2 Anemia Part II Flashcards
1
Q
What factors can vary the clinical presentations of patients with anemia? (5)
A
- Etiology
- Severity
- Onset (acute vs. chronic)
- Age
- Underlying condition of the patient
2
Q
At what Hgb level do symptoms typically start becoming apparent in anemic patients?
A
Hgb < 10
3
Q
Define Macrocytosis
A
RBCs are larger than usual size
MCV > 100
4
Q
What can cause falsely elevated MCV levels? (2)
A
- Large number of reticulocytes
- RBC clumping mimicking larger RBCs
5
Q
Describe the disease process of megaloblastic anemia.
A
Defective DNA synthesis –> Disordered RBC maturation and accumulation of cytoplasmic RNA, reduced cell division –> Larger RBCs
6
Q
Name the 2 types of Megaloblastic Anemia.
A
- B12 deficiency
- Folate deficiency
7
Q
What kinds of medications can cause drug-induced megaloblastic anemia?
A
Meds that interfere with purine and pyrimidine metabolism (AKA that inhibit DNA synthesis)
Examples:
- Hydroxyurea
- Chemotherapies
- Antiretrovirals
8
Q
What is the difference between folate and folic acid? Which one is more bioavailable?
A
Folate = dietary vitamin B9 (occurs naturally)
Folic Acid = synthesized vitamin B9, added to processed foods; more bioavailable!
9
Q
What is the recommended daily intake of folic acid?
A
200-400 ng/day
10
Q
Which foods provide dietary folate?
A
- Fresh leafy veggies
- Citrus fruits
- Meat (beef, liver), Eggs
- Fortified cereals, rice
11
Q
Where does folate absorption primarily occur?
A
Jejunum
12
Q
List some causes of nutritional folate deficiency (7).
Sorry these ones suck :-(
A
- Alcoholism
- Hemodialysis patients
- Elderly patients
- Toward the end of pregnancy
- Anticonvulsant therapy (enzyme inhibition causes decreased folate absorption)
- Malabsorption syndromes (rare)
- Hemolytic anemias
13
Q
What are the clinical features (symptoms) of folic acid deficiency?
A
- Sx related to anemia (duh)
- Glossitis
- Vague GI sx
- NO neurologic abnormalities!
14
Q
A deficiency in WHAT can lead to neural tube defects during pregnancy?
A
Folic Acid!
15
Q
What are the associated lab findings for Folic Acid Deficiency anemia?
A
- Low serum folate level (<150 ng/mL)*
- Elevated homocysteine level
- Normal serum methylmalonic acid (MMA)*
*= different from B12 def. anemia (B12 and folate labs typically ordered together)
16
Q
What will the peripheral smear show w/ Folic Acid Deficiency?
A
-Macro-ovalocytes
-Hypersegmented neutrophils
(very similar to a B12 smear)
17
Q
What is the tx for folic acid def. anemia?
A
- Replacement therapy
- Treat any known underlying causes
- Be sure to r/o coexisting B12 deficiency!!!
18
Q
What is the ‘replacement therapy’ for folic acid deficiency?
A
- 1 mg PO daily (use more in patients w/ malabsorption)
- Recommend taking with food for better absorption
19
Q
Where do we get B12 from?
A
ONLY available from DIET
-Present in all animal products (meat, eggs, milk, etc.)
20
Q
What is the primary cause of B12 def.?
A
Inability to absorb!
21
Q
What is the recommended daily intake for B12?
A
1-2 ng
22
Q
Between folic acid def. and B12 def., which of the stores runs out fastest? About how long does each take?
A
- Folic acid = total body stores SMALL; anemia develops in 4-5 months w/ deprivation
- B12 = body has LARGE stores; typically takes years to develop
23
Q
List some causes of Vitamin B12 def. (5ish)
Sorry these ones suck :-(
A
- Pernicious anemia (MOST COMMON!)
- Decreased intake (freaking Vegans)
- Medications (Metformin, H2 antagonists, PPIs)
- Malabsorption (elderly)
- Any condition which impairs B12 absorption (chronic gastritis, gastric surgery, ileal disease/resection, etc.)
24
Q
What is pernicious anemia (PA)?
A
- Auto-immune disorder caused by an immune mediated destruction/loss of gastric parietal cells
- Results in IMPAIRED IF SECRETION!
25
What are some other associated issues with PA?
- Accompanied by decreased gastric acid secretion
- May be associated w/ other autoimmune diseases
- Atrophic gastritis = Increased risk of gastric cancer
26
What is the clinical presentation/sx of a Vit B12 def?
