precursors with a slightly ⇩ number of leukocytes. Severely anemic by 6 months of age. Characteristics: short stature. ⇩ birth weight. head, facial abnormalities. Treatment includes steroids and transfusional support

MICROCYTIC ANEMIA THALASSEMIC SYNDROMES: 3 BETAS (Minor) Beta Thalassemia Trait

Bx/B or B+/B Heterozygous abnormal β gene: Mimics IDA (except ⇧ RBC count). microcytic, hypochromic, may see basophilic stippling, target cells. ⇧⇧: RBC count = bone marrow is compensating. ⇧ Hemoglobin A2 (5%-10%). ⇩: Hgb, HCT.

MICROCYTIC ANEMIA THALASSEMIC SYNDROMES: 3 BETAS (Major) Cooley's anemia or Mediterranean anemia

Bx/Bx, Bx/B+, or B+/B+ Homozygously inherited: Little or no β chain synthesis: No Hgb A synthesized, majority Hgb F (up to 90%). Chronic overexpansion of the capable bone marrow (marrow increases output up to 20 times normal) makes thin and fragile bones ⇨ Biweekly or symptomatic transfusions. cardiac complications are leading cause of death. Characteristics: changes in facial structures = "bossing." failure to thrive. enlarged spleen. iron overload anemia, jaundice. microcytic, hypochromic/polychromasia, poikilocytosis, ⇧ nRBCs, HJ bodies, Hgb 6-9 g/dl (1/2 the normal). Treatment: transfusion (may lead to iron overload). iron chelation. bone marrow transplantation. stem cell transplantation

X-linked

Carried by mom.

NORMOCHROMIC ANEMIAS HEMOGLOBINOPATHIES Sickle cell anemia clinical considerations, diagnosis, and management.

Clinical considerations: chronic hemolytic anemia, recurrent painful attacks, bacterial infections, deterioration of tissue and organ function, shortened life expectancy. Normochromic, normocytic, > 80% Hgb S ⇩: Hgb (6-8 g/dL), HCT, red cell count ⇧: bilirubin, LDH, retic Slight ⇧ MCV Crisis: polychromasia. nRBCs. target cells. HJ bodies. sickle cells. Reversible: elliptical (blunt). Irreversible: thin pointed. Diagnosed: 6 months - 2 years of age Screening: dithionate solubility test: Hgb S precipitates. Management: = prevention of complications. Cooperative Study of SCD: database of info about SCD patients and their complications. Reduce crisis: prophylactic antibiotics, transfusion every 3-5 weeks ⇨ Hgb 10.0 g/dl. Hydroxyurea (chemo therapy).

NORMOCHROMIC ANEMIAS G6PD DISORDERS Drug-induced acute hemolytic anemia

Clinically normal until challenged by a drug. episode occurs within in 24 hours of ingestion/ injection of a drug. intravascular hemolysis. self-limiting. Aspirin, Phenacetin, Chloroquine, Chloramphenicol, Sulfacetamide, Napthalene, Vitamin K. ⇩: HCT, Hgb, ⇧ LDH, retics, Polychromasia, Bite cells. Abdominal pain, Hemoglobinuria.

NORMOCHROMIC ANEMIAS HEMOGLOBINOPATHIES Hgb SC

Combination of Hgb S and Hgb C. Hgb 8-10 g/dl. moderate anemia. slight reticulocytosis. less severe than sickle cell anemia but may still experience crisis. Target cells, nRBCs, polychromasia, Howell- Jolly bodies. Few sickled cells. SC crystals "Washington monument." 50% Hgb S and 50% Hgb C

MACROCYTIC ANEMIAS Non-megaloblastic anemia

Compensatory bone marrow response to hemolytic anemia. Secondary to: hypothyroidism. chronic liver disease. alcoholism. chemotherapy. post-splenectomy. MCV slightly ⇧. Treat underlying condition.

Pancytopenia

Deficiency of all three cellular components of the blood (RBCs, WBCs, and platelets).

