Hematology 1 - Exam 3 Flashcards

Question

What is Hemochromatosis? What are some characteristics?

Answer 1

- Accumulation of excess Fe, resulting in tissue damage. - Excess Fe stored in the liver, heart, and pancreas (leading to damage of these organs). - Can cause bronze skin pigmentation.

Answer 2

- Increased %Tf sat. (1st indication of HH). Diagnosis requires %Tf sat. > 50% for females and > 60% for males. - Increased serum iron - Increased serum ferritin - Normal or decreased TIBC.

Answer 3

Therapeutic phlebotomy or blood letting. Chelation therapy for acute poisoning.

Answer 4

- Males between 40-60 mostly - Joint pain and chronic fatigue - Homozygotes show majority of symptoms: CVD, liver cancer, osteoarthritis, & diabetes mellitus. - Also causes some cardiomegaly, early menopause, depression, infertility, and impotence.

Answer 5

1. Hereditary Hemochromatosis (HH): One of the most frequent genetic diseases is northern European Caucasians. Tf receptors appear to be permanently turned on (maybe due to mutant hepcidin). Patients absorb normal amount of iron, but transport more of it into the plasma. 2. Acquired Hemochromatosis: occurs secondary to other inherited hemolytic anemias. Common characteristics are anemia, ineffective erythropoiesis, and Fe overload. Usually have multiple transfusions, which leads to increased Fe storage due to no mechanism for iron excretion.

Answer 6

When excess iron is present: - increased ferritin - increased hemosiderin - free Fe increases (ferrous form) - ferrous Fe + O2 = superoxide & free radicals, leading to cell death. - All cells (except mature RBCs) require iron, and have the potential for damage.

Answer 7

Issues: - asymptomatic individuals frequently will have identifiable lab value abnormalities, so screening is a hot issue. - at home cheekbrush test is now available. Sample is mailed in for PCR and analysis, but is expensive. Recommendations: - have the genetic test only if you have a relative diagnosed with hemochromatosis. - middle-aged men should donate blood at least once per year. - otherwise healthy adults should avoid Fe supplements unless they have been specifically prescribed by a doctor.

Answer 8

IDA: Bone Marrow Fe - low or absent Serum ferritin - decreased Serum Fe - decreased TIBC - increased FEP - increased ACI: Bone Marrow Fe - normal or increased Serum ferritin - normal or increased Serum Fe - decreased TIBC - normal or decreased FEP - increased SA: Bone Marrow Fe - increased Serum ferritin - increased Serum Fe - increased TIBC - normal or decreased FEP - variable Pb poisoning: Bone Marrow Fe - normal Serum ferritin - normal Serum Fe - variable TIBC - normal FEP - increased Hemochromatosis: Bone Marrow Fe - increased Serum ferritin - increased Serum Fe - increased TIBC - normal or decreased

Answer 9

- Genetically diverse group of disorders (which may appear clinically similar) that are caused by decreased or absent production of globin chains. - Defect lies in the rate of synthesis of the chains (causing imbalanced globin chain production). - Occurs in high frequency in Mediterranean, middle East, India, and SE Asia.

Answer 10

Right before birth. - Gamma globin switches off, beta globin switches on.

Answer 11

Portland: ZG Gower I: EZ Gower II: AE Fetal: AG A1: AB A2: AD

Answer 12

- Micro, hypo RBCs - Increased mitosis of RBC precursors in order to make up for chronic hypoxia, frequently causes an increase RBC count & more numerous, but smaller RBCs, which consequently have less [Hgb]. - Occurs more in beta-thalassemias than alpha-thalassemias because betas have the greater hemolytic anemia due to precititation of highly unstable alpha4 tetramers. Greater hemolytic anemia = greater reticulocytosis = increased RBC count with worse MCV & MCH. - In alpha-thalassemia, defective chain production results in excess chain production in fetal and adult life. Involves a lack of hgb synthesis - cells have a shortened life span and cannot carry O2 effectively.

