Approach to the Patient with ANEMIA

1
Approach to the Patient with ANEMIA

• Lisa Mohr, MD
• Mike Tuggy, MD

2
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

3
Erythropoesis-Brief Hematology Review

• Bone marrow
• Pluripotent stem cells
• Chemical regulation
• Cytokines
• Erythroid specific growth factor
• Erythropoietin (EPO)
• Life span
• Reticulocyte- 4 days
• RBC 120 days

4
RBC-The important players

• Hemoglobin
• reversibly binds and transports 02 from lungs to
  tissues
• 4 globin chains iron

5
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

6
Definitions

• Anemia-values of hemoglobin, hematocrit or RBC
  counts which are more than 2 standard deviations
  below the mean
• HGB
• HCT

7
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??

8
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

9
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

10
Evaluation of the Patient (3)

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

11
Laboratory Evaluation

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

12
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

13
Differential Diagnosis

• Classification by Pathophysiology
• Blood Loss
• Decreased Production
• Increased Destruction
• Classification by Morphology
• Normocytic
• Microcytic
• Macrocytic

14
Blood Loss

• Acute
• Traumatic
• Variety of sources
• Melena, hematemesis, menometrorrhagia
• Chronic
• Occult bleeding
• Colonic polyp/carcinonma

15
Decreased Production

• Infectious
• Neoplastic
• Endocrine
• Nutritional Deficiency
• Anemia of Chronic Disease

16
Decreased ProductionINFECTIOUS

• Bacterial
• Tuberculosis
• MAI
• Viral
• HIV
• Parvovirus

17
Decreased ProductionNEOPLASTIC

• Leukemia
• Lymphoma/Myeloma
• Myeloproliferative Syndromes
• Myelodysplasia

18
Decreased ProductionENDOCRINE

• Thyroid Dysfunction
• Hypothyroidism
• Erythropoietin Deficiency
• Renal Failure

19
Decreased ProductionNUTRITIONAL DEFICIENCY

• Iron
• B12
• Folate

20
Macrocytic Anemia

• MCV 100
• MegaloblasticAbnormalities in nucleic acid
  metabolism
• B12, Folate
• Non-megaloblasticAbnormal RBC maturation
• Myelodysplasia
• ETOH, liver dz, hypothryroidism,
  chemotherapy/drugs

21
Microcytic Anemia

• MCV
• Reduced iron availability
• Reduced heme synthesis
• Reduced globin production

22
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

23
Microcytic AnemiaREDUCED HEME SYNTHESIS

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

24
Microcytic AnemiaREDUCED GLOBIN PRODUCTION

• Thalassemias
• Smear Characteristics
• Hypochromia
• Microcytosis
• Target Cells
• Tear Drops

25
Lab tests of iron deficiency of increased severity
26
Differential Diagnosis-Revisited

• Classification by Pathophysiology
• Blood Loss
• Decreased Production
• Increased Destruction

27
INCREASED DESTRUCTION

• Immune Mediated
• Non-immune Mediated

28
Increased DestructionIMMUNE MEDIATED

• Cold Agglutinin
• Paroxysmal nocturnal hemoglobinuria
• Post mycoplasmal hemolytic anemia
• Warm Agglutinin
• Drug induced
• Autoimmune hemolytic anemia
• Transfusion reaction

29
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)

30
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
• ROSfatigue, urine seems a little darker lately

31
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

32
M.L.s Initial Labs

• Only a CBC w/ diff was obtained
• WBC 8.2, HCT 32.2, MCV 79, Platelets 221,
  differential - normal

33
Initial Thoughts?

• Blood loss?
• Age places him at risk for colon CA
• Decreased Production?
• Alcohol use, Iron deficiency
• Increased Destruction?
• Darker urine lately

34
Further Work-up

• CAGE questions
• Peripheral Blood Smear
• Reticulocyte count
• Iron Studies
• Ferritin
• TIBC
• Saturation
• Urinalysis
• FOBT or colonoscopy referal

35
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

36
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

37
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!

38
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