2 Anemia Part II Flashcards
What factors can vary the clinical presentations of patients with anemia? (5)
- Etiology
- Severity
- Onset (acute vs. chronic)
- Age
- Underlying condition of the patient
At what Hgb level do symptoms typically start becoming apparent in anemic patients?
Hgb < 10
Define Macrocytosis
RBCs are larger than usual size
MCV > 100
What can cause falsely elevated MCV levels? (2)
- Large number of reticulocytes
- RBC clumping mimicking larger RBCs
Describe the disease process of megaloblastic anemia.
Defective DNA synthesis –> Disordered RBC maturation and accumulation of cytoplasmic RNA, reduced cell division –> Larger RBCs
Name the 2 types of Megaloblastic Anemia.
- B12 deficiency
- Folate deficiency
What kinds of medications can cause drug-induced megaloblastic anemia?
Meds that interfere with purine and pyrimidine metabolism (AKA that inhibit DNA synthesis)
Examples:
- Hydroxyurea
- Chemotherapies
- Antiretrovirals
What is the difference between folate and folic acid? Which one is more bioavailable?
Folate = dietary vitamin B9 (occurs naturally)
Folic Acid = synthesized vitamin B9, added to processed foods; more bioavailable!
What is the recommended daily intake of folic acid?
200-400 ng/day
Which foods provide dietary folate?
- Fresh leafy veggies
- Citrus fruits
- Meat (beef, liver), Eggs
- Fortified cereals, rice
Where does folate absorption primarily occur?
Jejunum
List some causes of nutritional folate deficiency (7).
Sorry these ones suck :-(
- Alcoholism
- Hemodialysis patients
- Elderly patients
- Toward the end of pregnancy
- Anticonvulsant therapy (enzyme inhibition causes decreased folate absorption)
- Malabsorption syndromes (rare)
- Hemolytic anemias
What are the clinical features (symptoms) of folic acid deficiency?
- Sx related to anemia (duh)
- Glossitis
- Vague GI sx
- NO neurologic abnormalities!
A deficiency in WHAT can lead to neural tube defects during pregnancy?
Folic Acid!
What are the associated lab findings for Folic Acid Deficiency anemia?
- 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)
What will the peripheral smear show w/ Folic Acid Deficiency?
-Macro-ovalocytes
-Hypersegmented neutrophils
(very similar to a B12 smear)
What is the tx for folic acid def. anemia?
- Replacement therapy
- Treat any known underlying causes
- Be sure to r/o coexisting B12 deficiency!!!
What is the ‘replacement therapy’ for folic acid deficiency?
- 1 mg PO daily (use more in patients w/ malabsorption)
- Recommend taking with food for better absorption
Where do we get B12 from?
ONLY available from DIET
-Present in all animal products (meat, eggs, milk, etc.)
What is the primary cause of B12 def.?
Inability to absorb!
What is the recommended daily intake for B12?
1-2 ng
Between folic acid def. and B12 def., which of the stores runs out fastest? About how long does each take?
- Folic acid = total body stores SMALL; anemia develops in 4-5 months w/ deprivation
- B12 = body has LARGE stores; typically takes years to develop
List some causes of Vitamin B12 def. (5ish)
Sorry these ones suck :-(
- 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.)
What is pernicious anemia (PA)?
- Auto-immune disorder caused by an immune mediated destruction/loss of gastric parietal cells
- Results in IMPAIRED IF SECRETION!
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
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!
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
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
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)
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
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”
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!
What are the clinical features of hemolytic anemia? (4)
- Typical anemia sx
- Jaundice
- Gallstones (usually billirubin stones)
- Dark urine
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
What will the peripheral smear show w/ hemolytic anemia?
- Immature RBCs
- Nucleated RBCs
- Schistocytes (fragmented RBCs)
What is a unique lab finding with intravascular hemoylsis HA?
Decreased serum haptoglobin
Binds Hgb released from lysed RBC = decrease free haptoglobin
Which test can we use to differentiate between the hemolytic anemias?
Direct antiglobulin (Coombs) test (DAT)
Define extravascular hemoylsis (HA).
Destruction of RBCs in the reticuloendothelial system:
- Spleen!!!!
