question

identify the laboratory tests included in the complete blood count (CBC)

answer

White blood cell (WBC) count Red blood cell (RBC) count Hemoglobin (Hgb or Hb) Hematocrit (Hct or Hmt) Platelet (Plt) count

question

the recommended anticoagulant for routine hematology tests and explain the mechanism by which it prevents blood from clotting.

answer

EDTA; prevents clotting by chelating calcium.

question

recommended time limits for analysis of blood that is in anticoagulant and describe changes that take place over time as blood is in the anticoagulant solution.

answer

Blood should be tested within 6 hours. CBC can be done up to 24 hours if stored at room temperature. Changes to leukocytes include vacuoles in cytoplasm, irregular borders, changes in nuclei-necrobiotic cells. Platelets increased in size and appear singly rather than clumped. Erythrocytes may shrink with excess EDTA; hematocrit may decrease.

question

Define anemia

answer

Decrease in O2 carrying and delivering capacity of the blood

question

Erythrocyte mass

answer

# of RBCs in circulation in the body. Normal: # produced=# destroyed.

question

how the bone marrow can respond to anemia and the capacity of the response to anemia

answer

If the bone marrow has normal function and nutrients it will increase production to compensate for the decreased red cell mass=compensated anemia.

question

6. State the reference intervals/reference values for hemoglobin, hematocrit, red cell count, white cell count, and platelet count in the peripheral blood of adults (male and female)

answer

Hemoglobin RI: Men-14-17.4g/dL Women: 12-16g/dL Hematocrit RI: Men: 0.42-0.52 L/L Women: 0.36-0.46 L/L RBC count: Men: 4.5-5.5 x 10^12/L Women: 4.0-5.0 x 10^12/L WBC count: Platelet count:

question

the limits of hemoglobin and hematocrit values below which anemia is considered to be present for various age and gender groups

answer

Hemoglobin: Men: <14.0 g/dL Female: <12.0 g/dL Hematocrit: Men: <0.42 L/L Female: <0.36 L/L

question

8. Identify three instances in which the hemoglobin level in the blood may not correlate with the presence of anemia.

answer

1. If plasma volume is altered 2. If atmospheric oxygen is decreased 3. If the hemoglobin is abnormal and doesn't function properly

question

the physiologic mechanisms by which the body adapts to anemia.

answer

increased oxygenated blood flow-less viscous blood flows faster, blood may speed up to vital organs and slow down to skin and kidney. Increased O2 utilization by tissues-2,3 BPG/2,3 DPG in RBC is increased (insert itself into Hgb) increased lactic acid/lactate, increased hydrogen ions, shift to right in ODC, causes decreased O2 affinity (give up O2 more readily)

question

the clinical manifestations of anemia.

answer

skin pallor, enlarged speel and/or liver, (splenomegaly, hepatomegaly, hepatosplemegaly)

question

Mean Corpuscular volume=MCV

answer

hct (L/L) x1000 RBC x (10^12/L) Average cell volume of RBC Reference intervals=80-100fL=normocytic >100fL=macrocytic <80fL-microcytic

question

Mean corpuscular or cell hemoglobin concentration=MCH

answer

hgb(g/dL)/ hct (L/L) Average concentration of hgb/dL of RBC Reference intervals=31-36g/dL=normochromic >36g/dL=hyperchromic or normochromic spherocytic; NO PALLOR 1/3 diameter of cell

question

Mean corpuscular or cell hemoglobin=MCH

answer

hgb(g/dL) x10 RBC (x 10^12/L) Average weight of hgb in pop of RBC Reference intervals=27-31pg >31pg=heavy vell, seen with macrocytes and spherocytes <27pg=light cell, seen with microcytic hypochromic cells

question

calculating the red cell distribution width (RDW).