Answer 13

- Large deletions are the prominent cause, may be in 1-4 alpha genes. - Severity ranges from no clinical abnormality with only 1 alpha gene deleted or suppressed, to lethal with all 4 alpha genes deleted or suppressed. - 2 loci on chromosome 16 = 4 alpha genes. - With decreased alpha chains, excess gamma or beta chains accumulate to form tetramers. (Hgb Bart = Gamma4, Hgb H = Beta4) - Without alpha chains, Hgb F in fetus & Hgb A1 in infant are both affected, so symptoms of (a-) thalassemias appear before birth and continue thereafter.

Answer 14

1. Hgb Bart or Hydrops Fetalis (- -/- -): alpha-thalassemia major or homozygous alpha thalassemia. No alpha globin produced, so Hgb Bart (gamma4) is primary hgb. It is nonfunctional, so condition is lethal. Infants are grossly edematous due to onset of congestive heart failure early in gestation and are commonly born stillborn (fetus survives until 3rd trimester due to hgb Portland, but then dies of anoxia). Disease may trigger toxemia in mom during pregnancy & postpartum hemorrhage later. 2. Hgb H Disease (- -/- a): hgb H = beta4. Caused by deletion of 3/4 hgb chains. Occurs after beta-gamma switch as hgb H replases hgb Bart. Huge decrease in alpha chain synthesis means RBC makes mostly B4 tetramers, which also has increased O2 affinity (10x hgb A). Symptomatic, but not fatal. Lifelong mild to moderate anemia (due to instability of Hgb H & instability of bone marrow to compensate. 3. Hgb H - Constant Spring Disease (- -/a^CS a): also classed as hemoglobinopathy because it is also an elongated hgb, due to alpha chain mutation. This disease is 1 normal & 1 mutated alpha gene on 1 chromosome 16, and 2 deleted genes on the other chromosome 16. So there are 2 normal beta chains, 1 normal alpha chain, & 1 abnormal alpha chain with 31 extra amino acids. 4. Alpha-thalassemia minor (- -/aa or - a/- a) or a-thal trait: caused by 2 normal and 2 abnormal genes. No real clinical disease. 5. Alpha-Thalassemia Silent Carrier (- a/a a): caused by only 1 deletion. 30% prevalence in African Americans.

Answer 15

1. Hgb Bart (- -/- -): Alkaline Hgb electrophoresis shows 80% hgb Bart, 20% hgb Portland (little or or no hgb H & no hgb A1). Peripheral blood smear loaded with nRBCs. Mostly found in Southeast Asians (especially Filipinos). 2. Hgb H Disease (- -/- a): electrophoresis shows Hgb H, decreased Hgb A1 & A2, and normal Hgb F. Peripheral blood smear (brilliant cresyl blue stain) shows target cells and micro, hypo. Treatments include transfusion therapy and splenectomy. 3. Hgb H - Constant Spring Disease (- -/a^CS a): alkaline electrophoresis shows Hgb H, A1, A2, and 1-3% Hgb constant spring. Peripheral blood shows target cells and micro, hypo. Lack of treatment and prognosis is same as Hgb H disease. 4. Alpha-Thalassemia minor (- -/aa or - a/- a) or alpha-thal trait: alkaline electrophoresis is virtually normal. Very few Hgb H inclusions. Decreased MCV & MCH. Peripheral blood shows poikilocytosis with target cells. No real clinical disease. 5. Alpha-Thalassemia Silent Carrier (- a/aa): alkaline electrophoresis is normal, thus condition is benign. Slightly decreased or normal MCV & MCH.

Answer 16

- 1 locus on chromosome 11 = 2 beta genes. - Without beta chains, excess alpha chains will accumulate. However, they are too unstable to stay as tetramers, so they precipitate instead and cause plasma membrane damage. Causes hemolytic anemia. - B^0 = no beta chain production, thus no Hgb A1 (similar in severity to SCD). - B^+ = reduced beta chain production, decreased Hgb A1, with variable severity.

Answer 17

- Increased RBC count - Decreased MCV & MCH - Normal or slightly decreased MCHC - Increased Hgb F

Answer 18

1. Beta-thalassemia Major (Cooley's Anemia): severe anemia. Symptoms appear in first 2 years of life with failure to thrive and skeletal abnormalities due to massive bone marrow expansion. 2. Beta-thalassemia Intermedia: moderate anemia, but normal growth in children. 3. Beta-thalassemia Minor: 1 normal beta gene. Mild or no anemia. 4. Beta-thalassemia Silent Carrier: genotype B^SC/B. No anemia & no treatment.

