Anemia

Definitions:

  • Hematocrit <41% in men or <36 in women
  • Hemoglobin <13.5 gm\dL in men or <12 gm\dL in women

a. Microcytic Anemia: 

1. Iron deficiency:

  • MCC: blood loss (GI, menstrual)
  • Presentation: depends on severity (usual presentation of anemia): fatigue, palpitations, SOB, pallor, nail changes (brittle, spoon-shaped), glossitis, pica.
  • Moderate – severe anemia -> systolic ejection murmur (“flow” murmur)
  • Labs: Hgb, MCV, MCH, ferritin, iron, retics, TIBC, RDW
  • Tx: most effective is oral therapy w\ ferrous sulfate tablets

 

2. Anemia of chronic disease:

  • Chronic inflammation -> hepcidin -> binds to ferroportin -> traps iron w\in macrophages + prevents gut iron absorption
  • Labs: Hgb, MCV, MCH, iron, retics, ↓ TIBC, ↑ ferritin
  • Tx: correct underlying cause. If renal ds or chemo\radio-therapy related anemia -> iron supplementation and erythropoietin

 

3. Sideroblastic anemia:

  • Defect in iron metabolism -> iron is trapped in the mitochondria of nucleated RBCs
  • Hereditary: defect in aminolevulinic acid synthase or vit B6 metabolism
  • Acquired: chloramphenicol, isoniazid, alcohol, lead poisoning
  • Can progress into AML
  • Labs: Hgb, MCV, ↑ ferritin, ↑ iron, ↑ retics, ↓ TIBC
  • Specific Dx: Prussian Blue stain of RBCs in BM -> ringed sideroblasts + basophilic stippling
  • Tx: best first step: pyridoxine -> response indicates underlying cacuse. Transfusion. BMT.

 

4. Thalessemia:

Alpha thalessemia:

  • 1 genes deleted -> normal pt
  • 2 genes deleted -> silent carrier or mild anemia (Hct 30-40%), very low MCV.
  • 3 genes deleted -> Hemoglobin H: profound anemia (Hct 20-30%), very very low MCV
  • 4 genes deleted -> Hemoglobin Barts: death in utero (hydrops fetalis)

Beta thalassemia:

  • Trait -> mild anemia + markedly low MCV
  • Major (Cooley anemia) -> sx start after the age of 6 mo (switch from fetal Hgb to adult Hgb) -> growth failure, hepatosplenomegaly, jaundice, bony deformities (extramedullary hematopoiesis) -> chronic anemia + transfusion dependence -> hemochromatosis, cirrhosis, CHF

Anemia 1

  • Labs: Hgb, ↓↓ MCV (disproportionate to the anemia), N ferritin, N iron, N TIBC, N RDW
  • Specific Dx: Hemoglobin electrophoresis.
  • Beta thalassemia: high levels of Hgb F and A2
  • Alpha thalassemia: normal levels of Hgb F and A2, if 3 genes deleted -> Hgb H
  • Blood smear -> target cells, poiklocytes
  • Tx:
    • Trait -> no Tx
    • Beta thalassemia major -> transfusion once\twice a mo
    • Chronic transfusion -> iron overload -> oral deferasirox (or deferoxamine via subQ pump)
    • Splenectomy reduces transfusion requirement (indicated in hypersplenism)
    • BMT
    • Iron supplementations is contraindicated

 


b. Macrocytic Anemia: 

1. Vitamin B12 (Cyanocobalamine) deficiency:

  • MCC: pernicious anemia -> autoimmune destruction of parietal cells -> ↓production of intrinsic factor
  • Sx: peripheral neuropathy, position\vibration\autonomic\motor\cranial nerves abnormalities, psychiatric, bowel\bladder\sexual dysfunx, glossitis, diarrhea, abd pain
  • Labs: Hgb, ↑ MCV, retics, B12
  • Smear: hypersegmented neutrophils, RBCs are oval macrocytes (while in hemolysis, liver ds, myelodysplasia give round macrocytes)
  • Specific Dx: antibodies to IF
  • Tx: replacement w\ vit B12 -> oral daily or parenteral (IM or subQ) monthly (recommended for neuropathy pts)
    • Early in Tx, pts might experience hypokalemia and fluid overload due to ↑ erythropoiesis, cellular uptake of K, and ↑ blood volume

 

2. Folic acid deficiency:

  • Causes: ↓ dietary intake, pregnancy, skin losses in eczema, ↑ loss from dialysis, phenytoin, alcohol
  • Same labs and presentation as vit B12 def, except folic acid
  • Tx: oral replacement

 


c. Hemolytic Anemia: 

  • Can happen in:
    • Spleen\liver -> extravascular
    • Vasculature itself -> intravascular -> hemoglobinuria
  • General Sx: splenomegaly, jaundice, icterus, pruritus, gallstones, hemosiderinuria
  • General Labs: normocytic anemia, ↑ LDH, ↓ haptoglobin “hemoglobin eats haptoglobin”, ↑ total bilirubin (indirect specifically), ↑ retics (unlike anemia of chronic ds)
  • All hemolytic anemia pt should get folate supplementation!

