Anemia Flashcards
WHO definition of anemia for females
Hct under 36%
Hgb under 12 g/dL
RBC under 4,000,000
WHO definition of anemia for males
Hct under 41%
Hgb under 13 g/dL
RBC under 4,000,000
What is the main hormone of erythropoiesis?
EPO
Describe EPO
- Hormone that regulates RBC production and speeds maturity of RBCs
- Secreted by kidney
- Binds to erythroid precursor receptors
What is the main EPO stimulus?
O2 availability
How are EPO levels affected by anemia severity? HCT levels?
- EPO levels increase in proportion to more severe anemia
- EPO levels are increased with LOW HCT
What substrates are needed for erythropoiesis?
Iron, B12, folate
RBC mass in African Americans? Elderly?
Decreased in both AAs and elderly
Describe volume status and anemia in acute bleeding
- Acute bleeding causes decreased intravascular volume
- Hgb and HCT are normal because of the decreased volume
- When normal volume is restored, patient will demonstrate anemia
How does dehydration affect Hgb/HCT/anemic status?
- Normal or elevated Hgb/HCT due to low volume
- Once hydrated, Hgb and HCT may reveal anemia
How does pregnancy status affect RBC mass?
- Plasma volume increases faster than RBC mass
- Patient may appear falsely anemic
In a person with normal BM, reticulocyte production index should be:
At least 2.5% (less than this indicates impaired RBC production)
Define microcytic anemia
MCV under 80
Main causes of microcytic anemia
TICS
- Thalassemia minor/major
- Iron deficiency
- Chronic/inflamm disease anemia
- Sideroblastic anemias and Pb poisoning
MC cause of anemia
Fe deficiency (microcytic)
Where is Fe found in the body?
70% in hemoglobin of RBCs
30% in the form of ferritin and hemosiderin
What is the body’s source of iron?
Diet only (but only 10% absorbed and usable)
Etiology of Fe deficiency anemia
- Insufficient iron intake
- Inadequate gut absorption (Celiac, Crohns, etc)
- Increased requirements/demands (children, pregnant women)
- Loss of blood
Notable clinical s/s of Fe deficiency anemia
- Angular cheilosis
- PICA (eating non-nutritive things)
- Koilonychia (spooning of nails)
- Plummer-Vinson Syndrome (esophageal webs, dysphagia, atrophic glossitis)
Labs to evaluate Fe deficiency anemia
- Serum Fe
- Transferrin
- TIBC
- Fe/TIBC ratio
- Serum Ferritin
Describe serum Fe
Amount of iron bound to transferrin in serum
Describe Transferrin
-Protein that binds iron and transports it to BM to be formed into Hgb
-Produced in liver
(reflection of liver function and nutrition)
Describe Total Iron Binding Capacity (TIBC)
- Total Transferrin in serum available to bind iron
- Indicates level of transferrin
If Fe stores are low, how is TIBC affected?
Fe low = TIBC high
If Fe stores are high, how is TIBC affected?
Fe high = TIBC low/normal
How is Fe/TIBC ratio affected in iron deficiency anemia?
DECREASED
Describe serum ferritin
Rough estimate of stored iron (inside cells)
How do lab values present in Fe deficiency anemia (Hgb/Hct/MCV/serum Fe/TIBC/% transferrin saturation/ferritin)?
Low Hgb/HCT Low MCV Low serum Fe Low % transferrin saturation Low ferritin HIGH TIBC
Treatment of Fe deficiency anemia
- ORAL Fe supplementation (ferrous sulfate 325 mg/65 mg elemental, 3x/day with meals)
- Patient education regarding iron therapy
How long does it take to correct Fe deficiency anemia with oral Fe supplementation? How long does it take to replete bone marrow stores?
6 weeks
6 months
What to avoid taking ferrous sulfate with and why?
Milk/dairy/Ca supplements because it decreases absorption of Fe
Patient education regarding Fe supplementation therapy?
