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Terms in this set (74)
What is the definition of anemia?
below normal spectrum
What are normal ranges of hemoglobin?
Men - 18 - 17 (likely a testosterone effect)
Women 12 - 15.2
What are normal ranges for hematocrit?
39-52% - Men
37-46% - Women
Mean cell volume; SIZE of RBC
What are the types of microcytic anemia?
1. Iron deficiency
3. Sideroblastic disease (lead poisoning)
4. Anemia of chronic disease (could be normacytic)
What is the most common cause of anemia?
What are causes of iron deficiency?
1. chronic blood loss (GI ulcer or menses)
2. Malignancy (in GI tract)_
3. Malabsorption (celiac or achlorhydria)
Iron Panel components
1. Iron levels (decreased in deficiency)
2. Ferritin (decreased in iron deficiency; may be earliest marker)
3. Total iron binding capacity (TIBC; increased in iron deficiency - iron hunger)
4. Percent saturation (decreased in iron deficiency - iron hunger)
What is the nature of Thalassemia?
- Congenital hemoglobin synthesis disorder
- Genetic disorders typically caused by deletions of alpha or beta globin genes (normal is 4 alpha and 2 beta
Defective Hb synthesis causes small red cells and decreased red cell production / increased
What is the hallmark of thalassemia in a smear?
- Microcytosis and target looking RBCs - you can see the bulls eye
How is beta thalassemia diagnosed?
- Hemoglobin electrophoresis
- Hemoglobins are separated by charge and size
What are early physical signs of thalessemia?
- bronze skin
- Others - vertigo, hair loss, memory loss, heart degen, hepatomegaly, elevated liver, testicular atrophy, arthritis
What conditions give rise to sideroblastic anemia?
- Nutritional deficiencies (e.g. copper, zinc, vitamin B6)
- Chronic alcohol use / abuse
- lead poisoning -Lead competes with iron for deposition into heme.
What does the iron panel reflecting sideroblastic anemia look like?
Iron - normal or elevated
TIBC - normal or decreased - capacity for iron incorporation is low
Ferritin - normal or increased
What is the role of ferritin?
Primary iron storage mechanism
How is lead poisoning treated?
Anemia of chronic disease
- Individuals with chronic, typically inflammatory illnesses can develop anemia of chronic disease
- Diseases include autoimmune (SLE), Chronic infectious (Hep C, TB) or Inflammatory immunodeficiency disorders
How is anemia associated with chronic renal insufficiency classified?
- Not typically considered anemia of chronic disease because it is NOT associated with an inflammatory component
- Mechanism is lack of erythropoietin production NOT inflammation
How does inflammation associated with chronic disease result in anemia?
- Believed to inhibit or interfere with iron uptake and transport
- Hepcidin is increased in inflammatory states - likely plays a role by preventing adequate uptake by cells
What values are typical of anemia of chronic disease iron panels?
Iron - normal or elevated
Ferritin - normal or increased
TIBC - normal or decreased
How is anemia of chronic disease treated?
- No specific treatment
- address underlying disease to reduce inflammation and improve anemia
What is the difference between B12 and folate deficiency in presentation?
B12 is associated with Neurological findings - memory loss, loss of vibratory sensation, etc.
What two organs receive less blood flow as a consequence of redistribution of blood flow during anemia via vasoconstriction?
The Skin and Kidneys
*Shunting of blood away from cutaneous sites is the
mechanism behind the clinical finding of pallor, a cardinal sign of anemia.*
What is the normal Mean Corpuscular Volume?
How do you define anemias based on MCV?
What does Mean Corpuscular Hemoglobin Concentration mean and how is it calculated?
What is the normal range?
MCHC is the average concentration of Hemoglobin in the RBC
MCHC = Hemoglobin/Hematocrit
(expressed in g/dL)
Normal = 32-36 g/dL
What is the technical definition of anemia in terms of hemogobin?
<12.5g/dL in females
<13.5g/dL in males
What is the mnemonic for remembering the different types of microcytic anemias?
*Anemia of Chronic Disease
*Iron Deficiency Anemia
What is the most common type of Microcytic Anemia?
Iron Deficiency Anemia
Lab Measurements of Iron Status
Serum Iron: The amount of circulating iron that is bound to transferrin
Total Iron Binding Capacity (TIBC):
Amount of transferrin in the blood
Serrum Ferritin: The amount of ferritin in the blood. This is
directly related to the amount of iron stored in your body
A general principle is that the Serrum Ferritin levels and TIBC levels are inversely related T/F?
as serrum ferritin levels go down, TIBC will go up and viceversa
What percentage of Transferrin is usually saturated?
