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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.