1. Hematology case
Nursing 870

2. Case
An 18 –year- old female presents to the NP for consultation. She complained of generalized weakness, lethargy and inability to perform her usual activities; with progression over the past few months.

3. What HPI Questions are Important to Ask?

4. HPI
General: No fever or weight loss, decreased appetite; desire to eat ice
HEENT: negative
Resp: Reported breathlessness with climbing stairs
CV: Reported palpitations with climbing stairs
GI: No abdominal pain, n,v or diarrhea
GU: Excessive menstrual bleeding x 6 months
MS: Reports leg cramping
Neuro: Periods of feeling lightheaded, no syncope

5. What PE is needed?

6. PE General: 98.2-110-18 108/62 Wt. 118, No change Skin: Pale skin
HEENT: pale gums, tongue was swollen, No enlarge nodes
Resp: Clear
CV/PV: Tachycardia, no murmurs, S3 or S4; pale nail beds
Abdomen: Normal
Neuro: Normal

7. Diagnostics
What labs are needed?

8. Diagnostics Red Blood Cell Count -3.5 million/mm3
Hemoglobin (Hb) -7 g/dl
Hematocrit (Hct)- 30%
Serum Iron – low
Mean Corpuscular Volume (MCV) – low
Mean Corpuscular Hemoglobin (MCH)-low
Mean Corpuscular Hb Concentration (MCHC)- low
Total Iron Binding Capacity in the Blood (TIBC)- high

9. What do the labs tell you?

10. Labs: CBC RBC: 3.5 million/mm3 Hb: 7 g/dl Hct: 30 %
Number of erythrocytes (RBC) in 1 cubic mm of blood, thin cell membrane so gases pass easily
Nrl: Male: x 106/ul, Female: x 106/ul
Made of Hgb, life span of 120 days
Production: erythropoesis
Need: Fe, B12, folic acid, B6 (pyridoxine)
RBC: transport O2
Waste product is bilirubin
Hb: 7 g/dl
Hgb, the oxygen carrying compound carried on each RBC
Nrl: Male: 14-18g/dl, Female: 12-16g/dl
Hct: 30 %
Hct: The percentage of blood that is the RBC
Nrl: Male: 41.5% %, Female: 35.9%-44.6%
CBC: Normals vary by age, gender, and race.
African Americans: lower Hg, WBC, neutrophil and platelets

11. Labs: CBC Mean Corpuscular Volume (MCV) – low
Average size of cell (Small: microcytic; Large: macrocytic)
Nrl:
Mean Corpuscular Hemoglobin (MCH)-low
Average weight of Hg in RBC (Low: hypochromic; High
Nrl:
Mean Corpuscular Hb Concentration (MCHC)- low
Avg concentration of Hb per RBC
Nrl: 32-36%

12. Labs Total Iron Binding Capacity (TIBC)- high (262-474g/dL)
Available binding sites
Serum Iron – low (Male: g/dL, Female g/dL)
Measures Fe in the blood
Serum ferratin - low (Male: mcg/L; Female mcg/L)
Reflects Fe storage in the body
Drops before serum Fe
Ferratin: Low ferratin diagnostic for IDA with microcytosis; Be aware false normal related to inflammation, hepatocellular damage and cancer
NRL ferratin with microcytosis: consider thallasemia; consider performing electrophoresis

13. What’s the most likely diagnosis?
What History, PE findings and labs support the diagnosis?

14. What’s the Treatment?

15. labs
CBC
This documents the severity of the anemia. In chronic iron deficiency anemia, the cellular indices show a microcytic and hypochromic erythropoiesis
MCV and MCHC=)have values below the normal range
Often, the platelet count is elevated (>450,000/µL)
WBCs usually within reference ranges ( ,000/µL).

16. labs
MCV remains normal in the early stages, then falls and the blood smear shows hypochromic microcytic cells
With further progression, anisocytosis (variations in red blood cell size) and poikilocytosis (variation in shape of red cells) develop
Severe Fe deficiency will produce a bizarre peripheral blood smear, with severely hypochromic cells, target cells, hypochromic pencil-shaped cells, and occasionally small numbers of nucleated red blood cells, with an increased platelet count

17. labs
Iron deficiency develops in stages. The first is depletion of iron stores. At this point, there is anemia and no change in red blood cell size.
Serum Fe
Decreases
Total iron-binding capacity (TIBC)
TIBC rises.
Ferritin
Will become abnormally low
A ferritin value less than 25 mcg/L is a highly reliable indicator of iron deficiency.
After iron stores have been depleted, red blood cell formation will continue with deficient supplies of iron. Serum iron values decline to less than 30 mcg/dL and transferrin saturation to less than 15%. A low serum iron and ferritin with an elevated TIBC are diagnostic of iron deficiency. While a low serum ferritin is virtually diagnostic of iron deficiency, a normal serum ferritin can be seen in patients who are deficient in iron and have coexistent diseases (hepatitis, anemia of chronic disorders). These test findings are useful in distinguishing iron deficiency anemia from other microcytic anemias

18. Function of Iron Essential for multiple metabolic processes
Oxygen transport
DNA synthesis
Electron transport
The major role of iron is to carry O2 as part of hemoglobin
O2 is also bound by myoglobin in muscle
Iron is a critical element in iron-containing enzymes, including the cytochrome system in mitochondria
Without iron, cells lose their capacity for electron transport and energy metabolism. In erythroid cells, hemoglobin synthesis is impaired, resulting in anemia and reduced O2 delivery to tissue.

