Anemia Flashcards
What is anemia?
Reduction of volume of red blood cells (RBC) or hemoglobin (Hgb) concentration
Reduced oxygen-carrying capacity of blood
Usually a sign of an underlying pathology
What is the pathophysiology involved with anemia?
Inadequate production of RBC
Nutritional deficiencies
Excessive destruction of RBC (too much lysis)
Blood loss
What are the three types of anemia?
Microcytic- cells are too small
Normocytic
Macrocytic- cells are too big
What are the causes of microcytic anemia?
Iron deficiency Sickle cell Heavy metal poisoning Chronic disease Thalasemia
What are the causes of normocytic anemia?
Blood loss Hemolysis Aplastic anemia Marrow failure Chronic disease Renal failure Endocrine disorders Acute infection
What are the causes of macrocytic anemia?
B12 deficiency
Folic acid def.
Alcoholism
What are the signs of anemia?
Tachycardia
Pallor
Decreased mental acuity
Increased intensity of cardiac murmurs
What are the symptoms of anemia?
Decreased exercise tolerance Fatigue Dizziness Irritability Weakness Vertigo Shortness of breath Chest Pain
What are the physical exam findings of anemia?
May have no symptoms Pale conjunctiva, mucous membranes, nail beds Postural hypotension, tachycardia Jaundice (with hemolysis) Neurologic findings (B12)
What are the lab parameters associated with anemia?
CBC: Hgb, Hct, platelets, WBC RBC indices: MCV, MCHC, RDW Iron studies: iron, TIBC, ferritin, percent transferrin saturation Reticulocyte count Folic acid/B12 level Bilirubin Coombs test
What is the most common cause if microcytic anemia?
Iron deficiency
How do thalassemias cause microcytic anemia?
Deficiency in production of α or βchain of Hgb
Autosomal recessive genetic disorder
Trait (1 copy of gene) protective against malaria
Most common in those of Mediterranean descent
How do you treat thalassemias that cause microcytic anemia?
Those who are autosomal recessive are supported with frequent, lifelong blood transfusions, iron chelation therapy, splenectomy
Only curative treatment is hematopoietic stem cell transplant
How does sickle cell disease cause microcytic anemia?
Production of abnormal Hgbβchain
Autosomal recessive genetic disorder
Trait (1 copy of gene) protective against malaria
Most common in those of African descent
Those who are autosomal recessive have HgbS – abnormal hemoglobin that can cause RBC to change to sickled shape after release of O2
Cells are weakened by constant sickling & un-sickling, and can lyse, leading to anemia
Who is considered at high risk for development of or developing complications from iron deficiency anemia?
Children < 2 years
Menstruating adolescent females
Pregnant women
> 65 years old
What is the pathophysiology of iron deficiency anemia?
Hgb is O2-binding protein in RBC
Iron is incorporated into Hgb and directly binds O2
Reduced iron supply leads to reduced production of Hgb
RBC are deficient of Hgb, therefore
Hypochromic
Microcytic
What dietary sources can iron be found in?
Meats Fortified cereals Grains Legumes Green leafy vegetables
What from is most dietary iron?
Ferric from (Fe3+)
What form of iron is best absorbed?
Ferrous form (Fe2+) Acid reduces ferric to ferrous (Have patients drink orange juice with iron so that its more absorbable.)
Where is iron absorbed? Is heme or non-heme iron absorbed more?
Absorbed mainly in duodenum via direct uptake
Heme iron 3x more absorbable than non-heme iron
Heme found in meat, fish, poultry
Non-heme found in fortified cereals, beans, leafy green vegetables
What compounds can reduce iron absorption by forming complexes?
Phytates from vegetables/grains, polyphenols from tea/coffee, and caclcium
What are the inadequate intake causes of iron deficiency?
Vegetarians/vegans
What are the impaired absorption causes of iron deficiency?
Chelation
Gastrectomy
Enteritis
Inflammatory bowel disease
What are the increased requirement causes of iron deficiency?
Infancy
Pregnant/lactating
What are the blood loss causes of iron deficiency?
Menstruation
Trauma
GI bleeding- ulcer, hemorrhoids, tumor, alcohol, steroids/NSAIDS
What are the iron deficiency anemia symptoms
Decreased exercise tolerance Fatigue Dizziness Irritability Weakness Vertigo Shortness of breath Chest Pain PICA IF VERY SEVERE DEFICIENCY
What are the lab findings associated with iron deficiency anemia?