answer

st dev of erythrocyte volume x 100 Mean MCV

question

State the significance of the RDW

answer

The RDW indicates if the erythrocytes are all the same volume (size) or if there is variation in the volume between the individual cells (anisocytosis)

question

List the red cell parameters that are measured directly on automated cell counter. State those that are calculated

answer

RBC count, Hgb, MCV, RDW measured MCHC, MCH, hct calculated

question

reticulocyte count significance

answer

Reticulocytes are an indicator of the bone marrow's ability to make red cells and release them to the peripheral blood. Polychromatophilic red cells + nonpolychromatophilic red cell-retics

question

raw reticulocyte count

answer

reticulocyte # in 1000 red cells total and determine percentage Reference intervals: 0.5-2.5%

question

absolute reticulocyte count

answer

Absolute retic count=the # of reticulocytes released to peripheral blood/day=percent raw retic count x erythrocyte count (report in 10^9) Reference intervals: 18-158 x 10^9/L

question

Corrected retic count

answer

[patient's hematocrit (L/L) x raw reticulocyte count] /0.45L/L Compares the patient's hematocrit to normal hematocrit

question

Morphological Classification of anemia

answer

by average size of the cells (MCV) and hgb concentration (MCHC) using indices and correlated with the appearance of the cells on a peripheral blood smear stained with Wright's stain: Normocytic, normochromic Macrocytic, normochromic Microcytic, hypochromic

question

Functional (pathophysiologic)

answer

uses the absolute reticulocyte count, the RPI or the IRF and/or iron studies Normal RPI is 1. In anemic person, RPI should be >2 to compensate for the anemia (replace the decreased number of erythrocytes in the peripheral blood) Proliferation defects-decreased production of erythrocytes by the bone arrow, RPI<2, usually normocytic, normochromic Maturation defects (nuclear or cytoplasmic) Orderly process of maturation of the erythrocytes in the bone marrow is impaired May be cytoplasmic maturation defect (usually lack of iron) or a nuclear maturation defect (usually lack of folic acid of vitamin B12) RPI<2 Morphology-either too small or too large, microcytic or macrocytic Survival defects-erythrocyte lifespan in the peripheral blood 2 Morphology usually normocytic, normochromic Classification using RDW and MCV

question

RBC indices: Clues to RBC changes

answer

MCV: Decreased MCV-Average size microcytic RR MCV-average size normocytic Increased MCV-average size macrocytic MCH: Decreased MCH-average weight decreased Hgb weight RR MCH-average weight normal Hgb weight Increased MCH-average weight increased Hgb weight MCHC: Decreased MCHC-average color hypochromic RR MCHC-average color normochromic Increased MCHC-average indicates either spherocytes or errors in hgb or hct RDW: Increased RDW: anisocytosis RI RDW: no variation in size Decreased RDW: error, not possible

question

anisocytosis

answer

variation in size of RBC

question

poikilocytosis

answer

variation in shape of RBC

question

Identify and interpret indices that are predictors of anisocytosis

answer

RDW; increased RDW

question

Define hemoglobin content/hemoglobinization of red blood cells

answer

The amount of hemoglobin in RBC

question

Identify and interpret indices that are predictors of increased or decreased hemoglobination of RBCs

answer

MCH, the measure of the average hemoglobin content per cell

question

Echinocyte

answer

burr cell or crenated cell; a red cell with 10-30 spicules distributed regularly over the surface, usually formed in vitro (artifact-glass effect, time factor, dirt, humidity, increased pH), can be formed in vivo (uremia, pyruvate kinase deficiency)

question

Acanthocyte

answer

spur cell; sheroidal cell with 2-20 spicules distributed irregularly over the surface; no pallor, but club-like projections; formed in vivo in old red cells or RBC lipid membrane problems

question

Spherocyte

answer

red cell with increased thickness so central cavity is reduced; no pallor; formed in vivo when pieces of membrane are removed or can be inherited leading to abnormalities of the RBC membrane; can be acquired or inherited.

question

Stomatocyte

answer

uniconcave red cell, look like money slot; formed in vitro due to a lower pH or cationic soaps on slide; formed in vivo in inherited or acquired lipid membrane problems; can be artifact

question

Codocyte

answer

target cell; bell-shaped cell with thin cell wall; dote of hemoglobin surrounded by ring of pallor; formed in vivo when the red cell surface is increased disproportionately to the volume; formed in vitro when smears are fanned dry.

question

Schizocyte

answer

fragmented RBC; red cell fragemented due to the localized membrane damage; triangular cell, a helmet or a keratocyte and a bite cell; triangular cells are formed from vascular fibrin threads or mechanical damage

question

Elliptocyte

answer

a pencil or oval shaped cell ranging from normocytic to macrocytic (oval macrocytes); can be inherited leading to membrane abnormalities or it can be acquired.