1) Coomb’s (-) = Hereditary = Not immune-related:

  • Sickle cell disease (AR)
  • Hereditary spherocytosis (AD)
  • Paroxysmal nocturnal hemoglobinuria (PNH) (NOT HEREDITARY!)
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency (XLR)

2) Coomb’s (+) = Acquired = immune related -> sudden, associated w\ constitutional sx:

  • Warm autoimmune hemolytic anemia
  • Cold-agglutinin hemolytic anemia
  • Drug-induced hemolytic anemia

 

1. Sickle cell disease:

Pathogenesis:

  • Autosomal recessive, homozygous: normal Hb A -> mutant Hb S
  • Point mutation: 6th position of B-chain: valine -> glutamic acid
  • Hypoxia, acidosis, temp changes, dehydration, infec -> Hb molecules polymerize -> RBCs sickle -> obstruct vessels -> ischemia

Sickle cell trait:

  • Heterozygous, identified by screening (clinically asx) -> genetic counselling
  • Not anemic, normal life expectancy
  • Associated w\ Isosthenuria (inability to conc urine)

Clinical features:

  1. Hemolytic anemia:
  • Jaundice, pallor
  • Pigmented gallstones
  • Leads to high-output CHF
  • Aplastic crisis: provoked by virus (human parvovirus B19) -> treated by blood transfusion (recovers in 7-10 days)
  1. Vaso-occlusion:
  • Painful crisis involving bone, multiple sites, self-limiting (2-7 d)
  • Hand-foot syndrome (dactylitis):
    • Avascular necrosis of metacarpal\metatarsal bones -> painful swelling of dorsa of hands + feet -> in infants\early child (4-6 mo)
    • Often first manifestation of SCD
  • Acute chest syndrome:
    • Due to repeated episodes of pulmn infarctions
    • Same presentation as pneumonia: chest pain, resp distress, pulmn infiltrates, hypoxia
  • Splenic infarctions (repeated episodes) -> autosplenectomy (large spleen in childhood -> not palpable by 4 yo; reduced to a small calcified ruminant)
  • Avascular necrosis of joints: MC hip and shoulder
  • Priapism:
    • Erection lasting for 30m-3hr due to vaso-occlusion, if lasting > 3hrs -> medical emergency
    • After passing urine, light exercise, cold shower -> usually subsides spont
    • Prevention: hydralazine or nifedipine or using antiandrogen
  • Delayed growth and sexual maturation; esp boys
  • CVA: due to cerebral thrombosis, mainly in children
  • Eye complications: retinal infarcts, vitreous hemorrhage, proliferative retinopathy, retinal detachment
  • Renal papillary necrosis + painless hematuria: common, may cease spont
  • Chronic leg ulcers: due to vaso-oculsion, typically: over lateral malleoli
  • Infections:
    • Functional asplenia -> more susceptible to infections (esp encapsulated bacteria: Hemophilus influenza and Strept pneumoniae)
    • Splenic malfunction -> predisposition to Salmonella osteomyelitis

Sickle cell disease 1

Diagnosis:

  • Labs: ↓ Hgb, ↑ retics (bc of chronic compensated hemolysis), ↑ LDH, ↑ bilirubin
  • Initial test: peripheral smear: Sickle-shaped RBCs (negative in sickle cell trait) + Howell-Jolly bodies (precipitated remnants of nuclear material in RBCs of asplenic pts)
  • Most accurate: Hb electrophoresis
  • The first clue to parvovirus is a sudden drop in reticulocyte level

Treatment:

