Anemia II Flashcards
Limits of macrocytic anemia in adults and kids
Adults is an MCV>100
Kids is an MCV>90
Causes of macrocytic anemia
Reticulocytosis
Megaloblastic anemias
Liver disease/alcoholism, hypothyroidism, gastric bypass surgery
What are megaloblastic anemias?
Defective DNA synthesis results in disordered RBC maturation, accumulation of cytoplasmic RNA, reduced cell division in bone marrow and larger RBCs
Types of megaloblastic anemias
Folate deficiency
B12 deficiency
Drug-induced (drugs that interfere with pyrine/pyrimidine metabolism-hydroxyurea, chemotherapies and antiretrovirals)
Peripheral smear and bone marrow of B12 and folate deficiencies
They will be identical so must find another way to differentiate
Where do people get folate from?
The diet (vitamin B9)- usually food is supplemented with it
Daily allowance of folate
400 mcg (600 in pregnant and 500 lactating)
Symptoms of folate deficiency
Anemia sxs duh Glossitis (pain, swelling, tenderness, loss of papillae) Vague GI symptoms NO NEUROLOGIC SYMPTOMS May see neural tube defects in pregnancy
Lab studies for folate deficiency
Decreased folate level
Increased homocysteine level and normal methylmalonic acid level
Treatment of folate deficiency
Treat the underlying cause again
Replacement therapy with folic acid: 1 mg PO daily and better absorbed with food
How does one get B12?
Only from diet (animal products)
1-2 micrograms a day
Deficiency usually develops over years because the body has large stores
How is B12 absorbed?
It is bound to intrinsic factor (gastric parietal cells) in the stomach and is then released from cobalamin-IF complex in ileum to be absorbed
What is the most common cause of B12 deficiency?
Pernicious anemia
What is pernicious anemia?
Deficiency of intrinsic factor that causes B12 malabsorption and megaloblastic anemia
There are autoantibodies against gastric parietal cells that impair IF secretion and gastric acid secretion
ITS AN AUTOIMMUNE DISORDER
Symptoms of pernicious anemia
Typical anemia sxs
Glossitis, jaundice, splenomegaly
Neurologic findings: decreased vibratory and position sense, ataxia, stocking-glove paresthesias, confusion, dementia, ataxia
Can be reversible if tx within 6 mos
What do you see on a peripheral smear in pernicious anemia?
Hypersegmented neutrophils (> 5 nuclear lobes)
Aniso and poikilocytosis
Macro-ovalcytes (large, oval RBCs)
Diagnostic tests in pernicious anemia
Decreased B12 level
+ Schilling test or antibodies to IF
Increased methylmalonic acid and homocysteine levels
Treatment for pernicious anemia
Daily IM/SQ injections of 1000 mcg B12 for 1 wk
Then weekly for a month and then monthly injections whole like
Treat reversible causes duh
What can happen when you treat B12 deficiency with folate?
Correcting the abnormal blood pic but the pt may develop serious, possibly irreversible neurological damage called subacute combined degeneration of the spinal cord
Cause of hemolytic anemias
Hemolysis of destruction of RBCs
Decreased RBC survival time (bone marrow can compensate with increased production when between 20-100 days but not below that)
Clinical presentation of hemolytic anemias
Anemia sxs
Jaundice
Gallstones (bilirubin stones)
Dark urine (Hb in urine)
Labs in hemolytic anemia
Increased retic count Increased UCB Increased LDH Decreased Hb Hemoglocinuria/urine hemosiderin Decreased haptoglobin in intravascular hemolysis Direct antiglobulin (Coombs) test (DAT)
Best way to classify hemolytic anemias
According to site of RBC destruction:
Intravascular: in blood stream
Extravascular: in reticuloendothelial system (spleen)
Reasons for intravascular hemolysis
Shear stress: mechanical heart valve
Lysis from bacterial toxins: clostridial sepsis
Thrombotic microangiopathies: TTP, HUS
Red cell enzyme defects: G6PD def
Hemoglobinuria, transfusions, infections, snake bites
Random causes of intravascular hemolysis
Footstrike hemolysis or runners macryocytosis (runners), march hemoglobinuria (bongo drummers)
What can you see with a mechanical heart valve?
Fragmentation syndrome, see shistocytes (broken RBCs)
Reasons for extravascular hemolysis
Hereditary spherocytosis
Sickle-cell anemia
Thalassemias
Hereditary G6PD def
Why is G6PD important?
