11-9 Understanding Anemia Flashcards
What is anemia? What is it not?
What it is:
a decrease in blood red cell mass or hemoglobin which results in a decreased oxygen-carrying capacity - a symptom
What it isn’t:
a disease, syndrome, or specific diagnosis
How is anemia defined?
Anemia is a laboratory measurement indicating the red cell mass measurement (Hgb or Hct) in a patient is:
< than 2.5 percentile value of reference range
determined by each testing laboratory based on:
ØAge and sex
ØAnalytical technique used by testing laboratory
ØGeographic factors such as location (altitude)
When thinking of how anemia is defined in a graph, what should you think of?
Something like this:
What are some of the main symptoms of anemia?
Fatigue
pallor - especially of conjunctiva and palmar creases
What are the symptoms of severe anemia?
Fainting
chest pain
angina
heart attack
How can anemia affect the eyes?
causes yellowing, and pale conjunctiva
How can anemia affect the skin?
Causes paleness, coldness and yellowing
How can anemia affect the respiratory system?
Causes shortness of breath
How can anemia affect the muscular system?
weakness
How can anemia affect the intestinal/GI system?
changed stool color
How can anemia affect the CNS?
Causes fatigue, dizziness, fainting if severe
How can anemia affect the blood vessels?
low blood pressure
How can anemia affect the heart?
palpitations
rapid heart rate
chest pain, angina, heart attack if severe
How can anemia affect the spleen?
enlargement
What are 3 reasons to be anemic?
Blood loss
increased destruction (hemolysis)
decreased RBC production
What are the mechanisms behind blood loss causing anemia?
acute and chronic (kind of a gimme card)
What are some specific examples of acute and chronic blood loss?
Acute: trauma
chronic: GI tract lesions, gynecological disturbances
Increased red cell destruction causing anemia can be the result of what general mechanisms?
Inherited genetic defects
acquired genetic defects
antibody-mediated destruction
microangiopathic hemolytic anemias
infections of red cells
toxic or chemical injury
membrane lipid anomalies
sequestration
Anemia can be caused by hemolysis from inherited genetic defects. What are some examples of these, and the specific disorders that cause them?
Red cell membrane disorders - ie Hereditary spherocytosis, hereditary elliptocytosis
Enzyme deficiencies
Hexose monophosphate enzyme deficiencies - ie G6PD deficiency, glutathione synthetase deficiency
Glycolytic enzyme deficiencies - ie Pyruvate kinase deficiency, hexokinase deficiency
Hemoglobin abnormalities
Deficient globin synthesis - thalassemia syndromes
Structurally abnormal globins (Hemoglobinopathies) - sickle cell disease, unstable Hbs
Acquired genetic defects can also cause anemia through hemolysis. What is a specific mechanism and disease here?
Deficiency of phosphatidylinositol-linked glycoproteins
- Paroxysmal nocturnal hemoglobinuria
Ab mediated destruction is a cause of hemolysis resulting in anemia. What are some specific examples?
Hemolytic disease of the newborn (Rh disease), transfusion reactions, drug-induced, autoimmune disorders
Microangiopathic hemolytic anemias can cause anemia via hemolysis. What are some mechanisms and specific examples?
Hemolytic uremic syndrome, disseminated intravascular coagulation, thrombotic thrombocytopenia purpura
Cardiac traumatic hemolysis - via defective cardiac valves
Repetitive physical trauma - via bongo drumming, marathon running, karate chopping
What infections can cause increased hemolysis, resulting in anemia?
malaria, babesiosis
What toxic or chemical injuries can result in hemolytic anemia?
Clostridial sepsis, snake venom, lead poisoning
What membrane lipid abnormalities can result in hemolytic anemia?
Abetalipoproteinemia, severe hepatocellular liver disease
What type of sequestration can result in hemolytic anemia?
hypersplenism
What are some causes of decreased red cell production?
