A Clinical Approach to Anemia

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Clinical approach to anemia

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A CLINICAL APPROACH TO THE PATIENT WITH

ANEMIADr Manish Chandra Prabhakar

MGIMS Sewagram

Objectives Review basic science of the RBC Define Anemia Review key aspects of history, physical

and lab evaluation Review a systematic approach to the

differential diagnosis Case-based application of clinical

concepts

RBC-The important players Hemoglobin

reversibly binds and transports 02 from lungs to tissues

4 globin chains & iron

RBC-The important players (2)

Iron key element in the production of hemoglobin absorption is poor

Transferrin iron transporter

Ferritin iron binder, measure of iron stores, *also

acute phase reactant*

Definitions Anemia-values of hemoglobin, hematocrit

or RBC counts which are more than 2 standard deviations below the mean HGB<13.5 g/dL (men) <12 (women) HCT<41% (men) <36 (women)

CASE Kishan Singh is a 66-year old male who

has not had any primary care for several years. When he tried to give blood last week, he was told that he was anemic. He presents to your clinic for evaluation.

What would you do??

Evaluation of the Patient HISTORY

Is the patient bleeding? Actively? In past?

Is there evidence for increased RBC destruction?

Is the bone marrow suppressed? Is the patient nutritionally deficient? Pica? PMH including medication review, toxin

exposure

Evaluation of the Patient (2)

REVIW OF SYMPTOMS Decreased oxygen delivery to tissues

Exertional dyspnea Dyspnea at rest Fatigue Signs and symptoms of hyperdynamic state

Bounding pulses Palpitations

Life threatening: heart failure, angina, myocardial infarction

Hypovolemia Fatiguablitiy, postural dizziness, lethargy,

hypotension, shock and death

Evaluation of the Patient (3)

PHYSICAL EXAM•Stable or Unstable?-ABCs-Vitals•Pallor•Jaundice-hemolysis•Lymphadenopathy•Hepatosplenomegally•Bony Pain•Petechiae•Rectal-? Occult blood

Laboratory Evaluation Initial Testing

CBC w/ differential (includes RBC indices) Reticulocyte count Peripheral blood smear

Laboratory Evaluation (2) Bleeding

Serial HCT or HGB Iron Deficiency

Iron Studies Hemolysis

Serum LDH, indirect bilirubin, haptoglobin, coombs, coagulation studies

Bone Marrow Examination Others-directed by clinical indication

hemoglobin electrophoresis B12/folate levels

Differential Diagnosis Classification by Pathophysiology

Blood Loss Decreased Production Increased Destruction

Classification by Morphology Normocytic Microcytic Macrocytic

Blood Loss Acute

Traumatic Variety of sources

Melena, hematemesis, menometrorrhagia Chronic

Occult bleeding Colonic polyp/carcinonma

Decreased Production Infectious Neoplastic Endocrine Nutritional Deficiency Anemia of Chronic Disease

Decreased ProductionINFECTIOUS

Bacterial Tuberculosis MAI

Viral HIV Parvovirus

Decreased ProductionNEOPLASTIC

Leukemia Lymphoma/Myeloma Myeloproliferative Syndromes Myelodysplasia

Decreased ProductionENDOCRINE

Thyroid Dysfunction Hypothyroidism

Erythropoietin Deficiency Renal Failure

Decreased ProductionNUTRITIONAL DEFICIENCY

Iron B12 Folate

Macrocytic Anemia MCV > 100 Megaloblastic:Abnorm

alities in nucleic acid metabolism B12, Folate

Non-megaloblastic:Abnormal RBC maturation Myelodysplasia

ETOH, liver dz, hypothryroidism, chemotherapy/drugs

Microcytic Anemia MCV <80 Reduced iron

availability Reduced heme

synthesis Reduced globin

production

Microcytic AnemiaREDUCED IRON AVAILABILTY

Iron Deficiency Deficient Diet/Absorption Increased Requirements Blood Loss Iron Sequestration

Anemia of Chronic Disease Low serum iron, low TIBC, normal serum

ferritin MANY!!

