Anemias

Question 1

Microcytic, Hypochromic anemias

Answer 1

Iron deficiency, thalassemias; decreased MCV, MCH, MCHC

Question 2

Normocytic, normochromic anemias

Answer 2

acute bleeding, and associated w/ chronic disease

Question 3

Macrocytic

Answer 3

B12 and folate deficiency

Question 4

Iron Deficiency Anemia

Answer 4

Microcytic, hypochromic, w/ anisopoikilocytosis; Major cause of microcytic anemia
Chronic blood loss leads to IDA
Iron Deficiency leads to heme production defect
Cause: Occult gastrointestinal bleed, nutritional deficit, malabsorption, hemolysis,
Clinical: Pallor, koilonychia (spoon nails), pagophagia, PICA,

Question 5

Iron Cycle

Answer 5

Iron mostly in hemoglobin
1g/day lost through exfoliated skin, but no natural method of excretion
Controlled by 3 proteins: Transferrin - delivers iron to cells, duodenum; Transferrin receptor - binds/absorbs iron laden transferrin at cell surface; Ferritin - binds iron for storage
Total body iron: 2-4g
Balance intake/loss

Question 6

Anemia of Chronic Disease

Answer 6

Most common anemia in hospitalized patients
Normocytic, normochromic anemia
Suppressed response to EPO due to inflammatory cytokines
Defective reutilization of iron, iron sequestered in phagocytes,
Low serum iron, low transferrin, low transferrin saturation, high serum ferritin, increased BM stores mostly in macrophages
Associated Chronic Diseases: Renal Failure - chronic bleed, hemolysis, decreased EPO; DM; inflammation; cancer, liver disease;
Alcoholism: directly toxic, nutritional deficiency, chronic bleeds, congestive splenomegaly/portal hypertension, lipopretein abnormalities (acanthocytes)

Question 7

Megaloblastic Anemias

Answer 7

Two most common causes: B12 and Folate deficiency
CBC shows pancytopenia
Macrocytic anemia, anisopoikilocytosis, and hypersegmented nuetrophils; BM shows giant bands and nuclear/cytoplasmic asynchrony
Clinical: anemia, atrophic glossitis, gastric gland atrophy, nuerologic deficits in B12 ONLY

Question 8

Vitamin B12 Deficiency

Answer 8

PERNICIOUS ANEMIA - most common cause = malabsorption (intrinsic factor dysfunction/deficiency)
Rarely due to dietary insufficiency, B12 stores last years except in strict vegans
Cause: likely autoantibodies against intrinsic factor; Type I - block binding of B12 and intrinsic factor
Type II - Bind B12/IF complex and stop absorption
Associated w/ autoimmune diseases: Hashimoto’s Thyroiditis, Adrenalitis, Grave’s Disease
Tests: Serum B12 levels, methylmalonic acid and homocysteine levels, Autoantibody tests;
Schilling test*
Treatment: IM B12, corrects anemia, corrects neurological deficits if

Question 9

Folate Deficiency

Answer 9

Usually Dietary insufficiency
Liver stores can deplete in 3-6 months
No neurologic deficits
Tests: Serum and RBC folate levels, homocysteine levels, Autoantibody tests
Treatment: Folate supplement, folate supplement partially corrects B12 deficiency but does not affect neurologic deficits

Question 10

Aplastic Anemia

Answer 10

Stem cell injury/suppression
Normocytic, normochromic anemia, pancytopenia, NO reticulocytosis, hypocellular BM = dry tap
Aquired Causes: IDIOPATHIC, autoimmune suppression by T cell mechanism (most common), chemicals, toxins, drugs, radiotherapy/radiation, viral infections (Hep., EBV, HIV, parvo),
Hereditary: Fanconi Anemia - AR, defects in DNA repair, congenital anomalies (hypoplastic radii, thumbs, organs), may evolve into MDS, acute or chronic myeloid leukemia
Treatment: Supportive - transfusions, antibiotics, immunosuppression, BM transplant if

Question 11

Pure Red Cell Aplasia

Answer 11

Normocytic anemia
No reticulocytosis
Few to absent erythroblasts in BM
Autoimmune disease - T cell or IgG autoantibody against RBC precursors; associated w/ SLE, CLL, lymphomas, THYMOMAS,
Primary - Diamond Blackfan Syndrome = severe anemia first year of life w/ other congenital anomalies
Secondary - infections: Parvovirus B19, solid tumors, rheumatic disease (SLE, sjogrens), drugs, idiopathic
Treatment: stop drugs if cause, thymoma resection, High dose IV immunoglobulin for parvo, Immunosuppression (ATG + cyclosporine)

