anemia: a case based approach: part-1

Anemia Part One

Anas Bahnassi

1 Week

Lecture Outline

Definition Pathophysiology

Detection Iron Deficiency Anemia

Predisposing Factors

Signs and Symptoms

Management

Definition

Anemia is a reduction in red cell mass. It often is described as a decrease in the number of (RBC/mm3) Or A decrease in the hemoglobin concentration in blood to a level below the normal physiologic requirement for adequate tissue oxygenation. The term anemia is not a diagnosis, but rather an objective sign of a disease.

Pathophysiology

A symptom of many pathologic conditions It is associated with nutritional deficiencies, acute and chronic diseases; it also can be drug induced. It can be caused by slower cell production or increased destruction (Secondary to hemolysis) or loss (Bleeding).

Pathophysiology

Blood Loss • Acute: trauma, ulcer, hemorrhoids • Chronic: ulcer, vaginal bleeding, aspirin ingestion

Inadequate RBC Production

• Nutritional deficiency: B12, folic acid, iron • Erythroblast deficiency: bone marrow failure (aplastic anemia,

irradiation, chemotherapy, folic acid antagonists) or bone marrow infiltration (leukemia, lymphoma, myeloma, metastatic solid tumors, myelofibrosis)

• Endocrine deficiency: pituitary, adrenal, thyroid, testicular • Chronic disease: renal, liver, infection, granulomatous, collagen

vascular Excessive RBC Destruction

• Intrinsic factors: hereditary (G6PD), abnormal hemoglobin synthesis

• Extrinsic factors: autoimmune reactions, drug reactions, infection (endotoxin)

Detection

Onset of anemia can be acute or can develop slowly, resulting in tissue hypoxia. Slowly developing anemias can be asymptomatic initially or include symptoms such as: Slight exertional dyspnea, increased angina, fatigue, or malaise. Uncorrected tissue hypoxia can lead to a number of complications in quality of life, cognition, and respiratory and gastrointestinal (GI) systems. May lead to changes in the kidney tissue oxygen tension.

Detection

In severe anemia, a hemoglobin (Hgb) <8 mg/dL, heart rate, and stroke volume often increased

Systolic murmurs, Angina pectoris, Congestive heart failure, Pulmonary congestion, Ascites, Edema.

Skin and mucous membrane pallor, jaundice, smooth or beefy tongue, cheilosis, and spoon-shaped nails (koilonychia) also may be associated with severe anemia of different causes of anemia.

Patient History

A time line, which begins with the onset of symptoms (and surrounding events) and extends to current status, is important. Because longstanding anemias can indicate hereditary disorders, the family history should be noted. Past Hgb or hematocrit (Hct) determinations, transfusion history, as well as occupational, environmental, and social histories may be valuable. A medication history can help eliminate drug reactions or interactions as the cause of the anemia.

Physical Examination

Pallor is most easily observed in the conjunctiva, mucous membranes, nail beds, and palmar creases of the hand. Postural hypotension and tachycardia can be seen when hypovolemia (acute blood loss) is the primary cause of anemia. Patients with B12 deficiency may exhibit neurologic findings, which include changes in deep tendon reflexes, ataxia, and loss of vibration and position sense; all are consistent with nerve fiber demyelination. Patients may be slightly jaundiced from bilirubin release.

Laboratory Evaluation

The cornerstone of this evaluation is the complete blood count (CBC). Male patients have higher hematocrit (Hct) values than do female patients. The Hct is increased in individuals living at altitudes above 4,000 feet in response to the diminished oxygen content of the atmosphere and blood. The morphologic appearance of the RBC provides useful information about the nature of the anemia.

Homework

You need to provide a handwritten table of normal hematological values

Don’t forget to mention your reference

?

Laboratory diagnosis of Anemia

Hematocrit

Hemoglobin

RBC count

Peripheral Blood Smear

Indices

Red Cells Morphology

Screening Procedure

Macrocytic Anemia

Normoccytic Anemia

Microcytic Hypochromic

Anemia

Low Hct, Low Hgb, Low RBC, High MCV,

Low B12, Schiling Test (+)

Or Low Serum Folate

Hct, Hgb, reticulocyte count,

Hgb, Bilirubin, relic

Coombs Test (+)

Defective nuclear maturation with decreased production

Pernicious anemia

Folate deficiency anemia

Blood loss, renal failure

Hematolyte anemia

Autoimmune hymolysis

Hct, Hgb, MCV,

Fe, MCHC, TIBC

Fe:TIBC < 15%

Iron deficiency anemia

Iron deficiency anemia

The daily iron intake and stores are unable to meet the RBC and other body tissue needs

