Iron deficiency anemia

- Clinical presentation

- Lab presentation

- Key features

- Treatment

Clinical presentation:

- fatigue out of proportion to anemic state

- pica

- koilonychia

- defects in immune function (granulocytic phagocytosis)

- ↓ mental alertness

- learning disability with attention disorder in children

-  General findings: pallor, HA, irritability, paresthesias, glossitis, angular cheilosis

Lab presentation:

- ↓ Hb, hct, MCV

- ↓ serum ferritin (careful b/c it is acute phase reactant and may be falsely low in infections, chronic disease, etc)

- ↑ TIBC 

- absent to minimal iron stains in bone marrow 

Treatment:

- ferrous sulfate is best

- treatment of megaloblastic anemias or CKD may uncover iron deficiencies

- rule out causes of iron deficiencies to find underlying problem

Anemia of chronic disease

- Clinical presentation

- Lab presentation

- Key features

- Treatment

Clinical presentation:

- occurs in a variety of inflammatory disorders (RA, TB, etc) and neoplasia as well as alcoholism

- generally mild, does not require treatment

Lab findings:

- RBC's usually normocytic but may become hypochromic, microcytic

- EPO elevations in response to anemia are blunted

- ↑ Hepcidin levels → storage of iron in macrophages

- ↓ TIBC, MCV, serum iron, iron saturation

- ↑ serum ferritin, free erythrocyte protoporphyrin

Key features:

- look for chronic diseases/infections (HCV), alcoholism, or malignancy and signs of anemia

- look for actions of increased hepcidin

Treatment:

- treat underlying disease

- in some case treating the anemia with EPO will improve symtoms

Types of hemoglobin

- composition

- chromosome loci

HbA = 2α + 2β chains

HbA2 = 2α + 2δ

HbF = 2α + 2γ

2 pairs of α chain loci on chromosome 16

Single pair of β and δ + 2 pairs of γ chains on chromosome 11

β-thalassemia minor

- etiology

- lab findings

Etiology:

- found in Mediterranean populations frequently

- caused by mutations leading to ↓ β-chain production

- α-chains precipitate due to lack of corresponding β, γ, or δ chains leading to:

   ~microcytic RBCs, mild/no anemia

   ~Target cells

   ~basophilic stippling

Lab findings:

- Hemoglobin electrophoresis = increased HbA2 band (2α+ 2δ chains)

- Target cells

- Basophilic stippling

- normal TIBC, serum iron, ferritin, and RDW 

α-thalassemias

- etiology

- subtypes

- key findings

- note on Hb H

Etiology:

- due to deletion of 1+ α-chain loci and relative failure of α-chain synthesis

Subtypes:

- 1 deletion: clinically silent

- 2 deletions: mild microcytic anemia

- 3 deletions: moderately severe hemolytic anemia characterized by detectable presence of Hb H (β₄) 

- 4 deletions: incompatible with life and result in intrauterine death (hydrops fetalis) due to precipitation of Hb Barts (γ₄)

Key findings:

- usually runs in families and diagnosis made by exclusion of other causes of microcytosis

- specialized labs using PCR or Southern blot can detect DNA mutations

Hb H:

- is a polymer of 4 β-chains, very unstable

- formed with 2+ deletions but is undetectable when only 2 deletions due to small amounts and rapid hemoglobin electrophoresis of single β-chains

Sideroblastic anemia

- etiology

- lab findings

- managment

Etiology:

- Heriditary forms:

    ~ X-linked: due to defects in heme biosynthesis due to ALA synthase defect

    ~ autosomal recessive: rare

- Acquired forms:

    ~ Idiopathic refractory anemias (myelodysplasia, preleukemia)

    ~ Secondary: alcohol, drug, or toxin induced (e.g. isoniazid, lead); associated with other disorders (e.g. inflammatory conditions, neoplasms)

Lab findings:

- iron-staining granules encircling nucleus of red cell precursors seen on bone marrow aspirate or biopsy

Management:

- supportive care

- transfusions

- pyridoxine administration

- deferoxamine (IV) or deferasirox (oral) to combat excess iron