Inherited genetic defects
Nutritional deficiencies
Erythropoietin deficiency
Immune-mediated injury of progenitors
Inflammation-mediated Fe sequestration
Primary hematopoietic neoplasms
Space-occupying marrow lesions
Infections of red cell progenitors
Unknown mechanisms
What are the specific diseases behind some of the causes of decreased red cell production resulting in anemia? (sorry for awkward wording)
Inherited genetic defects - defects leading to stem cell depletion - ie Fanconi anemia, telomerase defects; or defects affecting erythroblast maturation (thalassemia syndromes)
Nutritional deficiencies - B12 or folate (affects DNA synthesis) or Fe deficiency (affects Hb synthesis)
Erythropoietin deficiency - Renal failure, anemia of chronic disease
Immune-mediated injury of progenitors - Aplastic anemia, pure red cell aplasia
Inflammation-mediated Fe sequestration - Anemia of chronic disease
Primary hematopoietic neoplasms - Acute leukemia, myelodysplasia,
myeloproliferative disorders
Space-occupying marrow lesions - Metastatic neoplasms, granulomatous disease
Infections of red cell progenitors - Parvovirus B19 infection
Unknown mechanisms - Endocrine disorders, hepatocellular liver disease
What is MCV?
A red cell index useful in evaluation of anemia:
MCV = mean cell volume = average 10,000 measured red cells
Average red cell volume in femtoliters (fL)
reference range 80 - 100 fL
What are the 3 categories of MCV?
Microcytic = Decreased MCV
Low 60 –80 fL
Markedly low < 60 fL
Normocytic = Normal MCV 80-100 fL
Macrocytic = High MCV > 100 fL
What should you consider if someone has microcytic anemia?
Fe deficiency anemia
Thalassemic disorders
Anemia of inflammation/anemia of chronic disease (late; uncommon)
Sideroblastic anemia (eg, congenital, lead, alcohol, drugs; uncommon)
Cu deficiency, Zn poisoning (rare)
What dx’s should you consider if normocytic anemia is present?
Acute blood loss
Fe deficiency anemia (early)
Anemia of inflammation/of chronic disease (eg infection, inflammation, malignancy)
Bone marrow suppression (may also be macrocytic):
- BM invasion (eg leukoerythroblastic blood picture)
- Acquired pure red cell aplasia
- aplastic anemia
Chronic renal insufficiency
Endocrine dysfunction (hypthyroidism, hypopituitarism)
What are some dx’s you should consider for macrocytic anemia?
EtOH abuse
Folate deficiency
Vitamin B12 deficiency
Myelodysplastic syndromes
Acute Myeloid leukemias (eg erythroleukemia)
Reticulocytosis (hemolytic anemia, response to blood loss, response to appropriate nutrient - folate, B12, Fe)
Drug induced anemia (eg hydroxyurea, AZT, chemotherapeutic agents)
Liver disease
What is MCHC?
Mean cell hemoglobin concentration:
average hemoglobin concentration in a volume of red cells in grams/dL; surrogate measure of hemoglobin concentration within an average sized red cell.
Reference Range = 33 - 37 gm/dL
What is a relevant measure for chromaticity?
MCHC is relevant value for “chromaticity” (Hgb concentration)
How are red cells described in anemia?
“Chromic” designations are coupled with size as a second important quantitative measure of individual red cells in anemia.
When is “chromic” listed in anemia?
v“Chromic” is listed before red cell size when using RBC indices to characterize the red cells present in an anemia. For example, iron deficiency anemia is a: Hypochromic Microcytic Anemia
When is normochromic used?
“Normochromic” less frequently used; usually used in context of “Normochromic Normocytic” anemia, indicating red cells have normal amounts of hemoglobin and are of normal size… seen in hemolytic anemia
What is the exception for chromic?
“Chromic” designation not used for macrocytic; MCHC values are invariably low because relative hemoglobin production is not increased at a rate greater than the red cell increases in size.
