Approach to the Patient with ANEMIA

Lisa Mohr, MD Mike Tuggy, MD

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
ML is a 64-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 Production INFECTIOUS

Bacterial
Tuberculosis MAI

Viral
HIV Parvovirus

Decreased Production NEOPLASTIC

Leukemia Lymphoma/Myeloma Myeloproliferative Syndromes Myelodysplasia

Decreased Production ENDOCRINE

Thyroid Dysfunction
Hypothyroidism

Erythropoietin Deficiency
Renal Failure

Decreased Production NUTRITIONAL DEFICIENCY

Iron B12 Folate

Macrocytic Anemia
MCV > 100 Megaloblastic:Abnormaliti es in nucleic acid metabolism
B12, Folate

Nonmegaloblastic:Abnormal RBC maturation

Myelodysplasia

ETOH, liver dz, hypothryroidism, chemotherapy/drugs

Microcytic Anemia
MCV <80 Reduced iron availability Reduced heme synthesis Reduced globin production

Microcytic Anemia
REDUCED 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 Anemia REDUCED HEME SYNTHESIS

Lead poisoning Acquired or congenital sideroblastic anemia Characteristic smear finding: Basophylic stippling

Microcytic Anemia
REDUCED GLOBIN PRODUCTION
Thalassemias Smear Characteristics
Hypochromia Microcytosis Target Cells Tear Drops

Lab tests of iron deficiency of increased severity

NORMAL Fe deficiency Without anemia 60-150 300-390 30 Normal <20 Fe deficiency With mild anemia <60 350-400 <15 9-12 <10 Fe deficiency With severe anemia <40 >410 <10 6-7 0-10 Serum Iron Iron Binding Capacity Saturation Hemoglobin Serum Ferritin 60-150 300-360 20-50 Normal 40-200

Differential Diagnosis-Revisited
Classification by Pathophysiology
Blood Loss Decreased Production Increased Destruction

INCREASED DESTRUCTION
Immune Mediated Non-immune Mediated

Increased Destruction IMMUNE MEDIATED

Cold Agglutinin
Paroxysmal nocturnal hemoglobinuria Post mycoplasmal hemolytic anemia

Warm Agglutinin
Drug induced Autoimmune hemolytic anemia Transfusion reaction

Increased Destruction NON-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 M.L.-You appropriately

decide to obtain more history!
HPI: Ive been a little more tired than usual, but Ive been busy at work. Im 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 M.L.
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

M.L.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

Whats 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. 2004 Schrier, Stanley. Anemia of Chronic Disease. Up to Date. 2004 Schrier, Stanley. Anemias due to decreased red Cell Production. Up to Date 2004 Schrier, Stanley. Causes and diagnosis of anemia due to iron deficiency. Up to Date. 2004 Tierney, et al. Anemias. Current Medical Diagnosis and treatment. 2003. Pp469-489