An Approach to Anemic Patient

8/4/2019 An Approach to Anemic Patient

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Dr.Rabiya Ali

House Officer

Medical Unit IV


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Objectives Review basic science of the RBC

Define Anemia

Review key aspects of history, physical and labevaluation

Review a systematic approach to the differentialdiagnosis

Case-based application of clinical concepts


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What is blood? Plasma (60%)

-Water

-Dissolved ions and proteins Cellular components (40%)

-WBCs

-RBCs

-Platelets


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What is hemoglobin? Tetramer of 4 globin chains (proteins)

Each with a heme group containing iron

Can be distinguished by electrophoresis Chain types

Alpha

Beta

Gamma

Delta

Zeta and epsilon are embryonic


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Hemoglobin binds oxygen and carries it to tissues

Erythrocytes consist mainly of hemoglobin

Function of red blood cell dependent on: Hemoglobin type and content

Membrane stability

Energy production


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Survival and production of RBCs Formed in bone marrow

Pleuripotent stem cells

Chemical regulation

Cytokines

Erythroid specific growth factor

Erythropoietin (EPO)


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Erythrocytes Life span is 120 days (+/- 20 days)

Cleared in spleen(engulfed and destroyed by

phagocytic cells of the reticuloendothelial system.)

Reticulocytes are newly formed RBC in circulation.Reticulocytes remain in the circulation forapproximately 1 day before reticulin is excised by

reticuloendothelial cells with the delivery of themature erythrocyte into circulation.

Life span of Reticulocyte is 4 days. If no new production, Hb drops 1 gm/week.


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Erythrocytes Erythrocytes are highly deformable and increase their

diameter from 7 m to 13 m when they traversecapillaries with a 3-m diameter.

They possess a negative charge on their surface, whichmay serve to discourage phagocytosis.

Because erythrocytes have no nucleus, they lack a

Krebs cycle and rely on glycolysis via the Embden-Meyerhof and pentose pathways for energy.

Many enzymes required by the aerobic and anaerobicglycolytic pathways decrease within the cell as it ages.


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Erythrocytes In addition, the aging cell has a

decrease in potassiumconcentration and an increasein sodium concentration.

These factors contribute to thedemise of the erythrocyte atthe end of its 120-day lifespan.


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Other important elements Iron

Key element in the production of hemoglobin

Absorption is poor Transferrin

Iron transporter

Measured by total iron binding capacity

Ferritin Iron binder, measure of iron stores, *also acute phase

reactant*


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Definition of AnemiaAnemia is a condition that requires investigation to

determine the underlying etiology.

Anemia is strictly defined as a decrease in red bloodcell (RBC) mass. OR

Values of hemoglobin, hematocrit or RBC countswhich are more than 2 standard deviations below the

mean for age. HGB


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ANAEMIA

Physiologic: Hb below the levelneeded to deliver adequate oxygento cells.Clinical Features:

DEGREE LEVEL OF Hb PRESENTATION

Mild 10 - 11 Mild dyspnea on exertion, palpitation

Moderate 7 10 As with MILD ANEMIA, may also haveexcessive fatigue

Severe


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Causes Causes of anemia are numerous and multifaceted. A

family history may be useful in detecting hereditaryetiology. Diet and exposure to drugs and chemicals can be

useful. A geographic history and a thorough knowledge ofthe patient's health can be important in establishing anetiology.