What is a reticulocyte?
Reticulocyte: Immature erythrocytes contain remnant endoplasmic reticulum & ribosomes (Rough ER) that forms a reticulum (net) within RBC cytoplasm
What stains reticulocytes?
This remnant Ribosomal RNA reticulum stains blue with Methylene Blue
How do reticulocytes differ from typical RBCs?
Reticulocytes are 20-30% larger than mature red blood cells and circulate for 2-3 days before all remnants of the ribosomal-endoplasmic structures are extruded.
How much of the typical RBC population is made up of reticulocytes?
2%
Why do reticulocytes have residual RNA? When is it lost?
young red cells released from the bone marrow into the peripheral circulation that have residual ribosomal RNA. This ribosomal RNA is extruded during the first 24 to 36 hours of circulation
How are reticulocytes measured?
This residual RNA allows detection and measurement of reticulocytes as a distinct population.
What does the reticulocyte population give insight to?
Reticulocyte levels as a percentage of the peripheral red cell population provide a measure of the rate of production and release of red cells by the marrow into the peripheral blood.
What are the reference ranges for reticulocytes counts?
Reticulocyte Count:
adult reference range - 0.5 -1.5%
pediatric reference range – 3.0-7.0%
When should reticulocyte count increase?
Reticulocyte production should increase in response to any loss of red blood cells
When should reticulocytosis be present?
release of reticulocytes from marrow into peripheral blood should increase (reticulocytosis) 3-4 days after an episode of acute hemorrhage
When should reticulocyte counts peak?
The degree of reticulocytosis (reticulocyte count) should peak in 6-10 days after hemorrhage.
What should the relative concentration of reticulocytes be at peak reticulocytosis?
the relative concentration of reticulocytes may increase 4 to 6 fold with reticulocyte count increased to 6 - 8%
If a patient is anemic, how should their reticulocyte count be considered?
In anemia, reticulocyte count is “corrected” to adjust for the decreased existing number of red cells in the peripheral blood:
Reticulocyte Index = Reticulocyte Count X Patient Hematocrit
45% (normal Hct)
What are some common causes of reticulocytosis?
Acute blood loss or hemorrhage
Acute hemolysis
Hemolytic anemia
Response to therapy (Fe or other
nutritional correction of deficiency)
What’s this?
microcytic anemia
What is the diagnostic algorithm for microcytic anemia?
What are some common causes of microcytic anemia?
Iron Deficiency
Iron Deficiency Anemia
Anemia of Chronic Disease
Impairment Globin Synthesis
Alpha Thalassemia
Beta Thalassemia
Decreased/Abnormal Synthesis Protopoporphyrin-Heme
Lead Intoxication anemia
Sideroblastic anemia
Abnormal Hemoglobin
Hemoglobin C Disease
What should serum Fe, TIBC, solbule transferrin receptor (sTfR) and ferritin levels be for hypochromic, microcytic anemia?
•Hypochromic, Microcytic
–Serum Fe (50-170μg/dL)
–Total Iron Binding Capacity (TIBC) (250-400μg/dL)
–Soluble Transferrin Receptor (sTfR) (2-5mg/L)
–Ferritin (20-250ng/mL)
How should Fe deficiency anemia, anemia of chronic disease, and sideroblastic anemia change present as far as:
ferritin
TIBC
serum iron
sTfR
tests for changes in:
How should hypochromic, microcytic anemia be tested?
–Hemoglobin electrophoresis
•Hemoglobinopathies: thalassemias, hgb S, C
–Lead level
–Prussian blue Fe stain for ring sideroblasts in marrow
What’s this?
Normocytic
What is a diagnostic algorithm for normocytic anemia?
What are some common causes of normocytic anemia?