NORMOCHROMIC ANEMIAS Hereditary spherocytosis (HS)

Deficiency of membrane proteins: spectrin and ankyrin-responsible for elasticity and deformability-and minor membrane protein bands 3 and 4.2. Northern European, Autosomal dominant. Spleen shears off outside edge of RBC, forming spherocyte. Spherocytes: Cells unable to expand normally. Cell ion and gas transportation is disrupted. Cell lacks flexibility to deform in microvasculature. Occurs strictly in peripheral circulation Clinical Findings in HS: SLIGHT⇧: RDW, ⇧: bilirubin, jaundice, anemia, splenomegaly, cholelithiasis,. spherocytes, retic count 3-10%, 50% of patients have MCHC > 36%. HS Diagnosis: CBC, family history, osmotic fragility test tests cells in varying hypotonic salt concentrations: normal cells lyse at 0.45%; ⇧ osmotic fragility cells lyse at 0.65%. HS Treatment: partial splenectomy. transfusion as needed. prophylactic penicillin.

Thrombocytopenia

Deficiency of platelets in the blood. This causes bleeding into the tissues, bruising, and slow blood clotting after injury.

NORMOCHROMIC ANEMIAS Pyruvate Kinase Deficiency

Disorder of the Embden-Meyerof pathway: RBCs are unable to generate ATP from ADP ⇨ produce rigid, inflexible cells ⇨ moderate hemolysis. HCT: 18%-36%. marked polychromasia. few nRBCs. Fluorescent screen used for identification

Microcytic anemia

Disruption of hemoglobin synthesis due to either iron deficiency/malabsorption or abnormal production of α or ß globin chains. microcytic, hypochromatic, MCV < 80 fL, MCHC < 32%.

Africa

HE Subtype: Hereditary (HH) pyropoikilocytosis (HPP) Sickle cell anemia (Hgb S) - haplotype: Hgb G Phila - Hgb O Arab

MICROCYTIC ANEMIA Factors Affecting Iron Absorption

Health of gastric mucosa. health of GI tract. GERD. gastrectomy. gastric bypass. current iron stores: ⇩ iron = more iron needed for the body to run optimally. erythropoietic need, amount of iron ingested.

NORMOCHROMIC ANEMIAS HEMOGLOBINOPATHIES Sickle cell trait

Heterozygous inheritance of Hgb S. Hgb A ~ 60%, Hgb S ~ 40%. Protects against malaria. normal lives. crisis may occur: high altitudes, extreme exercise, air travel.

NORMOCHROMIC ANEMIAS HEMOGLOBINOPATHIES Sickle cell anemia

Homozygous and autosomal dominant (chromosome 11) Formation of Hgb S: valine replaces glutamic acid on the 6 th position of beta chain; HbS α2 β2 6Glu⇨Val Hgb S RBCs are rigid in areas of ⇩ oxygen: spleen, liver, kidneys, joints, extremities. ⇨ irreversibly sickled cells ⇨ obstruct blood vessels, slow circulation. ⇩ RBC life. Also sickled by: hypoxia, acidosis, dehydration, fever, exposure to cold. Hgb S found in: Africa, Mediterranean, Saudi Arabia, Central Africa, Turkey, Greece, India.

Overview of Microcytic Disorders.

IDA: ⇩s. Iron, ⇧TIBC, ⇩% Sat., ⇩Ferritin AOI/ACD: ⇩s.Iron, ⇩TIBC, ⇩% Sat., ⇧Ferritin SA: ⇧s. Iron, ⇩TIBC, ⇧ %Sat., ⇧Ferritin HH: ⇧s. Iron, ⇩TIBC, ⇧% Sat., ⇧Ferritin Thal. minor:⇧/x Iron, x TIBC, ⇧ %Sat., ⇧Ferritin

NORMOCHROMIC ANEMIAS HYPOPROLIFERATIVE DISORDERS Aplastic anemia

Immune causes: antibody directed against an antigen on stem cells/T lymphocytes suppress stem cell proliferation. Predisposition for aplastic episode: radiation, chemotherapy. chemicals. Benzene (direct or indirect). viruses EBV, HBV, and HCV. Symptoms: fatigue, heart palpitations, dyspnea, pancytopenia, normochromic. normocytic anemia. ⇧: infections, bleeding complications.