- Typical sx of anemia
- Glossitis, stomatitis
- GI sx
- NEUROLOGIC AND/OR PSYCHIATRIC ISSUES*** Different from Folic Acid def!
27
What specific neurological sx can Vit B12 def cause? (4) How long are these sx reversible for?
Reversible if treated within 6 MONTHS of onset:
- Decreased vibratory and position sense
- Ataxia (abnormal gait)
- Paresthesias (stocking-glove)
- Confusion/dementia
Vit B12 def = defective myelin synthesis in CNS
28
What are the associated lab findings for Vit B12 Deficiency?
- Elevated macrocytosis
- Occasionally, leukopenia or thrombocytopenia
- Low serum B12 levels***
- Elevated Homocysteine levels AND elevated serum MMA levels***
- If pernicious anemia present: Antibodies to IF and/or parietal cells + Increased gastrin
29
What will the peripheral smear show w/ Vit B12 Deficiency?
-Macro-ovalocytes
-Hypersegmented neutrophils
-Anisocytosis (size)
-Poikilocytosis (shape)
(very similar to folic acid def. smear)
30
What is the tx for Vit B12 def?
- Parenteral Vit B12 (Daily IM/SQ injections of 1000ng for 1 week, THEN weekly injections for 1 month, THEN monthly injections for life)
- Treat reversible causes
- PO repletion for mild disease, depending on cause
- Monitor potassium w/ tx
31
Why is it so important to differentiate between Vit B12 def and Folic Acid def (or both)?
- Folate replacement will correct blood picture of Vit B12 def, BUT...
- If Vit B12 also not replaced, pt may develop SERIOUS, POSSIBLY IRREVERSIBLE NEUROLOGICAL DAMAGE = "subacute combined degeneration of the spinal cord"
32
Describe the disease process behind hemolytic anemias.
- Hemolysis = destruction of RBC
- Hemolytic anemia = decreased RBC survival time
- Bone marrow cannot compensate for RBC survival time of <20 days!
33
What are the clinical features of hemolytic anemia? (4)
- Typical anemia sx
- Jaundice
- Gallstones (usually billirubin stones)
- Dark urine
34
What are the lab findings for hemolytic anemia in general?
- Anemia with increased reticulocyte count w/ polychromasia
- Increased unconjugated bilirubin
- Increase serum lactate dehydrogenase (LDH)
- +/- hemoglobinuria/urine hemosiderin
35
What will the peripheral smear show w/ hemolytic anemia?
- Immature RBCs
- Nucleated RBCs
- Schistocytes (fragmented RBCs)
36
What is a unique lab finding with intravascular hemoylsis HA?
Decreased serum haptoglobin
| Binds Hgb released from lysed RBC = decrease free haptoglobin
37
Which test can we use to differentiate between the hemolytic anemias?
Direct antiglobulin (Coombs) test (DAT)
38
Define extravascular hemoylsis (HA).
Destruction of RBCs in the reticuloendothelial system:
- Spleen!!!!
- Liver
- Lymph nodes
- Bone marrow
39
What can the destruction of RBC in the reticuloendothelial system (ex: spleen) result in?
Extravascular hemolysis
40
What disorder puts a patient at risk fro episodic hemolytic anemia?
-Pts with G6PD deficiency (x-linked recessive disorder)
41
Why are pts with G6PD at risk for hemolytic anemia?
Deficiency of protective enzyme against oxidative stress = oxidative stress = episodic hemolytic anemia
42
What are the oxidative stress triggers for pts with G6PD def?
- Drugs: sulfa, antimalarials
- Infections
- Fava beans
43
What are the clinical features of pts with G6PD def. related to hemolytic anemia?
No oxidative stress: asymptomatic, usually no splenomegaly
At times of episodic hemolysis:
- Back or abdominal pain
- Sx of anemia
- Splenomegaly due to RBC sequestration
- Jaundice
44
What are the associated lab findings for G6PD def. related to hemolytic anemia?
MUST BE TAKEN DURING HEMOLYTIC EPISODE...
- Increased reticulocytes
- Increased indirect bilirubin
- Low G6PD levels
45
What will the peripheral smear show w/ a G6PD hemolytic episode?
- Bite cells
| - HEINZ BODIES (denatured Hgb)
46
Tx for G6PD def. hemolytic episode?
- Self-limited (resolves as RBCs are replaced)
| - Avoid oxidative drugs
47
What is hereditary spherocytosis? What does it do the RBCs?