Answer 19

1. Beta-thalassemia Major: alkaline electrophoresis = increased Hgb F, slight increase Hgb A2, and absent Hgb A. Increased RBCs with decreased MCV & MCH. Peripheral blood = basophilic stippling, targets, teardrops, nRBCs. Treat with regular transfusions, Fe chelation therapy, and maybe bone marrow transplant. 2. Beta-thalassemia Intermedia: alkaline electrophoresis = increased Hgb F, decreased Hgb A. Increased RBCs, decreased MCV & MCH. Peripheral smear = some basophilic stippling & nRBCS, moderate targets. Treat with supportive care as needed. Few transfusions when needed. 3. Beta-thalassemia Minor: increased RBCs, decreased MCV & MCH. Peripheral blood = slight basophilic stippling & few targets. Commonly confused with IDA, however RBC count is > than you would expect for degree of micro, hypo. 4. Beta-thalassemia Silent Carrier: no anemia and no treatment. Very slight peripheral smear changes.

Answer 20

Iron Deficiency Anemia: RBC count - < 5.5 FEP/ZPP - increased RDW - increased Ferritin - decreased Serum Fe - decreased TIBC - increased %Tf Sat. - decreased Beta-thalassemia minor: RBC count - > 5.5 FEP/ZPP - normal RDW - normal to slightly increased Ferritin - normal to slightly increased Serum Fe - normal TIBC - normal %Tf Sat. - normal

Answer 21

Minor: Hgb A - 80-95% Hgb A2 - 3.5-7.5% Hgb F - 1-5% Intermedia: Hgb A - 0-30% Hgb A2 - 3.5-5.5% Hgb F - 20-70% Major: Hgb A - 0% Hgb A2 - 3.5-5.5% Hgb F - 90-96%

Answer 22

1. Hgb S-Thal Disease: genotypes S/B-thal or S/a-thal are double heterozygotes (a hemoglobinopathy and thalassemia in one). Hgb S/B^0 thal = like Hgb SS. Hgb S/B^+ thal = like Hgb AS. Similar treatments as well. 2. Delta/Beta Thalassemia: caused by decreased or absent [dB]. Both chains have thalassemia. Abnormal RBC morphology (micro, hypo) & variable anemia (mild-moderate). Alk electrophoresis = increased hgb F, decreased hgb A1, and variable A2. 3. Hgb Lepore (dB^lepore/dB^lepore): alpha chain is ok, but beta chain is a delta-beta fusion caused by unequal crossovers. Both a hemoglobinopathy and a thalassemia. Stable, has normal function except for slightly increased O2 affinity (shift to left). Severity depends upon whether other mutations are present in dB chains. 4. Hereditary Persistance of Fetal Hgb (HPFH): increased F in adults, but without clinical/hematologic features of a thalassemia (even through it is a thalassemia). Caused by deletion/inactivation of dB gene complex, resulting in persistence of gamma chains. Less symptomatic than dB-thal. No significant clinical abnormalities. 2 subpopulations: homozygous (100% Hgb F with slight micro, hypo cells) & heterozygous (much less Hgb F (15-35%) and near normal lab results).

