Hematology Lecture Disorders of Iron Kinetics & Heme Metabolism

Impaired Red Cell Production

Anemias associated with iron & heme

Iron Restricted anemia

Iron is the limited factor; Iron Deficiency Anemia (IDA); Anemia of Inflammation (AI)

Porphyria

Build up of porphyrins

SIderoblastic anemias

Failure to incorporate iron in protoporphyrin causing excess iron accumulation in developing RBCs

Hemochromatosis

Excess accumulations in iron

Iron-loading anemias

Impaired iron kinetics

Iron Deficiency Anemia Etiology

Deficient total body iron to uphold normal physiologic function

Functional iron deficiency (IDA)

Iron stores are adequate, but iron is not available to support normal erythropoiesis

Impaired absorption (IDA)

Inability to absorb iron through enterocyte into the blood causing a deficiency or iron in the body;

Chronic loss of hemoglobin (IDA)

Blood loss resulting in small amounts of heme iron from the body over a prolonged period

Stage 1 IDA

Progressive loss of storage iron but RBC production are normal; serum ferritin levels decrease; testing is not performed yet as patients appear healthy & this stage is common

Stage 2 IDA

Exhaustion of iron storage pool, but RBC production is normal as it is using the transport compartment & iron being recycled from cells (latent iron deficiency)

Stage 3 IDA

Iron stores, mobile iron, & serum iron are depleted preventing normal RBC development (frank anemia); serum ferritin levels are low; Hepcidin decreased; patient exhibits fatigue, weakness, & shortness of breath; pica

Iron Deficiency Anemia

Menstruating Females - IDA RISK

Females lose red blood cells during period; compounded by increased iron needs associated with growth

Pregnant/nursing females - IDA RISK

Leads to loss of nearly 1200mg of iron

Growing children - IDA Risk

Infants need iron supplemented formula by 6 months. Before that, breast milk is needed

CBC IDA

Anisocytosis, microcytosis, hypochromia in proportion to anemia severity

Decreased

Serum iron during IDA

Increased

TIBC during IDA

Decreased

Transferrin saturation during IDA

Decreased

Serum ferritin during IDA

Decreased

Hemoglobin content of retics during IDA

IDA Treatment

First therapy is to treat any underlying contributing cause; oral supplements of ferrous sulfate; intravenous iron

Anemia of Inflammation (AI)

Associated with systematic diseases - Chronic inflammatory conditions (rheumatoid arthritis), chronic infections (tuberculosis), & malignancies

Impaired ferrokinetics - Etiology of AI

Increased levels of hepcidin decreased iron absorption in the intestines & sequester iron in macrophages & hepatocytes causing bone marrow macrophages to show abundant stainable iron but developing erythroblasts show inadequate iron

Porphyrias

Disease that interfere with the production of protoporphyrins can also produce anemia; both hereditary and acquired; an enzyme in heme synthesis is missing causing excess porphyrins which are leaked from the cell as they age or die

Congenital Erythropoietic Porphryia

Autosomal recessive inheritance causing an uroporphyrinogen III synthase deficiency; patients have a decrease in heme production

Erythropoietic Protoporphyria

Autosomal recessive inheritance causing a ferrochelatase deficiency; increases in protoporphyrin in RBCs & feces; findings include photosensitivity, liver involvement, gallstones, and symptoms exacerbated by alcohol

X-Linked Erythropoietic Protoporphyria

Dominant inheritance causes ALA synthase 2 gain of function; increases in protoporphyrin in RBCs & possible feces; findings include photosensitivity, microcytic, hypochromic anemia with retic response is possible

Sideroblastic Anemias

Characterized by the presence in the bone marrow of ring sideroblasts; erythroblasts when stained with prussian blue show a ring of blue iron deposits around the nucleus

Acquired sideroblastic anemia

X-linked (paternal) - X-linked sideroblastic anemia

Mitochondrial (maternal) - pearson marrow-pancreas syndrome

Autosomal - erythropoietic protoporphyria