Anemia caused by decreased Erythrocyte ProductionDecreased hemoglobin synthesis

Iron-deficiency anemia

Thalassemia Sideroblastic anemia

Defective DNA synthesis in RBCs

Megaloblastic anemias

Diminished availability of erythrocyte precursors

Aplastic anemia Anemia of chronic disease

Iron-Deficiency AnemiaEtiology 1. Inadequate dietary intake.

2. Malabsorption.3. Blood loss.4. Hemolysis

Malabsorption: GI surgery: procedures that involve removal or bypass of the

duodenum Malabsorption syndromes: disease of duodenum in which the

absorption surface is altered or destroyedBlood loss: Major sources: GI & GU systemsGI: peptic ulcer, gastritis, esophagitis, diverticuli, hemorrhoids, neoplasia.GU: primarily from menstrual bleedingOther: postmenopausal bleeding in older woman, chronic renal failure & dialysis treatment

Clinical Manifestations

Early Course: may be free of symptomsChronic: general manifestations of anemia

Specific clinical symptoms:1. Pallor2. Glossitis (inflammation of the tongue)3. Cheilitis (inflammation of the lips)4. Headache, paresthesisas, & burning sensation of the tongue

Laboratory abnormalities

Hb/Hct: ↓MCV: ↓Reticulocytes: N or slight ↑or ↓Serum Iron: ↓TIBC: ↑Transferrin: N or ↓Ferritin: ↓Bilirubin: N or ↓

Diagnostic Studies

1. Stool Guaiac test2. Endoscopy & colonoscopy to

detect GI bleeding3. A bone marrow biopsy

History & physical examinationHct & Hb levels, RBC count, including morphologyReticulocyte count, serum iron, ferritin, transferrin, TIBCStool examination for occult blood

Collaborative Therapy

1. Main goal: treat underlying disease that is causing reduced intake or absorption of iron (malnutrition, alcoholism).

2. Efforts toward replacing iron.3. Teach the pt. which foods are

good sources of iron (liver & muscle meats, eggs, dried fruits, legumes, whole-grain & enriched bread & cereals, potatoes).

4. If iron deficiency is from acute blood loss- the pt. may require a transfusion of packed RBCs.

5. Iron dextran, sodium ferrous gluconate, iron sucrose IM or IV (parenteral iron)

Drug therapy: Five factors should be considered:1. Iron is absorbed best from the duodenum & proximal jejunum.

(Enteric-coated or sustained release capsules, release iron farther down in GI tract are counterproductive/expensive)

2. The daily dosage should provide 150 to 200 mg of elemental iron. Ingested in 3 to 4 daily doses, each tablet or capsule containing btwn 50 to 100mg of iron.

3. Iron is best absorbed as ferrous sulfate (Fe2+) in an acidic environment. Iron should be taken about an hour before meals, when the duodenal mucosa is most acidic. (Taking iron with Vitamin C (ascorbic acid) or OJ enhances iron absorption).

4. Undiluted liquid iron may stain the patients teeth; dilute it & ingest through a straw.

5. GI side effects of iron administration may occur; such as heartburn, constipation, & diarrhea. Ferrous gluconate may be used as substitute. All pts. should know stools will become black because the GI tract excretes excess iron. Constipation is common- start patient on stool softener or laxative.

ThalassemiaEtiology Group of diseases that have an autosomal

recessive genetic basis involving inadequate production of normal hemoglobin

Due to absent or reduced globulin protein Abnormal Hb synthesis

1. Heterozygous has one thalassemic gene & one normal gene- thalassemia minor

2. Homozygous person has two thalassemic genes- thalassemia major

Clinical Manifestations

Thalassemia major: Both physical & mental growth retarded Pale & other general symptoms that devlop in childhood by 2 years of age Pronounced splenomegaly & hepatomegaly Jaundice from RBC hemolysis Chronic bone marrow hyperplasia & expansion of marrow space Thickening of cranium & maxillary cavity

Lab Abnormalities

Hb/Hct: ↓MCV: N or ↓Reticulocytes: ↑Serum Iron: ↑TIBC: ↓Transferrn: ↓Ferritin: N∨↑Bilirubin: ↑

