anemia eval and management: speaker disclosures...

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Anemia Eval and Management: Hematologist’s Perspective

Steven Fein, MD,MPH

Hematology/Oncology

Baptist Health South Florida

Speaker Disclosures

• I disclose that I am a member of the speaker’s bureaus for American Regent, Pfizer Pharmaceuticals, Janssen and Boehringer Ingelheim PharmaceuticalsBoehringer Ingelheim Pharmaceuticals.

• I will not discuss off-label or unapproved usage.

What is anemia?

• 285.9D64.9

• A condition in which the number of red blood• A condition in which the number of red blood cells is below normal

• A disorder characterized by an reduction in the amt of hemoglobin in 100 ml of blood

Objectives

• Signs and symptoms of anemia seen in clinical practice

• Determine which lab and diagnostic tests to order or when to refer to hematologistg

• Hematologist’s perspective:– Iron deficiency anemia– Non-iron defic/non-malignant anemia– Heme malignancy

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Symptoms of anemia

• Asymptomatic

• “Symptomatic” anemia Hgb>8– Dyspnea or fatigue with exertion

• “Symptomatic” anemia Hgb<8– Dyspnea or fatigue without exertion

– Palpitations, bounding pulse, roaring in ears

• Jaundice, Icterus, Dark urine

• Angina, Syncope

Anemia evaluation rec by Baptist Health Quality Network

Testing by Primary Care

LOW MCV Iron, TIBC, ferritin, reticHgb electrophoresis (look for beta thal)GI, GU, or GYN referralG , GU, o G e e a

NORMAL MCV Iron, TIBC, ferritin, reticB12, folic acid, TSH, Creat

HIGH MCV Iron, TIBC, ferritin, reticB12, MMA, folic acid, TSH, Liver enzymesLDH, Direct Coombs

Baptist Health Quality Network suggested hematologist referrals

• Unexplained anemia (i.e., not iron defic)– Non-iron defic/non-malignant

– Heme malignancy

I d fi t di t l i• Iron defic not responding to oral iron– Chronic bleeding or iron malabsorption

– Intravenous iron easy and beneficial

• B12 deficiency of uncertain cause– Autoimmune or malnutrition

Why do we care about anemia?

• Why does the patient have anemia?

• Does the patient have cancer?

• Do they feel ill because of anemia?

• Do they need treatment for anemia?

• Do they need blood transfusions?

• Do they need a hematology referral?

• Do they need a bone marrow biopsy?

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Why do you test CBC’s?

• “Routine” CBC in healthy people– Screening for anemia or chronic bleeding– Screening for bone marrow disorders

(i.e. heme malignancies)( g )

• Diagnostic test for somebody who is ill– High WBC may be infection or heme malig– Anemia in somebody who is ill maybe impt– Heme malignancy may be discovered

Hematology consult for anemia

• 30yo AA woman G2P1

• 32 wks gestation, PTL

• c/o fatigue

• PMH: C sectionPMH: C section

• FHx “sickle cell”

• Exam: comfortable, no resp distress, not tachy

Hematology consult for anemia Hematology consult for anemia

IronTIBC% Iron sat

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• Unsuspecting patient got RBC against the advice of the hematologist

• Doubt she had a chance to discuss risk/benefit profile with a physician

Hematology consult for anemia

risk/benefit profile with a physician

• Most beneficial part of RBC was iron, already receiving but takes time to help

• Poor Obstetrician was called at 5am

Clinical practice anemia eval

• Iron deficiency • Non-iron deficiency


• Iron deficiency– Chronic bleeding

– Iron malabsortion

• Non-iron deficiency



• GYN

• GI tract

GU tract


• GU tract

(r/o malignancy)

– Iron malabsortion• GI tract surgery

• Autoimmune disease

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• GYN

• GI tract

GU tract


• GU tract

(r/o malignancy)





• GYN

• GI tract

GU tract

• Non-iron deficiency– What is the MCV?

– Production problem or destruction problem?

• GU tract

(r/o malignancy)



– Benign or malignant?



• GYN

• GI tract

GU tract

• Non-iron deficiency– What is the MCV?