↓ Hgb ↓ Hct ↓ MCV ↑ RDW ↓ Iron ↓ Ferritin ↑ TIBC ↓ Fe: TIBC ratio
How do you treat iron deficiency anemia?
Treat underlying disease Correct iron deficiency Dietary Encourage intake of foods high in iron Heme iron is easiest to absorb May not be able to meet needs if Vegetarian/vegan Problems with iron absorption Oral Supplementation
What are the dietary sources of heme iron?
Chicken liver Oysters Beef Turkey (dark>light meat) Chicken (dark>light meat)
What are the dietary sources of non-heme iron?
Cereal/oatmeal, fortified Soybeans Other legumes Tofu Spinach
What are the available iron replacement products?
FERROUS SULFATE FERROUS GLUCONATE Ferrous Fumarate Polysaccharide iron complex Carbonyl Iron
What should you watch for with iron replacement?
Amounts of elemental iron
Iron (FERROUS SULFATE, FERROUS GLUCONATE, Ferrous Fumarate, Polysaccharide iron complex, Carbonyl Iron)- administration
Can cause substantial GI intolerance
Give in divided doses (2 – 3 times daily)
Start with smaller doses to improve tolerance, then escalate
Best absorbed without food
Can take with food if GI intolerance occurs
Try to make GI a little more acidic by taking with OJ
Keep out of reach of children!
Risk of toxicity
Iron (FERROUS SULFATE, FERROUS GLUCONATE, Ferrous Fumarate, Polysaccharide iron complex, Carbonyl Iron)- adverse effects
Nausea/vomiting
Constipation- huge issue
Dark stool- make sure they know this
Iron (FERROUS SULFATE, FERROUS GLUCONATE, Ferrous Fumarate, Polysaccharide iron complex, Carbonyl Iron)- interactions
- Antacids- often have calcium which chelate with iron and will make it a clump that comes right out
- Tetracycline antibiotics
- Histamine-2 antagonists
- Proton pump inhibitors- change acidity
- Cholestyramine- screws up absorption of all
- Fiber
Iron (FERROUS SULFATE, FERROUS GLUCONATE, Ferrous Fumarate, Polysaccharide iron complex, Carbonyl Iron)- Goals and monitoring
Normalize Hgb
Responds in ~ 3 weeks
Should rise 2 – 4 g/dL in this time
Resolution within 1-2 months
Replete iron stores
Takes 3 - 6 months
Supplement iron for 3 – 6 months
Iron (FERROUS SULFATE, FERROUS GLUCONATE, Ferrous Fumarate, Polysaccharide iron complex, Carbonyl Iron)- failure of therapy
If Hgb rises < 2g/dL after 3 weeks of treatment
Reasons Poor patient compliance Inability to absorb iron Incorrect diagnosis Persistent bleeding
When is parenteral iron used?
Evidence of iron malabsorption
Intolerance of oral iron
Long-term noncompliance
Significant blood loss and refusal of transfusions
What are the parenteral iron drugs?
IRON SUCROSE
IRON DEXTRAN
Sodium Ferric Gluconate
Parenteral iron (Iron sucrose, Iron dextran, Sodium Ferric Gluconate)- Adverse effects
Flushing Hypotension Fever/chills Myalgia ANAPHYLAXIS- BLACK BOX WARNING Iron overload
Parenteral iron (Iron sucrose, Iron dextran, Sodium Ferric Gluconate)- monitoring
Weekly Hgb Hct Ferritin Transferrin saturation Monthly Serum iron (these take a long time to build up)
What are the causes of megaloblastic macrocytic anemias?
Vitamin B12 (cyanocobalamin) deficiency Folate deficiency Abnormal utilization of B12 or folate
What are the causes of non-megaloblastic macrocytic anemias?
Alcohol abuse
What is the pathophysiology of macrocytic anemias?
–Abnormal DNA synthesis in developing erythrocyte
B12 & folate are required cofactors
–Resulting RBC are macrocytic and immature
–Hypercellular bone marrow, full of “–blast” progenitor cells
Especially erythroid line
What are the drugs that are associated with megaloblastic anemia?