- Side effects: constipation, black stools, nausea, bloating, abd pain, diarrhea
- Do NOT take with TCAs, quinolones, antacids/PPIs and careful with Ca supplements
- Vit C (OJ) increases absorption
What increases absorption of Fe supplements?
Vit C (OJ)
Causes of Fe deficiency anemia treatment failure
- Unidentified blood loss
- Non-adherence to treatment
- Incorrect diagnosis
- GI malabsorption
Indications for IM/IV Fe supplementation
- Intolerant to oral Fe
- Cannot absorb oral Fe
- Rapid correction needed
- Dialysis pt
Define Thalassemia syndromes
- Hereditary
- Characterized by inadequate production of either alpha or beta-globin chain of Hgb
- Results in hypochromic microcytic anemia
Pathophys of Thalassemia syndromes
- Genetic defect results in decreased/absent synthesis of Alpha or Beta Hgb chains
- Leads to low Hgb synthesis (microcytic anemia)
- RBCs are destroyed, BM does not respond to EPO
What happens with the imbalance of globin chains in Thalassemia?
- Unaffected chain takes over, accumulates in RBC (Heinz bodies)
- Leads to free radical production that induces hemolysis and anemia
What does normal adult hemoglobin consist of?
- Hgb A (98%): 2 alpha, 2 beta
- Hgb A2 (1-3%): alpha 2, delta 2
- Hgb F (less than 1%): major Hgb of fetal life, alpha 2/gamma 1
What are the degrees of Thalassemia?
- Trait (lab features of anemia w/o significant clinical repercussions)
- Intermedia (occasional transfusion required or other moderate clinical impact)
- Major (life threatening and pt is transfusion dependent)
Who is MC affected by Alpha Thalassemias?
- SE Asia/China
- Positive fam hx
- Hx of life long hypochromic, microcytic anemia NOT responsive to Fe therapy
Degree of Alpha Thalassemia depends on what?
Number of genes affected (0 affected = normal, 4 affected = hydrops fetalis dies in utero)
What is required to make official diagnosis of Thalassemia?
Genetic testing
Who is MC affected by Beta Thalassemia?
- Mediterranean
- Positive fam hx
Classification of Beta Thalassemia?
- Minor (1 mutation resulting in mild anemia)
- Major (2 mutations resulting in severe transfusion dependent anemia)
What does Hgb electrophoresis show in Beta Thalassemia Minor?
Increased Hgb A2 and slight increase in Hgb F
What does Hgb electrophoresis show in Beta Thalassemia Major?
Predominant Hgb F, small amts of Hgb A2, little-no Hgb A
What is Cooley’s anemia?
Beta Thalassemia Major
Complications of Cooley’s anemia
- Growth retardation
- Severe anemia
- Abnormal facial structure
- Pathologic fractures
- Hepatosplenomegaly
- Jaundice
- CHF
- Short life span (under 30 yo)
What differentiates Thalassemias from Fe deficiency anemia?
- Lower MCV
- Normal/elevated RBCs
- Abnormal blood smear
- Elevated retics
- Iron studies are normal or transferrin sat/ferritin may be high
How to treat alpha trait of Beta minor thalassemia?
None required
Treatment of Alpha major thalassemia/Hemoglobin H disease?
- Folic acid
- Avoid iron
Treatment of severe Thalassemias
- Regular transfusions
- Folic acid
- Iron chelation (to prevent organ damage from iron overload)
- Splenectomy if hypersplenism results in increased transfusions/refractory symptoms
- Allogenic stem cell transplant
What is the treatment of choice for Beta Thalassemia Major?
Allogenic stem cell transplant
Treatment of iron overload?