MICROCYTIC ANEMIA Iron deficiency anemia

Impaired iron metabolism due to deficient iron intake or malabsorption. Iron-starved RBCs divide more rapidly, searching for iron, and are smaller because of these rapid divisions. Secondary to blood loss or to a disease process that depletes iron stores. ⇩: RBC count, Hgb, Hct, MCV, MCHC; Serum iron, Ferritin (drops at every stage), Iron saturation. ⇧: RDW, TIBC. Symptoms: Fatigue, pallor, vertigo, dyspnea, cold intolerance, lethargy. Possible cardiac problems (palpitations, angina), pica, cheilitis, koilonychias, infantile developmental delays and behavioral disturbances. *symptoms don't typically appear until stage III*

Chelosis

Inflammation and small cracks in one or both corners of the mouth.

NORMOCHROMIC ANEMIAS HEMOGLOBINOPATHIES Hgb C disease

Inherited homozygous substitution of lysine for glutamic acid at the 6th position on the beta chain; HbS α2 β2 6Glu⇨Lys. ⇩: Hgb A2 2-4%. Hgb 9-12 g/dl ⇧: MCHC. Hgb F 1-20% ⇧⇧: target cells. nRBCs. schistocytes mild symptoms. massive spleen. normochromic. normocytic. Hgb C 80%. crystals in PS (bars of gold). alkaline electrophoresis shows a single slow moving band at same position as A2.

MICROCYTIC ANEMIA SIDEROBLASTIC Hereditary hemochromatosis (HH)

Inherited iron overloading. Autosomal recessive disorder on chromosome 6p21.3. Abnormal HFE gene. Two mutations: C282Y and H63D. Affects >1 million Americans. ⇧: Serum Iron, Serum Ferritin, Transferrin Saturation. NORMAL: Transferrin, TIBC. *NOTE: Serum ferritin levels >150 μg/L and transferrin saturation levels >45% are indicative of HH.* Symptoms: chronic fatigue and weakness, cirrhosis of the liver, hyperpigmentation, diabetes, impotence, sterility, cardiac arrhythmias, tender/swollen joints, hair loss, abdominal symptoms. Treatment: therapeutic phlebotomy, iron-chelating agent (Desferal, Oral).

MICROCYTIC ANEMIA Anemia of chronic disorder/Anemia of inflammation (AOI/ACD)

Iron is blocked from reaching erythroid precursors; due to impaired release from macrophages; Impaired EPO production; Pronoromoblasts are not as responsive to EPO. Most common in hospital population due to secondary condition (renal failure, thyroid dysfunction, collagen vascular disease, malignancies). Symptoms: inflammation and secondary problems. Treatment: blood transfusions or Hepcidin (hormone). microcytic, anisocytosis, slight variation of color. ⇩⇩: Serum iron, TIBC. ⇩: MCV. BORDERLINE: RBC count, Hgb, Hct. NORMAL: MCHC. NORMAL/⇧: Serum ferritin.

Pappenheimer bodies

Iron overload granules found inside red blood cells

Hemoglobin Electrophoresis

Isolates Hgb bands. Quantified using densitometry. alkaline: cellulose acetate at pH 8.6: Hgb A2, C, E, O Arab migrate in the same position; Hgb S, D, and G travel together. acidic: citrate agar at pH 6.0: Hgb A, O, A2, D, G, and E migrate to the same point.

Koilocychia

Lateral elevation and central depression of the nail plate cause the nail to be spoon shaped. Due to iron deficiency.

Normochromic & Normocytic

MCV: 80-100 fl. MCH: 27-31 pg. MCHC: 32%-36%.

NORMOCHROMIC ANEMIAS Hereditary elliptocytosis (HE)

Membrane disorder; spectrin deficiency: commonly associated with alpha and beta regions; ⇩ thermal stability. affects all racial and ethnic groups, autosomal dominant. Clinical Subtypes of HE: 1. Common hereditary elliptocytosis, 2. Southeast Asian ovalocytosis, 3. Spherocytic hereditary elliptocytosis, 4. Hereditary pyropoikilocytosis.