Azathioprine 6 – mercaptopurine Cytarabine Fluorouracil Methotrexate Pentamidine Trimethoprim Triamterene Hydroxyurea Zidovudine Phenytoin Phenobarbital
Who is at high risk for developing Vit B12 deficiency?
Women
Elderly
Those using gastric acid-suppressing therapy
Alcoholics
What is the function of Vit B12?
DNA synthesis
With folate
Myelin synthesis - maintains integrity of neurologic system
Fatty acid biosynthesis and conversion of some amino acids
What dietary products contain Vit B12
Meat
Fish
Dairy
Fortified cereals
How is Vit B12 absorbed?
- Bound to proteins in saliva
- Released from salivary protein complexes in acidic environment of stomach, then binds to intrinsic factor released from parietal cells
- B12 - intrinsic factor complex absorbed via mucosal receptors in distal ileum
- Vitamin transported from ileal cells to portal circulation
- A small amount of B12 is absorbed via passive diffusion
What is necessary for Vit B12 to be absorbed?
Intrinsic factor
How is Vit B12 metabolized?
-In portal blood, vitamin is transferred to transcobalamin transport proteins
-Transcobalamin-II necessary for endocytosis into cells including bone marrow and liver
-Liver converts vitamin to coenzyme B12, necessary for:
Hematopoesis
Myelin maintenance
Epithelial cell production
What are the inadequate intake causes of vit B12 deficiency?
Strict vegans
Chronic alcholics
What are the malabsorption causes of vit B12 deficiency?
Pernicious anemia Gastric atrophy Gastrectomy/ileectomy Acid-suppressing therapy Inflammatory bowel disease
What are the abnormal utilization causes of vit B12 deficiency?
When iron is taken into the body it doesn’t work how it should. Doesn’t get into the liver like it should or transported to the blood.
What is pernicious anemia caused by?
- Absence of intrinsic factor
- Due to autoimmune parietal cell destruction, gastric atrophy, surgery
- Most common in African-Americans and those of northern European descent
- Higher risk of gastric cancer
What are the symptoms of pernicious anemia?
Decreased exercise tolerance Fatigue Dizziness Irritability Weakness Vertigo Shortness of breath Chest Pain GLOSSITIS- TONGUE IS BIG, RED, BEEFY, SHINY, ALMOST LOOKS BLOODY NUMBNESS, PARETHESIAS IN EXTREMITIES
What are the lab findings of pernicious anemia?
↓ Hgb ↓ Hct ↑ MCV – difference from iron deficiency ↑ RDW ↓ B12- important ↑ Methylmalonic acid (MMA) ↑ Homocysteine Mild leuko- and thrombocytopenia May have intrinsic factor antibodies Not seen in everyone with Vit B12 def
What is the treatment of pernicious anemia?
Goals
Reverse hematologic manifestations
Prevention/reversal of neurologic manifestations
Replace body stores
Consider even if B12 levels are at low end of normal
Supplementation usually necessary
Can encourage dietary intake as well
What are the dietary sources of B12?
Mollusks Beef liver Fortified cereal Salmon Beef Yogurt Tuna MIlk
Vit B12 Supplementation- ROA
Oral
1 – 2 mg/day for 1 month, then 125 – 500 micrograms/day
IM/SC
*Use this route if neurologic symptoms are present
Cyanocobalamin 1 mg/day for 1 week, then 1 mg/week for 1 month, then monthly thereafter
Hydroxycobalamin 1 mg/ month is alternative
Intranasal
Once weekly
Vit B12 Supplementation- adverse effects
Rebound thrombocytosis
Fluid retention
Anaphylaxis
Vit B12 Supplementation- evaluation of effect
Strength improves within days Glossitis improves in 24 hrs Bone marrow normoblastic in 24 hrs Hgb/Hct respond in week Leukocytes/platelets normal in 1 week
Vit B12 Supplementation- monitoring
CBC in 10 - 14 days, again in 2 – 3 months
MMA/homocysteine in 2 -3 months
Who is at high risk for folate deficiency?
Adolescents/teens
Elderly
Pregnant women
Alcoholics
What is the function of folate?
Works with DNA synthesis
Important for Protein, amino acid, purine & pyrimidine synthesis
Important in fetal development
What dietary sources contain folate?
Green leafy vegetables Citrus Mushrooms Diary Organ meats Fortified cereals
Where is folate absorbed?
In the small intestine
Converted to active form via B12-dependent reaction
What are the inadequate intake causes of folate deficiency?