Question 12

Sideroblastic Anemias

Answer 12

Rare
Failure to incorporate iron into protoporphoryin to form hemoglobin
Dimorphic (macro/micro), hypochromic,
High serum iron, high transferrin saturation, high ferritin
Hereditary: X-linked recesssive - due to defects in Amino-levulonic acid synthase (ALA synthase)
Aquired: Myelodysplasia, drugs, toxins (lead, zinc), nutritional deficiency
Treatment: pyradoxine (B6), treat underlying condition (remove toxin exposure, stop drug)

Question 13

Acute hemolytic anemia sx

Answer 13

fatigue, pallor, jaundice, splenomegaly, CHF

Question 14

Chronic hemolytic anemia sx

Answer 14

fatigue, pallor, jaundice, splenomegaly, CHF, gallstones, abnormal bone growth and fractures

Question 15

Hemolytic anemia lab findings

Answer 15

Unconjugated bilirubin
Decreased serum haptoglobin
Increased serum LDH
reticulocytosis
Schistocytes

Question 16

Extravascular hemolysis

Answer 16

Occurs outside bloodstream
Usually associated with inherited hemolytic anemias
Spherocytes on PB smear

Question 17

Intravascular hemolysis

Answer 17

Within bloodstream
Free hemoglobin released - leads to hemoglobinuria, hemosiderinuria
Usually associated with aquired hemolytic anemia

Question 18

Beta Thalassemia Major

Answer 18

Decreased production of HbA (a2b2)
Beta globulin gene on chromosome 11 - usually point mutations or partial deletions
Two possible abnormal Beta alleles: Beta0 and Beta+
Beta0 produces no beta globulin (degraded mRNA)
Beta+ produces reduced beta globulin
Beta0/Beta0 = none; Beta+/Beta+ = reduced; Beta0/Beta+ = reduced
Onset at 6-9 months as switch to adult hemoglobin
Severe anemia, compensation leads to abnormal bone growth, hepatosplenomegaly
Depend on transfusions for survival
Clinical: growth retardation, distorted facies, iron overload, Compensatory increase in HbA2 and HbF Microcytic, hypochromic anemia, anisopoikilocytosis

Question 19

Beta Thalassemia Minor

Answer 19

One normal/one abnormal allele of Beta globulin: B/B+ or B/B0
Microcytic, hypochromic anemia
important to differentiate from iron deficiency anemia: iron therapy improves IDA, but worsens Beta thalassemia minor
Increased or normal serum and BM iron in Beta thalassemia minor

Question 20

Alpha Thalassemia

Answer 20

Four alpha globin genes, severity based on # affected alpha genes (total deletion)
Loss all 4: Hemoglobin Bart = gamma tetramers, no hemoglobin of any form, Hydrops fetalis; Burr cells
Loss of 3: Hemoglobin H = Beta tetramers, precipitates in RBC and bitten off in spleen (bite cells), after splenectomy see Heinz bodies in RBC
Loss of 2: Alpha thalessemia trait - two types; Type I - deletion of both on one chromosome, Hb Bart at birth, HbH inclusions during life; Type II - deletion of one on each chromosome, Hb Bart at birth, NO HbH inclusion need gene mapping to confirm

Question 21

Sickle Cell Disease

Answer 21

Sickled cells - cytoskeletal damage (spectrin dimers instead of tetramers) lead to increased blood viscosity, microvascular occlusion, infarction
HbS - Valine replaces glutamate at position 6 of Beta, HbS has abnormal intermolecular bonding leading to polymerization and sickling
Homozygous (V6E) - HbF increased to ~10%, chronic hemolysis w/ vaso-occlusive crises (hand and foot syndrome [dactylitis = swollen fingers in infants] and avascular necrosis of femoral head), expanded BM for increased hematopoiesis, EMH, autosplenectomy - congestion, infarction, fibrosis (salmonella osteomylitis), chronic leg ulcers
Complications: Acute Chest Syndrome - dangerous microvascular occlusion in lung, fever, cough , chest pain, lung infiltrates, CVA, Infection/sepsis encapsulated organisms, aplastic crisis (parvo BM suppression), splenic sequestration crisis (rapid splenomegaly and hypovolemia), priapism, organ infarction, cerebral growth impairment, GALLSTONE formation from chronic extravascular hemolysis,
PB - severe anemia, Howell-Jolly bodies
Diagnosis: sickle cells in PB, sickling test, Hemoglobin electrophoresis, High performance liquid chromatography
Sickle tendency: Interaction w/ other Hb (HbA has low affinity severe hypoxia for sickling; HbF inhibits polymerization, can attenuate; HbD moderate affinity) HbC - (L6E) HbSC is sickle disorder but less severe than HbSS; Hb concentration (increase in MCHC - dehydration); thalassemias; increased pH or temp.

