Transcript Hematology Board Review.

Hematology Board
Review.
Soham Puvvada.
Objectives:
• Anemia: focus on Iron Deficiency
Anemia.
• Myeloproliferative disorders: focus
on P.Vera.
• Malignant Heme: focus on CLL.
• Peripheral Smear Review.
Anemia: deficiency in oxygen
carrying capacity of blood due to
decreased erythrocyte mass.
• General Categories:
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Production deficiency.
Maturation Defects.
Survival Defects.
Sequestration.
Blood Loss.
Underproduction Anemias:
• Kidney Disease: Normochromic, Normocytic with low retic count.
Target hgb=11-12; epo dosing: 100-150u/kg/wk. For epo to be
effective, Ferritin>100ng/ml and iron sat>=20%.
• Anemia of Hypometabolic States:
– Hypothyroidism, Addison Disease, Hypogonadism,
Panhypopituitarism (low growth hormone)
• Anemia from bone marrow damage:
– Aplastic anemia: treated with ATG, cyclosporine.
– PNH: chronic hemolytic anemia, iron def from urinary
losses, venous thrombosis, pancytopenia.
– Marrow infiltrative disorders.
Anemia of chronic disease:
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Seen in inflm conditions or chronic infections.
Most common anemia in hospitalized patients.
Hgb typically 9-11g/dl range/
Decreased retic count, decreased response to Epo.
Iron levels: normallow
Normochromic/normocytic->hypochromic/microcytic.
Impaired iron utilization despite normal to increased
stores.
• Iron replacement not usually necessary
• Treat underlying condition.
Maturation Defects
– Cytoplasmic:
• Impaired hgb synthesis – iron deficiency
• Protoporphyin deficiency – sideroblastic anemia
• Globin synthesis deficiency - thalassemias
– Nuclear: DNA synthesis defects – folate,b12
• B12 def: Serum methylmalonic acid and homocysteine
become elevated before b12 levels fall below the normal
range.
• Folate def: RBC folate levels more reliable than serum
folate; may be increased with concurrent b12 def,
increased serum homocysteine, normal methymalonic acid.
• B12 def must be ruled out in folate def patients because
supplemental folate can improve the anemia of b12
deficiency but NOT the neurologic sequelae.
Iron Deficiency Anemia.
Increased iron requirements:
– Blood loss: menstruation, GI bleeding.
– Intravascular hemolysis (PNH, hemolysis
secondary to prosthetic valve)
– Pregnancy, lactation
Inadequate iron supply:
– Poor nutrition
– Absorbed in proximal small bowel: gastric
bypass surgery, achlorhydria, celiac disease,
IBD.
• Most common cause of thrombocytosis in adults.
Comparison of Iron Deficiency and
AOCD.
Iron Deficiency
AOCD
MCV
<85
72-100
MCHC
<32
<36
Iron
Low (<60)
Low (<60)
TIBC
High (>400)
Low (<250)
TIBC sat
Low <15 (usu <10%)
Low to normal (220%)
Ferritin
Low (<15)
Normal to High (>35)
Soluble Transferrin
Receptor
High
Normal
Stainable Marrow
Iron
Absent
Present
Treatment:
• Reticulocytosis in 4-7 days
• Increased hemoglobin in first several weeks (4-6 classically)
• Anemia usually resolves in 4-6 months (depending on etiology of
iron deficiency)
• Continue oral replacement for several months after anemia has
resolved to replete iron stores.
• Oral Iron: treatment failure sec to non-compliance, treat
constipation
• Parental Iron: dextran: can give total dose replacement in
single dose, rate of anaphylaxis 0.6%.
• Ferrlecit® (Sodium Ferric Gluconate): Usually do not give as a
single dose as total replacement can cause hypotension from
excess of free iron
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MKSAP QUESTIONS:
• 64 y.o man is evaluated for worsening dyspnea and
gradual increase in exercise tolerance over the
past 2 months associated with COPD. He had an
ACS event 2 years ago and his medications include
daily aspirin, bronchodilators, inhaled
corticosteroids, aspirin and statin. On exam, P=90,
BP=130/90, R=20/min. Labs include Hgb
=9.6g/dl(96 x109 L), and MCV=78fL. Stool is
positive for occult blood. Iron deficiency anemia
is diagnosed. Upper endoscopy reveals chronic
gastritis and the daily aspirin is stopped.