Collaborative Care

Thalassemia minor: requires no treatment because the body adapts to the reduction of normal hemoglobin

Hep C may result in cirrhosis & hepatocellular carcinoma

Cardiac complications from iron overload, pulmonary disease, & hypertension – early death

Hepatic, cardiac, & pulmonary organ function should be monitored

Endocrinopathies (hypogonadotrophic hypogonadism) & thrombosis –complications

Hematopoietic stem cell transplantation remains the only cure- risk outweigh the benefits

Thalassemia major: Symptoms are managed with blood transfusions or

exchange transfusions in conjunction with oral deferasirox (Exjade) or IV or subcutaneous deferoxamine (Desferal)

Folic acid is given if there is sign of hemolysis Zinc may be needed (reduced with chelating

therapy) as well as ascorbic acid during chelation therapy (increases the excretion of iron)

Iron supplements should not be given Splenectomy Hep C is present in most patients older than 25

years- because of receiving blood transfusions before they were screen for hep C

Megaloblastic Anemias: Caused by impaired DNA synthesis

Presence of large RBCs Result from cobalamin (vitamin B12) & folic acid deficiencies

Other: drug-induced suppression of DNA synthesis, inborn errors, & erythroleukemia

Cobalamin (Vitamin B12) DeficiencyEtiology Most common cause

is pernicious anemia: a disease in which the gastric mucosa is not secreting IF because of antibodies being directed against the gastric parietal cells and/or IF itself

GI surgery: Gastrectomy, gastric

bypass Patients who have had a

small bowel resection involving the ileum

Crohns disease, ileitis, celiac disease, diverticuli of the small intestine, chronic atrophic gastritis

Deficiency is the result from loss of IF-secreting gastric mucosal cells or impaired absorption of cobalamin in the distal ileum.

Long-term users of H2-histamine receptor blockers & proton pump inhibitors, & vegetarians

Pernicious anemia: caused by the absence of IF- from either gastric mucosal atrophy or autoimmune destruction of parietal cells

Clinical Manifestations:

GI: Sore, red, beefy, & shiny tongue Anorexia, nausea, & vomiting Abdominal painNeuromuscular: Weakness, paresthesias of feet & hands Reduced vibratory & position senses Ataxia Muscle weakness Impaired thought processes ranging from confusion to dementia

Diagnostic Studies:

Hb/Hct: ↓MCV: ↑Reticulocytes: N or ↓Serum Iron: N∨↑TIBC: NTransferrn: Slight ↑Ferritin: ↑Bilirubin: N∨slight ↑

If serum cobalamin levels are low & folate levels are normal cobalamin deficiency.A serum test for anti-IF antibodies may be done = specific for pernicious anemia.Schilling test- radioactive cobalamin is administered to patient- absorption of cobalamin when IF is added is diagnostic of pernicious anemiaMMA- elevated in cobalamin

Collaborative Care:

Pt should be instructed on adequate dietary intake to maintain good nutritionParenteral or intranasal administration of cobalamin is the treatment of choice

High-dose oral cobalamin & sublingual cobalamin are available for those in whom GI absorption is intact

Folic Acid DeficiencyEtiology Dietary deficiency

Malabsorption syndromes Drugs interfering with absorption/use of folic acid- Methotrexate & Antiseizure drugs Alcohol abuse Anorexia

Hemodialysis patientsClinical Manifestations:

Disease develops insidiously Symptoms may be attributed to other coexisting problems such as cirrhosis or esophageal

varicesGI:

Dyspepsia Smooth, beefy red tongue

The absence of neurologic problemsCollaborative Care

Treated with replacement therapyUsual dose is 1 mg per day by mouthPatient should be encourage to eat foods containing large amounts of folic acid

Ensure that injuries are not sustained because of the diminished sensations to heat & pain resulting from the neurologic impairmentProtect the patient from falling, burns, & trauma

