6.2.09 puvvada heme review.ppt
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Hematology BoardReview.
Soham Puvvada.
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Objectives: Anemia: focus on Iron DeficiencyAnemia.
Myeloproliferative disorders: focuson P.Vera.
Malignant Heme: focus on CLL.
Peripheral Smear Review.
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Anemia: deficiency in oxygencarrying capacity of blood due to
decreased erythrocyte mass. General Categories:
Production deficiency.
Maturation Defects. Survival Defects.
Sequestration.
Blood Loss.
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Underproduction Anemias:
Kidney Disease:Normochromic, Normocytic with low retic count.Target hgb=11-12; epo dosing: 100-150u/kg/wk. For epo to beeffective, 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 urinarylosses, venous thrombosis, pancytopenia.
Marrow infiltrative disorders.
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Anemia of chronic disease:
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: normallow
Normochromic/normocytic->hypochromic/microcytic.
Impaired iron utilization despite normal to increasedstores.
Iron replacement not usually necessary
Treat underlying condition.
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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 normalrange. 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 b12deficiency but NOT the neurologic sequelae.
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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.
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Comparison of Iron Deficiency andAOCD.Iron Deficiency AOCD
MCV
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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, treatconstipation 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 fromexcess of free iron
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MKSAP QUESTIONS:
64 y.o man is evaluated for worsening dyspnea andgradual increase in exercise tolerance over thepast 2 months associated with COPD. He had anACS event 2 years ago and his medications includedaily aspirin, bronchodilators, inhaledcorticosteroids, 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 ispositive for occult blood. Iron deficiency anemia
is diagnosed. Upper endoscopy reveals chronicgastritis and the daily aspirin is stopped.
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Which of the following is the mostappropriate treatment for this patients
anemia?
A. Blood Transfusion
B. IV Iron
C. Oral Iron D. Erythropoetin.
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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
patients cardiac hx is not a reason to instituteblood transfusion.
No indication of renal disease, and therefore noreason to do epo
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78 y/o woman is evaluated for increasing
forgetfulness. The problem has been slowlyprogressive over the past 7 months. She is able tolive independently and has not had difficultieswith ADL. The remainder of the hx and exam arenon 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
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Which of the following is the most
likely diagnosis? A. Folate Deficiency
B. Vitamin B12 deficiency
C Autoimmune Hemolytic Anemia D. Myelodysplasia
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Answer=B: Vit b12
deficiency. B12 def: increased methylmalonic acid andhomocysteine concentrations
Folate def: elevated homocysteine
concentration only, MMA nl. Supp folate will reverse anemia-not helpwith neuropysch s/s-B12 replacement doesnot always reverse neurological findingsbut can prevent further deterioration ofmental status.
M t ti D f t td th l i
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Maturation Defects contd: thalassemia:target cells/hypochromic,microcytic.
Beta thal: Trait-asymptomatic. B thal intermedia: anemic, not transfusion dependent. B thal major: cooleys 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 -/ CBC normal Trait: 2 genes absent-/- mild anemia.Electrophoresis is normal. Globin chain analysis
Hgb H disease: 3 genes absent --/-: severe anemia, CHF 4 genes absent: --/-- hydrops fetalis 30-40 wksgestation.
.
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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
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Warm Autoimmune HemolyticAnemia
Most common type, occurs at 37C
IgG mediated: Fc receptor mediated RBCdestruction 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.
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Cold Agglutinin Disease
IgM ab recognize carbohydrate I-Ag system andcause complement fixation.
Temp below 37C.
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
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MKSAP Questions:
A 20 y/o woman is evaluated for excessivefatigue. The remainder of the history andphysical exam are non contributory. Labs show
Hgb of 10g/dl, MCV=60fL, RBC count=5.5 millioncells/ul. The leukocyte, platelet counts andresults of Hgb electrophoresis are normal.Peripheral smear is shown.
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Which of the following is the mostlikely composition of her gene
alleles?A. /-, /
B. /-, /-
C. -/-, -/D. -/-, -/-
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Answer: B-2 genes missing-
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.
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27 y/o woman with 2 year hx of SLE presentswith new onset fatigue and shortness of breathfor 10 days duration. Her meds includehydroxychloroquine and ibuprofen. Medical hx isotherwise non contributory. On exam,
pulse=109/min, R=14/min, BP=130/80. Other thanpale conjunctivae and pallor, exam normal.