– Low MCV alpha thal• GU tract

(r/o malignancy)



– High MCV• B12/folate

• Liver dysfunctiojn

• Hypothyroidism

• Meds-antibiotics



• GYN

• GI tract

GU tract

• Non-iron deficiency– Low MCV alpha thal

– High MCV

• B12/folate


• Hypothyroidism


• GU tract

(r/o malignancy)



– Production problem• Anemia of chronic dz

• Epo deficiency CKD

– Destruction problem• Autoimmune (AIHA)

• Non-autoimmune

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• GYN

• GI tract

GU tract

• Non-iron deficiency– Low MCV alpha thal

– High MCV

• B12/folate


• Hypothyroidism


P d ti bl• GU tract

(r/o malignancy)



– Production problem

• Anemia of chronic dz

• Epo deficiency CKD

– Destruction problem

• Autoimmune (AIHA)

• Non-autoimmune

– Heme malignancy• Myeloma, lymphoma,

MDS, MPD, leukemia

Iron deficiency anemia is common

• Iron deficiency with anemia means severe iron deficiency, justifies more evaluation

Causes of iron deficiency

Decreased absorption• Malabsorption

• Malnutrition

• Acid suppression

Excess loss

• Chronic bleeding

• Chronic wounds

• Excessive phlebotomy• Acid suppression

• Gastric bypass

• Excessive phlebotomy

• Chronic hemolysis

Iron is the oxygen carrier

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Chewing ice is not just a habit

Symptoms of iron deficiency

• Feeling tired and “weak”• Palpitations• Headache• SOB with minimal exertion• Brittle hair and nails• Increased vulnerability to infection • Craving ice• Disturbed sleep, concentration, memory• Abdominal pain

Iron deficiency affects the whole body

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Spectrum of Iron deficiency

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Diagnosing Iron Deficiency

Young healthy Older people with comorbidities

Bleeding, lo MCV

Ferr<50

h/o bleeding, bruising,

Low MCVFerr 50

Fe low

TIBC high

Low MCV

Ferritin too low for patient

(no specific number)

Fe/TIBC <20%

BM biopsy shows no iron

Diagnosing iron deficiency Iron Deficient Patient #1

• 24yo AA woman with one prior pregnancy, now 30 weeks pregnant– Has chewed ice throughout pregnancy

Has had severe fatigue– Has had severe fatigue

– Heavy menstrual bleeding as a teenager

– Hgb 7.5, Fe 30, TIBC 450, Ferr 10

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Iron Deficient Patient #1

• Young women with iron deficiency anemia– Commonly associated with heavy menses

– Pregnancy causes iron depletion

African American and Hispanic women have– African American and Hispanic women have higher prevalence of iron defic anemia

– IDA increases risk of adverse events for both fetus and mother

– Maybe associated with preterm labor

– Higher chance of peripartum transfusion


• 30yo woman with gastric bypass 4 yrs ago– Increasingly fatigued, SOB with exertion

– Not bleeding

Hgb 5 5 Fe 3 TIBC 400 Ferr 2 TSH 3 3– Hgb 5.5, Fe 3, TIBC 400, Ferr 2, TSH 3.3


• Iron deficiency common among those who have gastric bypass surgery– Maybe more common in women

Usually several years later– Usually several years later

– Oral iron supplements not useful

– Vitamin B12 defic not as common

• Intravenous iron infusion logical

• May need chronic “maintenance” iron


• 74yo man with colon ca metastatic to liver– Receiving FOLFIRI chemotherapy

– h/o diabetes mellitus, takes oral meds

Good functional status but tired– Good functional status but tired

– Creat 1.4

– Hgb 9, Fe 15, TIBC 280, Ferr 350

– Prescribed erythropoietin injections

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• Cancer-associated anemia– Fatigue

– Decreased survival

Chemo not as effective– Chemo not as effective

– Leads to hospitalizations and transfusions

• Iron deficiency common among cancer pts

• GI malignancies may cause chronic bleed

• Functional anemia common


• 68yo woman with CKD, Creat 2.1– h/o PVD, CAD, s/p MI, stenting

– Intermittent chest pain and SOB

Takes apixaban for atrial fib/stroke prevention– Takes apixaban for atrial fib/stroke prevention