Answer 23

1. Hgb Electrophoresis - at alkaline & acid pHs. 2. Hgb F Quantitation - alkaline denaturation tube test (accurate and precise). - Principle = since Hgb F resists denaturation, it stays soluble, can be filtered out of the remaining supernatant & then measured. - Add strong alkali to blood sample to denature Hgbs. Incubate. - Add saturated ammonium sulfate (NH4+)2SO4 to precipitate all denatured Hgb. - Expressed as % of alkaline-resistant Hgb. 3. Hgb A2 Quantitation - ion exchange microcolumn chromatography. 4. Brilliant Cresyl Blue Stain - for Hgb H inclusions (blueish-green). 5. Acid Elution Test (Kleihauer-Betke (K-B) Slide Test)- for Hgb F. KB can be used to distinguish HPFH from a thalassemia with increased Hgb F. - Principle = at pH 3.5, all Hgbs will elute from RBCs except for Hgb F. Peripheral blood smear is immersed in acidic buffer, then stained. All other hgbs elute from RBCs & thus don't pick up the stain. Hgb F containing cells will stain, white RBCs with eluted hgb appear as "ghosts." (Also used by blood bank to determine extent of Fetal Maternal Hemorrhage [FMH], for use in calculating Rhogam dosages.) - HPFH has pancellular increase in Hgb F (all cells dark, in uniform pattern). - Thalassemias have heterocellular increase in Hgb F (non-uniform staining, with variable intensity). 6. FEP/ZPP levels - normal in thalassemias, but increased in IDA. 7. Genotype analysis - using PCR & gene sequencing.

Answer 24

- A disease state involving the Hgb molecule. - Due to genetic mutation in 1 or more genes that affect Hgb synthesis. - Mutation affects either the quality or quantity of Hgb synthesis. - Structural defects = qualitative - Thalassemias = quantitative

Answer 25

There are 6 functional human globin genes located on 2 different chromosomes. - Alpha & zeta are located on chromosome 16 and are alpha-like genes. (2 alpha & 1 zeta gene per chromosome). - Beta, gamma, delta, and epsilon are located on chromosome 11 and are beta-like genes. (2 gamma & 1 beta, delta, and epsilon gene per chromosome).

Answer 26

- Inherited as codominant traits.

Answer 27

- Traditional Hematology: CBC and microscopic. - Hgb carries an electrical charge depending on the amino acid sequence of globin chains and the pH of the surrounding environment. Allows for Hgb electrophoresis testing using cellulose acetate (pH = 8.4) and citrate agar gel (pH = 6.2). - HPLC (high performance liquid chromatography). - PCR

Answer 28

- Homozygous Beta-hemoglobinopathies: both beta genes are mutated, resulting in absence of Hgb A. (Hgb SS or Hgb CC). - Heterozygous Beta-hemoglobinopathies: only one gene is mutated, the other is normal. Attempt to minimize the impact of abnormal Hgb presents variant Hgb in lesser amounts than Hgb A. (Hgb AS or Hgb AC).

Answer 29

Point mutation at 6th amino acid in beta chain. Valine substitutes for glutamic acid.

Answer 30

- Presence of just one sickle cell gene confers resistance to cerebral infection by Plasmodium falciparum (when a malaria infected RBC sickles, the parasite dies). - Common in African populations.

Answer 31

- Deoxygenation in capillaries is normal process for all RBCs, causing Hgb to switch from relaxed to tense forms as it offloads O2. - When this occurs in SCD, Hgb S structure changes shape, bringing its hydrophobic, sticky, and mutated valines into contact. It results in polymerization of Hgb, locking up of spectrin's flexibility, and bizarre deformation of the RBC. - Usually reversible sickling, but dependent on time, temperature, pH, and O2 tension. - Deformation damages K+ channels, so RBC loses K+, and dehydration results, leading to formation of intracellular crystals & further deformation. Hgb molecules can stack up like fire wood. - RBCs become more fragile & lyse more easily. - Sickle cells lead to increased blood viscosity and slow blood flow. Reduced blood flow prolongs exposure to hypoxic environment, and lower tissue pH decreases the oxygen affinity, which further promotes sickling. - Some RBCs sickle irreversibly, which are removed by spleen. - Reversible sickle cells are responsible for vaso-occlusive complications. - Chronic injury response means "sickle cell crisis." Patients have increased #s circulating endothelial cells, which triggers the extrinsic coagulation pathway & promotes formation of microthrombi, which cause further necrosis.

