Anemia Flashcards
What is anemia?
Decreased number of RBC or less than normal quantity of hemoglobin (Hgb) in the blood
What is the consequence of a reduced hemoglobin count?
Results in decreased oxygen carrying capacity
What is the process of RBC development called?
Erythropoiesis
Where does erythropoiesis take place in adults?
RBC are formed in the bone marrow in the spine, ribs, sternum, clavicle, pelvic crest, ends of long bones
Where does erythropoiesis occur in children?
Most bone marrow space
What is a significant component of RBC’s that give them oxygen carrying abilities?
Hemoglobin (two main components)
Protein component (2 alpha/ 2 beta chains)
Heme: porphyrin ring + iron
Does hemoglobin always contain 2 alpha and 2 beta chains?
No, in fetuses hemoglobin contains alpha and gamma chains (beta chains replace gamma subunits with beta subunits)
What is the main hormone that promotes the development of RBCs (erthropoiesis)?
Erythropoietin
-Stimulates stem cells to differentiate
- Increase release of reticulocytes from bone marrow
- Induces Hb formation
What is the feedback loop mechanism that controls erythropoeisis?
When tissue oxygen concentration is low, signals are sent to the kidney to increase production and secretion of EPO (a erythropoiesis promoter hormone)
What are some conditions that may cause anemia?
- Nutritional deficiencies
- Acute or chronic diseases
- Drug induced
What are the three main causes of anemia?
- Blood Loss
- Inadequate RBC production
- Excessive RBC destruction
What are some causes for blood loss?
Trauma
Ulcers
Hemorrhoids
Any drugs that can increase any of the above (ex. Warfarin)
What are some reasons for inadequate RBC production?
- Nutritional deficiency (vitamin B12, iron, folic acid)
- Erythroblast deficiency (bone marrow failure, or bone marrow infiltration (tumours or cancers)
- Endocrine deficiencies
- Chronic disease (ex. renal, liver, infection)
What are some reasons for excessive RBC destruction?
Autoimmune
Drugs
Infection
How can anemias be classified by RBC size?
- Microcytic (small cell)
- Normocytic
- Macrocytic (large size)
a. megaloblastic
b. non-megablastic
How can anemias be classified by RBC colour?
- Hypochromic (pale)
- Normochromic (normal colour)
- Hyperchromic (darker)
What is the cause of microcytic anemia?
Primarily a result of Hb synthesis failure or Hb insufficiency
- can be due to issues with “heme” portion or the “globin” portion
What is the cause of normocytic anemia?
RBCs are normal sized, but there is a low number of them
- Decreased production
- Increased destruction or loss of RBCs
What is the cause of megaloblastic macrocytic anemia?
Impaired DNA synthesis due to vitamin B12 and folate deficiencies
Slow maturing nuclei (more immature compared to cytoplasm)
What is the cause of non-megaloblastic anemia?
Not caused by impaired DNA synthesis
ex. liver disease
How quickly can anemia develop?
Can be acute or develop slowly
The signs and symptoms associated with anemia are associated with the degree of RBC reduction and how long patient has had anemia
What is the end result of long-standing anemia?
Decreased oxygen carrying capacity of the blood
Symptoms:
- Fatugue, dizziness, weakness, SOB, tachycardia
- Decreased mental acuity
- Pallor (pale skin), cold extremities
How is anemia diagnosed?
- Medical history
- Physical examination
- Laboratory evaluation
What are some important questions to ask about medical history for anemia?
- Past or current bloodwork if available
- Comorbid conditions
- Occupational, environmental, and social history
- Transfusion
- Family history
- Medications (cytotoxic agents, anti retroviral drugs, folate antagonists, immunosuppressants)
What are some physical examination tips for anemia?
- Pallor (pale skin and is easiest to determine from conjuctiva and nail bed)
- Postural hypotension, tachycardia, (hypovolemia - acute blood loss)
- Neurologic findings (B12 deficiency)
- Jaundice (hemolysis)
- Bleeding gums, blood in stool, urine, hemmorhage
What are some useful lab values for anemia?