- Autosomal dominant disorder w/ mild hemolytic anemia
- RBCs maintain normal MCV but have a smaller surface area
- Have increased cell fragility (get trapped inside spleen then phagocytized by splenic macrophages)
48
In regards to hereditary spherocytosis, what is different about patients who have undergone a splenectomy?
RBC life-span is normal (RBC life-span reduced if they still have a spleen)
49
What are the clinical features/sx of hereditary spherocytosis?
- Often asymptomatic; adapt well
- May have mild jaundice/scleral icterus
- Pigmented black gallstones!***
- Splenomegaly
- Chronic hemolysis creates need for increased folate (inadequate intake = megaloblastic anemia)
50
What are the lab findings associated with hereditary spherocytosis?
- Negative Coombs
- Hyperchromic microcytosis
- Osmotic Fragility test: RBCs demonstrate increased hemolysis on exposure to hypotonic fluid due to RBC membrane defect
- RBCs are dense w/ globular appearance and lack central pallor
51
What is the tx for hereditary spherocytosis?
SPLENECTOMY!
| -Tx of choice for severe disease
52
What is a risk for pts w/ hereditary spherocytosis undergoing a splenectomy? How can you help this?
Asplenia = increased risk of infection
- Important to ensure they have appropriate pneumococcal vaccinations
- Delay splenectomy until adulthood, if possible
- Folate supplementation in the meantime
53
What is sickle cell disease?
Autosomal recessive disorder which affects Hgb structure; RBCs become sickle shaped when deoxygenated, causing painful symptoms
- Homozygous form: Hb SS = disease sx
- Heterozygous form: HbS + HbA = carrier
54
What are the signs/sx of sickle cell anemia in childhood?
- Initial sx often swelling of the digits
- Delayed growth and development
- Usually starts at age 4-6 mos (Hgb F switching to adult Hgb)
55
What type of infection can cause an aplastic crisis in a pt with sickle cell anemia?
Parvovirus B19 infection
56
What are 3 hypoxic conditions that put patients with sickle cell anemia at risk?
- Dehydration
- High altitude
- Intense exercise
57
What are the clinical features of sickle cell disease?
- Chronic hemolysis
- Vaso-occlusive ischemic tissue injury
- CHF, pulmonary HTN, dyspnea
58
What can occur w/ chronic hemolysis in patients with SCD?
Aplastic crisis = sudden decrease in Hgb (life threatening!)
59
What can occur w/ vaso-occlusive ischemic tissue injuries in patients with SCD?
-PAIN CRISIS (most common feature of this disease)
-ACUTE CHEST SYNDROME
^^^Know these 2 for sure. Can also have
-Osteonecrosis of femoral head and humeral head
-CVA, MI
-Splenic infarcts due to functional asplenia
-Skin ulcers (tibia common location)
-Renal infarcts resulting in inability to concentrate urine
60
What are the lab findings associated with SCD?
- Normocytic, normochrmoic anemia
- Increased reticulocyte count
- Thrombocytosis may be present
- Hgb electrophoresis!!!! Reveals HbS
61
What is the best test to confirm SCD diagnosis?
Hgb electrophoresis
62
What will be seen on peripheral smear in patient with SCD?
- A few sickled RBCs
- Nucleated RBCs
- Target cells
- HOWELL-JOLLY BODIES (but not specific to SCD)
- Thrombocytosis
63
What is the tx for SCD?
- Avoid precipitating factors
- Analgesics, fluids, and O2 during pain crisis***
- Hydroxyurea (chemo) to decrease incidence of painful crises***
- RBC transfusions if needed
- Vaccination against encapsulated organisms
- Folate supplementation
- Bone marrow transplant (only current curative tx)
64
What is the cause of Autoimmune Hemolytic Anemia (AIHA)?
- Autoantibodies adhere to surface of RBCs > Induce hemolysis
- RBCs w/ Ag:Ab complex are phagocytized by macrophages > spherocytes formed > become smaller and are destroyed in the spleen
65
What is the difference between primary vs. secondary AIHA?
Primary: No underlying systemic disorder
Secondary: Identifiable underlying systemic illness
66
Name the 2 different autoantibodies that determine the clinical manifestations of AIHA?
IgM: Cold agglutinins
IgG: Warm agglutinins
67
What are patients with AIHA at increased risk for?