Iron chelation therapy (deferasirox)
Define sideroblastic anemia
Abnormal iron metabolism in bone marrow
Etiology of sideroblastic anemia
- Acquired: primary (MDS), secondary (drugs, Pb poisoning, chronic ETOH)
- Hereditary
Pathophys of sideroblastic anemia
- BM produces ringed sideroblasts instead of healthy RBCs
- Iron is available but it cannot incorporate into Hgb
What is the diagnosis of sideroblastic anemia based on?
BM biopsy with Prussian blue stain
Treatment of sideroblastic anemia
- Remove toxic agents
- Antidote: iron chelation
- Vitamins (folic acid, pyridoxine)
Define normochromic normocytic anemias
- Low Hgb/HCT
- MCV 80-100
Common causes of normochromic normocytic anemias
- Anemia of chronic disease
- Early Fe deficiency
- Myelodysplasia or marrow failure
- Acute blood loss
- Anemia a/w renal failure
Why do inflammatory conditions cause anemia? How are serum Fe levels?
- Reduced iron uptake in the gut and transfer to BM
- Reduced responsiveness to EPO
- Serum Fe is low
Why does organ failure cause anemia? How are serum Fe levels?
- EPO levels are decreased and RBC mass decreases
- Serum Fe is normal
Describe anemia in the elderly (how are serum Fe levels?)
Decreased EPO production due to RBC production resistant to EPO (serum Fe is normal)
If anemia of chronic disease is severe enough, what is the treatment?
RBC transfusions or parenteral EPO (goal Hgb 10-12)
Primary causes of macrocytic anemias
B12 deficiency
Folate deficiency
What defines a macrocytic anemia?
MCV over 100
Onset of B12 deficiency?
Takes over 3 years to occur if ALL intake and absorption of B12 stops
Where does absorption of B12 occur? Where is B12 stored?
Absorption in terminal ileum, stored in liver
Etiologies of B12 deficiency
- Strict vegan diet
- Pernicious anemia (MC)
- Abd surgery
- Pancreatic insufficiency
- Severe Crohn’s
- Tapeworm, GI bacterial or fungal overgrowth
MC cause of B12 deficiency?
Pernicious anemia (auto-antibody destruction of intrinsic factor leading to atrophic gastritis)
What is a notable clinical feature of B12 deficiency?
Complex neuro syndrome - peripheral nerves affected first (stocking like paresthesias, dementia)
Lab findings of B12 deficiency
- Macrocytic RBCs on blood smear
- Low retics
- Low serum B12
- Low WBC/platelets (severe cases)
How to confirm low serum B12?
Methylmalonic acid is HIGH
Homocysteine is HIGH
Treatment for B12 deficiency anemia
- Pernicious anemia: 1 mg B12 IM qd x 7 days then weekly for 4-8 wks, then monthly for life
- Folate can reverse hematologic abnormalities but NOT neuro symptoms
What may happen if treatment for B12 deficiency anemia is delayed for greater than 6 months?
Neuro problems may NOT respond to treatment (folate can reverse hematologic abnormalities but NOT neuro)
Why is it essential to obtain both B12 AND folate levels in macrocytic anemias?
- If treatment is delayed more than 6 months, neuro problems may not respond to treatment
- Folate can reverse hematologic problems but not neuro symptoms
Where is folic acid found? What are the daily requirements? How does the body store it?
- Most fruits and veggies
- Daily required 50-100 mcg
- Body stores about 5 mg which is good for 2-3 months
Causes of folate deficiency anemia?
- Inadequate dietary intake
- Reduced absorption (rare)
- Increased requirements (pregnancy, malignancy, infants/children)
- Meds (MTX, phenytoin, bactrim)
Clinical presentation of folate deficiency anemia?
- Onset can be seen in just a few months (FASTER than B12 deficiency)
- Similar symptoms to B12 but NO NEURO SYMPTOMS
What is diagnostic for folate deficiency anemia?
RBC folic acid level under 150 ng/mL (preferred over serum level - less than 5.0 ng/mL)
Treatment of folate deficiency anemia
- Oral folic acid 1 mg/day
- Avoid ETOH and folic acid antagonist meds
- Treat malabsorption, r/o B12 deficiency
Total correction of folate deficiency anemia can occur in how long?