Poor diet
What are the malabsorption causes of folate deficiency?
Sprue/celiac disease
Alcoholism
What are the hyperutilization causes of folate deficiency?
Pregnancy
Chronic hemolysis
Myelofibrosis
Autoimmune diseases
What are the abnormal utlization/interference with metabolism causes of folate deficiency?
Alcoholism
What are the drug causes of folate deficiency?
Sulfa drugs
Methotrexate
Phenytoin
What are the symptoms of folate deficiency?
Decreased exercise tolerance Fatigue Dizziness Irritability Weakness Vertigo Shortness of breath Chest Pain
What are the lab values associated with folate deficiency?
↓ Hgb ↓ Hct ↑ MCV ↑ RDW ↓ Folate ↓ RBC Folate ↑ Homocysteine **You MUST rule out B12 deficiency**
What is the treatment of folate deficiency?
Reverse hematologic manifestations
Replace body stores
Provide for healthy fetal development
What are the dietary sources of folate?
Chicken liver Beef liver Cereal Lentils Other legumes Pasta Spinach
Folate supplementation- ROA
Supplementation can mask B12 deficiency*
1 mg PO daily for at least 4 months
Folate supplementation- evaluation of effect
Strength improves within days
Hbg/Hct repsond in 2 days
Folate supplementation- monitoring
CBC in 1 month
What causes normocytic anemias?
Due to increased blood loss – Trauma, GI bleed, malignancy
Reduced production
What are the primary causes of normocytic anemias?
Marrow failure
Myeloproliferative disorder
What are the secondary causes of normocytic anemias?
Renal failure
Endocrine Disorders
Anemia of chronic disease
What are the increased destruction causes of normocytic anemias?
Hemolytic disorders
What are the sources of blood loss that could cause normocytic anemia?
Source
Injury
Upper GI bleed (variceal, non-variceal [ulcer, Mallory-Weiss tear, malignancy, etc.])
Lower GI bleed (hemorrhoids, malignancy, etc.)
Patient may be hypovolemic, tachycardic
Especially with large-volume losses
More likely if blood loss was rapid
How is blood loss managed?
-Surgical or medical management of injury GI bleed Proton pump inhibitor (upper) Banding of varices (upper) Injection of sclerosing agent
- Fluid resuscitation
- Blood transfusion
When is a blood tranfusion indicated?
1 “Unit of blood” is 300 cc of packed RBCs
Raises Hgb by 1 mg/dL by and Hct by 3%
Indications
Hgb < 7 mg/dL (higher cutoff for patients with severe cardiovascular disease)
> 30% blood loss
What is type and cross?
To prevent hemolysis of given RBCs
Type
Screen for blood type & antibodies (A-B-O)
Rh (D) antigen
Cross - Match units of blood to type that patient needs
What are the risks of blood transfusion?
Transmit disease
Very small risk – blood is screened
Iron overload
Each unit of RBC contains 200 – 250 mg of iron
What is the 2nd most common cause of anemia?
Anemia of chronic disease
When is anemia of chronic disease most common?
Frequently occurs in elderly
Most common with diseases that last a few months
What is the pathophysiology of anemia of chronic disease?
Not 100% understood
Hypoproliferation of RBC due to
Chronic inflammatory processes increase cytokines
Interleukin-1 & Tumor necrosis factor (TNF) released
Reduced response to EPO (erythropoetin)
Reduced transferrin synthesis
What are the major abnormalities associated with anemia of chronic disease?
Major abnormalities
Limited release of iron from marrow – impaired iron mobilization
Impaired marrow response to EPO
Shortened survival of RBC
What are the chronic infections that cause anemia of chronic disease?
Tuberculosis
HIV
Subacute bacterial endocarditis
Osteomyelitis
What are the chronic inflammation causes of anemia of chronic disease?
Rheumatoid arthritis
SLE
IBD
GOut
What are the renal failure causes of anemia of chronic disease?
Renal failure
What are the malignancy causes of anemia of chronic disease?
Carcinoma
Lymphoma
Leukemia
Multiple myeloma
What are the less common causes of anemia of chronic disease?
Alcoholic liver disease
CHF
COPD
What are the symptoms of anemia of chronic disease?