Chronic infection, inflammation, cancer, liver disease

Microcytic AnemiaREDUCED HEME SYNTHESIS

Lead poisoning Acquired or

congenital sideroblastic anemia

Characteristic smear finding: Basophylic stippling

Microcytic AnemiaREDUCED GLOBIN PRODUCTION

Thalassemias Smear

Characteristics Hypochromia Microcytosis Target Cells Tear Drops

Lab tests of iron deficiency of increased severity

NORMAL Fe deficiencyWithout anemia

Fe deficiency With mild anemia

Fe deficiency With severe anemia

Serum Iron 60-150 60-150 <60 <40

Iron Binding Capacity

300-360 300-390 350-400 >410

Saturation 20-50 30 <15 <10

Hemoglobin Normal Normal 9-12 6-7

Serum Ferritin 40-200 <20 <10 0-10

Differential Diagnosis-Revisited

Classification by Pathophysiology Blood Loss Decreased Production Increased Destruction

INCREASED DESTRUCTION Immune Mediated Non-immune Mediated

Increased DestructionIMMUNE MEDIATED

Cold Agglutinin Paroxysmal nocturnal hemoglobinuria Post mycoplasmal hemolytic anemia

Warm Agglutinin Drug induced Autoimmune hemolytic anemia Transfusion reaction

Increased DestructionNON-IMMUNE MEDIATED

Extra-corpuscular Macro-circulatory

Hypersplenism Extracorporeal circulation

Micro-circulatory DIC TTP HUS

Intra-corpuscular RBC Wall (membrane or enzyme defects) Heme or globin abnormalities (HbS, C)

Back to Kishan Singh-You appropriately decide to obtain more history!

HPI: “I’ve been a little more tired than usual, but I’ve been busy at work. I’m getting close to retirement. Nothing else is unusual. I avoid doctors if I can”

PMH: Inguinal hernia repair 20 yrs ago FH: F & MGF-heart attack(age 80), brother-

alcoholism SH: Married x44yr, smokes 1ppd, “a couple

beers/night” MEDS: daily multivitamin ALLERGIES: none ROS:+fatigue, +urine seems a little darker lately

More on K Singh P.E. findings

T 98.4 HR 98 Resp 20 BP 112/70 Gen: NAD, appears younger than stated age HEENT: skin and conjunctiva slightly pale NECK: no adenopathy or thyromegally Chest: CTAB CV: RRR, no murmur ABD: no HSM, soft, normoactive bowel sounds GU: normal male Rectal: no masses, prostate smooth/not

enlarged, guaiac negative stool

K Singh’s Initial Labs Only a CBC w/ diff was obtained:

WBC: 8.2, HCT 32.2, MCV 79, Platelets 221, differential - normal

Initial Thoughts? Blood loss?

Age places him at risk for colon CA Decreased Production?

Alcohol use, Iron deficiency Increased Destruction?

“Darker urine” lately

Further Work-up CAGE questions Peripheral Blood Smear Reticulocyte count Iron Studies

Ferritin TIBC % Saturation

Urinalysis FOBT or colonoscopy referal

More Results CAGE screen reveals no positive

responses Smear reveals microcytic, microchromic

RBCs Retic count is interpreted as “low” Urinalysis negative for hemoglobin FOBT: not completed by patient Iron Studies

Ferritin: 10 TIBC: 350 % Sat: 15

What’s next? Rule out Sources of Bleeding

Counseling regarding colon CA and referral for colonoscopy

Consider oral iron therapy Dietary counseling (iron sources, limiting

etoh, etc) Encourage follow-up for health care

maintenance Vaccinations (Tetnus/pneumovax) Other cancer screening Cholesterol Screen

Diagnosis Colonoscopy

revealed small suspicious lesion in sigmoid colon, pathology revealing adenocarcinoma. – Excised surgically, no mets.

Routine labs, one year later, reveal an HCT of 40%. He feels “better than ever”!

References Schrier, Stanley.Approach to the patient

with anemia. Up to Date. 2014 Schrier, Stanley. Anemia of Chronic

Disease. Up to Date. 2004 Schrier, Stanley. Anemias due to

decreased red Cell Production. Up to Date 2014

Schrier, Stanley. Causes and diagnosis of anemia due to iron deficiency. Up to Date. 2014

Tierney, et al. Anemias. Current Medical Diagnosis and treatment. 2013.

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