2 months
Describe hemolytic anemias
Frequently normochromic and normocytic (BUT may be macrocytic)
Intrinsic causes of hemolytic anemias
RBC defects
- G6PD deficiency
- Sickle cell
- Hereditary spherocytosis
- Thalassemia
Extrinsic causes of hemolytic anemia
Extracellular causes
- Immune
- Drug induced
- TTP
- HUS
- DIC
- Infection
- Burns
- Hypersplenism
Define G6PD deficiency
Hereditary enzyme defect that causes episodic hemolytic anemia in response to oxidative stress
Pathophys of G6PD deficiency
- Excess oxidized glutathione that forces Hgb to denature and form Heinz bodies
- Heinz bodies cause RBC membrane damage which leads to extravascular hemolysis (in spleen)
Who is MC affected by G6PD deficiency?
American black men
Treatment of G6PD deficiency
- Self limiting: older RBCs are removed and replaced with younger RBCs w/adequate enzyme levels
- Treat underlying cause
Describe sickle cell disease
- Autosomal recessive (Valine for glutamine in beta chain of Hgb)
- Hgb becomes sickled from deoxygenation
- Hgb S is formed (unstable and polymerizes under stress)
What is the genetic makeup of sickle cell disease?
Homozygous Hgb S
What is the genetic makeup of sickle cell trait?
Heterozygous for Hgb A and S
little tendency to sickle unless there’s severe hypoxia
How is sickle cell disease diagnosed?
Confirmed by Hgb electrophoresis
What is the MC complication of sickle cell disease?
Vaso-occlusive complications (specifically, pain crisis)
- Pain in long bones, back, chest, abd
- 2 to 6 days duration
Treatment of sickle cell disease
- Supportive
- Prevent sickle cell crises by monitoring for conditions that demand O2 from RBCs
- Consider BM transplant
When to assume Sickle Crisis until proven otherwise?
Patient with Hgb AS or SS presents with pain and distress
Define autoimmune hemolytic anemias (AIHA)
Acquired disorder resulting from autoantibodies targeted toward RBC membrane antigens (resulting in extravascular hemolysis in spleen/liver)
Types of AIHA
- IgG mediated = warm
- IgM mediated = cold
Describe warm AIHA
- IgG mediated
- MC than cold/IgM AIHA
Causes of warm AIHA
- Primary/idiopathic
- Secondary to lymphoid malignancies, SLE, viral infections, drugs
Describe cold AIHA
- IgM binds to RBC in temps under 37 C
- Produces complement fixation and activation leading to intravascular hemolysis (within RBCs)
Causes of cold AIHA
- Idiopathic
- Lymphoproliferative diseases (Waldenstroms, lymphoma, CLL)
- Post-infectious (EBV, measles, mumps, CMV)
Clinical signs of warm AIHA
- Rapid onset/life threatening
- Fatigue
- Dyspnea
- Angina/heart failure
Clinical signs of cold AIHA
- Occurs on exposure to cold
- Mottled/numb fingers or toes
- Acrocyanosis
- Episodic low back pain
- Dark colored urine
Lab findings of AIHA
- Positive Direct Coombs test
- High reticulocyte count
- High indirect (unconjugated) bilirubinemia
- High serum LDH
- Immature RBCs
- Free serum Hgb
Treatment of warm AIHA
- Prednisone taper (1st line)
- Transfusion maybe
- Splenectomy maybe
- Treat underyling disorder
If rapid hemolysis in warm AIHA, what is the treatment?
Therapeutic plasmapheresis (rituximab, Danazol, IVIG)
Treatment of cold AIHA
- Symptomatic
- Rituximab (IV weekly x4 wks)
- If severe, cyclosporine
Prednisone and splenectomy are INEFFECTIVE for which type of AIHA?
Cold