2.5 g out of total 3.5 g found in Hgb Only 0.5-1mg/day is lost Menstruating women lose 0.5-2.5% more/day Average diet contains 6mg Fe/1000Kcal. We need 10-12 mg Fe/day Menstruating, pregnant, and lactating mothers need 20mg Fe/day

Causes of iron deficiency anemia

Blood Loss Menstruation, gastrointestinal (e.g., peptic ulcer), trauma

Decreased Absorption Medications, gastrectomy, regional enteritis

Increased Requirement Infancy, pregnant/lactating women

Impaired Utilization Hereditary, Iron use

Predisposing Factors

A diet lacking in certain vitamins. iron, vitamin B-12 and folate Intestinal disorders. affects the absorption of nutrients: Crohn's disease and celiac disease. Menstruation. Pregnancy. Chronic conditions. cancer, kidney or liver failure or another chronic condition Family history. Other factors. A history of certain infections, blood diseases and autoimmune disorders, alcoholism, exposure to toxic chemicals, and the use of some medications can affect red blood cell production and lead to anemia.

A case approach understanding for iron deficiency anemia

A35-year-old woman, is seen in the clinic. Chief complaints include weakness, dizziness, and epigastric pain. PMD 5-year history of peptic ulcer disease, 10-year history of heavy menstrual bleeding, 20-year history of chronic headaches. Current Meds Tetracycline (250 mg BID) for acne, ibuprofen (400 mg PRN) headaches, and daily esomeprazole (40 mg). Initial Physical Exam Decreased exercise tolerance. Pale, lethargic, black woman appearing older than her stated age. Her vital signs are within normal limits; HR100 beats/min. notable for pale nail beds and splenomegaly.

FH Patient has 3 children


A35-year-old woman, is seen in the clinic. Significant laboratory results Hgb, 8 g/dL (normal, 14 to 18) Hct, 27% (normal, 40% to 44%) Platelet count, 800,000/mm3 (normal, 130,000 to 400,000) Reticulocyte count, 0.2% (normal, 0.5% to 1.5%); Mean corpuscular volume (MCV), 75 µm3 (normal, 80 to 94); Mean corpuscular hemoglobin (MCH), 23 pg (normal, 27 to 31); Mean corpuscular hemoglobin concentration (MCHC), 30% (normal, 33% to 37%); Serum iron, 40 µg/dL (normal, 50 to 160); Serum ferritin, 9 ng/mL (normal, 15 to 200); Total iron-binding capacity (TIBC), 450 g/dL (normal, 250 to 400); 4+ guaiac stools (normal, negative).


What are the factors predisposing this patient to Iron Deficiency Anemia? Her history of heavy menstrual bleeding The 4+ stool guaiac The GI blood loss may be secondary to chronic use of nonsteroidal anti-inflammatory drugs, recurrent peptic ulcer disease, or both. Many women of childbearing age have a borderline iron deficiency that becomes more evident during pregnancy because of the increased iron requirements. Absorption of dietary iron may be compromised by her use of proton pump inhibitors and tetracycline .


What subjective or objective signs, symptoms, and laboratory tests are typical of this patient’s Iron Deficiency Anemia? Subjective: Weakness and dizziness could be a result of her severe anemia. Generally, until the anemia is severe, such symptoms occur with equal frequency in the nonanemic population. Objective: Increased heart rate, decreased exercise tolerance, and pale appearance are consistent with tissue anoxia and the cardiovascular response that may be seen in iron deficiency anemia. Laboratory tests: Low serum iron, low serum ferritin, and elevated TIBC are typical of the laboratory findings associated with iron deficiency anemia


How can you manage this patient’s Iron Deficiency Anemia? What is the dose of iron provided? and for how long? Control of the underlying causes of anemia, which in this case are many: Iron stores are low because of GI blood loss, multiple childbirths, heavy menstrual flow, decreased dietary iron absorption, and perhaps, an inadequate diet. GI blood loss should be corrected, her dietary intake should be analyzed and modified, and supplemental iron should be prescribed to replenish her stores and correct the anemia.