Complete blood count (CBC)
a. Hemoglobin (Hb)
b. Hematocrit
c. RBC count
d. RBC indices (MCV, MCH, MCHC)
What is hematocrit?
Percentage of blood volume composed of RBCs
What are MCV values?
MCV (mean corpuscular volume)
In simple terms: “Average RBC volume”
What are MCH values?
MCH (mean corpuscular hemoglobin)
In simple terms: “Average mass of hemoglobin/RBCs
What are MCHC values?
MCHC (mean corpuscular hemoglobin concentration)
In simple terms: “average concentration of Hb within a volume of packed RBC”
Increased MCHC = RBCs have darker red colour
What are RDW values?
RDW (Red blood cell distribution width)
RDW describes the range of RBC size in a given sample
What are some lab tests besides CBC done in anemia diagnosis and treatment?
- RBC morphology
- Reticulocye count
- Iron studies
- Peripheral blood smear
- Stool for occult blood
- Bone marrow aspiration and biopsy
What is the definition of anemia by hemoglobin count?
Men: less than 130g/L
Women: less than 120g/L
What factors can shift normal hemoglobin levels?
Age
Elevation (higher elevation = higher hemoglobin)
Smokers (higher hemoglobin)
Pregnancy
What are some characteristics of iron-deficiency anemia?
Most common nutritional deficiency worldwide
Negative state of iron balance in which daily iron intake are unable to meet RBC and other body tissue needs
What are some causes of iron deficiency anemia?
- Lack of dietary intake (vegetarians, vegans)
- Blood loss (menstruation, GI bleeds, trauma)
- Decreased absorption (celiac disease, medication, gastrectomy)
- Increased requirements (infancy, pregnant/lactating women)
- Impaired utilization (hereditary, iron use)
How can iron deficiency anemia be responsible for mortality?
Rarely a direct cause of death
Moderate-severe iron deficiency anemia can cause hypoxia or aggravate underlying pulmonary/CV disorders
What is the impact of iron deficiency anemia in elderly patients?
- Increased risk of hospitalization and mortality
- Decreased quality of life and physical functioning
What is the impact of iron deficiency anemia in pregnant patients?
- Low birth rates
- Pre-term delivery
- Perinatal mortality
Hence all pregnant women should be screened for anemia
Where can iron be found in the body?
Body contains 3-5g of iron (2g are found in hemoglobin)
Significant amount is stored as ferritin in the liver, spleen, bone marrow
Small fraction in plasma (most is bound to transferrin)
What hormone regulates iron metabolism?
Hepicidin
promotes storage of iron (supressed in response to hypoxia or iron deficiency)
What is the iron absorption pathway?
- Fe3+ (ferric) is obtained from diet
- Fe3+(ferric) is converted into Fe2+ (ferrous) iron in the stomoach due to acidity
- Fe2+ is absorbed by the small intestine via active transport
- Once abssorbed, free iron binds to a transferrin (transport protein)
- Iron from transferrins is incorportated into hemoglobin or storage as ferritin
What is serum iron?
Concentration of iron bound to transferrin
Best interpreted from TIBC (total iron binding capacity) values
If iron stores are low, TIBC is high and vice versa
What is ferritin?
It is storage iron
Most sensitive, but non-specific and is elevated in inflammatory conditions, liver disorders
What does the Tsat value represent?
Tsat (% transferrin saturation)
A measure of how much serum iron is actually bound
What are some expected lab values in iron deficiency anemia?
Decreases seen in the following:
Ferritin
Serum iron
Transferrin
Hb and Hematocit (delayed decline)
Increases in the following;
TIBC
RBC morphology:
Decreased MCV (microcytic)
Decreased MCHC (hypochromic)
What are the two main sources of iron?
Heme iron:
- Derived from animal proteins
- Better absorbed, more consistent absorption
- Less affected by dietary factors
Non-heme iron:
- Plant sources
- Fruits and vegetables, nuts, beans, grains, iron-fortified foods (lower absorption rate)
- Requires acidic GI pH for absorption (conversion from Fe3+ to Fe2+)
What are some substances/food that can limit iron absorption?
