Anemias Flashcards
1
Q
Three Steps to Evaluating Anemias
A
- RBC sized: MCV
- microcytic: hemoglobin synthesis deficits (iron deficiency, thalassemia)
- macrocytic: defects in cell division (B12 and folate deficiency)
- normocytic
- Blood smear examing for abnormalities in RBC and leukocytes
- Kinetic analysis: estimating red cell delivery and absolute retic count
- ***optional bone marrow biopsy
2
Q
Iron Deficiency
A
- Microcytic Anemia
- MCV: low in proportion to anemia (may be normal in early stages)
- Serum iron: LOW
- TIBC: HIGH (want to have lots of seats on the train)
- Transferrin Saturation: LOW (noone to fill the seats)
- Serum Ferritin: LOW (iron stores in the body) <30
- Marrow Iron: Not present
- Causes: malnutrition, pregnancy, menstration, GI blood loss (think about who demographic is for cause adult men/post-menpausal women vs. young woman)
- Retic count: Normal (which is not normal, hypoproliferative, expect to see higher counts if anemic)
- PB smear: Aniso and poikilo in severe cases, hypochromic, microcytes, cigar-shaped RBCs
- Clinical Sx: Glossitis (painful red tongue, lack papillae), pica, spoon nails, brain metabolism abnomalities
- Tx: Oral ferrous salts, oral polsacc complex with Fe, IV Fe dxtran/sucrose (parenteral)
- Notes:
- following tx hgb concentrations rise within two weeks
3
Q
Thalassemia Trait
A
- Microcytic Amenia
- MCV: low even in absence of anemia
- Serum iron: normal
- TIBC: normal
- Transferrin Sat: normal
- Serum ferritin: normal
- Marrow iron: present
- Causes: genetic
4
Q
Anemia of Inflammation/Chronic Disease
A
- Microcytic anemia (with prolonged infection)
- MCV: normal or slightly low
- Serum Iron: LOW (due to sequestration of iron in macrophages)
- TIBC: normal or low
- Transferrin sat: normal or low
- Serum ferritin (in relation to stores): normal or high, >100
- Marron iron: Present
- Causes: Infection, autoimmune, cancer
- inflammation that lasts for weeks leads to anemia
- Retic count: normal (hypoproliferative anemia)
- PB smear: not many shift cells
- Tx: eliminate cause of inflammation
- Notes:
- decrease Epo: less RBC production in marrow (relatively low considering degree of anemia)
- increase hepcidin: hepcidin binds with ferroportin and closes channel, inhibits release of iron from stores
- most important mechanism is reduction of plasma iron
- correlation with temp elevation, plasma iron drops; returns to normal after cessation of fever
5
Q
Hypoproliferative Anemias
A
- lower than expected marrow erythorid cellularity and red cell production for the degree of anemia
- iron deficiency, chronic inflammation
- Mechanisms
- insufficient supply of iron for hgb synthesis (due to iron deficiency or sequestration)
- low erythropoietin levels for degree of anemia
- marrow damage
- decrease erythropoietin anemias:
- chronic kidney disease: due to destruction of the renal EPO-producing mechanism, very low hematocrit percentages with uncorrespondingly low EPO; red cell indices are normal; few reticulocytes in circulation
6
Q
Iron Overload
A
- MCV: normal
- Serum Iron: High
- TIBC: Normal
- Transferrin sat: High
- Serum ferritin: High
- Marrow iron: Present
- Causes: hereditary hemochromatosis (mutation in HFE gene that codes for hepcidin, deminished release), Chronic ineffective erythropoiesis, repeat transfusions, dietary
- iatrogenic: caused by medical treatment, in this case repeated transfusion
- Clinical Sx: Cirrhosis, hepatocellular CA, endocrine failure, joint disease, bronzing of skin, heart failure, IN GENERAL TISSUE DAMAGE
- acute poisoning: GI necrosis (nausea, vomiting, blody diarrhea)
- Tx: Phlebotomy, iron chelation
- Notes: Hgb is normal, decreased hepcidin release from liver (for whatever reason depending on cause)!!!