Question 22

Hereditary Spherocytosis

Answer 22

Mutations in the RBC membrane skeleton protein ankyrin leads to deficiency of spectrin because lack of anchor - spherical shape less deformable
Clinical: usually chronically compensated; jaundice; splenomegaly; gallstones; anemic crises due to parvo, hematosuppression, or folate deficiency
Diagnosis: Osmotic Fragility Test; only notable disease w/ microcytosis and increased MCHC; negative Coomb’s; +family history
Treatment: folic acid, Splenectomy (treatment of choice) spherocytosis persists, but site of hemolysis removed

Question 23

Glucose-6-phophate Dehydrogenase Deficiency

Answer 23

G6PD gives RBC antioxidant protection, RBC becomes denatured in times of oxidant stress due to inadequate production of NADPH needed to maintain GSH levels; stability of G6PD is functional defect
Heinz bodies from denatured hemoglobin
Mediterranean variant: severe decrease,

Question 24

Warm Antibody Hemolytic Anemia

Answer 24

Antibodies reactive at body temperature
Mostly due to IgG antibodies - spleen eliminates IgG coated cells
Drug induced: methyldopa (L-dopa) - antibody against Rh blood group antigen; Penicillin-hapten - antibody against drug attached to RBC; tetracyclines, cephalosporins, tolbutamide
Disorders: Lymphatic malignancies (CLL, ect.); autoimmune disorders (SLE, rh arthritis, ulcerative colitis)
Treatment: treat underlying conditions, corticosteroids, blood transfusions, gammaglobulins, plasmaphoresis, splenectomy
May antedate onset of disease by months or years

Question 25

Cold Agglutinin Immune Hemolytic Anemia

Answer 25

Monoclonal IgMs are induced at colder temps
RBC destruction by agglutination or serum complement activation
IgM target Blood group antigens (A, ,B, O, i, I), fix C3 (C3 coated RBCs eliminated by spleen, NO splenomegaly)
May present w/ acrocyanosis
Acute Type: acute, self limited hemolysis; atypical pneumonia (cold agglutinin to I); Infectious Mononucleosis (cold agglutinin to i)
Chronic Type: lymphoid malignancy or idiopathic
Treatment: treat underlying condition, warm environment

Question 26

Paroxysmal Cold Hemoglobinuria

Answer 26

IgG autoantibody (Donath-Landsteiner antibody) = biphasic hemolysis - Binds at low temp and then causes hemolysis via complement (intravasclar) as warmed - hemoglobinuria
Associated with recovery from infections (M. pneumoniae; Infectious Mononucleosis
Test for Donath-Landsteiner antibody
Treament: keep warm

Question 27

Transfusion Hemolytic anemia

Answer 27

Severe intravascular hemolysis of donor RBCs by complement fixation
Diagnosis: Direct Coomb’s, test for serum haptoglobin, LDH, serum bilirubin, serum and urine hemoglobin
Treatment: Stop transfusion immediately if suspect

Question 28

Hemolytic Disease of Newborn

Answer 28

Transplacental transmission of anti-Rh antibodies to Rh+ fetus
Production of anti-Rh antibodies due to previous transfusion or pregnancy (Rh+ blood exposure)
Treament: Rhogam

Question 29

Microangiopathic Hemolytic Anemia

Answer 29

Abnormalities in microcirculation (fibrin deposit, narrow vessel)
DIC, HUS, TTP, HELLP (Hemolysis, elev. liver, low platelets)

Question 30

Alcoholic Liver Disease

Answer 30

Acanthocytes - spur cells

Due to abnormal lipid in RBC membrane

Question 31

Paroxysmal Nocturnal Hemoglobinuria

Answer 31

Mutation in Pig-A gene (Phosphatidyl Inostitol Glycan class A gene) - controls synthesis of glycosyl phosphatidyl inostitol (GPI) anchor
GPI needed for some membrane proteins (CD55, CD59, CD14, CD16)
CD59 = membrane inhibitor of reactive lysis; CD55 = DAF
Screening test: Sucrose lysis test
Diagnosis: Flow cytometry
Chronic form more common, but actually paroxysmal and nocturnal in 25%
May progress to Aplastic anemia; Myelodysplasia; Acute Myeloblastic Leukemia
Treatment: Iron supplements, Prednisone, BM transplant

Question 32

Mechanical Factors

Answer 32

Prosthetic heart valves: artificial valves affected more

March Hemoglobinuria: after exercise

Burn Injury: barbell/rod shapes on smear