Isoelectric Focusing

Method of choice for most newborn screening in the U.S.: acidic polyacrylamide gel at pH 3-10 migrates to isoelectric point where net charge is negative

NORMOCHROMIC ANEMIAS HEMOGLOBINOPATHIES VARIANT HEMOGLOBINS Hgb S-Beta thalassemia

Microcytic. hypochromic. nRBCs. target cells. polychromasia. sickle cells. splenomegaly. ⇧: RDW, retics. clinical picture can be as severe as sickle cell anemia, with virtually no Hgb A. B^0 = more severe. alkaline elctrophoresis shows 2 bands present: HbgS and HgbA.

NORMOCHROMIC ANEMIAS HEREDITARY ELLIPTOCYTOSIS (HE) Common hereditary elliptocytosis

Mild common HE: elliptical cells. no clinical symptoms. Severe common HE: fragmented cells. moderate hemolysis. jaundice. may require transfusions.

MICROCYTIC ANEMIA Sideroblastic anemias (acquired and inherited)

Mitochondrial overload. Inherited: congenital, sex-linked, or autosomal recessive; enzyme deficiency, Hereditary hemochromatosis (HH). Acquired secondary to: alcoholism, lead poisoning, isoniazid or chloramphneical use. Dimorphic, hypo/normochromic, Grape-like-clustered Pappenheimer bodies. ⇧ serum ferritin and serum iron: Iron accumulation leads to the presence of iron deposits in the RBC precursors in the marrow, termed "ringed sideroblasts."

MICROCYTIC ANEMIA Thalassemic syndromes discussion

Not linked to iron problems. ⇩ or absent globin synthesis of the alpha and/or beta chains: not enough functional hemoglobin A produced. ⇧ RBC production with ⇩ Hgb microcytic, hypochromic Can affect multiple organs due to iron deposits. May require transfusions. Alpha thalassemias: 1. Hydrops barts fetalis(major), 2. Hgb H disease(intermedia), 3. alpha thalassemia trait(minor), 4. silent carrier(minima). Beta thalassemias: 1. beta thalassemia(major) , 2. intermedia, and 3. trait(minor).

Acrocyanosis

Numbness and bluish tone to fingertips and toes.

NORMOCHROMIC ANEMIAS HEREDITARY ELLIPTOCYTOSIS (HE) Hereditary pyropoikilocytosis (HPP)

Poor growth and facial deformities. Rare recessive disorder in African Americans. ⇩: Hemoglobin <6.5 g/dl, MCV 50-75 fL, MCHC <36%. Red cell budding. rare elliptocytes, and spherocytes in circulation. RBC crenation. cells fragment at temperatures lower than normal.

Chelation

Procedure to remove a heavy compound, such as a heavy metal.

NORMOCHROMIC ANEMIAS Hereditary xerocytosis

Rare autosomal dominant. Xerocytes: RBC dehydrated, irreversible K+ loss and hemoglobin puddles at one end. ⇩: osmotic fragility, MCHC, RBC surface-to-volume ratio.

NORMOCHROMIC ANEMIAS HYPOPROLIFERATIVE DISORDERS Fanconi's anemia

Rare autosomal recessive disorder: bone marrow shows macrocytic process: thrombocytopenia, leukopenia; develops before red cell depletion. Characteristics: short stature. hyperpigmentation on trunk and neck. microcephaly. broad nose. structural abnormalities of kidney. ⇩: neutrophils, ⇧: lymphocytes, Hgb F. Only therapy is bone marrow transplantation.

NORMOCHROMIC ANEMIAS HEMOGLOBINOPATHIES VARIANT HEMOGLOBINS Hgb D Punjab

Rare clinical varient. Both hetero and homo are nonclinical. Higher incidence in Great Britain due to occupation at Punjab region of India and Pakistan for marriage.