question

Drepanocyte

answer

sickle cell; a red cell deformed by rod-like polymers of abnormal hemoglobin S

question

Dacryocyte

answer

tear drop; a pear shaped red cell with a more or less extended tail; can be formed in vitro (artifact) when making a smear; they are in vivo when found going in different directions in zone 3 of smear

question

Hemoglobin C crystal

answer

seen in red cells in hemoglobin C disease; appears as a dark red rectangular crystal pointed at 2 ends

question

Polychromasia

answer

diffuse basophilia, regenerative macrocyte, polychromatohilic red cell, early reticulocyte, shift RBC; represents young reticulocytes; RR<1/1000 RBC; no pallor, darker cell.

question

Reticulocyte

answer

immature red cell; RR-0.5-2.5%; NEED SUPRAVITAL STAIN

question

Nucleated RBC

answer

nucleated RBC in peripheral blood; RR=0.5 x 10^9/L in term infants; usually only see in newborns; if nucleated RBC, usually it is the later erythroid stages: orthochromic or polychromatophilic normoblast stage

question

Basophilic stippling coarse or fine

answer

Coarse seen on Wright stain and represents aggregated ribosomes; fine stippling seen on Wright stain and represents RNA from polychromatophilic RBC where slide was dried too slowly (artifact)

question

Siderosomes

answer

iron granules in the cytoplasm; siderosomes in nonnucleated RBC=siderocyte (RR=zero) Siderosomes in nucleated RBC=sideroblast (RR=0-3 siderosomes/normoblast in 20-80% of normoblasts) SPECIAL STAIN NEEDED: PRUSSIAN BLUE IRON STAIN (iron=blue dots)

question

siderocyte

answer

siderosomes in nonnucleated RBC

question

sideroblast

answer

Siderosomes in nucleated RBC

question

Pappenheimer bodies

answer

mitochondrial iron plus protein; seen on Wright stain as purple-blue cluster of grapes

question

Howell Jolly bodies

answer

DNA/nuclear remnant; seen on Wright stain, dark purple, larger than pappenheimer body

question

Cabot Ring

answer

faint to distinct red ring resulting from an anomalous mitosis and the fusion of the remaining spindle fibers (microtubules), can be seen on Wright stain as a faint purple ring

question

Heinz body

answer

precipitated denatured hemoglobin and is not seen on wright stain; formed when hemoglobin is denatured in vivo; NEED SPECIAL STAIN supra vital, new methylene blue

question

Rouleaux

answer

when red cells stack in a row like coins stacked up, seen zone 3 and/or 2 of peripheral smear; formed when the normal repelling between red cells is altered; increased protein can produce the effect; look in zone 2-significant, big picture

question

Agglutination

answer

red cells connect together in clumps; occurs when anitbodies to red cells connect to antigens on the red cell surface; in vivo=person has major problems.

question

sites in which iron is distributed in the body and state the approximate amount in each site

answer

Hemoglobin-50-75% Myoglobin-3.5% Other tissue iron-0.2% Transferrin (transport)-0.1% Ferritin (storage)-10-20% Hemosiderin (storage)-5-10%

question

mechanism of iron absorption

answer

Heme iron: detached from globin in the intestine, whole heme molecule is taken into mucosal cell, iron split from porphyrin ring, iron goes to same pool inside the mucosal cell as the non-heme iron Non-heme iron: ferric complexes are broken down, iron is reduced to Fe++ and bound to chelators. Chelators, gastric HCl, ascorbic acid and others help to stabilize the ferrous form.

question

State the site of iron absorption

answer

Duodenum

question

4. Describe the iron transport system and the mechanism by which transferrin delivers iron to a cell

answer

Within mucosal cell, carried across mucosal to blood side and taken into the blood. Iron changes valency with each change in location. Combines with apoferritin to form ferritin storage form.

question

transferrin

answer

a protein made in the liver in response to Fe stores; function is to transport Fe from storage (mainly in macrophages) or from cells involved in absorption (mucosa) to other cells throughout the bodywhere Fe is utilized (mainly developing erythrocytes); can bind 1 or 2 atoms of Fe3+

question

Transferrin receptor

answer

erythrocyte precursors in the bone marrow have transferrin receptors; each TIR can bind 2 molecules of transferrin

question

hemosiderin

answer

storage of large amounts of Fe normally in macrophages

question

ferritin

answer

stores excess soluble iron in the cytoplasm of all cells (Fe2+); stimulated by excess iron in the cell