Hgb= 5.2 g/dl, compared with a normal value 3months ago. Peripheral smear is notable for
spherocytes, and polychromasia
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Which of the following is the mostappropriate initial treatment for
the patient? A. Oral Ferrous Sulfate
B. Corticosteroid therapy
C. Erythropoetin D. Plasmapheresis.
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Answer: B-corticosteroids. The patient has warm AIHA.Polychromasia results from reticulocytosis.
First Rx-steroids.
IVIG and splenectomy are also treatmentoptions.
Plasmapheresis is not used.
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Anemia of
Sequestration:hypersplenismusually from portalhypertension orsplenicsequestrationcrises
Anemia of Blood
loss: selfexplanatory.
when loss exceeds
marrow productionmay result in amaturation defect(iron, b12, folate)
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Myeloproliferative Disorders.
CML
Polycythemia Vera
Essential Thrombocythemia.
High risk of thrombosis.
Myelofibrosis with Myeloid Metaplasia Extramedullary hematopoesis-
hepatosplenomegaly/portal HTN.
Dry tap on bone marrow.
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Polycythemia Vera.
Characterized by erythrocytosis. Proliferative phase, spent phase, secondary AML
Proliferative : Pruritus, erythromelalgia, s/s ofhyperviscosity, 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.
D
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Diagnosis:
First r/o causes of secondary erythrocytosis.
Lab findings: 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
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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 prominenterythroid and megakaryocytic proliferation.
Revised WHO criteria for
diagnosis:
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Treatment:
Phlebotomy, goal HCt
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MKSAP questions
50 y/o man is evaluated for recent onset of
pruritus while showering. He has previously been inexcellent health, eats a normal diet, never smoked,does not take meds. On exam there are ruddyfacies 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 5years ago, WBC=11,000, MCV=79fL, plateletcount= 550,000/ul. Chem nl except for serumiron concentration and serum ferritinconcentration. Results of upper and lowerendoscopy nl.
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Which of the following is the mostappropriate 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.
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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 pts plt count 600,000, hydroxyureapreferable since it would lower counts of all 3cell lines.
Anagrelide used to lower plt count-more in ET.
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CLL
CLL and SLL are malignant monoclonal accumulation
of immunologically incompetent mature B-lymphocytes 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
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Presentation
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 Richters transformation; into high grade
lymphoma-usually DLBCL.
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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
Weakly positive surface immunoglobulin stain CD5 + CD23+
CD79b or CD22 weakly + FMC7 negative
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Prognosis/Treatment:
CLL with somatic mutations of IgG heavychain region has indolent course: mediansurvival 25 years.
CLL without such mutations-with surrogatemarker ZAP 70 =much worse prognosis,median survival 8 yrs.
Treatment options mirror those forFollicular lymphoma indolent verysuccessful in inducing remission, but notcure
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MKSAP question 32 y/o woman is evaluated in ED for acute onsetof fevers, chills nausea, and weakness. Two weeksago, she presented to her physician for asymptomatic UTI and was treated with bactrim.After 5 days of Rx, she is unable to continue themedication because of nausea, vomitting. Onexam, she is acutely ill, mottled, lethargic.Hr=140/min, BP=70/30 mmhg. An indwelling foleycath is inserted, 20 cc conc. Urine obtained andsent for culture.
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Labs show a HCt of 38%, Leukocyte count of200/ul, and platelet count=155,000/ul. In theICU, she is given high volume IV fluids, and IV
antibiotics. The peripheral blood smear shows nocirculating blasts. Which of the following is themost appropriate next step in treatment?
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A. Prednisone
B. Cytarabine and Anthracycline
chemotherapy. C. Granulocyte Colony Stimulating
factor.
D. IVIG.
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Answer: C-GCSF. Sorry, couldnt 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.
P i h l S R i
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Peripheral Smear Review:Morphology Interpretation:
Schistocytes/RBCfragments Microangiopathic hemolytic Anemia (MAHA) TTP, HUS, HELLP, DICBurns
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 fragmentationof nucleus occurs normally and usually removed by spleen
HypersegmentedPMNS Megaloblastic anemia ( b12, folate)
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schistocytes
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Burr cells
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Spur cells
T t lls
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Target cells
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Hypochromic microcytic anemia
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Spherocytes
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Tear drop cells
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THE END! References: MKSAP Hematology-Oncology.