Which of the following is the most
appropriate treatment for this patient’s
anemia?
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A. Blood Transfusion
B. IV Iron
C. Oral Iron
D. Erythropoetin.
Answer: C=Oral Iron.
Response to oral iron is fast-less than 1 week.
in the ICU setting, liberal transfusion strategy was
associated with a high overall mortality rate. the
patient’s cardiac hx is not a reason to institute
blood transfusion.
No indication of renal disease, and therefore no
reason to do epo
78 y/o woman is evaluated for increasing
forgetfulness. The problem has been slowly
progressive over the past 7 months. She is able to
live independently and has not had difficulties
with ADL. The remainder of the hx and exam are
non contributory.
Hgb=7.8g/dl, WBC= 3800/ul, MCV=110, Plt=127,000.
LDH=565, Dbili=0.3, Tbili=4.8, B12=325pg/ml,
Folate=12ng/ml, Homocysteine=2.57 mg/l,
Methylmalonic acid=400nmol/L
Which of the following is the most
likely diagnosis?
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A. Folate Deficiency
B. Vitamin B12 deficiency
C Autoimmune Hemolytic Anemia
D. Myelodysplasia
Answer=B: Vit b12
deficiency.
• B12 def: increased methylmalonic acid and
homocysteine concentrations
• Folate def: elevated homocysteine
concentration only, MMA nl.
• Supp folate will reverse anemia-not help
with neuropysch s/s-B12 replacement does
not always reverse neurological findings
but can prevent further deterioration of
mental status.
Maturation Defects contd: thalassemia:
target cells/hypochromic,microcytic.
• Beta thal:
– Trait-asymptomatic.
– B thal intermedia: anemic, not transfusion dependent.
– B thal major: cooley’s anemia: severe, growth
retardation, iron overload. Hemoglobin electrophoresis:
persistent elevation of hgbF, variable levels of hgbA2,
and absent HgbA.
• Alpha thal:
– Silent carrier:1 gene absent -α/αα CBC normal
– Trait: 2 genes absent-α/-α mild anemia.
Electrophoresis is normal. Globin chain analysis
– Hgb H disease: 3 genes absent --/-α: severe anemia, CHF
– 4 genes absent: --/-- hydrops fetalis 30-40 wks
gestation.
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Survival Defects:
– Intrinsic (inherited defects)
• Membrane cytoskeleton - spherocytosis,
elliptocytosis
• Metabolic enzymes – G6PD
• Hemoglobinopathies – Sickle Cell
– Extrinsic (acquired)
• Antibody or complement mediated –
Autoimmune hemolysis, malaria
• Microangiopathy –DIC, vascular hemolysis
Warm Autoimmune Hemolytic
Anemia
• Most common type, occurs at 37°C
• IgG mediated: Fc receptor mediated RBC
destruction by splenic macrophages
• ± complement mediated.
•  retic count, microspherocytes on smear.
• DAT positive.
• May be caused by drugs.
• Treatment: Steroids: prednisone 1mg/kg/day with
taper-20% achieve remission.
• Splenectomy if recurrent dz, or if steroids fail.
• Also can use IVIG, Rituximab, Danazol.
Cold Agglutinin Disease
• IgM ab recognize carbohydrate I-Ag system and
cause complement fixation.
• Temp below 37°C.
• Intravascular hemolysis can result.
• Smear shows RBC clumping and agglutination.
• Therefore, spurious elevations in MCV/MCHC.
• Does not respond to steroids or splenectomy
• Usually anemia is mild, treat by maintaining warm
envt.
• If severe, alkylating agents/CD 20 ab
MKSAP Questions:
• A 20 y/o woman is evaluated for excessive
fatigue. The remainder of the history and
physical exam are non contributory. Labs show
Hgb of 10g/dl, MCV=60fL, RBC count=5.5 million
cells/ul. The leukocyte, platelet counts and
results of Hgb electrophoresis are normal.
