Anemia

anemia

• group of diseases characterized by a decrease in either hemoglobin or the volume of red blood cells

• results in decreased oxygen carrying capcity of the blood

• can result from inadequate RBC production, increased RBC destruction, or blood loss

• associated with an increased risk of hospitalization and mortality, reduced quality of life, and decreased physical functioning

• can be classified on the basis of morphology of the RBC, etiology, and pathophysiology

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• anemia in men is defined as Hb < __ g/dL

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• anemia in women is defined as Hb < __ g/dL

maturation disorders

• iron deficiency anemia, folate deficiency anemia, and vitamin B12 deficiency anema all fall into the category of ____ anemia

red blood cell production

• complete maturation takes about 1 week

• hb and iron are incorporated gradually into the cell

• eventually released into circualtin from bone marrow as a reticulocyte

• becomes an erythrocyte in a couple days

reticulocyte

• immature red blood cell released from bone marrow into circulation

erythrocyte

• mature RBC formed from reticulocyte

120 days

• erythrocyte normal survival time

erythropoietin

• 90% produced by the kidneys

• initiated and stimulated the production of RBCs

• regualted by a feedback loop

• decrease in tissue O2 signals kidneys to increase production and release therefore increasing the production and maturation of RBCs

gneral clinical presentation of anemia

• fatigue/weakness

• dizziness

• irritability

• decreased mental acuity

• pallor, pale mucous membranes

• tachycarida

• shortness of breath/decreased exercise tolerance

• edema

• some may have: dry skin, chapped lips, brittle nails

acute rapid onset anemia presentation

• cardiorespiratory symptoms:

• palpitations/tachycardia

• angina

• orthostatic hypotension/lightheadedness

• breathlessness

• hypotension

chronic onset anemia presentation

• weakness/fatigue

• headache

• vertigo

• faintness

• dyspnea on exertion

• sensitivity to cold

• loss of skin tone

• pallor

hemoglobin (Hgb or Hb)

• normal 12-16 g/dL

• represents the amount per volume of whole blood

• estimate the oxygen carrying capacity

• heavy smokers may have increased concentration

• in pregnancy, Hb decreases due to dilution

hematocrit (Hct)

• normal 36-50%

• the actual volume of RBCs in a unit of whole blood, expressed as a percentage

• approximately 3X the Hb value

RBC count

• in RBCs/mL3

• indirectly estimates the Hb content of the blood

• seldom used

RBC indices

• MCV (mean cell volume)

• MCH (mean cell hemoglobin)

• MCHC (mean cell hemoglobin concentration)

MCV (mean cell volume)

• Hct/RBC count

• normal 80-100 fl/cell

• represents average RBC size (microcytic, normocytic, macrocytic)

causes of increased MCV

• folate or B12 deficiency

• chronic alcoholism

• chronic liver disease

causes of decreased MCV

• iron deficiency

• thalassema

• anemia of chronic disease

• sickle cell disease

MCH (mean cell hemoglobin)

• Hb/RBC count

• normal range 27-33 pg/ml

• amount of Hb in a RBC (hyperchormic, normochromic, hypochromic)

MCHC (mean cell hemoglobin concentration)

• Hb/HCT

• concentration fo Hb in average RBC

• independent of cell size (useful in distinguishing between microcytosis and hypochromia)

reticulocyte count

• normal 0.5-2%

• indirect assessment of new RBC production

• about 1% of RBCs are normally replaced daily= reticulocyte count of 1%

• circulate in the blood for approximately 2 days before maturing into RBCs

microcytic anemia

• result of a deficiency in Hb synthesis resulting in RBCs containing insufficient Hb

• usually due to iron deficiency or impaired iron utilization

• microcytosis and hypochromia are the abnormalities that provide evidence

abnormalities that show microcytic anemia

• low MCV (microcytosis)

• low MCH (hypochromia)

iron absorption

• most people lose about 1mg of iron daily

• normal western diet contains mainly iron in the nonabsorbable ferric (Fe3) state

• iron from animal source (heme iron) is about 3X more absorbable that non heme iron found in vegetables, fruits, dried beans, nuts, and dietary supplements

• vitamin C enhances absorption

• calcium (milk), grains/brans, and tea/coffee can reduce absorption

transferrin

• plasma protein that delivers iron to the bone marrow for incorporation into the Hb molecule

serum iron level

• normal: male= 50-160 mcg/dl, female = 40-150 mcg/dl

• measures iron bound to transferrin

• levels are decreased to normal in iron deficiency anemia and anemia of chronic disease

total iron binding capacity (TIBC)