Decreased exercise tolerance Fatigue Dizziness Irritability Weakness Vertigo Shortness of breath Chest Pain CHRONIC, MILD TO MODERATE SX MAY NOT BE DISTINGUISHABLE FORM SX OF OVERLYING DISEASE CAN BE ACCOMPANIED BY IRON DEFICIENCY ANEMIA IN SOME PATIENTS
How is anemia of chronic disease diagnosed?
There is no definitive test
This is a diagnosis of exclusion
Anemia in someone who is chronically ill
No other definite etiology
What are the lab findings associated with anemia of chronic disease?
↓ Hgb ↓ Hct Normal or Slightly ↓ MCV Normal RDW ↓ Iron ↑ or normal Ferritin ↓ TIBC ↓ Reticulocyte count
What is the treatment of anemia of chronic disease?
- Treat underlying disease
- Replace iron IF deficient
- Not for patients with high ferritin
- Blood transfusion if severe anemia & symptomatic
- Erythropoietic agents
- Useful since these patients can have a deficiency of EPO
What are the erythopoetic agents?
Epoetin Alfa (Procrit®, Epogen®) Darbopoetin Alfa (Aranesp®)
Erythropoetic agents (Epoetin Alfa (Procrit®, Epogen®), Darbopoetin Alfa (Aranesp®))- MOA
Stimulates RBC production & maturation, like endogenous EPO
Erythropoetic agents (Epoetin Alfa (Procrit®, Epogen®), Darbopoetin Alfa (Aranesp®))- indications
Anemia associated with chronic renal failure
Anemia due to chemotherapy for non-myeloid malignancies
Anemia associated with HIV therapies causing myelosupression
No consistent guidelines for EPO use in patients with anemia of chronic disease
VERY EXPENSIVE
When in a chemo patient should erythropoetin agents not be used?
Do not begin in chemo patients with Hgb > 10 g/dL
Erythropoetic agents (Epoetin Alfa (Procrit®, Epogen®), Darbopoetin Alfa (Aranesp®))- Goals
Maintain Hgb sufficient to avoid RBC transfusions
Chronic renal failure - Hgb 10 – 12 g/dL
Hgb should NOT exceed 12 g/dL in any patient
Hgb should not rise > 1 g/dL within 2 weeks
Erythropoetic agents (Epoetin Alfa (Procrit®, Epogen®), Darbopoetin Alfa (Aranesp®))- Dose adjustments
As goal Hgb is approached, dosing should be reduced
If Hgb > 12 g/dL – withhold dosing, might resume at reduced dose after Hgb drops below 10 g/dL
Can increase dose at 4 week intervals if Hgb increase < 1 g/dL
**Discontinue therapy if inadequate response in 12 weeks
Erythropoetic agents (Epoetin Alfa (Procrit®, Epogen®), Darbopoetin Alfa (Aranesp®))- supplementation
Bone marrow will utilize iron in Hgb production
Patients may need iron supplementation during therapy
If ferritin drops below 100 ng/mL
If transferrin saturation drops below 20%
Erythropoetic agents (Epoetin Alfa (Procrit®, Epogen®), Darbopoetin Alfa (Aranesp®))- monitoring
Monitoring Hgb/Hct weekly Resolution of symptoms Iron studies Side effects USE MINIMUM EFFECTIVE DOSE of EPO agent
Erythropoetic agents (Epoetin Alfa (Procrit®, Epogen®), Darbopoetin Alfa (Aranesp®))- adverse effects
Adverse effects
Infusion reactions: fever, chest pain, N/V, back pain
Edema
Severe hypertension (renal failure patients)
Seizures
Allergic reactions
Black Box Warnings
Shortened time to tumor progession & increased mortality in breast, cervical, head & neck, lymphoid, & non-small cell lung cancer, especially when targeting Hgb >12 g/dL
Increased risk of death and serious cardiovascular & thromboembolic events in renal failure patients targeting higher Hgb (≥ 13.5 vs. > 10)
Erythropoetic agents (Epoetin Alfa (Procrit®, Epogen®), Darbopoetin Alfa (Aranesp®))- BLACK BOX WARNING!!!!
Shortened time to tumor progession & increased mortality in breast, cervical, head & neck, lymphoid, & non-small cell lung cancer, especially when targeting Hgb >12 g/dL
Increased risk of death and serious cardiovascular & thromboembolic events in renal failure patients targeting higher Hgb (≥ 13.5 vs. > 10)
