Ipapburke Hematology Test 1- Microcytic

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MCV in Microcytic Anemias

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< 80

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Differentials for Microcytic Anemias (4)

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Thalassemias, Iron Def. Anemias, ACD, Sideroblastic Anemia

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Mechanisms for Iron Def. Anemia (3)

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Blood Loss, Inadequate Absorption, Inadequate Intake

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Causes of Blood Loss that can Lead to Iron Def. Anemia (2)

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GI Bleed, Menses

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Causes of Inadequate Absoprtion that can Lead to Iron Def. Anemia (2)

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Inflammation, PPI

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Causes of Inadequate Intake that can lead to Iron Def. Anemia

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poverty, fad dieting

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MC Microcytic Anemia worldwide

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Iron Def. Anemia

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Iron Def. Anemia MC in these populations

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Kids- rapid growth and poor nutrition; Women- menses and pregnancy

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Storage protein for iron

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Ferritin

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Where most excess iron is stored

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liver

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Serum ferritin has a direct relationship to?

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amount of iron stored in body

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Transports iron from storage sites to bone marrow

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Transferrin

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Hormone made in hepatocytes in response to cytokines

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Hepcidin

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Hepcidin has a inverse relationship to?

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intestinal absorption of iron

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Hepcidin binds with what cell wall protein?

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ferroportin

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Function of ferroportin

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allows iron to leave storage

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Insoluble iron formed when excess iron is present

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hemosiderin

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Hemosiderin often absorbed by?

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circulating macrophages

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Iron Metabolism increases with? (4)

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anemia, hypoxia, increase erythropoiesis, decreased iron stores

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Iron Metabolism decreases with? (2)

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inflammation, increased iron stores

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Stages of Development of Iron Def. Anemia (6)

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Negative iron balance; decrease in iron stores; fall in serum iron/transferrin levels; hypochromic reticulocytes; decrease in hemoglobin; decrease in MCV

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Early signs of Anemia (6)

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fatigue; tachycardia; palpitations; tachypnea on exertion; pallor; lightheadedness

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Signs of Severe Anemia (5)

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angina, dizziness, fainting, tachycardia, murmur

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RDW in Iron Def. Anemia

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usually increased, but may normalize if chronic

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Gold Standard lab or diagnosis of Iron Def. anemia

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Bone Marrow Biopsy

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Ferritin Levels in Iron Def. anemia

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under 30 --> diagnostic of Iron. Def. anemia

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Lab value that is DIAGNOSTIC for Iron Def. Anemia

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Ferritin under 30

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Normal Ferritin Values

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30-250 ng/ml

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Serum Iron Levels in Iron Def. Anemia

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under 40 --> but not diagnostic as they can change in a matter of hours

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Normal Serum Iron levels

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40-160 mcg/dl

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Normal TIBC values

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200-400

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What is TIBC?

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transferrin ability to bind more iron

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Normal transferrin saturation

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20-50%

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What is the transferrin saturation a ratio of?

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free circulating iron to transferrin

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Is the Transferrin saturation increased or decreased in Iron Def. Anemia?

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may be decreased (not diagnostic, but helpful)

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Method for evaluating for GI blood loss

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"double dip"- EGD and colonoscopy

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Method for evaluating for decreased iron absorption

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oral iron absorption test

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Method for evaluating for decreased intake of iron

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history

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MC therapy for Iron Def. anemia

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oral replacement

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Goal for oral replacement in Iron Def. Anemia

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100 mg/day

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Usual dose of oral iron

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325 mg/day with citric acid (usually allows absorption of 150-200 mg/day

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Risk in use of IV iron replacement

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anaphylaxis

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When do you use IV replacement of iron?

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only when patient has severe anemia and cannot tolerate oral replacement

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Risks with IM iron

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painful and hemosiderin deposits

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SE of oral iron replacement

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constipation and tarry dark stools

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Duration it may take for iron replacement to improve Iron Def. Anemia

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up to 2 months

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Glossitis

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Inflammation or infection of the tongue- swelling, color change, loss of papillae

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Cheilosis

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scaling and fissures at corner of mouth

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Koilonychia

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"spoon nails"- change in color, shape, and texture of nails due to iron def. anemia

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Pica

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appetite for non-nutritive substances

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Plummer-Vinson Syndrome

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dysphasia due to esophageal webs, glossitis, and iron def. anemia (triad)

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Schatzki's rings

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narrowing of lower part of esophagus that causes dysphagia in iron def. anemia

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MCV In Thalassemias

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<80; often less than 70

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Mechanism in Alpha Thalassemias

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deletion of alpha hemoglobin chains with no substitution

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Mechanism in Beta Thalassemia

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point mutations; Beta chains replaced by gamma and delta chains

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Patients with Thalassemia are typically from where?

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Mediterranean; equatorial Asia and Africa

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Definition of Thalassemia

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heterogenous hereditary D/O that is a defect in globin chain synthesis leading to significant microcytosis

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Clinical Feature of SEVERE thalassemias

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chronic hemolytic complications

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Main clinical feature of thalassemias

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microcytosis out of proportion to clinical anemia

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Treatment for mild thalassemias

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none; avoid unnecessary iron replacement and sulfa drugs that may increase oxidative stress and lead to increased hemolysis

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Treatment for severe thalassemias

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freq. transfusion, folate, splenectomy, possible bone marrow transplant

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Diagnosis of thalassemia

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R/O Iron Def. Anemia; RDW WNL; electrophoresis; in complex cases- genetic testing

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Alpha Thalassemia on electrophoresis

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normal

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Beta Thalassemia on electrophoresis

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abnormal b/c of delta and gamma substitions

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Complications of frequent transfusions in thalassemia treatment

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iatrogenic iron overload which can negatively affect bone marrow transplant

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Anemia associated with disturbed mitochondrial metabolism

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sideroblactic anemia

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Which is most common as a cause of sideroblastic anemia- acquired or hereditary?

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acquired---- drugs and toxins, esp. alcohol

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Common drug causes of sideroblastic anemic

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ETOH, INH, cycloserine, busulfam, chloramphenicol

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2 Copper chelators that can cause sideroblastic anemia

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penicillamine, Trientene

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3 Toxin causes of sideroblastic anemia

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lead, zinc, and auto-Ab

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Describe iron uptake in sideroblasts

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normal iron uptake; poor incorporation in heme

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Tx for sideroblastic anemia

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treat reversible causes; supportive- blood transfusions; pyridoxine 100-200 mg/day po increased to 500 mg/day; folic acid

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Symptoms of sideroblastic anemia

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fatigue, decreased tolerance f/ activity; dizziness

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What will sideroblastic anemia show on blood smear?

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basophilic stipling esp. with lead poisoning

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When Iron Def. Anemia is refractory to replacement therapy, what differential might you suspect?

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sideroblastic anemia

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Cytokine levels in Iron Def. Anemia

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normal

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Cytokine levels in Anemia of chronic Disease

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increased

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Ferritin Levels in Anemia of Chronic Disease

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normal to increased

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Ferritin Levels in Iron Def. Anemia

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Reduced

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Transferrin Levels in Anemia of Chronic Disease

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reduced to normal

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Transferrin levels in Iron Def. Anemia

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increased