Phytates (grains, brans)
Polyphenols/tannins (coffee/tea)
Calcium and other ions
H2 receptor agonsists + PPIs (reduce stomach acidity which limits Fe3+ conversion to Fe2+)
Gasterectomy/bariatric surgery/achlorhydria
What are some factors that can cause improved iron absorption?
- Increased stomach acidity
- Eating heme and non-heme sources at the same time
- Cook with cast-iron or stainless steel pots/pans (increases amount on non-heme iron)
What are the iron demands for pregnant women?
27mg
What are some iron-deficiency anemia specific symptoms?
- Typical anemia symptoms
Other special symptoms:
- Brittle, spoon-shaped nails
- Pica (cravings for chalk, dirt sand)
- Pagophagia (compulsion to eat ice)
- Smooth tongue
What dosage forms does iron come prepared as?
- Tablets (most common)
- Liquid (often used in pediatrics)
- IV (only used when oral dosage forms are not effective)
Are enteric coated iron tablets useful clinically?
No, by the time the enteric coating is erroded, the tablet is no longer in the stomach (region of high iron absorption)
What are the elemental iron levels in iron tablets?
Ferrous gluconate (11%)
Ferrous sulfate (20%)
Ferrous fumerate (33%)
What are some side effects associated with oral iron supplementation?
- N/V, constipations (sometimes diarrhea)
- Dark stools (warn patients)
What are some instructions for taking oral iron supplements?
- Remembering to take on empty stomach (best absorption)
- How to take iron in relation to other meds
- Avoiding interactions with other foods/drinks/meds/minerals
How are iron doses in pediatrics determined?
weight based (depending on severity of anemia)
3-6mg/kg/day
What are some side effects associated with iron poisoning?
- Severe vomiting
- Diarrhea
- Abdominal pain
- Dehydration and lethargy
- Bloody vomit or stool
What are some modification to iron supplementation therapy to help improve tolerability?
- Lower dose (longer to correct anemia)
- Taper up dose (help build tolerance)
- Alternate day dosing
- Take with food
- Take before bed
What is the most common type of iron used for IV supplementation?
Iron Sucrose (20mg elemental iron/mL)
What are some side effects associated with IV iron supplementation?
- Systemic reactions (mylagias/arthralgias)
- N/V
- Flushing
- Itching
- Fever
- Injection-site reactions
Can be managed by reducing infusion rate
What are some characteristics of Vitamin B12?
Vitamin B12 is required for proper RBC formation, neurological function, and DNA synthesis
- The body can’t make it, so it must be consumed
- Large stores in the liver & low daily requirements (but can be slowly depleted)
What are some sources of Vitamin B12?
Everything that walks, swims, or flies contains B12
Plants do not contain B12 naturally, unless fortified
How is most Vitamin B12 absorbed into the body?
B12 is bound to proteins in food
Stomach acid breaks the B12-protein complex and now B12 is free
Intrinsic factor (aids B12 transport within the GI tract) released by the stomach binds to free VItamin 12
Once in the small intestine, B12 and intrinsic factor separate. The free B12 binds to trans-cobalmain II (helps move B12 into the blood)
What is the alternate absorption pathway for Vitamin B12?
Some Vitamin B12 can be absorbed via diffusion (1%) and occurs only when large amounts of Vitamin B12 are ingested
What are some causes of Vitamin B12 deficiency?
- Inadequate intake
- Malabsorption (age, pernicious anemia, limited stomach activity)
- Inadequate utilization (ex. inhibition of transcobalmain)
What is intrinsic factor deficiency (pernicious anemia)?
It is an autoimmune disease that affects the gastric mucosa due to the destruction of parietal cells, achlorhydria, and intrinsic factor deficiency
This results in a reduced absorption of Vitamin B12, causing pernicious anemia
What are the consequences of pernicious anemia?
