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156 Cards in this Set
- Front
- Back
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oval macrocytes |
megaloblastic anemia |
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round macrocytes |
reticulocytosis |
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microcytosis & hypochromia |
thalassemia, sideroblastic anemia, iron deficiency anemia, anemia of chronic disease |
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decreased serum iron, increase TIBC, decreased sideroblasts and iron stores, decr. ferritin |
iron deficiency anemia |
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incr. serum iron, decr. TIBC, incr. sideroblasts and iron stores, incr. ferritin |
sideroblastic anemia |
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Burr cells |
uremia |
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Acanthocytes/spur cells |
liver disease, some hereditary defects |
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target cells |
hemoglobinopathies - thalassemia, to some extent in iron deficiency anemia, hemoglobin C disease |
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elliptocytes |
hereditary elliptocytosis (if >25%) |
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Howell-Jolly bodies |
splenectomy, sickle cell anemia, megaloblastic anemias, post-chemotherapy |
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coarse basophilic stippling |
thalassemias, lead poisoning |
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Pappenheimer bodies |
sideroblastic anemia, hemolytic anemia, sickle cell disease |
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hemoglobin crystlas |
Hemoglobin C disease |
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Heinz bodies |
hemolytic episodes of G6PD deficiency |
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Reticulocytes |
Hemolytic anemias, response to other anemias |
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Rouleaux formation |
multiple myeloma, Waldenstrom's macroglobulinemia (monoclonal immunoglobulin accumulation) |
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Erythrocyte Microaggregation |
cold agglutinin disease |
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sideroblasts with ringed form |
sideroblastic anemia |
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low MCV anemia with high RDW |
iron deficiency anemia |
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normal RDW |
11.0-17.0% |
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megaloblastic anemia with hypersegmented neutrophils and macro-ovalocytes |
vitamin B12 deficiency |
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protein defect in hereditary elliptocytosis and pyropoikilocytosis |
alpha spectrin (most common) |
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protein defect in hereditary spherocytosis |
ankyrin (most common) |
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ankyrin gene locus |
chromosome 8p11.2 |
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staining for AE1 |
eosin-maleimide (EMA) |
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alpha chain inclusion bodies |
Beta-thalassemia |
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H bodies |
alpha-thalassemia |
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denatured hemoglobin |
Heinz bodies |
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target cell - decreased volume |
Hemoglobin C, thalassemias, iron deficiency |
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target cell - increased membrane |
liver Dz, LCAT deficiency, asplenism |
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severe acanthocytes, echinocytes, & target cells |
advanced hepatocellular Dz |
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decreasing oxygen affinity for hemoglobin? |
increase temperature, increase CO2, decrease pH, increased 2,3-DPG |
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Hgb synthesis occurs in: |
cytoplasm and mitochondria heme group is added in mitochondria |
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normal adult hemoglobin |
HgbA = alpha2beta2 |
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fetal hemoglobin |
HgbF = alpha2gamma2 |
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Hgb A2 |
alpha2delta2 |
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beta globin gene location |
chromosome 11 |
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alpha globin gene location |
chromosome 16 |
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Hemoglobin S mutation |
beta chain position 6: glutamic acid to valine |
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heterozygous sickle cell trait |
A: S = 60:40 |
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homozygous sickle cell anemia |
no HgbA |
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Dx of Hemoglobin S |
Solubility test: place RBCs in saponin (detergent) solution; HgbS is insoluble in phosphate buffer, will form tactoids |
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Blood smear of sickle cell Dz |
normocytic anemia with sickle cells, schistocytes, thrombocytopenia, and siderocytes |
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siderocytes |
RBCs with iron inclusions (Pappenheimer bodies) seen on Wright-Giemsa blood stain |
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Prussian blue stain |
blue = increased reticuloendothelial "iron stores" |
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Hemoglobin S bone marrow aspirate will show... |
erthryocyte hyperplasia low M:E ratio |
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Hemoglobin C mutation |
beta globulin chain position 6: glutamic acid (acidic) -> lysine (basic) |
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Hemoglobin C heterozygous |
target cells present, patients present clinically well Hgb A: Hgb C = 60:40 |
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Hemoglobin C homozygous |
