Lecture 1: Anemia Flashcards
Definition of anemia…what classify as anemia in male vs female?
*Decreased hemoglobin (Hgb) concentration or red blood cell (RBC) volume/mass
*World Health Organization defines anemia as:
o Hgb <13 g/L in males
o Hgb <12 g/L in females
Anemia Pathophysiology: Hypoproliferative
*Bone marrow damage
*Iron deficiency
*Decreased stimulation due to: Chronic kidney disease, Inflammation
Anemia Pathophysiology: Maturation Disorders
*Cytoplasmic defects
o Thalassemia
o Iron deficiency
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*Nuclear maturation defect
o Folate deficiency
o Vitamin B12 deficiency
Anemia Pathophysiology: Hemorrhage/hemolysis
*Blood loss
*Intravascular hemolysis
*Autoimmune disease
Clinical Presentation…
Signs and symptoms depend on rate of anemia development, and age and cardiovascular status of the patient… what are some common signs and symp? (GENERAL)
Signs and symptoms specific to anemia cause
1.) Sudden blood loss = cardiorespiratory symptoms
-Chest pain
-Angina
-Fainting
-Palpitations
-Tachycardia
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2.) Iron Deficiency Anemia
-Glossitis
-Koilonychia
-Pica
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3.) Vitamin B12 deficiency (Neurologic symptoms including)
-Neuropathies (numbness, paresthesia)
-Movement disorders (ataxia, diminished vibratory sense, decreased proprioception, imbalance)
-Visual disturbances
-Psychiatric symptoms (irritability, personality changes, memory impairment, depression)
Common Laboratory Tests for Anemia
When assessing patients for anemia…steps on what to do/ assess?
Microcytic Anemia – Iron Deficiency Anemia…what are the causes of iron deficiency?
How to know? Low Hgb, low MCV = Microcytic anemia – consider iron deficiency!
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Iron deficiency = most common nutritional deficiency in developing and developed countries… Common Causes of Iron Deficiency (critical component of treatment revolves around identifying and addressing cause of iron deficiency)
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1.) Inadequate Dietary Intake
Iron poor diets (vegan/vegetarian)
Malnutrition
Disease-related (dementia, psychosis)
Blood Loss —> Acute (e.g. Trauma/GI hemorrhage), Chronic (e.g. heavy menses, blood donations, peptic ulcer disease, inflammatory bowel disease, intestinal cancer, hemorrhoids, GI hemorrhage), Drug-induced bleeding (e.g. NSAIDs, steroids, antiplatelets, anticoagulants)
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2.) Decreased Iron Absorption
High gastric pH (e.g. proton pump inhibitors, achlorhydria)
Gastrointestinal diseases (e.g. celiac disease, inflammatory bowel disease, gastrectomy, gastric bypass, autoimmune gastritis)
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3.) Increased Iron Requirements
Pregnancy
Lactation
Infants
Rapid growth (e.g. adolescence)
Microcytic Anemia – Iron Deficiency Anemia – Lab Findings?
LOW
Hgb, MCV
Reticulocyte count
Serum iron, ferritin, TSAT
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HIGH
TIBC
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NOTE: Heme iron in meat, fish, poultry is 3 times more absorbable than nonheme iron found in vegetables, fruits, dried beans, nuts, grain products, and dietary supplements ( veggie sucks for iron! opt for dah meat!)
Microcytic Anemia Iron Deficiency Anemia – Treatment
o Identify and address source of iron deficiency
o Iron from food unlikely sufficient to replete iron stores in setting of iron deficiency
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Talk about oral iron supplement and dosing
Commonly available salts: ferrous gluconate (11% elemental iron); ferrous sulfate (20% elemental iron); ferrous fumarate (33% elemental iron)
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Recommended dose: evolving – evidence suggests that excessive dosing may be counterproductive (historically dosed 65 to 200 mg elemental iron per day, in two to three divided doses)
* Alternate-day dosing associated with increased fraction iron absorbed (could dose three times a week)
* Giving doses more frequently than once daily does not result in increased iron absorption (daily dosing is acceptable if patient unable to adhere to every other day schedule)
* Appropriate dose not well established
* Approach used by some is to initiate therapy with one tablet/dose, typically 65 mg elemental iron (adjust based on response and adverse effects)
* Could use doses up to 200 mg elemental iron (no increase in fraction iron absorbed, but increased total iron absorbed with every other day dosing)
Microcytic Anemia Iron Deficiency Anemia – Treatment
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Talk about Iron absorption and duration of tx
Oral iron absorption in iron-depleted patients is low (5-28% when taken without food)
Food decreases absorption by as much as 50% (2-13% when supplement taken with food in iron-depleted patients,) best to take on an empty stomach (1h before/2h after meals) – however many patients experience GI symptoms with oral iron products
Increased absorption in acidic environment – ascorbic acid/vitamin C may enhance absorption to minimal extent (lack of high-quality studies to support practice)
Slow release/Sustained release/Enteric-coated – Iron absorbed in duodenum and upper jejunum; iron released too far distally in the intestinal tract with these special formulations; less GI irritation, but also decreased iron absorption, therefore not recommended as initial therapy (some clinicians prefer not to use at all)
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Treatment duration varies
* 6-8 weeks to normalize hemoglobin concentration
* Up to 6 months to allow for iron stores to return to normal
Microcytic Anemia Iron Deficiency Anemia – Treatment
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Talk about adverse effects and drug interactions of iron
Microcytic Anemia Iron Deficiency Anemia – Treatment
Parenteral Iron indications: intolerance to oral iron (IV iron absent of the GI side effects of iron,) malabsorption, nonadherence, poor response to oral therapy…list some examples
Iron dextran (INFeD)
Iron sucrose (Venofer)
Ferric carboxymaltose (Injectafer)
Ferric derisomaltose (Monoferric)
Ferumoxytol (Feraheme)
Sodium ferric gluconate (Ferrlecit)
Microcytic Anemia Iron Deficiency Anemia – Treatment
Adverse Effects of IV iron
Macrocytic Anemia ( caused by Cyanocobalamin (B12) deficiency OR folate deficiency)…
Macrocytic Anemia – Lab Findings
o LOW hemoglobin and HIGH MCV
o LOW serum levels of B12 and/or folate
…. 3 major causes of B12 deficiency?????????