Causes intrinsic factor deficiency (malabsorption of Vitamin B12)
Associated with increased risk of gastric cancer
What are some symptoms associated with Vitamin B12-deficiency anemia?
Typical anemia symptoms + neurological symptoms (numbness, diffoculty maintaining balance, depression)
What are some factors that can cause Vitamin B12 deficiency?
- Diet (vegans must use B12 supplements)
- Age
- Any GI surgery, intestinal disease, etc
Drugs
- H2RAs & PPIs (reduce stomach acidity = B12 malabsorption)
- Colchicine (used for gout)
- Metformin
What are some lab changes seen in B12-deficiency anemia?
See decrease in:
- serum or plasma Vitamin B12 levels
See increase in:
- Serum homocysteine level (early)
-Methylmalonic acid (MMA) levels
RBC:
- Macrocytic (Increased MCV)
- Normochromic (normal MCHC)
How are patients screened for pernicious anemia?
Antibodies to intrinsic factor and parietal cells
Why is treating B12 anemia important?
- In infants (failure to thrive, movement disorders, developmental delays)
- Irreversible neurological damage
- Increased homocysteine levels are a risk factors for CV disease and some links to Alzheimer’s
How is Vitamin B12 deficiency treated?
- Correct underlying cause
- Replenish stores
- Reverse symptoms (or slow progression if reversible)
B12 supplementation (cyanocobalamin oral or IM)
IM is used for patients with pernicious anemia
What is a common Vitamin B12 dose given to patients with deficiency, but no pernicious anemia?
Initial treatment:
30ug daily SC/IM x 5-10 days or 500-2000ug daily PO
Life-long treatment:
100-200ug monthly SC/IM or 250ug daily PO
What is a common Vitamin B12 dose for deficiency with more severe symptoms (pernicious anemia, severe malabsorption issues, poor adherance)?
Initial treatment:
100ug daily SC/IM x 1 week; 200ug weekly SC/IM until Hb normalizes
Life-long maintenance:
100ug monthly SC/IM or 1000-2000ug daily PO
What are some disadvantages associated with Vitamin B12 in IM dosage form?
More expensive, inconvienient, injection related side effects
What is folate?
It is a water-soluble B-vitamin (easily destroyed by cooking or processing)
It is not produced by the body, so it must be taken in the diet
A derivative of folate (tetrahydrofolate) is a cofactor in DNA synthesis
What are some good sources of folate?
- Leafy green vegetables
- Fruits (citrus fruit)
- Dried beans and peas
- Beef liver
- Fortified cereals
- Supplements
What are some common DRIs for folate
All Adults (400mcg/day)
Pregnant women (600mcg/day)
Lactating women (500mcg/day)
What are some causes of folate deficiency?
- Inadequate intake
- Increased requirements
- Malabsorption
- Certain drugs (anticonvulsants, metformin, methotrexate, TMP)
What are some symptoms associated with folate-deficiency anemia?
Similar to those seen with B12 deficiency but without neurological symptoms
What happens to lab values in patients with folate-deficiency anemia?
Serum folate (decreases, can be delayed)
Homocysteine (increased)
RBC:
Macrocytic, normochromic (indistinguishable from B12 deficiency)
Why should folate deficiencies be treated?
- Pregnancy (low folate = low birth weight and neural tube defects)
- Children (low folate = slow growth rate)
- General morbidity related to anemia
How is a folate deficiency treated?
Give oral supplements, even in patients with absorption problems
1mg/day of folic acid is usually sufficient
5mg/day is reserved for absorption compromised and drug-induced deficiency
Can take 4 months for folate deficient RBCs to cycle out of the body
What deficiency is seen in tandem with folate deficiency?
Vitamin B12 deficiency can present similarly to folate deficiencies. So it is a good idea to test for both if one of these is suspected
What is hemolytic anemia?
Decreased survival time of RBCs secondary to destruction in the spleen or circulation
- RBC lifespan can be as short as 5 days
RBC:
Usually normocytic and normochromic
- Increased numbers of reticulocytes
What is the cause of Hemolytic Anemia?