- Liver
- Lymph nodes
- Bone marrow
What can the destruction of RBC in the reticuloendothelial system (ex: spleen) result in?
Extravascular hemolysis
What disorder puts a patient at risk fro episodic hemolytic anemia?
-Pts with G6PD deficiency (x-linked recessive disorder)
Why are pts with G6PD at risk for hemolytic anemia?
Deficiency of protective enzyme against oxidative stress = oxidative stress = episodic hemolytic anemia
What are the oxidative stress triggers for pts with G6PD def?
- Drugs: sulfa, antimalarials
- Infections
- Fava beans
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
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
What will the peripheral smear show w/ a G6PD hemolytic episode?
- Bite cells
- HEINZ BODIES (denatured Hgb)
Tx for G6PD def. hemolytic episode?
- Self-limited (resolves as RBCs are replaced)
- Avoid oxidative drugs
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)
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)
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)
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
What is the tx for hereditary spherocytosis?
SPLENECTOMY!
-Tx of choice for severe disease
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
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
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)
What type of infection can cause an aplastic crisis in a pt with sickle cell anemia?
Parvovirus B19 infection
What are 3 hypoxic conditions that put patients with sickle cell anemia at risk?
- Dehydration
- High altitude
- Intense exercise
What are the clinical features of sickle cell disease?
- Chronic hemolysis
- Vaso-occlusive ischemic tissue injury
- CHF, pulmonary HTN, dyspnea
What can occur w/ chronic hemolysis in patients with SCD?
Aplastic crisis = sudden decrease in Hgb (life threatening!)
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
What are the lab findings associated with SCD?
- Normocytic, normochrmoic anemia
- Increased reticulocyte count
- Thrombocytosis may be present
- Hgb electrophoresis!!!! Reveals HbS
What is the best test to confirm SCD diagnosis?
Hgb electrophoresis
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
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)
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
What is the difference between primary vs. secondary AIHA?
Primary: No underlying systemic disorder
Secondary: Identifiable underlying systemic illness
Name the 2 different autoantibodies that determine the clinical manifestations of AIHA?
IgM: Cold agglutinins
IgG: Warm agglutinins
What are patients with AIHA at increased risk for?
VTE
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
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
What are the lab findings for AIHA?
- Peripheral smear: Polychromasia, spherocytosis, and nucleated RBC
- Positive Coombs (DAT) test (if RBC stick together = + test)
What does tx of AIHA depend on?
- Warm vs cold disease
- Age
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
What is the tx for warm AIHA?
- FIRST LINE: Corticosteroids!
- Rituximab
- Splenectomy
- Immunosuppressants, IV immunglobin
How does Rituximab (AIHA tx) work?
Ab that targets B cell lymphocytes
What is intravascular hemolysis?
Destruction of RBCs within the blood stream
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)
What causes a hemolytic transfusion reaction?
Abs to RBCs directed against the ABO/Rh blood grouping antigens
(RBCs attacked following transfusion)
Along with a blood transfusion reaction, what else might cause a hemolytic transfusion reaction?
Hemolytic disease of the newborn (HDN) seen in erythroblastosis fetalis
Which test can detect antibodies that coat a patient’s transfused RBCs?
Coombs test
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
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
What is paroxysmal nocturnal hemoglobinuria?
RARE acquired stem cell mutation resulting in complement mediate RBC lysis
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
How do you dx paroxysmal nocturnal hemoglobinuria?
- Flow cytometry
- Osmotic fragility test
- Coombs NEGATIVE
What is the tx for paroxysmal nocturnal hemoglobinuria?
- Monoclonal Ab against complement C5
- Steroids
- Stem cell transplant
Describe aplastic anemia.
Acquired abnormality of hematopoietic stem cells
-May be total, or selective for RBCs, WBCs, or platelets
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
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
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
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)
What are the causes of normochromic, normocytic anemias with NORMAL reticulocyte count and NORMAL bone marrow? (3)
- Anemia of chronic disease
- Hypothyroidism
- Liver disease
What are the causes of normochromic, normocytic anemias with NORMAL reticulocyte count and ABNORMAL bone marrow? (2)
- Cancers: Myelofibrosis, leukemia, myeloma, metastases
- Renal failure