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CausesGenetic -Hemoglobinopathies,

-Thalassemias,-Enzyme abnormalities of the glycolytic pathways,-Defects of the RBC cytoskeleton-Congenital dyserythropoietic anemia-Abetalipoproteinemia-Fanconi anemia

Nutritional -Iron deficiency-Vitamin B-12 deficiency-Folate deficiency-Starvation and generalized malnutrition

Hemorrhage

Immunologic - Antibody-mediated abnormalities

Physical effects -Trauma-Burns-Frostbite-Prosthetic valves and surfaces

Drugs and chemicals -Aplastic anemia-Megaloblastic anemia

Chronic diseases and malignancies -Renal disease

-Hepatic disease-Chronic infections-Neoplasia-Collagen vascular diseases

Infections -Viral - Hepatitis, infectious mononucleosis, cytomegalovirus-Bacterial - Clostridia, gram-negative sepsis-Protozoal - Malaria, leishmaniasis, toxoplasmosis

Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome


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Clinical Presentation


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Case Mr. ABC is a 64-year old male who has not had any

primary care for several years. When he tried to giveblood last week, he was told that he was anemic. Hepresents to your clinic for evaluation.

What would you do??


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History


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Is the patient bleeding??

Actively? In past?

-Melena

-Hemorrhoidal blood loss

-Inquire aboutgastrointestinal complaints that may suggestgastritis, peptic ulcers, hiatal hernias, or diverticula.

-In a female petient carefully document pregnancies,abortions, and menstrual loss.


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Is there evidence for increased RBC destruction?

Abnormal urine color

Jaundice

PMH including medication review, toxin

exposure??


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Is the bone marrow suppressed?

Obtain a history of :

-Fever

-The occurrence of purpura, ecchymoses,and petechiae.


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Is the patient nutritionally deficient? Pica?

A thorough dietary history is importantin a patient who is anemic.

Specifically question patients regardingconsumption of either clay or laundrystarch. This history will not be providedspontaneously. These substances renderiron less absorbable.

Changes in body weight are importantwith regard to dietary intake and can

suggest the presence of malabsorptionor an underlying wasting disease ofinfectious, metabolic, or neoplasticorigin.


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Nutritional deficiencies may beassociated with unusual symptomsthat can be elicited by a history.Patients with iron deficiencies

frequently chew or suck ice(pagophagia).

In vitamin B-12 deficiency, earlygraying of the hair, a burningsensation of the tongue, and a loss of

proprioception are common. Paresthesia or unusual sensations

frequently described as pain also occurin pernicious anemia.


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Patients with folate deficiencies may have a soretongue, cheilosis, and symptoms associated withsteatorrhea.

Color, bulk, frequency, and odor of stools and whetherthe feces float or sink can be helpful in detectingmalabsorption.


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Is there any underlying disease??

Cold intolerance can be an important symptom ofhypothyroidism or lupus erythematosus, paroxysmal

cold hemoglobinuria, and certainmacroglobulinemias.

Explore the presence or the absence of symptomssuggesting an underlying disease, such as cardiac,

hepatic, and renal disease; chronic infection;endocrinopathy; or malignancy.


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Inquire about any non specific

symptoms Tiredness

Lightheadedness

BreathlessnessAnkle swelling

If patient had any co-existing disease like Angina therecould be worsening of that.


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Physical Examination


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Stable or Unstable?

-ABCs-Vitals

Pallor( conjuctiva and mucous membranes)

Jaundice-Hemolysis

Thinning of the lateral aspects of the eyebrows

Coarseness of hair

Puffiness of the face Angular stomatitis


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Gum hypertrophy Tongue : Colour and smoothness Nail defects(Koilonychia) Hands: perfusion, skin crease pallor Lymphadenopathy

-Infection or neoplasia Petechiae or purpura Telengiectasia Abnormal pigmentation

Ankle Edema- Bilateral: cardiac, renal, or hepatic disease.-Unilateral: lymphatic obstruction due to a

malignancy that cannot be observed or palpated.