7
Q
Hereditary Hemochromatosis
A
- Iron Overload syndrome
- mutation in the HFE gene that affects release of hepcidin
- Hepcidin (secreted from the liver) is responsible for binding to ferroportin and closing gate
- THE LIVER ALWAYS BEHAVES AS THOUGH THE PATIENT IS IRON DEFICIENT
- Genetics: autosomal recessive
- Clinical Sx: bronze skin, liver failure, diabetes
- Transferritin sat: HIGH >40-50%
- Ferrin
- Tx: phelobotomy of 500cc whole blood, ~250mg iron
- Notes:
- developed in Celtic or Viking ancestor
- little affect in non-Caucasians and women (due to iron losses during menstration & pregnancy)
8
Q
Sickle Cell Anemia
A
- DzL genotype: SS, SC, Sß0, Sß+, SE, SS-alpha
- MCV: Microcytosis
- Anemia: Chronic hemolytic anemia
- Serum iron: High it tx with transfusions
- Serum ferritin: normal
- Hgb: Low but generally, SS~~* Lab/Blood: High LDH, High unconjugated bilirubin
- Retic count: High
- PB smear: Sickled cells, polychormatic RBCs, Howell-Jolly bodies (nuclear fragments), nucleated RBCs, cigar-shaped RBCs
- Clinical Sx: Vaso-occlusion crisi, dactylitis, pulmonary HTN, CVA, silen cerebral infacts, acute chest syndrome, splenic infactions, osteonecrosis, priapism, retinopathy, nephropathy
- Tx: Stem cell transplant, hydroxyurea, vaccination, penicillin, transfusion & chelation
~~
9
Q
alpha-Thalassemia
A
- Dz Genotypes:
- Thal-trait: - alpha,alpha -
- Hgb H: - alpha, - -
- Hydrops fetalis: - - , - -
- MCV: Micorcytic (mild in thal-trait, severe in HgbH, and Hydrops)
- Anemia:
- Minor: mild or absent (normal)
- Hgb H: moderate to severe
- Hydrops: generally lethal
- Serum iron: High if tx with transfusions
- Serum ferritin: normal
- Hgb: Low, but generally Hydrops
- Retic count: high
- PB smear: Aniso and Poikilo, hypochromia, target cells, inclusion bodies (seen with supravital stain, present in HgbH)
- Clinical Sx: Splenomegaly, hemolysis, erythroid marrow expansion, iron overload (exasterbated by repeated transfusions), gallstones
- Tx:
- Thal-trait: none
- HgbH: folic acid, avoid oxidants, transfusion, splenectomy
- Hydrops: early diagnosis (in utero), transfusion before second half of pregnancy
10
Q
ß-Thalassemia
A
- Dz Genotypes:
- Minor: ß/ß0 or ß/ß+
- Intermedia: ß+/ß+, ß+/ß0, ß/ß0
- Major: ß0,ß0
- MCV: microcytic (even with minor)
- Anemia:
- minor: mild or absent
- indermedia/major: severe
- Serum iron: High if tx with tranfusions
- Serum ferritin: Normal
- Hgb: Low but generally, minor
- Retic count: High
- PB smear: Traget cells, nucleated RBCs, poikilo, precipition of insoluble alpha4
- Clinical Sx: hemolysis, hepatosplenomegly, iron overload (due to repeated transfusions), marrow expansion, gallstones (due to bilirubin and calcium aggregates)
- Notes: ineffective erythropoiesis (due to the production of toxic alpha-hemoglobin tetramers, subsequent cell damage, and death in the marrow)
11
Q
B12 (Cobalamin) Deficiency
A
- MCV: megaloblastic (>100)
- Causes: vegan/vegetarian diet, pernicious anemia, lack of IF (intrinsic factor made by gastic parietal cells binds B12), blind loop syndrome (bacterial overload, competitors for B12 absorption), lack of transcobalmin II (necessary to carry B12 from small intestine to liver for storage), B12 destruction by NO
- CBC indications: decrease WBC, decreased platelets
- Lab/blood: decrease serum B12, increase LDH, increase bilirubin, increase serum homocysteine, increase methylmalonate
- Retic count: not increased due to ineffective erythopoiesis
- Nucleus: Less condensed and less circular, smaller nucleus to cytoplasm ratio