– Denies bleeding but urine micro hematuria

– Hgb 8.5, Fe 20, TIBC 210, Ferr 500

– Prescribed oral iron supplement 6 months ago


• CKD associated with iron defic anemia– Increased risk of stroke or CHF

– More frequent hospitalization

Increased risk of progression to ESRD– Increased risk of progression to ESRD

– Maybe decreased survival

• Chronic bleeding and functional Fe defic

• Ferritin not interpretable in chronic inflammatory states

How to treat iron deficiency

Intervention Hemoglobin Iron

Address chronic or acute bleeding

Stop decreasing

Oral iron supplement Weeks-months Slow

IV iron supplement Days-weeks Fast

RBC transfusion Hours Fast

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Oral iron supplements

Reasons oral iron not beneficial

• Noncompliance/non-adherence is common– Potential for nausea and constipation – Frequent dosing (2-3x per day)– Decreased absorption when taken with mealsp– Benefit slow, so not perceived to be effective

• Persistent blood loss may exceed oral iron dose or GI absorption

• Chronic inflammatory state may impede iron absorption or utilization

Who should try oral iron?

• Consider oral iron as a first line treatment for young healthy outpatients

• Early stage iron deficiencyF t ti 15 20%– Fe saturation 15-20%

– Hgb>11 g/dL

• Not for gastric bypass patients

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Stop decreasing




Who needs RBC transfusion?

Bleeding after trauma or surgery

Post‐partum bleeding

Who needs RBC transfusion?Cancer patients receiving cytotoxic chemotherapy

MDS patients receiving palliative treatment

Thalassemia patients

What if you needed a transfusion?

• Would you accept a transfusion without investigating the risks and benefits?

• What questions do you have about blood?R ti ?– Reactions?

– Infection?– Will it make me heal faster or slower?

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Stop decreasing




IV iron formulations

1981 Infed Iron dextran Iron defic

1999 Ferrlecit Ferric gluconate CKD on HD

2000 Venofer Iron sucrose CKD

2009 Feraheme Ferumoxytol Adult CKD

2013 Injectafer Ferric

Carboxymaltose

Iron defic

CKD not HD

IV iron versus oral iron in postpartum anemia,

based on baseline Hgb

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Objectives




RBC size on a blood smearMicrocytic Macrocytic

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Non-iron defic/Non-malig Case 1

• 72yo man with fatigue over several weeks• Denies blood loss• Soc: lives alone, cooks for himself• Exam: P 90 SBP 110 not orthostatic• Data: Hgb 5.3 HCT 15 MCV 122

– WBC 4.1 Plt 125 Retic 1% TB 1.9 LDH 2750

• What is the most likely cause of anemia?• Answer: ?

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• 72yo man with fatigue over several weeks• Denies blood loss• Soc: lives alone, cooks for himself• Exam: P 90 SBP 110 not orthostatic• Data: Hgb 5.3 HCT 15 MCV 122

– WBC 4.1 Plt 125 Retic 1% TB 1.9 LDH 2750

• What is the most likely cause of anemia?• Answer: Vitamin B12 deficiency

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• 64yo woman with progressive dyspnea for the past few weeks

• Soc: formerly alcohol dependent

D t HGB 5 1 HCT 15 MCV 112• Data: HGB 5.1 HCT 15 MCV 112– WBC 4.6 Plt 109,000 RDW 21

• What is the most likely cause of anemia?

• Answer: ?

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• 64yo woman with progressive dyspnea for the past few weeks

• Soc: formerly alcohol dependent

D t HGB 5 1 HCT 15 MCV 112• Data: HGB 5.1 HCT 15 MCV 112– WBC 4.6 Plt 109,000 RDW 21


• Answer: Folate deficiency

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Non-iron defic/Non-malignant

• Is there a problem with production or destruction?

Retic should be high during anemia– Retic should be high during anemia• Low retic may suggest production problem

– LDH and haptoglobin suggest hemolysis

– Direct Coombs test looks for anti-RBC antibody

– RDW=RBC distribution width

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Production or destruction problem?