many target cells, mild hemolytic anemia rare! |
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Hemoglobin C blood smear |
Target cells, Hemoglobin C crystals crystals may be read as lymphocytes!! |
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Hemoglobin SC blood smear |
irregularly shaped RBCS, somewhere between sickle cell and C crystal |
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Hemoglobin E mutation |
beta globulin chain position 26: glutamic acid -> lysine |
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Heterozygous Hemoglobin E |
Hgb A: Hgb E = 70:30 |
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Homozygous Hemoglobin E |
present with microcytic, hypochromic anemia, patients may be clinically ok |
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Hemoglobin E gel electrophoresis |
must test using both acidic and basic plates to differentiate between HgbE and HgbC acidic plate: one band (A&E combined) basic plate: two bands (A & E separate) |
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where is Hemoglobin E common? |
SE asia (malaria protection?) |
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Hemoglobin G mutation |
alpha globulin chain positive 68: Asparagine --> lysine |
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Hemoglobin G heterozygous |
asymptomatic 2 bands: major band in A pos., 25% band in S pos. (HgbG moves like HgbS) |
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double heterozygotes Hgb G-Philadelphia & Hgb S |
clinically asymptomatic |
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Cyanosis |
blue discoloration of the skin & mucous membranes; high deoxy-Hgb |
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Methemoglobinemia |
reversible oxidation produce of Hgb (can't carry O2) cause: drugs, toxic chemicals, hereditary defect treat hereditary defects w/ ascorbic acid, riboflavin |
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Glucose-6-Phosphate Dehydrogenase purpose |
provides reducing equivalents to glutathione reductase for reduction of peroxide to water
maintain heme iron in ferrous state protect against exo- and endogenous oxidants |
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Two clinically significant G6PD variants |
G6PD A- = moderately reduced half life G6PD Mediterranean = XLR, protect from P. falciparum?, markedly abn. fxn |
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G6PD deficiency clinical |
episodes of intra- and extravascular hemolysis after oxidative stress (antimalarials, sulfonamides, fava beans, injection esp. typhoid fever) |
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when G6PD deficient RBC is exposed to oxidants.... |
hemoglobin denatures to form Heinz bodies |
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how do you stain for Heinz bodies? |
supravital (crystal violet) stain |
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cells that form in G6PD deficiency |
Bite cells and spherocytes (Heinz bodies plucked out by macrophages) |
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can you see precipitated hemoglobin with wright-giemsa stain? |
NO!! |
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can you see Howell-Jolly bodies with Wright-Giemsa stain? |
YES!! |
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what does catabolism of porphryin produce? |
1 CO and 1 bilirubin per heme molecule degraded |
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macrophage morphology after phagocytosing RBCs |
1st: RBCs lose color, look like vacuoles 2nd: 4d, hemosiderin visible- dark brown/black 3rd: hematin pigment- red/yellow crystals 4th: months later - can see iron (siderophage) |
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Hematoidin |
chemically identical to bilirubin formed at old sites of hemorrhage amorphous or crystalline pigment |
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Total bilirubin |
unconjugated bili + bili-glucuronides |
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Direct bili |
bili-glucuronides |
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Indirect bili |
Total - bili-glucuronides increased after hemorrhage |
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unconj. bili is transported via... |
albumin |
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alpha thalassemia |
hemolytic excess beta chains formed = beta4 tetramers (Hemoglobin H), relatively stable, soluble precipitate as H bodies |
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alpha thalassemia in fetal life |
excess gamma chains => gamma-4 tetramers (Hemoglobin Barts) |
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anemia in alpha thal is caused by |
inadequate Hgb synthesis, excess unpaired alpha chains |
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alpha thal: -/- -/- |
Hydrops fetalis... FATAL!! |
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alpha thal: -/- -/alpha |
HbH disease: severe, like beta-thal intermedia |
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alpha thal: -/- alpha/alpha; -/alpha -/alpha |
alpha-thal trait (a-sx) |
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Hemoglobin H Disease |
Hgb H has extremely high oxygen affinity, so inefficient => tissue hypoxia disproportionate to Hgb concentration moderately severe anemia |
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tissue hypoxia disproportionate to Hgb concentration |
Hemoglobin H Disease |
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beta-thalassemia |
excess alpha chains = damage RBC & precursors |
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beta-thal clinical |
profound anemia, expanded ineffective erythropoiesis, iron deposition |
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beta-thal major/intermedia/minor |
major = homozygous beta-0 or beta-+ (severe, blood transfusions) intermedia = homozygous beta-+ or Beta-0/beta (severe, no blood trans.) minor = beta-0/beta or beta-+/beta (a-sx, mild/absent anemia, RBC abnormalities) |