Clinical features of Iron Deficiency Anemia
*Koilonychia (spoon nails)
Lab Findings of Iron Deficiency Anemia
*Decreased Ferritin, Increased TIBC
*Decreased Serum, Decreased % Saturation
What is the most common type of anemia seen in Hospitalized patients?
Anemia of Chronic Disease
Pathogenesis of Anemia of Chronic Disease
*Hepcidin is an acute phase protein and the primary regulator of iron absorption.
* During inflammatory states, macrophages produce interleukin-6 (IL-6) and interleukin-1 beta (IL-1β), which up-regulate hepatic production of hepcidin.
*Hepcidin causes proteolysis of ferroportin (an iron efflux channel).
* This results in inhibition of iron release from enterocytes and macrophages.
When is hepcidin production increased?
When is hepcidin production decreased?
Hepcidin is increased during inflammatory states and during high iron states
Hepcidin is decreased during low iron states
What are the lab findings of Anemia of Chronic Disease?
*Increase Ferritin (because of increased hepcidin which => inreased storage of iron)
*Decreased Serum Iron; Decreased % Saturation
(can be distinguished from Iron Deficiency Anemia because of the increased ferritin and the decreased TIBC)
What two factors lead to the production of anemia in Anemia of Chronic Disease?
Anemia is caused by the following factors:
Reduced transfer of iron to developing erythroid precursors (due to
hepcidin-induced inhibition of ferroportin)
Inappropriately low levels of erythropoietin and reduced efficiency of erythropoiesis
(due to suppression by inflammatory cytokines such as TNF-α and IL-1β)
Ring sideroblasts are erythroblasts with iron-loaded mitochondria visualized by Prussian blue staining as a perinuclear ring of blue granules
*Iron is transferred to erythroid precursor to make heme
*Enters the mitochondria to bind with protoporphyrin
*If protoporphyrin is deficient (Sideroblastic Anemia), iron remains trapped in the mitochondria
Iron Study findings of Sideroblastic Anemia
Serum ferritin: INCREASED
Serum iron: INCREASED (iron-overload)
Transferrin (%) saturation: INCREASED
Eventually the iron buildup inside the cell => lysis of the cell due to fentin reaction and its free radicals
=> leaked out iron becomes taken up by bone marrow macrophages => INCREASED FERRITIN/ DECREASED TIBC
=> some of the leaked out iron also remains in the serum => INCREASED SERUM IRON/ INCREASED TRANSFERRIN SATURATION
Which other condition has Iron Study Findings that are very similar to that of Sideroblastic Anemia?
Alcoholism and Sideroblastic Anemia
heme synthesis disrupted
most common cause of acquired sideroblastic anemia
Would you expect a high or a low reticulocyte count in sideroblastic anemia ?
Decreased synthesis and increased destruction of RBCs in the marrow would result in a low reticulocyte count
What are the two main considerations in the differential diagnosis of normocytic anemia?
Underproduction or Hemolysis
A corrected Reticulocyte Count
> 3% : indicates good marrow response: Suggests peripheral destruction
<3%: indicates poor marrow response: Suggests underproduction
What assays is the best test to assess the bone marrow's response to anemic stress?
The Reticulocyte Count is falsely elevated with an anemia T/F?
*Reticulocyte count is measured as a percentage of total RBCs
*Decrease in total RBCs (due to anemia) falsely elevates the percentage of reticulocytes
*Corrected by multiplying reticulocyte count by Hct/45
Unconjugated bilirubin is _________ (Water/Fat soluble)
Hemoglobin is _________ (Water/Fat soluble)
Unconjugated Bilirubin is fat soluble
Hemoglobin is water soluble
What is the most common cause of inherited hemolytic anemia in Northern Europeans?