Answer 32

Any situation that produces excessive deoxygenation of RBCs. Hyperthermia & hypothermia Dehydration Infection Violent exercise Labor & delivery High altitude transitions

Answer 33

1. Vaso-Occulusive or Pain Crisis: rigid, sickled cells increase blood viscosity & cause vascular occlusions & micro-thrombi (i.e. strokes), resulting in tissue necrosis. This type is the #1 cause of death in adult SS patients. 2. Infectious Crisis: precipitated by infection (S. aureus, S. pneumoniae, H. flu). Primary cause of death in SCD children. 3. Bone and Joint Crisis: pain occurs in bones and joints as sickled cells accumulate in bone shafts. The bone marrow actually infarcts. 4. Splenic Sequestration Crisis: occurs when enough sickled cells are trapped in hypoxic, convoluted, splenic microcirculation. This becomes a vicious cycle as the spleen enlarges & then traps even more cells. Hypovolemic shock can ensue. 5. Aplastic Crisis: decreased bone marrow hematopoiesis thought to be triggered by infection/fever. Common with parvovirus B19 infection. Results in temporarily (5-10 days) decreased RBC count, Hgb, Hct, & RPI.

Answer 34

Due to painful extramedullary hematopoiesis. Usually first clinical finding in infants with severe SCD. (Huge, swollen hands/fingers!!)

Answer 35

- Normo, normo anemia (cells are normal when produced in bone marrow). - Moderate > marked Anisocytosis - Target cells & sickled cells - Polychromasia (due to reticulocytes) - Basophilic stippling - Increased RDW - Howell-Jolly & Pappenheimer bodies present (indicates overwhelmed or nonfunctional spleen). - Less present without crisis.

Answer 36

- Hgb Solubility Test - most common screening test: > blood added to reducing agent sodium dithionite, and a lysing agent that releases the hgb from the RBCs. > Deoxygenated hgb S is insoluble and precipitates remain clear. > False positive results with hyperlipidemia. > False negative results with low Hct or RBC counts.

Answer 37

1. Hgb Electrophoresis: alkaline. Shows 80-90% Hgb S. Remainder is F & A2. 2. HPLC (high performance liquid chromatography): can quantify low amounts of A2 and F. 3. DNA sequencing: definitive test.

Answer 38

1. Prevent crises by avoiding precipitating situations (get enough sleep, good nutrition, & adequate prenatal care). 2. Hydroxyurea - for ages 3 & ^, anitineoplastic drug somehow induces increased Hgb F production, which reduces sickling & RBC stickiness. Since it decreases WBC count, it also inhibits overall inflammatory response. Side effect is macrocytosis. 3. During crisis: > Keep patient hydrated > Provide pain relief with opiates > Exchange transfusions as needed can create chronic problems with Fe overload & alloimmunization since "average" SS patient with frequent cries receives 1 transfusion per month. 4. Bone Marrow Transplant - only known cure (but requires HLA-matched sibling without SCD (although AS is okay), so only 200 patients world-wide have been treated this way so far). 5. Gene therapy - predicted useable in 10-20 years (already cured SCD in mice). 6. New anti-sickling Agents - NAC (N-acetylcysteine) - strong reducing agent, still in clinical trials. Sickled cells produce increased fee radicals, but have less GSH to mop them up. NAC actually reverses irreversibly sickled cells in vitro. 7. Prophylactic Penicillin - begins at 3 months of age, dramatically reduces infectious crises, morbidity, and mortality in children. 8. Pneumococcal Vaccine in Children - disease was a major cause of death. 9. Stem cell transplants from cord blood - requires huge donor bank.

Answer 39

With treatment, lifespan 45-50 years.

Answer 40

- Caused by heterozygous AS. - Hgb A compensates for presence of abnormal S, so these patients usually have no symptoms. - On rare occasion can have crises in states of extreme tissue hypoxia (severe hypothermia, acute respiratory infections, and pulmonary embolisms (PEs)).

Answer 41

- RBC morphology mostly normal except for a few targets & very rare sickled cells (even when not in crisis). - Positive solubility test. - 30-45% Hgb S on Hgb electrophoresis (~60% hgb A).

Answer 42

- Usually no treatment. - Typically have normal life span & quality of life. - Have increased resistance to malaria.