• noraml 250-400 mcg/dl

• measures the amount of iron which can be bound by transferrin in the blood

• increased in iron deficiency

iron deficiency markers

• combination of low serum iron and high TIBC

transferrin saturation

• normal 20-50%

• iron deficiency 15% or lower

• reflects the extent to which iron binding sites are occupied on transferrin

ferritin

• normal: male= 46-637 mcg/L, female = 10-260 mcg/l (or ng/ml)

• most senstitive and earliest indicator of iron defiency or iron overload

• stored iron- indicates the amount of iron stored in the liver, spleen, and bone marroe

• decreased only in iron deficiency anemia → diagnostic of iron deficiency anemia

ferritin

• decreased only in iron deficiency anemia

iron deficiency anemia

• most common nutritional deficiency in developing countries

• results from prolonged negative iron balance: increased demands or hematopoiesis, increased loss, decreased intake/absorption

• onset depends on initial iron stores and the imbalance between iron absorption and iron loss

• routine screening in all pregnant women

causes of iron deficiency anemia

• inadequate dietary intake: vegetarians, elderly

• inadequate absorption from the GI tract: malabsorption, gastrectomy, chronic diarrhea, celiac disiase, IBD, atrophic gastritis, diet interactions (brans/grains)

• increased demands: infancy, pregnancy, lactating females, adolescent girls

• chronic blood loss: hemorrhoids, PUD, gastritis, GI carcinoma, diverticulitis, heavy menstration

• certain diseases: rheumatoid arthritis, renal disease

iron deficiency anemia presentation

• brittle nails

• nail spooning

• angular stomatitis or cracked lips

• glossitis

• achlorhydria

• craving for nonfood items (pica): ice dirt, paint, starch

• may have restless leg syndrome

iron deficiency anemia lab findings

• low serum iron (could also be normal)

• low ferritin

• high TIBC

iron deficiency anemia treatment

• focused on replenishing iron stores

• dose depends on patient’s ability to tolerate the administered iron (improves with small initial doses and gradual escalation to full dose)

• usually consists of dietary supplementation and administration or oral iron preparations: fe2+ sulfate, succinate, lactate, fumarate, glutamate, and gluconate are absorbed similarly

• new studies show improved absorption and tolerability with lower dosing or every other day dosing

• hemoglobin levels should increase after one month of oral iron supplementation

• continue treatment for 3-6 months after anemia is resolved

best absorbed iron

• Fe2+ form

• from mear, fish, and poultry

• iron fortified cereals

• ascorbic acid (orange juice) increases

reduced absorption of iron

• with tea, coffee, and milk

• but may improve tolerability

2,4

• take iron supplementation __ hours before or__ hours after taking an antacid

iron supplementation adverse rea/heartburnction

• GI

• N/V, constipation, diarrhea, dark stools, abdominal pain, dyspepsia

iron supplementation counseling points

• store out of reach of children and pets as small amounts can result in fatal overdose

• food decreases absorption, however many people take it with food to improve tolerability

strategies to improve iron tolerability

• increase interval

• take with food or milk

• switch to a formulation with a lower amount of elemental iron

• switch from a tablet to a liquid (can titrate dose better)

ferrous sulfate

• 20% elemental iron

• 60-65mg/324-325 mg tablet

• 18mg iron/5ml syrup

• 44 mg iron/5ml elixir

• 15mg iron/0.6 ml drop

ferrous gluconate

• 12% elemental iron

• 36mg iron/ 325 mg tablet

• 27mg iron/ 240 mg tablet

drugs that decrease iron absorption

• acid suppressing antacids, histamine 2 antagonists, proton pump inhibitors (decrease gastric acidity)

• tetracycline and doxycycline

• bile acid sequestrants

medications affected by iron

• levodopa, penicillamine (chelates)

• methyldopa, levothyroxine (decreases efficacy of drugs)

• fluouroquinolones (forms ferric complex)

• tetracyclines and doxycycline (when given within 2 hours of iron salt)

• mycophenolate (decreases absorption)

indications for parenteral iron

• intolerance to oral therapy

• malabsorption (gastric bypass, inflammatory bowel disease)

• long term non-adherence

parental iron

• recommended that resuscitation equipment and trained staff be available during administration (IV diphenhydramine, epinephrine, methylprednisolone)

• BB warning for iron dextran and ferumoxytol regarding severe allerfic reactions

parenteral iron adverse effects

• IV: serum sickness (lymhoadenopathy, myalgia, arthralgia, fever, and headache) can occur within 4-48 hours after infusion