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Systemic Examination Hepatomegaly

Splenomegaly

Raised JVP Flow murmurs on cardiac auscultation

Tachycardia

Tachypnoea

Postural hypotension

Joints deformity, swelling or restricted movement


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Optic Fundi

-Haemorrhage

-Hyperviscosity-Engorged veins

-Papilloedema

Rectal examination

Neurologic examination


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WorkUp for anemia


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Initial Testing

CBC with differential and platelets

Evaluation of smear with red cell indices

Reticulocyte count

Peripheral blood smear


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Bleeding

-Serial HCT or HGB Iron Deficiency

-Iron Studies (Iron/TIBC/Ferritin)

Hemolysis

-Serum LDH, indirect bilirubin, haptoglobin,urine for hemosiderin.Coombs(Direct & Indirect),coagulation studies

Hemoglobin electrophoresis

B12/folate level

Bone Marrow Examination Workup for GI blood loss

-Stool ( FOB and microscopy)

- Gastroscopy, Sigmoidoscopy or colonoscopy


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Differential Diagnosis Classification by Pathophysiology

Blood Loss

Decreased Production

Increased Destruction (hemolysis)

Classification by Morphology

Normocytic 80-100 fl

Microcytic < 80 fl Macrocytic >100 fl


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Decreased Production Infectious

Neoplastic

Endocrine Nutritional Deficiency

Anemia of Chronic Disease


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Endocrine Thyroid Dysfunction

Hypothyroidism

Erythropoietin Deficiency Renal Failure


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Nutritional Deficiency Iron

B12

Folate (B9)Vitamin B6

Vitamin C


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Approach to Anemia


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Microcytic Anemia MCV


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Reduced Iron Availability Iron Deficiency Deficient Diet/Absorption

Increased Requirements

Blood Loss

Iron Sequestration

-Note: Make sure there is no source of GI bleeding

Consider malignancy if there is GI bleeding

Anemia of Chronic Disease

Low serum iron, low TIBC, normal serum ferritin MANY!!

Chronic infection, inflammation, cancer, liver disease


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Reduced Globin ProductionAlpha

Thalassemia

Beta

Genetically determined, often familial.

Defects in the production of Hb Two processes involved

Decreased production of Hb

Imbalance of globin chain production

Smear Characteristics

Hypochromia

Microcytosis

Target Cells

Tear Drops


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Reduced Heme Synthesis Lead poisoning

-Blocks placement of Fe into heme

- May cause neurological damage

-Usually related to lead-based paints andindustrial exposures

-Characteristic smear finding: Basophilicstippling

-Test for a SERUM LEAD LEVEL

Acquired or congenital sideroblasticanemia

-Ring sideroblasts in bone marrow


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Diseases Iron TIBC Ferritin

Iron Deficiency

Anemia ofCh.Disease

Ch. Hemolysis

Hemochromatosis or

Pregnancy

Sideroblastic

anemia


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Macrocytic Anemia MCV > 100

Megaloblastic:

-Abnormalities in nucleic acid

metabolism B12, Folate,Cytotoxic drugs

Non-megaloblastic:

-Abnormal RBC maturation Myelodysplasia

-Alcohol, liver disease,hypothryroidism,


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Evolving Cobalamin Deficiency

Usual sequence: Serum Cobalamin falls

Serum methylmalonic acid & homocysteine rise

MCV rises within the normal range, with

-hypersegmentation of neutrophils MCV rises above normal

Anemia and/or neuropathy


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Macrocytosis of Alcoholism

25-96% of alcoholics

MCV elevation usually slight (100-110 f l)

Minimal or no anemia Macrocytes round (not oval)

Neutrophil hypersegmentation absent

Folate stores normal


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Normochromic,Normocytic

Anemia Most commonly caused by anemia of chronic disease

Early iron deficiency often causes normocytic anemiaas well

NormocyticMCV(80-100)

Reticulocyte count

Marrow failureAplastic anemia

MyelofibrosisLeukemia/metastasis

Renal failureAnemia of ch. disease

Acute blood lossSickle cell diseaseG6PD deficiency

Hereditary spherocytosisAIHAPNH


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Anemia of Chronic disease Common