Often idiopathic
10% are caused by immune reactions, malignancy, and drugs (ACEi, NSAIDs, antibiotics)
Can be caused by a G6PD enzyme deficiency (an enzyme that usually protects RBCs against oxadative stress)
How is hemolytic anemia treated?
Correcting or controlling the underlying cause (can be difficult as most cases are idiopathic)
Steroids and other immunosuppressive agents have been used for the management of autoimmune hemolytic anemias
Splenectomy is sometimes indicated in an attempt to reduce RBC destruction
What is the cause of sickle cell anemia?
Autosomal recessive Hgb disorder characterized by a DNA substitution at the beta-globulin gene
Resulting in an abnormal type of Hb called hemoglobin S
HbS distorts the shape of RBC, especially when exposed to low oxygen levels
Can cause ischemia, pain, chronic organ damage
What are some symptoms associated with sickle cell anemia?
- Impaired growth and development
- Enlarged spleen
- Chronic damage to many organs
- Vaso-occlusive crises (sludging of sickled cells in microvasculature, occurs with exposure to heat/cold, exercise, infection, stress, high altitude)
What lab tests are used to confirm sickle cell anemia diagnosis?
Hb electrophoresis (HbS present)
RBC:
Normochromic, normocytic
Presence of sickled cells
What is anemia of inflammation?
It is a term used to describe both anemia of chronic disease and anemia of critical illness
Inflammatory process causes disturbances to iron homeostasis
What are some causes of anemia of chronic disease?
Chronic inflammatory, infection, or malignancy
Can occur as early as 1-2 months after the onset of these processes
Treatment is aimed at correcting the underlying pathology
What are some symptoms associated with anemia of chronic disease?
May be mild, non-specific
Hard to differentiate from symptoms associated with concurrent chronic disease
What causes anemia due to CKD?
Erythropoiesis is decreased in patients with CKD (erythropoietin is produced in the kidneys)
What are some symptoms associated with anemia due to CKD?
General anemia symptoms, angina, ischemia on ECG, CHF
How is anemia due to CKD treated?
Iron
Erythropoietin Stimulating Agents (Erythropoeitin or darbepoeitin)
Transfusions
What types of anemia are responsive to the stimulation of erythropoeisis?
- Patients with CKD
- HIV-infected patients receiving anti-retroviral therapy
- Chronic hepatitis C patients receiving ribavirin
- Patients receiving chemotherapy for nonhematologic cancers
- Surgery patients
- Patients with low-rsk myelodysplastic syndrome
What is the prevalence of anemia in patients that are critically ill?
Found almost universally in this patient population
What are some contributing factors for anemia in critically ill patients?
- Sepsis
- Frequent blood samples, surgical blood loss, active bleeding
- Immune-mediated functional iron deficiency
- Decreased erythropoietin (EPO) production
- Reduced RBC life span
What are some lab values for anemia in patients who are critically ill?
Decreases:
- Serum iron, TIBC, iron/TIBC ratio
- Serum ferritin is normal to high
Treatment:
- Address cause of critical illness
- exogenous EPO may or may not improve clinical outcomes
What is aplastic anemia?
Failure of pluripotent stem cells in bone marrow
Hematopoiesis is interrupted
What are some causes of aplastic anemia?
70% of cases are idiopathic
Can be related to toxicity from drugs/chemicals, cognitive defect, viruses
ex. Allopurinol. chloramphenicol, NSAIDs, sulfonamides
- Immune-mediated suppression of stem cell function
What are some symptoms of aplastic anemia?
Variable, depends on which cell line is affected most
- Anemia symptoms (fatigue, pallor)
- Bleeding
- Fever, infection
What are some lab results seen in patients with aplastic anemia?
Normochromic, normocytic RBC
Very low blood counts
What are some treatment options for aplastic anemia?
Supportive care, removal of causative agent
Bone marrow transplant or immunosuppression if not possible