• hypotention and flushing associated with too rapid injection

• IM: soreness and inflammation at the sie of injection and brown skin discoloration

iron deficiency anemia monitoring and follow up

• recheck Hg/Hct, iron studies values within 4 weeks after treatment initiation to check repsonse

• adverse effects: tolerability of medication, GI side effects

• symptom improvement

• if minimal improvement or worsening, evaluate whether etiology of anemia is correct

macrocytic anemia

• vitamin b12 deficiency anemia

• folate deficiency anemia

vitamin B12 (cobalabin) deficiency etiology

• inadequare intake (rare): vegans, chronic alcoholics, elderly patients consuming tea and toast diet

• decreased absorption/malabsorption syndromes: pernicious anemia, inadequare gastric acid production, IBD, intestinal resection, gastric acid suppressing agents

• inadequate utilization

vitamin B12

• aids in the synthesis of building blocks for DNA and RNA, is essential in maintaining the integrity of the neurologic system, and helps with energy production

vitamin B12 deficiency lab findings

• low B12 levels (<150 pg/ml) (cyanocobalamin or cobalamin)

• levels may be normal despite an existing deficiency due to tissue stores

• MCV usually elevated > 100 fl

• low reticulocyte count

• low Hct

vitamin B12 deficiency presentaiton

• neuropsychiatric abnormalities

• paresthesias (bilateral) in extremities

• diminished vibratory sensation in LE

• irritability

• demential like symptoms

• psychosis

• gastic mucosal atrophy

• swollen, red tongue or bleeding gums

• muscle weakness, ataxia, dysphagia, anorexia, vision loss

vitamin B12 deficiency treatment

• goals: reversal of hematologic manifestations, replacement of body stores, and prevention/resoltuion of neurologic manifestations

• oral: 1,000-2,000 mcg/day

• IM or deep SQ: 1000 mcg daily of cyanocobalamin x 1 week to saturate B12 stores, then decrease to 1000 mcg weekly x 1 month, then monthly thereafter for maintenance (preferred for patients exhibiting neurologic symptoms until resolution of symptoms)

• evidence shows that oral replacement is as efficacious as parental supplementation

• bone marrow becomes normoblastic in 2-3 days, reticulocytosis occurs in 3-5 days, Hb begins to rise in 1 week (normalizes in 1-2 months)

• continue for life if pernicious anemia

• counsel on foods high in vitamin b12 content

foods high in vitamin B12

• fortified cereal, salmon, trout

vitamin b12 deficiency monitoring and follow up

• recheck vitamin B12, Hb/Hct within 4 weeks after treatment initiation, then every 3-6 months

• symptom improvement including neurologic symptoms

• if minimal improvement or worsening, evaluate whether etiology of anemia is correct

folate deficiency etiology

• one of most common vitamin deficiencies in UD

• decreased intake: elderly patients, alcoholics, lower socioeconomic status, and chronically ill patients

• decreased absorption: malabsorption syndromes such as tropical sprue, celiac disease, and crohn’s disease

• increased folate requirements: pregnancy, hemolytic anemia, myelofibrosis, malignancy, chronic inflammatory conditions

• medications: phenytoin, primidone, phenobarbital, triamterene, azathioprine, trimethoprim-sulfa, methotrexate

folic acid

• necessary for the production of DNA and RNA

• humans unable to synthesize sufficient amount to meet total daily requirement, so depend on dietary resources

• once absorbed, must be converted to the active form (tetrahydrofolate)

• body stores 5-10mg primarily in the liver

foods rich in folate

• fresh green leafy vegetables and citrus fruits

• dairy products

• yeast

• mushrooms

• liver

• kidney

• destroyed by cooking or processing

folate deficiency presentation

• similar to B12 except no neurologic manifestations

• wasted appearance

• diarrhea

• glossitis

• early graying of the hair

• loss of skin elasticity

folate deficiency lab findings

• MCV elevated

• low reticulocyte count

• low HCT

• normal B12

• serum folate decreased

folate deficiency treatment

• 1mg-5mg daily for 4 months

• sufficient time for all folate deficient RBCs to be cleared from circulation

• correct the underlying cause

• long term folate may be required in conditions associated with increased folate requirements

folate deficiency in pregnancy

• periconceptional folic acid supplementation is recommneded to decrease the occurence of neural tube defects

• neural tube defects occur during the 3-4th week of life

• prenatal vitamins usually have a higher amount of folic acid compared to multivitamins to ensure adequate supplementation

• women of childbearing years should maintain adequate folic acid intake

folic acid deficiency monitoring and follow up

• recheck folate, hg/hct values within 4 weeks after treatment initiation

• symptom improvement

• if minimal improvement or worsening, evaluate whether etiology of anemia is correct