How can you manage this patient’s Iron Deficiency Anemia? What is the dose of iron provided? and for how long? If no iron is being lost through bleeding, the required daily dose of elemental iron can be calculated using a formula that assumes that 0.25 g/dL/day is the maximal rate of hemoglobin regeneration. Elemental iron (mg/d) = 0.25g Hgb/100mL blood/day. (approx. 5000mL of Blood) (3.4mg Fe/1g Hgb) Daily elemental iron need is 42.5 mg Fe/day Absorption rate for iron in iron deficient state is approx. 20% Daily elemental iron oral intake should be approx. 2oomg/d.


How can you manage this patient’s Iron Deficiency Anemia? What is the dose of iron provided? and for how long? Ferrous Sulfate contains 20% elemental iron: Daily ferrous sulfate dose is then 200X5 = 1000 mg FeSO4/day Or 325mg TID. What are the differences between different iron supplements? The ferrous form of iron is absorbed three times more readily than the ferric form. Although ferrous sulfate, ferrous gluconate, and ferrous fumarate are absorbed almost equally, each contains a different amount of elemental iron.


The patient is asking if SR formulations will provide better option, what would you tell her? SR preparations fall into three groups: (a) those claimed to increase GI tolerance or decrease side effects, (b) those formulated to increase bioavailability, (c) those with adjuvants claimed to enhance absorption.

These products can be given once daily, they increase compliance. Claims that SR iron preparations cause fewer GI side effects have not been substantiated by controlled studies. In fact, these products transport iron past the duodenum and proximal jejunum, thereby reducing the absorption of iron. Poor absorption and poor hematologic responses might occur with ferrous sulfate SR capsules, they should not be used for initial treatment.


The patient is asking if SR formulations will provide better option, what would you tell her? Adjuvants are incorporated into many iron preparations in an attempt to enhance absorption or decrease side effects. Products contain ascorbic acid (vitamin C), which maintains iron in the ferrous state. Doses up to 1 g increase iron absorption by only 10%; however, smaller doses of vitamin C (e.g., 100 mg) do not significantly alter iron absorption. Stool softeners are added to iron preparations to decrease the side effect of constipation. Generally, these combinations contain suboptimal doses of stool softener and are unwarranted. If constipation does develop, appropriate doses of stool softeners should be taken. In general, generic preparations of iron salts without adjuvant agents provide the best value.


What are the goals of therapy? How will you monitor her? Normalize the Hgb and Hct concentrations and replete iron stores. (a) If the doses of iron are adequate, the reticulocyte count will begin to

increase by the third to fourth day and peak by the seventh to tenth day of therapy.

(b) By the end of the second week of iron therapy, the reticulocyte count will fall back to normal.

(c) The Hgb response is a convenient index to monitor in outpatients.

(d) Hematologic response is usually seen in 2 to 3 weeks with a 1 g/dL increase in hemoglobin and a 6% increase in the hematocrit


What are the goals of therapy? How will you monitor her? (a) Anemia can be expected to resolve in 1 to 2 months; however, iron

therapy should be continued for 3 to 6 months after the hemoglobin is normalized to replete iron stores.

(b) Therapy duration is related to the absorption pattern of iron. (a) During the first month of therapy, as much as 35 mg of elemental

iron is absorbed from the daily dose. (b) With time, the percentage of iron absorbed from the dose

decreases, and by the third month of therapy, only 5 to 10 mg of elemental iron is absorbed.


What are the information that you need to provide to your patient? Oral iron therapy produces dark stools. Take iron on an empty stomach. Constipation does not appear to be dose related. Oral iron therapy can be initiated with a single tablet of ferrous sulfate 325 mg/day; the dose is increased by increments of one tablet per day every 2 to 3 days until the full therapeutic dose of ferrous sulfate, 325 mg three times daily, can be administered.


What are the information that you need to provide to your patient? Potential drug interactions Proton pump inhibitor, inhibits serum iron absorption by increasing the pH of the stomach and decreasing the solubility of ferrous salts. Antacids can increase stomach pH and certain anions (carbonate and hydroxide) also are thought to form insoluble complexes when combined with iron. What to do: Take iron at least 1 hour before or 3 hours after the proton pump inhibitor dose. Absorptions of both iron and tetracycline are decreased when administered concomitantly, the iron should be taken 3 hours before or 2 hours after the tetracycline dose as well.


When would parenteral iron therapy be indicated for this patient? Failure to respond to oral iron therapy can be caused by: 1. Nonadherence, 2. Misdiagnosis (e.g., inflammation), 3. Malabsorption : can be evaluated by measuring iron levels every 30 minutes for

2 hours after the administration of 50 mg of ferrous sulfate. If her plasma iron levels increase by >50%, absorption is adequate.