Peripheral smear is shown.
Which of the following is the most
likely composition of her α gene
alleles?
A.
B.
C.
D.
α/-, α/α
α/-, α/-/-, -/α
-/-, -/-
Answer: B-2 genes missing-α
thal trait.
• Choice A=alpha thal carrier
• Choice C= Hgb H disease, 3 genes
absent, severe anemia, CHF
• Choice D=hydrops fetalis.
• REMEMBER, in alpha thal trait-Hgb
electrophoresis is normal.
• 27 y/o woman with 2 year hx of SLE presents
with new onset fatigue and shortness of breath
for 10 days duration. Her meds include
hydroxychloroquine and ibuprofen. Medical hx is
otherwise non contributory. On exam,
pulse=109/min, R=14/min, BP=130/80. Other than
pale conjunctivae and pallor, exam normal.
Hgb= 5.2 g/dl, compared with a normal value 3
months ago. Peripheral smear is notable for
spherocytes, and polychromasia
Which of the following is the most
appropriate initial treatment for
the patient?
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A. Oral Ferrous Sulfate
B. Corticosteroid therapy
C. Erythropoetin
D. Plasmapheresis.
Answer: B-corticosteroids.
• The patient has warm AIHA.
Polychromasia results from reticulocytosis.
• First Rx-steroids.
• IVIG and splenectomy are also treatment
options.
• Plasmapheresis is not used.
• Anemia of
Sequestration:
hypersplenism
usually from portal
hypertension or
splenic
sequestration
crises
Anemia of Blood
loss: self
explanatory.
when loss exceeds
marrow production
may result in a
maturation defect
(iron, b12, folate)
Myeloproliferative Disorders.
• CML
• Polycythemia Vera
• Essential Thrombocythemia.
– High risk of thrombosis.
• Myelofibrosis with Myeloid Metaplasia
• Extramedullary hematopoesishepatosplenomegaly/portal HTN.
• “Dry tap” on bone marrow.
Polycythemia Vera.
• Characterized by erythrocytosis.
• Proliferative phase, spent phase, secondary AML
• Proliferative : Pruritus, erythromelalgia, s/s of
hyperviscosity, thrombosis (arterial or venous),
hemorrhage, GI s/s.
• Spent phase: anemia, leukopenia, myelofibrosis,
hepatosplenomegaly.
• Exam: may show dilated retinal veins as well as
gouty arthritis.
Diagnosis:
• First r/o causes of secondary erythrocytosis.
• Lab findings:
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– Hgb/Hct
– WBC in 45%
– Plts in 65%
– Basophilia (seen in all MPDs)
 Uric acid (can lead to gout) and B12
 Leukocyte alkaline phosphatase score
Low epo levels
Positive JAK2 V617F
Revised WHO criteria for
diagnosis:
• Major:
– Hgb>18.5 in men/16.5 in women.
– Presence of JAK2 V617F.
• Minor:
– Epo.
– Endogenous erythroid colony formation in vitro
– BMBx showing hypercellularity with prominent
erythroid and megakaryocytic proliferation.
Treatment:
• Phlebotomy, goal HCt<45%
• Low Dose aspirin to decrease risk of
thrombosis.
• Hydroxyurea.
• Interferon Alpha.
MKSAP questions
• 50 y/o man is evaluated for recent onset of
pruritus while showering. He has previously been in
excellent health, eats a normal diet, never smoked,
does not take meds. On exam there are ruddy
facies and a palpable spleen tip. FOBT is negative.
O2 sat=99% RA. Labs show a Hgb of 61.0%
compared with a value of 44.5% documented 5
years ago, WBC=11,000, MCV=79fL, platelet
count= 550,000/ul. Chem nl except for  serum
iron concentration and serum ferritin
concentration. Results of upper and lower
endoscopy nl.
Which of the following is the most
appropriate management of this
patient?
• A. Phlebotomy and Anagrelide.
• B. Oral iron supplementation and low
dose aspirin.
• C. Hydroxyurea and Aspirin,
325mg/day.
• D. Phlebotomy and low-dose aspirin.
Answer :D-phlebotomy
and low dose aspirin.