Common Hematology Complaints
Dyspnea on exertion (DOE)
Onset of sx's
Signs of bleeding
-Gums, rectal bleeding, menorrhagia
-Petechiae, purpura, nails
Palpate for lymphadenopathy
Synthesis of blood cells
Pluripotent hematopoietic stem cells in bone marrow divide & differentiate into:
120 day life span
Reticulocyte - precursor to RBC
-Last 4 days; 3 days in bone marrow & 1 day in peripheral blood (lose their reticulum (RNA) & become mature RBC's)
RBC mass decreased in anemia & bleeding
RBC count ≈ 5 million/microL (5.0 x 1012/liter)
Reticulocytes make up ≈ 1% of total circulating RBC's
Bone marrow produces ≈ 50,000 reticulocytes/microL (5 x 1010/liter) of whole blood daily to maintain RBC mass
↑ RBC production w/ high levels of erythropoietin (EPO)
Decreased Hb or Hct
Hb < 13.5 g/dL
(Normal 14 - 18 g/dL)
(> middle age: 12.4 - 14.9 gm/dL)
Hct < 41%
(Normal 40 - 54%)
Hb < 12 g/dL
(Normal 12 - 16 g/dL)
(> middle age: 11.7 - 13.8 gm/dL)
Hct < 36%
(Normal 36 - 48%)
Higher hemoglobin and hematocrit in smokers
-Thalassemia - inherited blood disorder with less hemoglobin and less RBCs
-Sickle cell disease
Iron deficiency anemia
Vit B12 deficiency anemia
Folic Acid (Folate) deficiency
Most common sx's
-Loss of papillae
-Spoon shaped nails in iron def. anemia
Peripheral blood smear
-Serum iron, % sat., TIBC
-Stop iron supplement 24hrs prior to testing
RBC Distribution Width (RDW, RBCDW)
variability of RBC size
Iron Deficiency Anemia
cause of anemia worldwide
Inadequate supply of iron for synthesis of hemoglobin
-GI tract bleeding
-Chronic aspirin or NSAID use
-Menstrual blood loss
-Low iron intake
Iron Deficiency Anemia common causes
Increased Iron Demands
-Pregnancy & lactation
-Heavy menstrual bleeding
Iron Deficiency Anemia signs & sxs
Shortness of breath
Abnormal cravings of nonfood substances (clay, ice, paper)
Spoon shaped nails
Anemia of chronic disease
Normal ferritin level
↓ Serum iron
Significantly ↓ MCV
Normal or ↑ RBC count
↑ serum iron
↑ % iron saturation
Iron Deficiency AnemiaTreatment
Identify cause of anemia
Ferrous sulfate (or glucanate) 325 mg po tid
halfway towards normal w/in 3 weeks
baseline w/in 2 months
Continue Tx up to 6 months to restore iron stores
Cannot be absorbed with presence of caffeine, will increase with vit C
Parenteral iron only if pt's anemia does not improve w/ oral iron
Risk of anaphylaxis
Anemia of Chronic Disease etiology
Anemia asst w/ inflammatory disease &
impaired marrow response to erythropoietin (or not being made) --> cells not made
-Chronic kidney disease (CKD)
Anemia of Chronic Disease Pathophysiology
Impaired marrow function 2° to chronic inflammation, infection or malignancy:
Most common cause
: T cell mediated autoimmune suppression of hematopoiesis
Anemia of Chronic Disease Signs & Sx's
Weakness, fatigue, pallor
Clinical features correspond to those of the causative condition
-Chronic kidney disease (CKD) -->
pts lose iron & folate during hemodialysis
Pts can have co-existing iron def or folate def
Anemia of Chronic Disease Diagnostic Studies
-Normochromic normocytic anemia OR hypochromic microcytic anemia
↓ Serum iron
* (total iron binding capacity)
Serum ferritin normal or ↑
Increased cytokines, decreased erythropoiten
Anemia of Chronic Disease Treatment
Treat underlying disease
CKD --> hemodialysis & erythropoietin
Malignancy --> chemo, radiation therapy, erythropoietin
Autoimmune inflammatory disease (RA) --> NSAIDs, DMARD's, erythropoeitin
DMARDs --> disease modifying antirrheumatic drugs
Methotrexate, etanercept (embrel), infliximab (Remicade)
Hereditary disorders characterized by reduction in synthesis of globin chains
- Alpha thal --> SE Asian & African population
- Beta thal --> Mediterranean descent
Greek or Sicilian
(+) FH of thalassemia
Most prominent feature:
Microcytosis out of proportion to degree of anemia
Thalassemia Diagnostic Studies
- Hb between 3 & 6 gm/dL
- ↓ MCV @ 55-70 fl
- Poikilocytosis, target cells
Serum iron studies normal
Hb electrophoresis - Confirms Dx
Genetic or acquired defective heme synthesis
- Hb synthesis reduced due to inability to synthesize heme
Iron accumulates in mitochondria
Sideroblastic Anemia Etiology
ETOH abuse -
Myelodysplastic syndromes: Disorders of hematopoietic stem cells in bone marrow
Pyridoxine (Vit B6) deficiency
Sideroblastic Anemia Bone Marrow
A. Basophilic stippling (ribosome remnants)
B. Howell Jolly Bodies (DNA remnants)
C. Cabot's rings (mitotic spindle remnants)
D. Heinz bodies (denatured Hb)
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