4. Continuing blood loss equal to or greater than the rate of RBC production. 5. Other indications include intolerance to oral therapy, required antacid

therapy, or significant blood loss in patients refusing transfusion. If malabsoription is documented, she would be a candidate for injectable iron.

Megaloblastic anemia

It can have several causes: (a) anemia associated with vitamin

B12 deficiency (b) anemia associated with folic acid

deficiency (c) anemia caused by metabolic or

inherited defects associated with decreased ability to utilize vitamin B12 or folic acid.

Megaloblastosis results from impaired DNA synthesis in replicating cells, which is signaled by a large immature nucleus. RNA and protein synthesis remain unaffected, and the cytoplasm matures normally.

Symptoms include fatigue; exaggeration of pre-existing cardiovascular or pulmonary problems; a sore, pale, smooth tongue; diarrhea or constipation; and anorexia. Edema and urticaria also may be present.

A case approach to vitamin B12 deficiency anemia

a 55-year-old woman, Chief complains Progressive confusion and lethargy 9 months ago. A CBC at that time revealed only mild leukocytosis. Today, she comes to the emergency department with a 4-week history of frequent (three to five per day) stools containing bright red blood. She reports continued lethargy, dizziness, ataxia, and paresthesias in her hands and feet.


a 55-year-old woman, Laboratory findings of interest Hgb, 12.8 g/dL (normal, 12 to 16); MCV, 90 µm3 (normal, 76 to 100); Iron, 150 mcg/dL (normal, 50 to 160); B12, 94 pg/mL (normal, 200 to 1,000); Folate, 21 ng/mL (normal, 7 to 25); Bilirubin, 3.0 mg/dL (normal, 0.1 to 1.0); Lactate dehydrogenase (LDH), 520 U/L (normal, 50 to 150). A subsequent bone marrow aspirate demonstrates megaloblastic erythropoiesis, giant metamyelocytes, and a low stainable iron. A barium swallow and follow-through show numerous jejunal and duodenal diverticuli. Jejunal and duodenal aspirates reveal aerobic and anaerobic bacterial overgrowth.


What signs, symptoms, and laboratory findings are typical for vitamin B12 deficiency in this patient? Signs and symptoms consistent with B12 deficiency include confusion, dizziness, ataxia, and paresthesias. Other signs and symptoms may be caused by other underlying conditions. The patient initially presented with a mild leukocytosis. Evaluation 9 months later shows a low Hgb, a low serum vitamin B12 level, Hypersegmented PMN. The high LDH and bilirubin levels reflect intramedullary hemolysis of megaloblastic RBC consistent with vitamin B12 deficiency, even though the MCV is within normal limits.


What signs, symptoms, and laboratory findings are typical for vitamin B12 deficiency in this patient? The presence of megaloblastic erythropoiesis and giant metamyelocytes in the bone marrow also is consistent with vitamin B12 deficiency. History of bloody stools and diverticuli suggests substantial long-term blood loss, which increased demand for iron and vitamin B12 to replace RBC. Concurrent iron deficiency can mask megaloblastic changes in RBC, which explains the suspiciously normal MCV (dimorphic anemia). The serum folate concentration is also falsely normal. Although the RBC folate level is likely to be low, serum folate concentrations are normal because monoglutamated folates leak from cells into the serum in vitamin B12 deficient states


How should vitamin B12 deficiency be treated? The cause of vitamin B12 malabsorption must be corrected before the patient is given oral vitamin B12 therapy. Presence of diverticuli is not the cause of vitamin B12 malabsorption because diverticuli typically do not extend into the distal ileum. Instead, given patient's medical history, the most likely cause of vitamin B12 malabsorption is bacterial usurpation of luminal vitamin B12. Patient should first be treated with a broad-spectrum antibiotic (e.g., tetracycline) or a sulfonamide for 7 to 10 days, then begin daily oral vitamin B12 supplementation to replenish her body stores. In this case, normal levels of intrinsic factor permit oral therapy. The recommended daily dose of vitamin B12 is 25 to 250 mcg. Patient o should begin to absorb vitamin B12 in her diet after the antibiotic therapy.

Pharmacottherapy Anas Bahnassi PhD CDM CDE

[email protected]

http://www.twitter.com/abpharm

http://www.facebook.com/pharmaprof

http://www.linkedin.com/in/abahnassi

mailto:[email protected]

http://www.twitter.com/abpharm

http://www.facebook.com/pharmaprof

http://www.linkedin.com/in/abahnassi

anemia: a case based approach: part-1

Health & Medicine