question

two storage forms of iron

answer

Hemosiderin and ferritin

question

minimum daily requirement of iron intake at various ages in males and females

answer

Infants, children, and adolescents: 10-15mg/day Menstruating female: 20-30mg/day Pregnancy: 15-30mg/day Adult male, postmenopausal female: 5-10mg/day

question

Serum Ferritin test

answer

earliest test in the plasma to indicate iron stores; parallels concentration of storage iron in body; acute phase reactant so won't see iron deficiency with infection; RI: adult males: 20-300ug/L, adult females: 12-200ug/L

question

Total iron binding capacity

answer

transferrin levels; RI: 250-450ug/dL of Fe can be bound

question

Serum iron

answer

the amount of iron in the plasma; RI: males: 65-180ug/dL, females: 50-180ug/dL

question

% saturation of transferrin

answer

Serum iron x 100 TIBC RI: males: 20-50% females: 15-50%

question

laboratory method of staining and evaluating iron storage in a bone marrow specimen

answer

Prussian blue stain: siderocytes NOT NORMAL

question

iron deficiency anemia peripheral blood parameters

answer

basic erythrocyte tests all decreased in stage 3; smaller cells with decreased hemoglobin; microcytic, hypochromic

question

iron deficiency anemia peripheral blood smear findings

answer

Anisocytosis, poikilocytosis (target cells, elliptocytes) WBC may be slightly increased with chronic bone marrow stimulation, platelets may be increased or decreased (bigger in size indicate younger platelets)

question

iron deficiency anemia bone marrow morphology

answer

Mild to moderate erythroid hyperplasia, ragged cytoplasm in polychromatophilic normoblasts, iron stains: absent macrophage iron, decreased sideroblast count

question

iron deficiency anemia Tests of iron status: serum iron, TIBC, % saturation of TIBC, serum ferritin, free erythrocyte protoporphyrin, zinc protoporphyrin

answer

Serum iron decreased, TIBC, % saturation decreased, serum ferritin decreased, free erythrocyte protoporphyrin increased, zinc protoporphyrin increased

question

the causes of iron deficiency anemia

answer

Nutritional deficiency: poor diet (intake does not meet need), loss (slow blood loss), patients treated with EPO, malabsorption (not absorbing)

question

sequential stages in development of iron deficiency anemia. Explain the results of laboratory tests during each stage.

answer

Stage 1: iron depletion-iron stores are being depleted, storage of iron in blood decreases. Serum ferritin decrease, transferrin receptor decrease Stage 2: iron deficient erythropoiesis-stores have been depleted, iron from phagocytized erythrocytes being recycled; transport iron decreases; TIBC (transferrin) increased, serum iron decreased Stage 3: iron deficiency anemia-hypochromic cells, functional iron decreases; changes in blood smear, CBC, MCV, MCH, MCHC

question

typical clinical findings associated with iron deficiency anemia

answer

hypoxia-weakness, lethargy, headaches, koilonychias, glossitis, muscle dysfunction, gastritis, Pica (craving ice, dirt, starch), immune system dysfunction

question

Describe methods of treatment for iron deficiency anemia and explain the laboratory's involvement in evaluation of the patient's response to treatment

answer

Iron given as ferrous sulfate, reticulocyte count peak in 8-10 days, hemoglobin increases 1g/month, CHr (reticulocyte hgb content) increase, IRF (immature reticulocyte fraction) increase, RPI increase

question

List three other conditions in which cells on the peripheral blood smear appear microcytic and hypochromic.

answer

Sideroblastic anemia, anemia of chronic disease, beta thalassemia

question

sideroblastic anemia by three characteristic features.

answer

Iron present just not being utilized; bone marrow releases ringed sideroblasts; 1. Dimorphic red cell picture (hypochromic, normochromic) 2. Ringed sideroblasts (>/=15% ring sideroblasts) 3. Increased iron stores

question

causes of siderblastic anemia

answer

Hereditary-x chromosome linked, porphyrias; acquired-B6 deficiency; toxins, drugs, alcohol, lead poisoning; secondary to malignancy

question

morphology of a ringed sideroblast. Differentiate a normal sideroblast from a ringed sideroblast

answer

Disturbances in enzymes of heme synthesis pathway cause formation of ringed sideroblasts=iron surrounding nucleus +/- 1/3-2/3 of nucleus. Normal sideroblast=nucleated erythrocyte with iron granules in the cytoplasm.