Acute Blood Loss
Autoimmune Hemolytic
Anemia of Chronic Disease
Infection
Inflammation
Malignancy
Anemia of Chronic Renal Failure
Bone Marrow Failure
Aplastic Anemia
Marrow Replacement
fibrosis/malignancy
Sickle Cell Anemia
What should you test for in normocytic anemia?
–CBC
- Reticulocytes (0.5-1.5%)
- Serum Fe
- TIBC
- Peripheral smear review
What’s this?
Hemolytic anemia - a normocytic anemia
What are some common categories of extravascular destruction of RBCs in an adult?
intrinsic red blood cell defects
extrinsic red blood cell defects
What are some examples of intrinsic red blood cell defects taht cause extravascular destruction of RBCs in adults?
Enzyme deficiencies (eg, G6PD or pyruvate kinase deficiencies)
Hemoglobinopathies (eg, sickle cell disease, thalassemias, unstable hemoglobins)
membrane defects (eg hereditary spherocytosis, elliptocytosis)
What are some specific examples of extrinsic red blood cell defects that cause extravascular destruction of red blood cells in adults?
Liver disease
Hypersplenism
Infections (eg, Bartonella, Babesia, Malaria)
Oxidants (eg, dapsone, nitrites, aniline dyes)
Other agents (eg lead, copper, snake and spider bites)
Large granular lymphocytic leukemia
Autoimmune hemolytic anemia (warm or cold-reacting, drugs)
Intravenous immune globulin infusion
What are some common causes of intravascular destruction of RBCs in adults?
Microangiopathic hemolytic anemia (eg, TTP, HUS, aortic stenosis, prosthetic valve leak)
Transfusion reactions (eg, ABO incompability)
Infection (eg clostridial sepsis, severe malaria)
Paroxysmal cold hemoglobinuria; cold agglutinin disease (on occasion)
paroxysmal nocturnal hemoglobinuria
Following IV infusion of Rho(D) immune globulin
Following IV infusion with hypotonic solutions
snake bites
Exposure to compounds with high oxidant potential (eg Cooper in Wilson’s Disease)
What should you test for in laboratory analysis of hemolytic anemias?
Reticulocytes
Coombs Test
Haptoglobin
Hb electrophoresis
Bilirubin
RDW
Peripheral smear
In lab Dx of hemolytic anemia, what should the following be testing for:
Reticulocytes
Coombs Test
Haptoglobin
Hb electrophoresis
Bilirubin
RDW
Peripheral smear
What will the results be?
How is the Direct Coombs test done?
Blood sample is taken from patient with immune-mediated hemolytic anemia, with Ab on the RBC surface.
The patient’s washed RBCs are then incubated with antihuman Ab (Coombs reagent).
RBCs agglutinate: antihuman Ab form links between RBCs by binding to the human Ab on the RBCs.
What’s this?
macrocytic/megaloblastic anemia
What is a diagnostic algorithm for macrocytic anemia?
What does megaloblastic mean?
For our purposes, Megaloblastic = Macrocytic
The term megaloblastic describes marrow changes in red cell precursors that result in peripheral blood red cells that are macrocytic and oval (macro-ovalocytes)
What are some common causes of macrocytic anemia?
Macrocytic Anemia
vitamin b12 deficiency
Decreased Intake
Inadequate diet, vegetarianism
Impaired Absorption
Intrinsic factor deficiency
Pernicious anemia
Gastrectomy
Malabsorption (Ileal resection)
folic acid deficiency
Decreased Intake: dietary deficiency
ethanol abuse
Impaired Absorption: malabsorption
Increased Loss: hemodialysis
Increased Requirement: pregnancy,
greatly increased hematopoiesis
Impaired Utilization
folic acid antagonists
metabolic inhibitors DNA synthesis
& folate metabolism- methotrexate
How is macrocytic anemia diagnosed with labs?
•Macrocytic (Megaloblastic)
–Reticulocytes
–Peripheral smear
–B12/Folate level
What is an overall algorithm for Dx of anemia?