VTE
68
What are causes/associated conditions for AIHA? (6)
- Autoimmune or connective tissue disorders (SLE, RA, etc.)***
- Hematologic malignancy (CLL)***
- Infection (Mycoplasma*, EBV*, HIV)
- Immunodeficiency (prior organ/stem cell transplant)
- Prior blood transfusion
- Drugs
69
What are the clinical features/symptoms of AIHA? (5ish)
- Typical sx of hemolytic anemia (Pallor, jaundice, splenomegaly)
- General: fevers, fatigue, weakness, dyspnea
- Lymphadenopathy
- Hemoglobinuria - dark urine
- Acrocyanosis - dark purple to gray discoloration of fingertips, toes, or nose in exposure to cold
70
What are the lab findings for AIHA?
- Peripheral smear: Polychromasia, spherocytosis, and nucleated RBC
- Positive Coombs (DAT) test (if RBC stick together = + test)
71
What does tx of AIHA depend on?
- Warm vs cold disease
| - Age
72
What is the tx for cold AIHA?
- Cold does not typically need to be treated in most children (mild to self-limited)
- Avoid cold exposure!!!
- Rituximab
- Plasmapheresis if necessary
73
What is the tx for warm AIHA?
- FIRST LINE: Corticosteroids!
- Rituximab
- Splenectomy
- Immunosuppressants, IV immunglobin
74
How does Rituximab (AIHA tx) work?
Ab that targets B cell lymphocytes
75
What is intravascular hemolysis?
Destruction of RBCs within the blood stream
76
What is fragmentation syndrome? What is seen on a peripheral smear?
- Type of intravascular hemolysis caused by mechanical heart valve
- Peripheral smear shows schistocytes (fragmented RBC)
77
What causes a hemolytic transfusion reaction?
Abs to RBCs directed against the ABO/Rh blood grouping antigens
(RBCs attacked following transfusion)
78
Along with a blood transfusion reaction, what else might cause a hemolytic transfusion reaction?
Hemolytic disease of the newborn (HDN) seen in erythroblastosis fetalis
79
Which test can detect antibodies that coat a patient's transfused RBCs?
Coombs test
80
During what time period can a hemolytic transfusion reaction occur?
- During or within 4 hours of transfusion
| - Delayed rxns can occur up to 4 weeks later
81
What are the sx of a hemolytic transfusion reaction? (8)
- FEVER
- Severe hypotension
- Severe flank pain
- Hemoglobinuria
- Pain at infusion site
- Chest tightness
- DIC (oozing from IV site)
- N/V/D
82
What is paroxysmal nocturnal hemoglobinuria?
RARE acquired stem cell mutation resulting in complement mediate RBC lysis
83
What are the clinical features of paroxysmal nocturnal hemoglobinuria?
- Hemolytic anemia
- Dark cola-colored urine at night/early AM w/ partial clearing during the day
- Venous thrombosis of large vessels
- Pancytopenia
84
How do you dx paroxysmal nocturnal hemoglobinuria?
- Flow cytometry
- Osmotic fragility test
- Coombs NEGATIVE
85
What is the tx for paroxysmal nocturnal hemoglobinuria?
- Monoclonal Ab against complement C5
- Steroids
- Stem cell transplant
86
Describe aplastic anemia.
Acquired abnormality of hematopoietic stem cells
| -May be total, or selective for RBCs, WBCs, or platelets
87
What are the causes of aplastic anemia? (4)
- 50% of cases are IDIOPATHIC***
- Chemical/drug exposure (benzene, chloramphenicol, chemo)
- Associated w/ viral illness (Epstein-Barr, cytomegalovirus, hepatitis)
- Ionizing radiation
88
What are the clinical features/symptoms of aplastic anemia? (5)
- Pancytopenia is the hallmark!!! (anemia, leukopenia, thrombocytopenia)
- Bone marrow: absence of precursors for normoblast, granulocyte, and megkaryocyte cells
- Weakness
- Infections
- Bleeding
89
What is the tx for aplastic anemia?
- Bone marrow transplant = preferred tx! ***
- Immunosuppressants if no BMT
- ID cause, if possible, and treat it
- Differentiate from other serious illnesses that may require different tx
- Hematology referral
- Transfusions as needed
90
What are the causes of normochromic, normocytic anemias with INCREASED reticulocyte count? (2)
- Prior or recent hemorrhage
| - Recent acute hemolysis (as opposed to chronic hemoylsis)
91
What are the causes of normochromic, normocytic anemias with NORMAL reticulocyte count and NORMAL bone marrow? (3)
- Anemia of chronic disease
- Hypothyroidism
- Liver disease
92
What are the causes of normochromic, normocytic anemias with NORMAL reticulocyte count and ABNORMAL bone marrow? (2)
- Cancers: Myelofibrosis, leukemia, myeloma, metastases
| - Renal failure