question

stain necessary to identify a ringed sideroblast.

answer

Prussian blue

question

typical peripheral blood morphology of sideroblastic anemia.

answer

Dimorphic red cell picture: microcytic/hypochromic and normocytic or macrocytic/normochromic; anisocytosis (RDW increased), poikilocytes, inclusions: pappenheimer bodies and coarse basophilic stippling; leukocytes and platelets normal or decreased; RPI <2; immature retic pop decreased

question

Describe the critical bone marrow features of sideroblastic anemia

answer

Erythroid hyperplasia, low RPI; ineffective erythropoiesis; >15% ringed sideroblasts, increased macrophage iron

question

sideroblastic anemia Tests of iron status

answer

ron studies: serum iron increased, TIBC normal or decreased, % saturation increased, serum ferritin increased

question

ineffective erythropoiesis

answer

erythrocytes die by apoptosis in the bone marrow and are not delivered to the peripheral blood

question

list conditions associated with anemia of chronic disease

answer

Chronic infections, chronic inflammatory disorders, cancers not due to bleeding, hemolysis or marrow involvement

question

peripheral blood morphology of anemia of chronic disease.

answer

Mild anemia not <9g/dL hemoglobin level; MCV normal to slightly microcytic; RPI<2

question

proposed mechanisms for the development of anemia of chronic disease

answer

Cytokines because of the immune or inflammatory response cause abnormal heme synthesis

question

anemia of chronic disease iron studies

answer

Serum iron decreased, TIBC decreased or normal, % saturation decreased or normal, serum ferritin normal or increased, transferrin receptor normal

question

results of iron stain of the bone marrow (sideroblasts and macrophage iron) in anemia of chronic disease

answer

decreased sideroblasts, normal to increased macrophage iron stores

question

21. Classify these three anemias by the three sets of criteria discussed in the introduction to anemias

answer

Iron deficiency anemia: Microcytic, hypochromic; by function: cytoplasmic maturation; RDW/MCV: RDW increased, MCV: microcytic Sideroblastic anemia: Dimorphic, microcytic/hypochromic and normocytic or macrocytic/normochromic; by function: cytoplasmic maturation problem; by RDW/MCV: RDW increased, MCV varies Anemia of Chronic disease: Normocytic, normochromic to hypochromic; microcytic if long time anemia; by function: cytoplasmic maturation defect; by RDW/MCV: RDW usually normal, MCV slightly low to normal.

question

macrocytic anemia

answer

Macrocytic anemia: MCV>100 fL, hgb decreased.

question

Classify macrocytic anemias by cell shape and color

answer

Macrocytic, normochromic

question

causes of megaloblastic anemias

answer

Vitamin B12 deficiency Folic acid deficiency

question

peripheral blood findings in megaloblastic anemias

answer

Decreased hgb, hct, rbc. Macrocytic/normochromic MCV increased (>100fL) MCH increased (heavier weight measurement) MCHC normal (normochromic) Extreme anisocytosis (RDW increased) Extreme poikilocytosis (oval macrocytes, tear drops (dacryocytes), others (hypochromic fragments) Red cell inclusions (howell jolly bodies, coarse basophilic stippling, nucleated RBCs, cabot rings) Pancytopenia-decreased # of all cell lines White cell changes-hypersegmented neutrophils Classic triad: Oval macrocytes, howell-jolly bodies, hypersegmented neutrophils

question

state the criteria for hypersegmented neutrophils

answer

>5 segments in >/= 5 neutrophils/100

question

identify the morphologic abnormalities associated with megaloblastosis in the bone marrow

answer

Nuclear-cytoplasmic asynchrony (cytoplasm ahead of nucleus in development, because DNA synthesis is impaired); hypercellular marrow with erythroid hyperplasia (M:E ratio decreased or reversed)-lots of erythroid production in bone marrow but aren't released into peripheral blood because they are abnormal, destroyed by macrophages; granulocyte abnormalities-giant band and metamyelocyte forms; karyorrhexis (fragmentation of the nucleus resulting in multiple howell jolly bodies in occasional cells); megakaryocytes also affected and become large in size; increased numbers of mitotic figures.

question

effect of vitamin B12 or folate deficiency on the maturation of wbcs and platelets.