Production

Bone marrow failure

Destruction

Hemolytic anemiafailureThalassemia

Nutrient defic (iron, B12, folate)

Drugs, chemotherapy

Epo defic (CRI or ESRD)

Anemia of chronic disease

MDS, Aplastic anemia

“Sideroblastic” anemia = MDS

IntravascularRBC membrane

Sickle cell disease

Microangiopathic: DIC, TTP, HUS

Extravascular

AIHA, Drug-induced 60

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Production or destruction problem?

Production

Bone marrow failure

Destruction

Hemolytic anemiafailure

Thalassemia

Nutrient defic (iron, B12, folate)

Drugs, chemotherapy

Epo defic (CRI or ESRD)

Anemia of chronic disease

MDS, Aplastic anemia

“Sideroblastic” anemia = MDS

IntravascularRBC membrane

Sickle cell disease

Microangiopathic: DIC, TTP, HUS

Extravascular

AIHA Drug-induced62

Aplastic anemia

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Sickle cell disease

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Sickle cell anemia

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• 30yo AA man with no prior health problems now with post-op DVT & PE

• Exam: mild scleral icterus, splenomegaly

D t H b 10 HCT 30 MCV 75• Data: Hgb 10 HCT 30 MCV 75 – TB 3 LDH 300

– Target cells seen on blood smear

• What is the most likely diagnosis?

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• 30yo AA man with no prior health problems now with post-op DVT & PE

• Exam: mild scleral icterus, splenomegaly

D t H b 10 HCT 30 MCV 75• Data: Hgb 10 HCT 30 MCV 75 – TB 3 LDH 300

– Target cells seen on blood smear

• What is the most likely diagnosis?

Answer: Sickle cell disease variant

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Hemolytic anemia

Intravascular Extravascular

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• 18yo man with no prior health problems now presenting with yellow eyes

• Exam: scleral icterus, spleen tip palpable

D t H b 14 HCT 38 MCV 84• Data: Hgb 14 HCT 38 MCV 84– Retic 2.2% TB 3.1 DB 0.4 AST 49 LDH 480


• Answer: ?

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• 18yo man with no prior health problems now presenting with yellow eyes

• Exam: scleral icterus, spleen tip palpable

D t H b 14 HCT 38 MCV 84• Data: Hgb 14 HCT 38 MCV 84– Retic 2.2% TB 3.1 DB 0.4 AST 49 LDH 480


• Answer: autoimmune hemolytic anemia

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Causes of AIHA

• Autoimmune disease– (lupus, RA)

• Hematologic malignancies – CLL, Non-Hodgkins Lymphoma

• Drugs (methyldopa)

• Cold agglutinins (complement)– mycoplasma, EBV, NHL

• “Idiopathic”

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Cold agglutinins

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Objectives




How we die in the U.S.

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Hematologic malignancies

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Hematologic malignancies

AML/MDS ALL

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MPDMPDLymphomaCLL

What is multiple myeloma?

• Means something different to each patient• A “blood cancer” like leukemia• A “bone cancer” like leukemia/lymphoma• “Too much protein” in the blood• Too much protein in the blood

• COMMON CAUSE OF ANEMIA– 25,000 new cases/yr in US

Sarah Newbury…the first known multiple myeloma patient 1844

Henry Bence Jones: Bone fractures and abnormal urine

protein

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Light chain deposition disease

Korngold and Lapiri 1956 (“KAPPA/LAMBDA”)

Why it’s called Multiple Myeloma

• Bone tumors throughout the skeleton

• Can be “missed” by a bone biopsy

• Confusing because many patients don’t h l bhave actual bone tumors– Diffuse bone infiltration

– Soft tissue variants, light chain deposition dz

– Systemic amyloidosis

What myeloma cells look like

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Monoclonal plasma cells secrete monoclonal “M” antibody

SPEP reveals lots of same-sized antibody to diagnose plasma cell disease

Myeloma is a systemic disease

C -- HyperCalcemiaR – Renal FailureA -- AnemiaB – Lytic Bone Lesionsy

Think SPEP when anything is weirdThink SPEP for all non‐iron deficient anemia

Take home messages

• Anemia is a common problem, usually caused by chronic bleeding/iron deficiency

H t l f l f IV i i f i• Hematology referral for IV iron infusion or for those with non-iron deficiency anemia

• Test SPEP to look for multiple myeloma

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anemia eval and management: speaker disclosures...

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