NORMOCHROMIC ANEMIAS HYPOPROLIFERATIVE DISORDERS Paroxysmal Cold Hemoglobinura

Rare hemolytic anemia caused by anti-P: attaches to the RBCs at lower temperature ⇨ activates complement at warmer temperatures ⇨ lysis occurs at body temperature. Severe lysis causes: hemoglobinemia. hemoglobinuria. ⇧ back pain. fever. chills. abdominal pain. some patients may require transfusion. Screening test: Donath-Landsteiner test: Pt's anticoagulated blood sample is aliquoted. First aliquot is the control and should incubate at 37C for 1 hour. Second aliquot is placed at 4C for 30 minutes and then incubated at 37C for 30 minutes. Aliquots should be centrifuged and observed for hemolysis: Control shows no hemolysis, Second aliquot shows hemolysis = evidence for PCH.

NORMOCHROMIC ANEMIAS HYPOPROLIFERATIVE DISORDERS Paroxysmal nocturnal hemoglobinuria (PNH)

Rare hemolytic anemia: RBCs abnormally sensitive to complement in acid environment. hemolysis occurs during sleep and upon arising (decreased pH) with hemoglobinuria present in morning. Nine cell surface proteins are missing from cells: PIG-A gene defect, CD 55/CD59; Intravascular lysis. Symptoms: Pancytopenia. ⇧ reticulocytes. Screening procedure: flow cytometry: WBCs can be examined for reactivity to anchored proteins: FLAER (fluorescent labeled aerolysin), has been used to detect smaller populations of abnormal leukocytes in PNH. sugar water test (optional). The Ham test (optional). Treatment: transfusion support. bone marrow transplantation.

NORMOCHROMIC ANEMIAS Hereditary stomatocytosis

Rare hemolytic disorder (autosomal dominant). Deficiency in membrane protein stomatin: regulates ions across membrane. Intrinsic defect in Na+ and K+ permeability. RBC swells due to ⇧ in intracellular sodium content. Stomatocytes―cell appears to have slit; Na + in the RBC ⇧, followed by ⇧ water and RBC swelling: RBC have slits or bars in center; "Smiling." 10%-30% stomatocytes present in peripheral smear. Rh null disease (membrane lacks Rh Antigens). ⇩: MCHC, MCV. Mild/moderate anemia may require splenectomy.

NORMOCHROMIC ANEMIAS HYPOPROLIFERATIVE DISORDERS Cold agglutinin syndrome

Rare hemolytic disorders, seen in >50 years old. caused by IgM autoantibody of wide thermal range: Complement is fixed on the red cells during cold temperatures of 0-5 C: Red cells agglutinate and hemolyze as body temperature increases to 20-25 C. Symptoms: Acrocyanosis, Weakness, Pallor, Weight loss.

NORMOCHROMIC ANEMIAS HEMOGLOBINOPATHIES VARIANT HEMOGLOBINS Hgb G Phila

Rare, yet high incidence is seen in Ghana. Therefore, also seen in African Americans.

Hemogloninopathies discussion

Result of defect in globin chain production: single amino acid substitution, abnormal synthesis of one of amino acid chains, fusion of hemoglobin (Hgb) chains, extension of amino acid chain.

MICROCYTIC ANEMIA Iron Laboratory Profile

Serum iron: Total iron in serum. Serum ferritin: Acute phase reactant; one of the most sensitive indicators of iron stores, drops at every stage of anemia. Transferrin: Iron transport vehicle. Total iron binding capacity (TIBC): Availability of binding to transferrin. Transferrin saturation: % (serum iron/TIBC) ÷ 100.

Saudi Arabia, Turkey, Greece, India

Sickle cell anemia (Hgb S) (Indian haplotype: Hgb D Punjab)

NORMOCHROMIC ANEMIAS HEREDITARY ELLIPTOCYTOSIS (HE) Spherocytic hereditary elliptocytosis.

Spherocytes and elliptocytes present. mild hemolysis. ⇧ osmotic fragility. gallbladder disease. splenomegaly. Northern European.

Anemia and the lungs

Susceptible to occlusions in the pulmonary space. chronic or acute lung conditions. more susceptible to pneumonia and acute chest syndrome.

TIBC

Total Iron Binding Capacity. Iron deficiency: Iron level ⇩ but the TIBC ⇧⇨ transferrin saturation ⇩⇩. Iron overload: Iron level⇧ and the TIBC ⇩ or normal ⇨ transferrin saturation ⇧.