Develops over 1 to 2 months

Non-progressive Usually mild to moderate

WBC, platelets normal or increased


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Causes

Thyroid disease Collagen Vascular Disease

Rheumatoid Arthritis

Systemic Lupus Erythematosus

Polymyositis

Polyarteritis Nodosa Inflammatory Bowel Disease

Ulcerative Colitis

Crohns Disease

Malignancy

Chronic Infectious Diseases Osteomyelitis

Tuberculosis

Familial Mediterranean Fever

Renal Failure


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Approach to hemolytic anemia-Anemia of increased destruction Normochromic, normochromic anemia

Shortened RBC survival

-Reticulocytosis

Tests to define the cause of hemolysis:- Hemoglobin electrophoresis

-Hemoglobin A2 (beta-thalassemia trait)

- RBC enzymes (G6PD, PK, etc)

- Direct & indirect antiglobulin tests (immune)-Cold agglutinins

- Osmotic fragility (spherocytosis)

-Acid hemolysis test (PNH)

- Clotting profile (DIC)


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Findings Consistent with

HemolysisSerum unconjugated bilirubin IncreasedSerum LDH (and LDH1:LDH2) Increased

Serum haptoglobin Decreased

Urine hemoglobin PresentUrine hemosiderin Present

Urine urobilinogen Increased

Cr51-RBC lifespan Decreased

Reticulocyte count Increased


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TreatmentThe purpose of establishing the etiology of an anemia is to permit

selection of a specific and effective therapy. Treatment of Iron deficiency anemia:

Therapy for iron deficiency anemia includes treatment of its underlyingcause and restoration of normal hemoglobin concentrations and ironstores. This can be accomplished by oral or parenteral administration.

-Oral iron therapy-Parenteral iron therapy

-Blood Transfusion packed RBCs should be reserved for patients who areactively bleeding and for patients with a severe and symptomaticanemia.Transfusion is palliative and should not be used as a substitute

for specific therapy.-Erythropoietin therapy


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Oral Iron therapy Several iron salts are available in tablet or liquid form for oral ingestion,

All of these are fairly simple and cheap, but usually two or three dosesare required daily. Ferrous sulfate, which supplies 65 mg of elementaliron per 200 mg tablet, is the most widely used oral iron preparation.

Iron dose (Adults):

-Recommended dose : 325 mg (65 mg elemental iron) tablets, 150 mg (30mg elemental iron)per 5 mL syrup -250 mL bottle

- 325 mg orally three times daily between meals separately from othermedications OR

- 10 mL syrup orally three times daily between meals separately from

other medications.

-Duration = 3 months

-Will respond in 10-21 days

-Hb should rise by 1gm/dL/week


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Oral IronAdverse Effects:

-GI complaints

-Contraindicated in: Hemosiderosis,hemochromatosis, and hemolytic anemia.

-Ferrous sulfate reduces absorption of levothyroxine andmethyldopa


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Parenteral Iron Indications for the use of intravenous iron include :

-Intestinal malabsorption e.g. due to gastrointestinal disease orsurgery.

-Intolerance or nonadherence,

-A hemoglobin level less than 6 g per dL (60 g per L) with signs ofpoor perfusion in patients who would otherwise receivetransfusion (e.g., those who have religious objections).

-Lack of effect of oral iron therapy.

-Patients in whom the chronic iron loss exceeds the rate ofreplacement possible with oral iron.

-Patients with a clinical need for rapid delivery of iron to iron stores,e.g. post operative and post partum patients or in cases ofautologous blood donation.

-Functional or absolute iron deficiency in connection to

erythropoietin therapy (r-HuEPO).