• Pt has P.vera:  hct,  wbc count, plt count.
• Phlebotomy with goal hct≤ 45%, low dose aspirin
to prevent thrombotic complications.
• If pt’s plt count≥ 600,000, hydroxyurea
preferable since it would lower counts of all 3
cell lines.
• Anagrelide used to lower plt count-more in ET.
CLL
• CLL and SLL are malignant monoclonal accumulation
of immunologically incompetent mature Blymphocytes in blood (>5000/mm3), bone marrow,
or lymph nodes
• Characteristic phenotype: CD19,CD20, CD23+ B
cells and also CD5+ (Tcell assoc antigen)
• Smudge cells on peripheral smear - reflect
fragility of cells
Presentation
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Often asymptomatic, identified on routine CBC.
Lymphadenopathy(80%), Hepatosplenomegaly(50%).
AIHA, ITP.
Hypogammaglobulinemia, increased susceptibility to
infections.
• Bone marrow failure
• 5% monoclonal gammopathy
• 5% develop Richter’s transformation; into high grade
lymphoma-usually DLBCL.
Diagnosis:
• Smear: smudge cells. ALC in CBC>5000.
• Bone Marrow: Normo to hypercellular bone marrow with
lymphocytes accounting for >30% of all nucleated cells.
• Flow: low levels of surface Ig. Expression of ≥1 B cell
Antigen, + CD5.
• 1 point for each of below, 4-5 points 97% accurate
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Weakly positive surface immunoglobulin stain
CD5 +
CD23+
CD79b or CD22 weakly +
FMC7 negative
Prognosis/Treatment:
• CLL with somatic mutations of IgG heavy
chain region has indolent course: median
survival 25 years.
• CLL without such mutations-with surrogate
marker ZAP 70 =much worse prognosis,
median survival 8 yrs.
• Treatment options mirror those for
Follicular lymphoma – indolent – very
successful in inducing remission, but not
cure
MKSAP question
• 32 y/o woman is evaluated in ED for acute onset
of fevers, chills nausea, and weakness. Two weeks
ago, she presented to her physician for a
symptomatic UTI and was treated with bactrim.
After 5 days of Rx, she is unable to continue the
medication because of nausea, vomitting. On
exam, she is acutely ill, mottled, lethargic.
Hr=140/min, BP=70/30 mmhg. An indwelling foley
cath is inserted, 20 cc conc. Urine obtained and
sent for culture.
• Labs show a HCt of 38%, Leukocyte count of
200/ul, and platelet count=155,000/ul. In the
ICU, she is given high volume IV fluids, and IV
antibiotics. The peripheral blood smear shows no
circulating blasts. Which of the following is the
most appropriate next step in treatment?
• A. Prednisone
• B. Cytarabine and Anthracycline
chemotherapy.
• C. Granulocyte Colony –Stimulating
factor.
• D. IVIG.
Answer: C-GCSF.
• Sorry, couldn’t find a good CLL question.
• Severe neutropenia secondary to bactrim.
• Her granulocyte count should recover in 10-12
days.
• GCSF will shorten the recovery period and may
help with the treatment of severe infection.
Peripheral Smear Review:
Morphology Interpretation:
Schistocytes/RBC
fragments
Microangiopathic hemolytic Anemia (MAHA) – TTP, HUS, HELLP, DIC
Burns
Valve hemolysis
Spherocytes
Autoimmune hemolytic anemia
Hereditary spherocytosis
Target Cells
thalassemia and other hemoglobinopathies. Also in liver disease.
Teardrop Cells
Myelofibrosis and other infiltrative bone marrow processes
Sometimes seen in thalassemia
Burr Cells
(echinocytes)
Uremic patients
Spur Cells
(acanthocytes)
Liver disease
Howell-Jolly bodies
Splenectomy or functionally asplenic patients – result of fragmentation
of nucleus – occurs normally and usually removed by spleen
Hypersegmented
PMNS
Megaloblastic anemia ( b12, folate)
schistocytes
Burr cells
Spur cells
Target cells
Hypochromic microcytic anemia
Spherocytes
Tear drop cells
THE END!
• References:
– MKSAP Hematology-Oncology.