19. Iron Deficiency Anemia
Generalized weakness, exercise intolerance, dyspnea, palpitations, history of blood loss during menstruation, tachycardia and low Hgb, all are suggestive of iron deficiency anemia
Iron deficiency is the most prevalent anemia in the world
Iron deficiency, is related in part, to abnormal iron metabolism

20. Iron Deficiency Anemia
Overview of iron metabolism
Balance of iron is controlled and designed to conserve iron for reutilization
There is no regulated excretory pathway for iron
Iron is only lost from the body with blood loss (via gastrointestinal bleeding, menses, or other forms of bleeding) and the loss of epithelial cells from the skin, gut, and genitourinary tract
Iron comes into the body by absorption from food or from medications and transfusions
The margin between the amount of iron available for absorption and the requirement for iron in growing infants and the adult female is narrow; this accounts for the great prevalence of iron deficiency worldwide— currently estimated at one-half billion people.

21. Fe deficiency Anemia causes
Increased demand for iron and/or hematopoiesis
Rapid growth (adolescence and infants)
Pregnancy
Erythropoietin therapy

22. Fe deficiency Anemia causes
Increased Fe loss
Chronic blood loss
Menses
Acute blood loss
Blood donation
Phlebotomy as treatment for polycythemia vera
Decreased iron intake or absorption
inadequate diet  
malabsorption from disease (Celiac, Crohn’s disease)
Malabsorption from surgery (post-gastrectomy)  
Acute or chronic inflammation

23. Diagnostics CBC Ferratin Fe IBC Bone Marrow aspirate
Stool for occult blood: useful to establish GI bleed
Others
Hemoglobinuria and hemosiderinuria
Hemoglobin electrophoresis
Transferrin receptor protein
A bone marrow aspirate can be diagnostic of iron deficiency. Bone marrow biopsy for evaluation of iron stores is now rarely performed because of variation in its interpretation.
Hemoglobinuria and hemosiderinuria can be detected by laboratory testing . This documents iron deficiency to be due to renal loss of iron and incriminates intravascular hemolysis as the etiology. Hemoglobin electrophoresis and measurement of hemoglobin A2 and fetal hemoglobin are useful in establishing either beta-thalassemia or hemoglobin C or D as the etiology of the microcytic anemia.  Serum Levels of Transferrin Receptor Protein-Because erythroid cells have the highest numbers of transferrin receptors on their surface of any cell in the body, and because transferrin receptor protein (TRP) is released by cells into the circulation, serum levels of TRP reflect the total erythroid marrow mass. Another condition in which TRP levels are elevated is absolute iron deficiency. Normal values are 4–9 μg/L determined by immunoassay. This laboratory test is becoming increasingly available and, along with the serum ferritin, has been proposed to distinguish between iron deficiency and the anemia of chronic inflammation

24. Differential Other causes of microcytic anemia
Anemia of chronic disease
Thalassemia,
Sideroblastic anemia
Lead poisoning
Anemia of chronic disease is characterized by normal or increased iron stores in the bone marrow and a normal or elevated ferritin level; the serum iron is low, often drastically so, and the TIBC is either normal or low.
Thalassemia produces a greater degree of microcytosis for any given level of anemia than does iron deficiency. Red blood cell morphology on the peripheral smear is abnormal earlier in the course of thalassemia.

25. Treatment Most important to establish the cause of the anemia
Ferrous sulfate, 325 mg three times daily, which provides 180 mg of iron daily of which up to 10 mg is absorbed (though absorption may exceed this amount in cases of severe deficiency), is the preferred therapy
Parenteral Fe
RBC transfusion
Oral Fe
First line treatment. An increase in the hemoglobin level of 1 g per dL (10 g per L) should occur every two to three weeks on iron therapy; however, it may take up to four months for the iron stores to return to normal after the hemoglobin has corrected. Ferrous sulfate in a dose of 325 mg provides 65 mg of elemental iron, whereas 325 mg of ferrous gluconate provides 38 mg of elemental iron. Sustained-release formulations of iron are not recommended as initial therapy because they reduce the amount of iron that is presented for absorption to the duodenal villi.
Parenteral Iron
The indications are intolerance to oral iron, refractoriness to oral iron, gastrointestinal disease (usually inflammatory bowel disease) precluding the use of oral iron, and continued blood loss that cannot be corrected. Because of the possibility of anaphylactic reactions, parenteral iron therapy should be used only in cases of persistent anemia after a reasonable course of oral therapy. 
Red Cell Transfusion
It should be considered for asymptomatic cardiac patients with hemoglobin less than 10 g per dL (100 g per L). Transfusion therapy is reserved for individuals who have symptoms of anemia, cardiovascular instability, continued and excessive blood loss from whatever source, and require immediate intervention. The management of these patients is less related to the iron deficiency than it is to the consequences of the severe anemia. Not only do transfusions correct the anemia acutely, but the transfused red cells provide a source of iron for reutilization, assuming they are not lost through continued bleeding. Transfusion therapy will stabilize the patient while other options are reviewed.

26. Other Considerations Diet Other
Foods high in Fe include red meats, egg yolks, dark green leafy veges, dried fruit (prunes, raisins, turkey, beans, liver, others)
Interfering substances include phytic acid in cereals, oxacylic acid in some leafy vegetables, tannates (tea)
Other
GI absorption of Fe enhanced by gastric acidic envt (Vit C)
Calcium, copper, zinc, lead and phosphate inhibit absorption

27. Other Considerations
Medications that raise the gastric pH (e.g., antacids, proton pump inhibitors, histamine H2 blockers) reduce absorption and should be avoided if possible

28. Prognosis
Fe deficiency anemia is an easily treated disorder with an excellent outcome
It may be caused by an underlying condition with a poor prognosis, such as neoplasia
Up to 10% of individuals >65 have GI cancer when evaluated for Fe deficiency anemia
The prognosis may be altered by a comorbid condition such as coronary artery disease.