Anemia and vaso-occlusive episodes

Trademark painful crisis: intense (body biting) Predisposition factors: fever, dehydration, cold, stress. Pain may be temporarily relieved by analgesic. Complications: Priapism: persistent painful erection of the penis around the age of 15 years, may persist for hours or even weeks. Retinopathy: ophthalmologic complications, may include retinal detachment, retinal lesions, possible blindness. Strokes, may cause paralysis.

Hgb O Arab

Uncommon, yet found in 0.4% of African Americans. Usually asymptomatic. Must be differentiated from alkaline elctrophoresis' identical migration as Hgb C by positively ID with acidic electrophoresis.

NORMOCHROMIC ANEMIAS G6PD DISORDERS Congenital nonspherocytic anemia

Varying anemia. chronic hemolysis mostly extravascular. hyperbilirubinemia. ⇩: haptoglobin ⇧: retics

Macrocytic anemic discussion

Vitamin B12 and Folic Acid (artifical: Folate) are required for normal DNA synthesis. - Deficiencies of either means that thymidine cannot be incorporated into DNA ⇨ cell division and nuclear maturation are impaired. - Intrinsic factor (IF) is necessary for B12 absorption. X: polychromasia, nRBCs ⇩ retics, life span: Ineffective erythropoiesis due to premature destruction of RBC precursors ⇨ MCV >100 (>110 in megaloblastic anemia). NORMAL: MCHC ⇧: MCH, bilirubin, LDH, MCV. bone marrow hyperplasia.

NORMOCHROMIC ANEMIAS Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD)

X-linked recessive disorder; seen in: drug-induced acute hemolytic anemia, favism, neonatal jaundice, congenital nonspherocytic anemia. Key part of phosphogluconate pathway: Keeps glutathione in the reduced state to help prevent oxidative stress. A catalyst in the first stages of oxidation in RBC metabolism. Lack of G6PD prevents formation of NADPH: NADPH required to reduce glutathione; Reduced glutathione prevents oxidative stress; Oxidative stress leads to hemolysis. Oxidative drugs create challenge and cause hemolysis. Diagnosis of G6PD Deficiency: Test when the hemolytic event ends: CBC, Enzyme status, Peripheral smear = Retic rich.

Anemia discussion

chronic hemolytic process, hypercellular bone marrow, RBC life span 10-20 days, reticulocytosis, ⇧ bilirubin, cholelithiasis, HCT: 20%-25%.

Dyspnea

difficult or labored breathing.

NORMOCHROMIC ANEMIAS HEMOGLOBINOPATHIES Hgb C trait

heterozygous inheritance Hgb A-C trait, 40% target cells. HgbA:HgbC ratio 60:40

Dyspepsia

indigestion

autosomal dominant

nonsex/mom or dad/1st 22 chromosomes.

NORMOCHROMIC ANEMIAS G6PD DISORDERS Favism

occurs within hours of contact of fava beans (residue, ingestion). Found in individuals of the G6PD Mediterranean or Canton type. fever. nausea. abdominal pain. hemoglobinuria. possible Heinz bodies. normochromic normocytic smear, polychromasia. ⇩: haptoglobin ⇧: bilirubin

MICROCYTIC ANEMIA Iron Absorption Enhancers

orange juice. vitamin C. pickles. soy sauce. vinegar. alcohol.

Anisocytosis

red blood cells of unequal size

Anemia and the spleen discussion

spleen loses ability to clear abnormalities ⇨ Howell-Jolly bodies ⇨ splenic atrophy ⇨ splenic sequestration, sepsis.

MICROCYTIC ANEMIA Iron Absorption Inhibitors

tea. coffee. oregano. milk.

NORMOCHROMIC ANEMIAS HEMOGLOBINOPATHIES VARIANT HEMOGLOBINS Hemoglobin E

⇧⇧⇧ SE Asia, 2nd most common Hgb variant worldwide, rising in US due to emigration. Homozygous = no clinical conditions. Microcytic, hypochromic, some target cells, some polychromasia. Alkaline elctrophoresis shows Hgb C or A2.

Reticulocytopenia

⇩ reticulocytes "aplastic crisis"