Ensures normal lifespan of RBCs and is involved in the oxidizing process
Deficiency or unstable Hb leads to oxidative damage and precipitation of Hb
What can oxidative drugs and infections do?
Cause episodic hemolysis (due to G6PD def)
What do pts look like in a hemolytic episode?
Usually healthy with no splenomegaly
Lab studies in G6PD deficiency
During an episode, reticulocytes and serum indirect bilirubin increase
Peripheral smear: Bite cells and Heinz bodies (denatured Hb)
G6PD low obvi
Treatment for G6PD deficiency
Usually hemolytic episodes are self-limited when red cells are replaced
Do not use oxidative drugs!
What is hereditary spherocytosis?
Autosomal dominant disorder with mild hemolytic anemia
What happens to the RBCs in hereditary spherocytosis?
Normal MCV but smaller surface area (dense, globular appearance and lack central pallor)- SPHERE SHAPE
They are poorly deformable so get trapped in splenic sinusoids and taken in by splenic macrophages
RBC life span lower in ppl with spleen but not when have splenectomy
Labs for hereditary spherocytosis
Osmotic fragility test: RBCs have increased hemolysis when exposed to hypotonic fluid due to RBC membrane defect
Treatment of choice for hereditary spherocytosis
Splenectomy (restores RBC life span and removes risk of future bilirubin gallstones)
What is the risk of splenectomy for hereditary spherocytosis?
Increases the risk of infections from encapsulated organisms so must have the right vaccinations and if possible, delay this until adulthood
When is sickle cell anemia seen most?
African-American descent
Most common feature of sickle cell anemia
Pain crises: Avascular osteonecrosis of femoral and humeral heads CVA MI Splenic infarcts (asplenism) Leg ulcers
After when do you see sickle cell symptoms?
Dehydration, hypoxia, high altitude or intense exercise
What are ppl with sickle cell at risk for?
Aplastic crisis and a sudden decrease in Hb
What do you seen on a peripheral smear in sickle cell?
Sickled/nucleated RBCs, target cells, Howell-Jolly bodies (nuclear remnants usually removed by spleen)
What is the best test to confirm sickle cell disease?
Hb electrophoresis (reveals the HbS)
Treatment of sickle cell disease
RBC transfusions when needed
Hydroxyurea (chemo) to decrease incidence of painful crises (suppress bone marrow function of all cell lines)
Can try a bone marrow transplant
What is autoimmune hemolytic anemia (AIHA)?
Immunologic destruction of RBCs mediated by autoantibodies directed against antigens on patients RBCs (clinical manifestations depend on the type of antibody produced)
What is primary vs secondary AIHA?
Primary: no underlying systemic disorder
Secondary: identifiable underlying systemic illness
What are people with AIHA at high risk for?
VTE
Common associations with AIHA
SLE (and other autoimmune/connective tissue disease)
Hematologic malignancies
Etc.
Clinical findings in AIHA
Sxs of hemolytic anemia
Fever and LAD
Hemoglobinuria
Acrocyanosis (dark purple to gray on fingertips, toes, nose in cold)
First line tx for AIHA
Corticosteroids
Other tx for AIHA
Depends if warm/cold disease and age (cold is usually self-limited in kids)
Rituximab: antibody to target B cell lymphocytes
Cytotoxic agents
Splenectomy
When do you see a hemolytic transfusion reaction?
During or within 4 hrs of transfusion (can be up to 4 wks later but much less severe then)
Common sxs of hemolytic transfusion reaction
FEVER, hemoglobinuria, hypotension, flank pain, pain at infusion site, chest tightness, N/V/D
Why does hemolytic transfusion reaction occur?
Incompatible blood and severity correlates with the amount transfused
Treatment for hemolytic transfusion reaction
Stop the transfusion obvi and treat with IVF, blood pressure support
Then submit a transfusion rxn work up
What is aplastic anemia?
Immune injury of hematopoietic stem cells that may be life threatening (may be total or select for different blood components)
Common causes of aplastic anemia
Most are idiopathic
Drugs/chemicals (benzene, chloramphenicol, chemo)
Viral illness (epstein-barr, cytomegalo, HBV)
Radiation
Genetic
What are the features seen in pancytopenia?
Progressive anemia: weakness/fatigue
Neutropenia: recurrent infections
Thrombocytopenia: bleeding/hemorrhage
What is the hallmark of aplastic anemia?
Pancytopenia (anemia, leukopenia, thrombocytopenia)
Bone marrow will not have precursors for those cells
What is the preferred tx for aplastic anemia?
Bone marrow transplant (if can’t, then must do immunosuppressive therapy)