Macrocytic Anemia ( caused by Cyanocobalamin (B12) deficiency OR folate deficiency)… signs and causes of folate deficiency
Macrocytic Anemia must treat underlying issue… treatment for B12 deficiency?
Early treatment is paramount, if not corrected within months, neurologic effects may be irreversible
Oral vitamin B12 (1000 – 2000 mcg) as effective as parenteral IM injections!!!
Oral vitamin B12 supplementation is effective in patients with pernicious anemia due to presence of alternate passive absorption pathway for B12 that is independent of intrinsic factor. Patients with pernicious anemia need lifelong vitamin B12 supplementation
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Dose: B12 1000 to 2000 mcg po daily for 1-2 weeks then 1000 mcg po daily
B12 injections first line for patients with severe deficiency or neurological symptoms….. Dose 1000 mcg IM daily x 1 week, then weekly for 1 month, then monthly for maintenance.
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Daily oral cyanobalamin may be administered after symptoms resolve and hematologic indices have normalized
Intranasal B12 spray (Nascobal®) efficacy has not been well studied, therefore should only be used for maintenance therapy after hematologic parameters have normalized and absence of nervous system symptoms
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Adverse effects with vitamin B12 are rare
Macrocytic Anemia must treat underlying issue… treatment for Folate deficiency? and AE?
- 1 mg po daily, deficiency related to malabsorption 1-5 mg po daily
- Parenteral folic acid available, rarely necessary
- Therapy continued for about 4 months, long-term folate administration may be needed with chronic conditions or if underlying cause of deficiency cannot be identified/corrected
- Adverse effects – not reported, considered nontoxic at high doses, rapidly excreted in urine
- Folic acid supplementation in women (who may become/plan to become pregnant) – minimum of 0.4 mg (400 mcg) po daily
Normocytic Anemias….Low Hgb, normal MCV must consider that disease states?
Chronic kidney disease
Chronic Infection
Chronic Inflammation
Malignancy
Acute blood loss (surgery, trauma)
Bone marrow failure (aplastic anemia)
Hemolysis
Sickle cell anemia
Normocytic Anemias: Anemia of Chronic Kidney Disease (CKD) -> causes, treatment, AE of tx?
cont…
use lowest effective dose to reduce the need for blood transfusion
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Cancer – Shortened overall survival and/or increased risk of tumor progression or recurrence (especially solid tumors); not indicated when the anticipated outcome is cure
Normocytic Anemias: Anemia of inflammation…common causes, and treatments?
Normocytic Anemias: Aplastic Anemia…..common causes and treatments?
o Bone marrow fails to make enough RBC, WBCs, and platelets
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o Causes:
Drugs (Chemotherapeutics – alkylating agents, antimetabolites, antimitotics); some antibiotics, carbamazepine, methimazole, propylthiouracil
Infectious diseases
Autoimmune disorders
o Risk of developing life-threatening infections or bleeding
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Treatment
Immunosuppressants
Blood transfusions
Stem cell transplant
Eltombopag (Promacta) = thrombopoietin nonpeptide agonist
Approved for treatment of severe aplastic anemia in patients unresponsive to immunosuppressive therapy
Normocytic Anemias: Hemolytic Anemia…causes?
o RBC destroyed and removed from bloodstream before their normal lifespan of 120 days
o Acquired: drug-induced, associated with immune disorder
o Inherited (sickle cell disease, glucose-6-phosphate dehydrogenase deficiency)
o Drug induced hemolytic anemia –> One mechanism involves medication binding to RBC surface and triggering development of antibodies that attack the RBC… This autoimmune reaction can persist for several weeks even after the medication has been discontinued
o Direct Coombs test is used to detect antibodies stuck to the surface of RBCs
o Drugs-Induced Hemolytic Anemia: Beta-lactamase inhibitors, Cephalosporins, Levodopa, Methyldopa, Penicillins – since 2008, piperacillin is the single most common drug to cause drug-induced hemolytic anemia, Platinum-based chemotherapy agents (carboplatin, cisplatin), Quinidine, Quinine, Rifampin, Ribavirin
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o Glucose-6-Phosphate dehydrogenase (G6PD) deficiency…
X-linked recessive genetic disorder that affects RBCs
Most common problem associated with G6PD deficiency is hemolytic anemia. Patients generally asymptomatic unless RBCs exposed to factors that trigger hemolysis.
G6PD is an enzyme that protects RBCs from harmful substances (for example reactive oxygen species). With G6PD deficiency RBCs hemolyze 24-72 h after exposure to oxidative stress
Infections, certain foods (fava beans), severe stress, and certain drugs are factors that can trigger RBC hemolysis
When hemolysis is severe – patients present with weakness, tachycardia, jaundice, hematuria
Once trigger removed, symptoms self-limiting and usually resolve after 8-14 days
High risk medications (if used, should be monitored closely and discontinued if hemolysis develops.): Chloroquine, Dapsone, Methylene blue, Nitrofurantoin, Primaquine, Probenecid, Sulfonamides
Blood Transfusions? When would you opt for that?
Used in the setting of severe/life-threatening anemia with hemodynamic instability and/or evidence of end-organ ischemia
GO OVER CASES!
YES