Anemia of Chronic Disease (anemia of inflammation) Underproduction of RBCs Mild shortening of RBC survival RBCs are usually normocytic, normochromic, & hypoproliferative Immune driven Cytokines released by these conditions cause an increased uptake & retention of iron within macrophages Ex: Renal disease: the primary factor causing anemia is decreased erythropoietin (hormone made in the kidneys that

stimulates erythropoiesis) Myelosuppression & decreased erythropoiesis caused by disease, medications (chemotherapy), or radiation will

contribute to normochromic, normocytic anemia HIV & its treatments, hepatitis, malaria, & bleeding episodes contribute to this anemia Hypopituitary & hypothyroid Adrenal dysfunction caused by either adrenalectomy or Addison’s disease

Differentiated from anemia’s of other etiologies: Elevated serum ferritin & increased iron stores distinguish it from iron-deficiency Normal folate & cobalamin blood levels

Erythropoietin therapy (Epogen, darbepoetin) is used for anemia related to renal disease

Aplastic AnemiaEtiology: Pt. has peripheral

blood pancytopenia (↓ of all blood cell types- RBCs, WBCs, platelet) & hypocellular bone marrow

Two major groups:1. Congenital2. Acquired

(70% are idiopathic & thought to be autoimmune)

Congenital (Chromosomal alterations): Fanconi syndrome Congenital

dyskeratosis Amegakaryocytic

thrombocytopenia Schwachman-

Diamond syndrome

Acquired: Idiopathic/autoimmune Chemical agents & toxins (benzene,

insecticides, arsenic, alcohol) Drugs (alkylating agents,

antiseizure drugs, antimetabolites, antimicrobials, gold)

Radiation Viral & bacterial infections

(hepatitis, parvovirus)

Clinical Manifestations:

Abruptly (over days) or insidiously over wks to months

Can vary in mild to severe

Manifestation: fatigue & dyspnea

Cardiovascular & cerebral responses

Pt with neutropenia (low neutrophil count) is susceptible to infection & is at risk for septic shock & death

Even a low grade fever (above 100.4F) should be considered an emergency Thrombocytopenia is manifested by a predisposition to bleeding (petechiae,

ecchymosis, epistaxis)

Diagnostic Studies:

Hemoglobin, WBC, & platelet values are decreased Marrow is hypocellular with increased yellow marrow (fat content)

Collaborative Care:

Identifying the causative agent & providing supportive care until the pancytopenia reverses

Prevent complications from infection & hemorrhage

HSCT and ATG Cyclosporine or high-dose cyclophosphamide (Cytoxan) ATG- horse serum that contains polyclonal antibodies against human T cells

Acute Blood Loss: AnemiaEtiology: Result of sudden

hemorrhage Causes: trauma,

complications in surgery, & conditions or diseases that disrupt vascular integrity

1. Sudden reduction in the total blood volume that can lead to hypovolemic shock

2. If the acute blood loss is more gradual the body maintains its blood volume by slowly increasing the plasma volume

Clinical Manifestations:

Volume Lost (%) 10% - none 20%- no detectable signs or symptoms at rest, tachycardia with exercise & slight postural

hypotension 30%- Normal supine blood pressure & pulse at rest, postural hypotension & tachycardia

with exercise. 40% - blood pressure, central venous pressure, & cardiac output below normal at rest;

rapid, thread pulse & cold, clammy skin 50%- shock & potential death

Collaborative Care:

1. Replacing blood volume to prevent shock

2. Identifying the source of the hemorrhage & stopping the blood loss. (IV fluids used in emergencies include dextran, hetastarch, albumin, and/or crystalloid electrolyte solutions such as lactated Ringers solution.

3. Correcting the RBC loss- body needs 2 to 5 days to manufacture more RBCs in response to increased erythropoietin.

4. Supplemental iron

For postoperative patient: Monitor the blood loss from various

drainage tubes & dressings & implement appropriate actions

Administration of blood products

Chronic Blood Loss: AnemiaEtiology: (similar to those of iron-deficiency anemia)

Sources: Bleeding ulcers Hemorrhoids Menstrual &

postmenopausal blood loss

Effects: Depletion of iron

stores & considered as iron-deficiency anemia

Management: identifying the source & stopping the bleeding