answer

giant band and metamyelocyte forms; M:E ratio decreased or reversed

question

causes of vitamin B12 and folate deficiencies

answer

Folic acid: nutritional-decreased intake and/or increased need; defective absorption syndromes; inadequate utilization as with cancer chemotherapeutic drugs Vitamin B12: Malabsorption-pernicious anemia: lack of intrinsic factor; gastrectomy and many intestinal problems

question

List the dietary sources of vitamin B12 and folate

answer

Vitamin B12: animal tissues/dairy products Folic acid: many foods, especially green leafy vegetables; made by bacteria in intestines

question

the site of intestinal absorption of vitamin B12 and folate.

answer

Folic acid: Jejunum

question

Name the transport protein(s) for vitamin B12

answer

transcobalamins

question

storage site for vitamin B12 and folate

answer

Vitamin B12: mostly in liver, some in heart and kidneys Folate: liver

question

reference intervals, daily dietary requirements and the length of time of body stores for vitamin B12 and folate

answer

Vitamin B12: RDA: 5-7ug/day, storage ~4 years Serum cobalamin RI: 200-835pg/mL Folate: RDA: 400ug/day, storage 3-6 months Serum folate RI: >2.5ng/mL Red cell folate RI: 160-700ng/mL

question

commonly ordered laboratory tests used in the diagnosis of vitamin B12 and folate deficiency

answer

Vitamin B12: Serum B12 assay, MMA Folate: folic acid assay, serum folate, red cell folate

question

two autoantibodies found in patients with pernicious anemias.

answer

Parietal cell and intrinsic factor antibodies

question

reticulocyte response in treatment of these deficiencies

answer

Reticulocyte count increase 10-12 days.

question

Identify why it is important for the physician to prescribe specific treatment for vitamin B12 and folic acid deficiencies

answer

Specific therapy would correct the anemia but not the neurologic symptoms; permanent disability would result

question

Using peripheral blood findings, differentiate the anemias of liver disease, alcoholism and stimulated erythropoiesis from each other and from a megaloblastic anemia

answer

Liver disease-round macrocytes; cells have excess cholesterol and phospholipids in the membrane-target cells (codocytes), spur cells (acanthocytes) Alcoholism-macrocytosis my be megaloblastic or nonmegaloblastic (oval macrocytes) Stimulated erythropoiesis-hemolytic anemia or after blood loss; macocytic cells due to shift/early retics

question

Discuss the classifications of hemolytic anemia

answer

Group I: extracorpuscular and acquired: immune Group II: extracorpuscular and acquired: non-immune Group III: extracorpuscular and inherited Group IV: intracorpuscular and inherited Group V: intracorpuscular and acquired Extravascular destruction intracellular destruction

question

lab tests and results used to diagnose hemolytic anemias.

answer

Signs of increased RBC destruction: Bilirubin, plasma alpha unconjugated increased, but negative bilirubin in the urine Haptoglobin absent Hemoglobin, hematocrit, RBC decreased Glycosylated hemoglobin decreased Free hemoglobin increased Hemopexin decreased Lactate dehydrogenase enzyme increased Methemalbumin increased Urine urobilinogen increased Hemoglobinuria, hemosiderin in the urine Plasma iron turnover increased Reticulocyte absolyte number increased: RPI>2 Blood smear: poikilocytes specifically identified, polychromasia, nucleated RBCs Bone marrow: erythroid hyperplasia in the bone marrow Possible blood smear morphology: Acanthocytes-Abetalipoproteinemia, splenectomy Autoagglutination-cold agglutins, immunohemolytic disease Codocytes and basophilic stippling-thalassemia Codocytes-iron deficiency, liver disease, splenectomy Drepanocytes/sickle cells-sickle cell disorder Echinocytes-liver disease, pyruvate kinase deficiency, phosphoglycerate kinase deficiency, uremia Elliptocytes-hereditary elliptocytosis Schizocytes-microangiopathic anemia Spherocytes-hereditary spherocytosis, immunohemolytic anemia, burns, RBC chemical injury

question

Define hemoglobinopathy. Explain the fundamental abnormality in hemoglobinopathies

answer

Hemoglobinopathies are clinical diseases that result from a genetically determined abnormality of the structure of the hemoglobin molecule. They are caused by mutations in the genes for one of the globin chains; heme is normal.

question

Define the molecular abnormalities of HbS, HbC, and HbE.

