6.2.09 puvvada heme review.ppt

7/27/2019 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.

6.2.09 puvvada heme review.ppt

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