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beta thal major labs/blood smear |
Hgb as low as 2-3 g/dL high retic & NRBC incr. HgbF and A2 NO iron deficiency blood smear: anisopoikilocytosis!! -hypochromic, microcytic, Howell-Jolly bodies, siderocytes & basophilic stippling |
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Perls' stain (Prussian blue) |
iron stains blue, nuclear materials (nucleus, Howell-Jolly bodies) stained red |
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mutations causing B+ Thalassemia |
promoter region mutations (prevent RNAp from binding normally) "ectopic" splice sites formed within the intron |
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mutations causing B-0 Thalassemia |
mutations causing premature termination of mRNA translation mutations that alter normal splicing junctions so normal splicing doesn't occur (most common) |
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beta thalassemia major pathophysiology |
excess alpha chains => unstable aggregates (alpha4) => precipitate chains & degradation products damage protein 4.1, decrease spectrin/band 3 ratio in RBC precurors |
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Delta-beta Thalassemia |
decrease in both delta and beta globulin chians = decr. Hgb A and Hgb A2 less common, less severe |
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Hereditary Persistence of Fetal Hemoglobin |
fetal Hgb production into adulthood due to mutation of beta-globulin gene cluster can be asymptomatic alleviates certain hemoglobinopathies |
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Paroxysmal Nocturnal Hemoglobinuria |
clonal stem cell disorder; production of abn. RBCs, granulocytes, platelets |
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PNH erythrocytes are susceptible to... |
complement-mediated intravascular lysis |
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PNH erythrocytes lack |
GPI-linked proteins and enzymes (complement defense proteins) |
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gene responsible for PNH |
phosphatidyl inositol glycan A (PIG-A), on X chromosome |
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PNH blood smear |
normocytic anemia (common) microcytic hypochromic anemia (sometimes) - lose iron in urine neutropenia & thrombocytopenia! |
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PNH clinical presentation |
chronic intravascular hemolysis w/ or w/o obvious hemoglobinuria; hemosiderinuria usually present |
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normal reticulocyte count |
0.5-1.5%; absolute count = 10,000-75,000 mm^3 |
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Microcytic anemia definition |
MCV < 80 fL (small cells) |
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Causes of microcytic anemia |
Heme problems: Iron deficiency anemia (most common), anemia of chronic Dz, sideroblastic anemia, lead toxicity Globin problems: Thalassemia! |
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iron facts |
2.5gm F, 6gm M 80% of iron in Hgb & myoglobin, 20% stored as ferritin or hemosiderin in macs of marrow, spleen & liver transport via transferrin serum iron approx 120 (males) |
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iron absorption in duodenum |
regulated by hepcidin (synthesized in liver, blocks ferroportin 1 transporter) |
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Fe deficiency etiology |
dietary lack (common!) incr. requirements (preggers) chronic blood loss impaired absorption (not common) |
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Fe deficiency clinical features |
nonspecific, pale, weak, malaise, dyspnea on mild exertion peculiar behavior (pica) Plummer-Vinsion syndrome (nail issues, atrophic glossitis, esophageal webs) |
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Fe deficiency Dx |
CBC - low Hgb, low MCV smear- hypochromic & microcytic iron studies - Fe < 30, transferrin sat'd <15%, TIBC incr., ferritin <10 |
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Fe deficiency in females |
young = menses, pregnancy old = colon cancer |
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Fe deficiency in males |
young = peptic ulcer old = colon cancer |
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Anemia of chronic Dz |
don't use iron efficiently chronic = TB, osteomyelitis immune = SLE, RA cancer cytokines (IL-1, -6, TNF, IFNs) decr. erythropoietin increased induction of hepicidin = decr. iron absorption |
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anemia of chronic dz Dx |
normal-low serum iron, lots of iron in marrow high iron sat'd EPO may be helpful |
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Sideroblastic anemia |
disturbed heme synthesis (mito problem in erythroids) hereditary or acquired (alcoholism, pyridoxine deficient, myelodysplastic syndromes) |
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hallmark of sideroblastic anemia |
ringed sideroblasts in bone marrow! |
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Lead toxicity |
interfere with hemezinc protoporphyrin and with iron absorption & utilization basophilic stippling, microcytic cells |
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bone marrow hyperplasia in.... |
thalassemia "crew cut" appearance of skull |
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Macrocytic anemia definition |
MCV > 96 (big cells) |
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Macrocytic anemia causes |
Megaloblastic (immature cell) anemia = impaired DNA synthesis - B12 and folic acid deficiencies Reticulocytosis Liver Dz Myeloproliferative & myelodysplastic Dz Drugs (post-chemo) |
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B12 deficiency |
dietary deficiency (rare) impaired absorption - intrinsic factor (pernicious anemia, total gastrectomy), pancreatic insufficiency, ileal dz bacteria, fish tapeworm increased requirement (preggers, hyperthyroid, cancer) |