- Marrow findings: Hypercellular marrow, low G:E ratio 1:1 (normal 2-3:1), megaloblasitc changes in RBC and granulocyte series, giant band cells, giant erythroid precursors
- Clinical Sx: frequent neurologic injury, neural rube defects in pregnancy, glossitis
- leads to demyelination of lateral and dorsal spinal cord tract
- Dx: Schilling test (urine radioactivity test)
- serum B12 should be measure in all patients with dementia and neuropathy
- Tx: gastric juice, liver extract (increase IF), “the red vitamin”
- bone marrow function: normal within 48 hrs
- reticulocytosis: 48-72 hrs, max by day 8-10
- hgb: increase 1st week, normal 2-3 months
- Notes: pancytopenia (plasma RBC, WBC, and platelet count ALL low), giving folate worsens neurologic sx
12
Q
Folic Acid (Folate) Deficiency
A
- MCV: megaloblastic (>100), retarded DNA synthesis reduces number of cell divisions the cytoplasm makes
- Causes: poor diet, alcoholism, *pregnancy*, celiac disease, chronic hemolysis, anticonvulsants (Phenytoin); short biological half-life ~1 mo
- CBC indications: decrease WBC, decrease platelets
- Lab/blood: decrease serum folate, increase homocysteine, normal methylmalonate (MMA)
- Retic count: not increased due to ineffective erythropoiesis
- Nucleus: Less condensed and less circular, smaller nucleus to cytoplasm ratio
- Marrow findings: Hypercellular marrow, low G:E ratio, megaloblastic changes in RBC and granulocyte series (late stage cells still have relatively immature nucleus), giant band cells, giant erythroid precursors, hypersegmentation of neutrophils, dysynchrony (RBD development of cytoplasm and nucleus does not match)
- Clinical Sx: No neurologic injury (compare to prevalence in B12 Deficiency), neural tube defects in pregnancy even with small deficit
- Tx: moderate supplemental folic acid
- Notes: pancytopenia, RBC folate level does NOT provide useful info for DDx
13
Q
How vitamin deficiencies occur.
A
- Inadequate intake
- folic acid: alcoholics, institutionalized patients
- B12: diet lacking in meat
- Malabsorption
- folate: celiac disease, some drugs
- B12: lack of Intrinsic factor
- Increased utilization or loss
- pregnancy or hemolysis
- Drug inhibition
- Folate: Methotexate
- B12: NO
- Genetic defects
- B12: defect in transcobalmin II
14
Q
Pernicious Anemia
A
- severe atrophy of gastric mucosa
- aquired loss of intrinsic factor (necessary to bind B12 and facilitate absorption in the ileum)
- Cause: loss of gastric parietal cells
- autoimmune distruction: most likely
- physical or chemical injury
- surgical removal
- Serology: autoantibodies
- gastric parietal cells: low specificity
- intrinsic factor: high specificity, almost diagnostic of disease
- Clinical sx:
- second half of life disease: >40 yo
- juvenile form: rare, inherited recessive trait
- other symptoms similar to B12 deficiency
- Tx: failure to absorb B12 is permanent, lifetime supplement of B12
15
Q
G-6-PD Deficiency
A
- Cause: Genetic (X-sex-linked chromosome)
- Anemia: hemolytic
- Hgb: normal between attacks, low during
- Lab/Blood:
- decrease: G-6-PD, NADPH, GSH, hepatoglobin
- increase: ROS, lipid peroxidation, LDH, congated bilirubin, urine heme, and hemosiderin
- Retic count: high
- PB smear: Heinz bodies (hemoglobin aggregates visible with supravital stain), bite cells
- Clinical Sx: hemolytic anemia, extramedullary hematopoiesis
- Tx: avoid oxidants (including drugs and fava beans)
- Notes: cannot accurately test immediately afer hemolytic event, often asymptomatic