  • Pt education: avoid high altitudes, maintain fluid intake, treat infections promptly
  • Vaccination (S. pneumoniae, H. influenza, Neisseria meningitides)
  • Prophylactic penicillin for children (4 mo – 18 yr)
  • Folic acid supplement (bc of chronic hemolysis)
  • Painful crises: hydration, morphine, keep pt warm, supplemental oxygen
  • Hydroxyurea: enhances Hb F levels -> interferes w\ sickling, reduces incidence of painful crises, accelerates healing of leg ulcers
  • Blood transfusion: based on clinical condition and not Hb levels
  • Exchange transfusion indications -> ACS, stroke, priapism, visual disturbance from retinal infarction. If exchange transfusion is not available -> give PRBCs

 

2. Hereditary spherocytosis:

  • Autosomal dominant -> loss of spectrin in RBC membrane
  • Sx: mile\moderate sx of anemia, splenomegaly, jaundice
  • Labs: ↓ Hgb, -\↑MCV, MCHC, ↑retics, ↑ LDH, ↑ bilirubin
  • Blood smear -> spherocytes 🙂
  • Negative Coomb’s test
  • + Osmotic fragility test -> cells have an ↑ sensitivity to lysis in hypotonic solution
  • Tx: folate + elective splenectomy

 

3. Paroxysmal nocturnal hemoglobinuria (PNH):

  • Idiopathic\not hereditary -> clonal defect of GPI in RBC membrane -> complementation -> intravascular hemolysis
  • Why occurs at night? Complementation is encouraged by the slightly acidotic state during sleep
  • Sx: anemia sx, dark\cola\tea-colored urine when pt wakes up -> normalizes as the day goes on, increased risk of venous thrombosis (hepaticBudd-Chiari”, dermal “painful skin nodules)
  • Dx: acidified serum lysis “Ham” test, flow cytometry for CD55\CD59
  • Tx: iron + folate, steroids if severe, elective anticoagulation (mandatory if pregnant or thombo-embolic events have occured)

 

4. G6PD:

  • X-linked recessive (more in boys) -> deficiency in G6PD -> reduction of NADPH (antioxidant)
  • Sx: children + acute -> linked to infection, drugs (sulfas, nitrofurantoin), foods (fava beans)
  • Blood smear -> Heinz bodies + Bite cells
  • Tx: stop offending agent + hydration

 

5. Autoimmune\warm hemolytic anemia:

  • Causes: idiopathic, lymphoproliferative ds (CLL, lymphoma), autoimmune ds (SLE, RA, scleroderma)
  • Initial test -> Positive Coomb’s test = direct antiglobulin test (DAT)
  • Negative cold-agglutinin titer
  • Tx: folate + steroids, transfusion if necessary

 

6. Cold-agglutinin hemolytic anemia:

  • Causes: usually linked to an infection -> Mycoplasmia, EBV, HIV
  • Key differentiator: worsend w\ exposure to cold -> purplish discoloration of fingers\toes
  • Initial test -> Positive Coomb’s test = direct antiglobulin test (DAT)
  • Positive cold-agglutinin titer
  • Tx: folate + avoid cold conditions, Rituximab if necessary

 

7. Drug-induced hemolytic anemia:

  • MCC: cephalosporin abx, levofloxacin, nitrofurantoin, rifampin, methyldopa
  • Initial test -> Positive Coomb’s test = direct antiglobulin test (DAT)
  • Tx: stop the drug + folate

 


d. Aplastic Anemia:

  • Bone marrow failure -> pancytopenia (anemia, leukopenia, thrombocytopenia)
  • Causes:
    • Radiation
    • Toxins: benzene
    • Drugs: NSAIDs, chloramphenicol
    • Alcohol
    • Chemo: alkylating agents
    • Infections: hepatitis, HIV, CMV, EBV, parvovirus B19
  • Sx: bleeding (thrombocytopenia), fatigue (anemia), infections (neutropenia)
  • Dx: pancytopenia, BM biopsy (confirmatory)
  • Tx: BMT (if young and healthy), immunosuppressive agents (anti-thymocyte globulin, cyclosporine, prednisone)

 


Random notes:

  • Ferritin and hepcidin are acute phase reactants -> elevated in any pt w\ inflammation
  • TIBC = transferrin
  • Hereditary spherocytosis, PNh, G6PD -> are at an increased risk of aplastic anemia (esp w\ parvovirus B19)

 

Anemia Hgb MCV RDW Retics Ferritin Iron TIBC
Iron deficiency
Anemia of chronic disease
Sideroblastic
Thalessemia ↓↓ N   N N N

 

 


Download the PDF version: here


References:

  • Kaplan step 2 lecture notes
  • Paul Bolin’s videos
  • Step up to medicine

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

w

Connecting to %s

%d bloggers like this:
search previous next tag category expand menu location phone mail time cart zoom edit close