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Pernicious anemia |
autoimmune destruction of gastric mucosa slow onset, achlorhydria, incr. gastric cancer risk |
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pernicious anemia - who? |
elderly, n. european |
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pernicious anemia Sx |
severe anemia, leukopenia, thrombocytopenia degeneration of posterolateral spinal tracts (later - pain & temp) excrete methylmalonic acid in urine |
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pernicious anemia Rx |
parenteral B12 |
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Folic acid deficiency |
absorbed in proximal jejunum macrocytic anemia, leukopenia, thrombocytopenia NO neuro sx neuro-tube closure issue in fetus |
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folate deficiency causes |
diet (indigent populations, alcoholics, tea &toast) intestinal Dz incr. requirement (preggers, cancer) impaired use (anti-cancer drugs such as methotrexate) |
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megaloblastic anemias - smear & BM |
smear = macrocytic, hyperchromic w/ hypersegmented neutrophils BM = giant bands/metamyelocytes, erythroid hyperplasia, megaloblastic maturation |
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macrocytic, hyperchromic anemia w/ hypersegmented neutrophils |
megaloblastic anemia |
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hemolytic anemia characteristics |
short RBC life incr. erythropoietin levels w/ incr. erythropoiesis incr. retic incr. Hgb degradation products (indirect bili, low jaundice) |
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onset of hemolytic anemia |
rapid! with dyspnea on exertion
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RBC membrane defects (HA causes)
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hereditary spherocytosis/elliptocytosis paroxysmal nocturnal hemoglobinuria |
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RBC enzyme defects (HA) |
G6PD, pyruvate kinase |
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defects of Hgb synthesis (HA) |
Hemoglobinopathies Thalassemias |
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extrinsic abnormalities - hemolytic anemia |
Ab-mediated hemolysis (immune hemolytic) secondary to trauma, artificial valves infections (malaria, Clostridia sepsis) |
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hemolytic anemia general effects |
bone marrow: erythroid hyperplasia (hypercellularity, decr. M:E) reticulocytosis: peripheral polychromatophilia, slightly incr. MCV sometimes accumulation of LDH and Hgb catabolism products |
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Hereditary Spherocytosis |
crises - viral inf. (parvo), stress (appendicitis) sudden anemia, splenomegaly, jaundice normal MCV |
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HS Dx |
osmotic fragility test (when not in crisis) |
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G6PD deficiency |
XLR reduces NADP -> NADPH = convert ox. glutathione to red. glutathione no glutathione => Hgb denatures => Heinz bodies |
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hemolytic episodes after oxidative stress (antimalarials, sulfa drugs, infections, fava beans) |
G6PD deficiency |
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Immune hemolytic anemias |
acquired, positive direct antiglobulin test (Coombs test), extra-/intravascular hemolysis |
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Autoimmune hemolytic anemia: Warm Antibody |
IgG type cause - primary or idiopathic secondary: lymphoma or autoimmune |
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Autoimmune hemolytic anemia: Cold Antibody |
IgM type cause - acute = mycoplasm or mono chronic = idiopathic or lymphoma also called cold agglutinin Dz |
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paroxysmal cold hemoglobinuria |
immune hemolytic anemia |
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PNH can evolve into... |
aplastic anemia and acute leukemia |
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Cryoglobulins |
proteins that become insoluble at reduced temps (below 37) consist of IgM directed against Fc region of IgG |
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Cryoglobulin problems |
type 1 = monoclonal type 2 & 3 = mixed; association with Hepatitis C; weakness, palpable purpura, arthralgias |
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Microangiopathic anemia |
hemolytic anemia due to trauma to RBCs cardiac valve prostheses, narrowed/obstructed vasculature burns |
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causes of narrowed vasculature |
DIC fibrin strands cut RBCs malignant hyperT TTP, HUS |
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microangiopathic anemia smear |
many schistocytes, broken-up cells (burr cells, helmet cells) |
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Aplastic anemia definition |
failure/suppression of multipotent myeloid stem cells |
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Aplastic anemia etiology |
idiopathic -stem cell defect, AI chemical - chloramphenicol radiation, viral inf., fanconi anemia |
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S/E of chloramphenicol |
aplastic anemia! |
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Red Cell Aplasia |
aplasia of only erythroid elements primary secondary: Parvo (Fifth disease), thymoma |
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Myelophthisic anemia |
space occupying mass that can cause marrow failure |
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diffuse liver dz and chronic renal failure can cause... |
marrow failure |
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Polycythemia |
increase in total RBC mass (incr. in Hgb/Hct) |
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polycythemia vera |
closely related to chronic leukemia very high Hgb (>20 g/dL) Rx: phlebotomy |