answer

HbS-glutamic acid is replaced by valine in the 6th position of the beta globin chain. HbC-glutamic acid is replaced by lysine in the 6th position of the beta globin chain HbE-glutamic acid is replaced by lysine in the 26th position of the beta chain

question

State the incidence of sickle cell disease, sickle cell trait and hemoglobin C disease in the US population

answer

SS: 0.3-1.3% of African Americans (1 in 375) SA: 8-10% of African Americans CC: 0.02% of Aftican Americans C-trait: 2-3% of African Americans

question

Identify the world geographic areas in which these conditions are most prevalent.

answer

HbS and HbC: Africa HbE: Southeast Asia

question

pathophysiology of sickling and the result of sickling of rbcs in the circulation.

answer

HbS: hgb molecules in the deoxy state of HbS are less soluble than HbA, attach and stack upon one another. The fibers distort the shape of the cell so that it becomes crescent shaped with pointed ends. Sickle cells travel through vessels more likely to polymerize and stack up; eventually irreversible. Can cause death (plug blood vessels)

question

Identify laboratory tests and results useful in the laboratory diagnosis of sickle cell disease and of Hgb C disease

answer

SS: Solubility test (positive in both homozygous and heterozygous patients) Sodium metabisulfite test (not conclusive for HbS). Definitive test Hemoglobin electrophoresis: Homozygous: no HbA, ~85% HbS, 15% HbF. CC: Hemoglobin electrophoresis: No HbA, >90% HbC, <7% HbF AC trait: ~60% HbA, ~40% HbC (globin chains that are normal form quicker)

question

State the clinical features and inheritance patterns of sickle cell disease, sickle cell trait, hemoglobin C disease, HbC trait.

answer

SS: blood flow is blocked and tissue injury occurs; early childhood, bilateral painful swelling of hands; red cells pool in the spleen and cause slenomegaly and occlusion of splenic vessels. Atrophy and autosplenectomy by adulthood (asplenia); affects many other body systems. SA: No clinical signs under normal conditions; sickling can occur: hypoxia (airplane or mountains), respiratory infections, anesthesia, congestive heart failure. Traits protect from malaria. CC: splenomegaly but usually asymptomatic; red cells become rigid and trapped in the spleen; life span of RBCs is usually 30-55 days.

question

typical peripheral blood smear findings in sickle cell disease and sickle cell trait

answer

SS: chronic hemolytic anemia; normocytic/normochromic anemia because of extravascular hemolysis; increased polychromasia and NRBCs; Anisocytosis: shift retics/regenerative macrocytes. Poikilocytes: sickle cells, target cells; RPI increased, Inclusions: NRBCs, siderocytes (pappenheimer bodies), coarse basophilic stippling; Autosplenectomy changes: howell-jolly bodies, acanthocytes, target cells and pappenheimer bodies, NRBCs. Neutrophilia and thrombocytosis SA: few targets, no sickle cells; sickle screening tests are positive.

question

the typical peripheral blood smear findings in hemoglobin C disease, HbC trait and HbE disease.

answer

HbC: Mild anemia, normocytic/normochromic, lots of target cells, spherocytes, HbC crystals on smear only; increased reticulocyte count HbC trait: target cells, mild hypochromasia, no anemia, no symptoms, no HbC crystals HbE: target cells prominent

question

Define thalassemia

answer

Quantitative defects in the production of the globin chains resulting in decreased amounts of some of the hemoglobin molecules

question

Distinguish between alpha and beta thalassemias

answer

Alpha thalassemias-decreased production of the alpha globin chain Beta thalassemias-decreased production of the beta globin chain

question

State the geographical distribution of the thalassemias

answer

Alpha: Africa, middle east, SE Asia, parts of the Mediterranean, southern Europe; US immigrants Beta: Africa, Mediterranean, S. Europe, SE Asia, and middle east

question

Describe genetic defects that lead to the various thalassemia syndromes

answer

Beta zero, beta plus; nonfunctional alpha

question

Distinguish between thalassemia major, intermedia, minor, and silent carrier

answer

Thalassema major: severe hemolytic anemia-homozygous (two abnormal beta globin genes) Intermedia: moderate hemolytic anemia Minor: minor anemia; heterozygous beta zero/beta or beta plus/beta Silent carrier: normal

question

Identify possible genotypes for alpha and beta thalassemias and relate to clinical pictures