Answer 43

- Amino acid point substitution of lysine for glutamic acid at 6th position beta chain position. - 2nd most common Hgb variant after Hgb S. - Milder than Hgb S. - Particularly common in black populations. - Hgb C polymerizes under low O2 tension, but the structure of the polymers differs from Hgb S. > Hgb S polymers are long and thing, and Hgb C polymers form a short, thick crystal within the RBC. > Hgb C crystals do not change the shape of RBC. > Vaso-occlusion does not occur. - These crystals are removed by spleen, but if the spleen is nonfunctional, crystals will appear in peripheral blood RBCs. - Patients may exhibit splenomegaly & abdomial pain, but usually no other clinical symptoms. - No treatment required.

Answer 44

- Mild to moderate normo, normo anemia. - Some microcytosis and mild hypochromia. - Variable target cells, few spherocytes. - No symptoms or anemia. - 40% target cells - % Hgb A > % Hgb C - Increased retic count (4-8%). - Decreased RBC survival (due to spleen removal). - Hgb C crystals in peripheral blood (shaped like thick or elongated hexagons) - may appear free with no evidence of cell membrane. - Negative hemoglobin solubility test. - Definitive diagnosis made with electrophoresis. - With Hgb CC, cellulose acetate electrophoresis shows no Hgb A & shows Hgb C (co-migrating with A2, E , and O). - With Hgb AC, electrophoresis shows 60% Hgb A, and 30% Hgb C. - C will migrate as separate band on citrate agar at an acid pH.

Answer 45

- The most common double heterozygous syndrome resulting in a structural defect of the Hgb molecule. > Involves 2 different amino acid substitutions on each of the 2 beta globin chains. - Milder clinical symptoms than SCD. Less frequent and less disabling vaso-occlusive complications. - Normo, normo anemia. - Many target cells & folded or "pocketbook" cells.

Answer 46

- SC crystals have fingerlike projections, producing "Washington monument" or "mitten cells." - Positive solubility test results. - On cellulose acetate electrophoresis, Hgb C & Hgb S in equal amounts. - When crises occur, supportive therapy same as for SS patients. - Relatively normal life span (60-70 years), but can have diminished quality of life (retinal lesions).

Answer 47

- 3rd most common Hgb variant - Southeast Asian populations (13%). - Laos, Cambodia, Thailand. - Substitution of lysine for glutamic acid in 26th position. - Homozygous state (>90% Hgb E) presents as a micro, normo anemia with many target cells. - Hgb AE trait state exists. - Can occur in combination with beta-thalassemia.

Answer 48

- Group of variants that migrate in an alkaline pH at the same electrophoretic position of Hgb S (due to their charge). - Mild, hemolytic anemia (like CC & AC). - Negative solubility test, no sickling. - Cellulose acetate electrophoresis shows 95% Hgb D, which migrates to same position as S. - On citrate agar, Hgb D co-migrates with Hgb A1 & A2. - HPLC (high performance liquid chromatography) for confirmation. - Patients clinically normal, but may have some splenomegaly.

Answer 49

- Common in Arabic populations. - Mild hemolytic anemia with many target cells. - Needs to be differentiated from Hgb C by electrophoresis. - Glutamic acid replaced by lysine in 121st amino acid of beta chain (same as Hgb C, but with different substitution point).

Answer 50

- Involves amino acid substitutions that disrupt physical contact between heme & globin. - Result is Hgb denaturation, then precipitation of globin chains, leading to formation of Heinz bodies. - Predisposes RBCs to develop hemolytic anemia.

Answer 51

Denatured hemoglobin.

Answer 52

- Mild to severe, with episodes of hemolysis & subsequent jaundice. - Most common = Hgb Koln (old name: congenital Heinz body hemolytic anemia). - All patients are heterozygous.

Answer 53

- Decreased MCV, MCH, & MCHC (due to Hgb lost when Heinz bodies removed by spleen). - Anisocytosis, poikilocytosis, polychromasia, basophilic stippling, and "bite cells."

Answer 54

1. Hgb Chesapeake: increased O2 affinity = shift to left. (alpha chain variant). 2. Hgb Kansas: decreased O2 affinity = shift to right. - substitution mutations are such that they:

Answer 55

1. Hgb Chesapeake: increased O2 affinity = shift to left. (alpha chain variant). 2. Hgb Kansas: decreased O2 affinity = shift to right. - substitution mutations are such that they: > Disrupt 2,3 DPG binding sites > Disrupt binding of heme to globin > Stabilize iron in oxidized Fe3+ state > All of these will cause either an increase or decrease in delivery of O2.