answer

Beta: Beta zero/beta zero; beta zero/beta; beta zero/beta plus; beta plus/beta; beta plus/beta plus; beta/beta Alpha: a-/aa (Silent carrier); a-/a- (a-thalessemai trait) or --/aa; --/-a (HbH disease); --/-- (death)

question

Thalassemia blood smear morphology

answer

Alpha: microcytic/hypochromic B major: extremely microcyte/hypochromic, numerous NRBCs, extreme poikilocytosis (target cells, bizarre shapes) anisocytosis, inclusions (coarse basophilic stippling, howell jolly bodies, pappeneimer bodies) B minor: no anemia or mild; erythrocyte count often quite high; gairly normal to anisocytosis and poikilocytosis; target cells and coarse basophilic stippling A trait: mild anemia, target cells, coarse basophilic stippling, poikilocytosis HbH: moderate to marked anemia; target cells, coarse basophilic stippling, poikilocytosis

question

Thalassemia iron studies results

answer

Beta: all normal

question

Thalassemia Hemoglobin electrophoresis results

answer

Homozygous Beta zero: no HbA, up to 98% HbF, normal HbA2 Homozygous Beta plus; beta zero/beta plus: Small amount of HbA, 60-95% HbF, normal HbA2 Het beta zero; het beta plus: Increased HbA2 (3.5-7%), increased HbF in 50% of patients (1-2%), remainder is HbA (90-95%) HbH: 2-40%

question

Identify the globin composition of hemoglobin H and hemoglobin Bart's

answer

HbH=4 aggregated Beta chains Hb Bart's=4 aggregated gamma chains

question

Hyperproliferative anemias

answer

decreased production (proliferation) by the bone marrow due to depletion, damage or inhibition of the stem and/or progenitor cells

question

Classify the hypoproliferative anemias by pathophysiology and erythrocyte indices

answer

Production, RPI <2 Mactocytic to normocytic/normochromic Pancytopenia (decrease in all cell types)

question

Aplastic anemia lab findings

answer

Aplastic anemia: Pancytopenia: Hgb <7g/dL Reticulocytes<1% ("corrected) RPI<2 Total leukocytes <1.5 x 10^9/L Neutrophils <0.5 x 10^9/L Platelets <20 x 10^9/L Erythrocyte morphology: normocytic/normochromic (sometimes macrocytic with round macrocytes), anisocytosis and poikilocytosis vary (usually not a lot of these) Serum Iron increased Bone marrow: "dry tap"; core biopsy shows replacement by fat (DIAGNOSTIC AND DIFFERENTIATES FROM OTHER HYPERPROLIFERATIVE ANEMIAS; granulocytes, erythrocytes, megakaryocytes decreased to absent

question

Myelophthisic anemia lab findings

answer

Myelophthisic Anemia: Pancytopenia or thrombocytosis or leukocytosis Leukoerythroblastic Marked anisocytosis Marked poikilocytosis-tear drops and schizocytes coarse basophilic stippling, pappenheimer bodies, polychromasia Bone marrow: dry tap; finding invading cells on bone marrow smears or core biopsy

question

clinical findings of aplastic anemia

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Insidious onset; weakness and fatigue; fever and infections; bruises or nosebleeds; acute onset, fast course leading to death

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Etiology and pathogenesis of aplastic anemia

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Etiology: acquired (>90%)-primary, idiopathic (>50%) Secondary-exposure to toxic agents, paroxysmal nocturnal hemoglobinuria Constitutional types: inherited and rare-Fanconi anemia, familial aplastic anemia. Pathogenesis: a disorder of the pluripotential stem cell or its environment and growth factors; depletion of hematopoietic cells and replacement by fat

question

Treatment and prognosis of aplastic anemia

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Bone marrow transplant, usually with peripheral stem cells (patients 50yrs: immunotherapy with antithymocyte or antilymphocyte globulin Prognosis: without treatment-3 months With transplant and/or immunosuppressive therapy- 2 year survival is 60-90%

question

the red cell abnormality and mechanism of cell destruction in paroxysmal nocturnal hemoglobinuria (PNH).

answer

Red cells are hemolyzed by complement because of a lack of markers on cell surface

question

the principles and expected results of the laboratory tests used to identify PNH

answer

Flow cytometry-CD59, CD55 are decreased Sucrose hemolysis test-positive HAM test-cells incubated in acidified serum, complement induced by acid; PNH cells will lyse

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