Answer 56

- Inherited MetHgb reductase deficiency. - Toxin exposure in newborns - overwhelms GSH's reducing ability. - Inherited cytochrome deficiencies - interferes with NADH regeneration via electron transport chain. - Genetic mutation in globin chain sequence (only one called Hgb M). - 5 genetic variants known (can affect alpha or beta chain). - Most common in Japanese populations. - Amino acid substitution prevents Fe3+ reduction, so Fe remains in ferric state. - This is a type of auto-oxidation, which denatures globin chains, triggers Hgb precipitation, and forms hemolytic anemia.

Answer 57

- Only heterozygous (20-35% Hgb M). Homozygous condition is not consistent with life. - Brownish blood due to chronic cyanosis (which appears cutaneously as a lavender-blue, rather than normal blue-gray seen in ordinary cyanosis). - No treatment available. - Compensatory Erythrocytosis develops to compensate for chronically low O2 delivery.

Answer 58

- Acid elution cytochemical method used to quantitate feto-maternal hemorrhage. - Identifies cells containing Hgb F based on the fact that they resist acid-elution to a greater extent than normal cells. - Can also be used when persistence of hgb F is suspected such as hereditary persistence of hgb F in sickle cell anemia, acquired aplastic anemia, thalassemia, and other hemoglobinopathies. Fetal cell % = (# fetal cells * 100%) / total # RBCs counted

Answer 59

- Receptors in kidney are sensitive to changes in O2 tension/concentration. - Decrease in O2 tension = more EPO made by kidney & released into bloodstream to stimulate bone marrow normoblasts. - Bone marrow then allows for the early release of reticulocytes, increases number of mature erythrocytes, and increases the rate of maturation of erythroid precursors, so there's accelerated release effect into peripheral blood. - EPO can cause increased retic count & increased RPI (retic production index). - Normal bone marrow response can increase erythropoiesis 6-8 fold, but takes a full week for complete response to occur.

Answer 60

1. Erythrocytosis - erythrocytosis & polycythemias are disorders that present with an increase in circulating RBC (increased Hct). 2. Anemias - disorders that present with decrease in circulating RBCs (decreased Hct).

Answer 61

Relative: apparent decrease in RBC mass, but there is no true hemolytic disorder (caused by fluid shifts in pregnancy & IVs). Absolute: true decrease in RBC mass resulting from impaired RBC production, blood loss, or accelerated RBC destruction or hemolysis.

Answer 62

CBC ◦ Hemoglobin ◦ Hematocrit - packed red cell volume ◦ MCV - mean cell volume ◦ MCH - mean cell hgb ◦ MCHC - mean cell hgb concentration ◦ RDW - red cell distribution width Reticulocyte Count Schilling’s Test – tests for B12 in urine TIBC – total iron binding capacity Serum Ferritin – primary form of iron storage Serum Iron – amt of iron bound to transferrin Transferrin – transports iron

Answer 63

 CBC results  Retic count  Peripheral Blood Smear Evaluation (Differential)  Assessment of RBC morphology  Bone Marrow Evaluation  Other lab tests

Answer 64

- Reticulocyte count divides the anemia into 2 groups: ◦High result means there’s shortened RBC survival ◦Low result means there’s decreased production of RBCs - The anemia can then be divided into further subgroups based upon MCV, MCH, and MCHC values ◦Microcytic, macrocytic, normochromic, normocytic, and hypochromic Can be classified on the basis of their physiological cause ◦Heme and globin disorder ◦DNA disorder ◦Bone marrow failure ◦RBC survival disorders Can also be classified according to their common RBC morphology ◦Macrocytic ◦Microcytic ◦Normocytic

Answer 65

Effective: bone marrow is able to produce functional RBCs that replace the daily loss of RBCs. Ineffective: bone marrow produces erythroid precursor cells that are defective. Insufficient: decrease in erythroid precursors in bone marrow, resulting in decreased RBC production and anemia.