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Available products:

-Dexferrum (iron dextran)

-Ferrlecit (Na ferric gluconate complex)

-Venofer (iron sucrose or iron saccharate complex)

-Jectofer (iron sorbitol; for IM use only)

The iron dose to give may be calculated from the following formula

-Total iron deficit [mg] =body weight [kg] x (target Hb-actual Hb) [g/dl] x 2.4* + depot iron [mg]

-* 2.4 is a factor that takes into account the patient's blood volume, hemoglobiniron content , and conversion from g/dL to mg/L

-2.4 = 0.07 x 0.0034 x 10000:

Where:Blood volume: ~7% of body weightIron content of haemoglobin ~0.34%Conversion from g/dl to mg/l =10000

-Depot iron =500 mg.


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Contraindications:

-Known hypersensitivity to iron sucrose , evidenceof iron overload (ferritin > 800 ng/mL and/or

TSAT > 50%), or evidence of severe infection (suchas sepsis or osteomyelitis)


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Erythropoietin therapy Erythropoietin is available as a therapeutic agent

produced byrecombinant DNA technologyinmammalian cell culture. It is used in treating anemia

resulting from chronic kidney disease andmyelodysplasia, from the treatment ofcancer(chemotherapyand radiation), and from other criticalillnesses (heart failure).

parenteral iron is given along with recombinanterythropoietin therapy.
http://en.wikipedia.org/wiki/Recombinant_DNA_technologyhttp://en.wikipedia.org/wiki/Cell_culturehttp://en.wikipedia.org/wiki/Anemiahttp://en.wikipedia.org/wiki/Chronic_kidney_diseasehttp://en.wikipedia.org/wiki/Cancerhttp://en.wikipedia.org/wiki/Chemotherapyhttp://en.wikipedia.org/wiki/Radiationhttp://en.wikipedia.org/wiki/Heart_failurehttp://en.wikipedia.org/wiki/Heart_failurehttp://en.wikipedia.org/wiki/Radiationhttp://en.wikipedia.org/wiki/Chemotherapyhttp://en.wikipedia.org/wiki/Cancerhttp://en.wikipedia.org/wiki/Chronic_kidney_diseasehttp://en.wikipedia.org/wiki/Anemiahttp://en.wikipedia.org/wiki/Cell_culturehttp://en.wikipedia.org/wiki/Recombinant_DNA_technology


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Back to Mr. ABC-You appropriately

decide to obtain more history! Personal Hx: Ive been a little more tired than usual, but Ive

been busy at work. Im getting close to retirement. Nothing elseis unusual. I avoid doctors if I can

PMH: Inguinal hernia repair 20 yrs ago

Family Hx: Father & mother had 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


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Examination Findings T 98.4 HR 98 Resp 20 BP 112/70 Gen: NAD, appears younger than stated age

skin and conjunctiva slightly pale

NECK: no adenopathy or thyromegally Chest: CTAB/L

CV: RRR, no murmur

ABD: no HSM, soft, normoactive bowel sounds

GU: normal male Rectal: no masses, prostate smooth/not enlarged, guaiac

negative stool


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Initial Thoughts Blood loss?

Age places him at risk for colon CA

Decreased Production?

Alcohol use, Iron deficiency

Increased Destruction?

Darker urine lately


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Further Workup CAGE questions Peripheral Blood Smear

Reticulocyte count

Iron Studies Ferritin

TIBC

% Saturation Urinalysis

FOBT or colonoscopy referal


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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


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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 (Tetanus/pneumovax) Other cancer screening Cholesterol Screen


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Diagnosis Colonoscopy revealed smallsuspicious lesion in sigmoidcolon, pathology revealing

adenocarcinoma. Excisedsurgically, no mets.

Routine labs, one year later,reveal an HCT of 40%. He

feels better than ever!


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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 toDate 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

Ferri: Ferri's Clinical Advisor 2009, 1st ed. Copyright 2009 Mosby, AnImprint of Elsevier

Cuciti C, Mayer DC, Arnette R, Spielman FJ.

Int J Obstet Anesth. 2005 Oct;14(4):362-4.PMID: 16140521

Chandler G et al. Intravenous iron sucrose: establishing a safe dose. AmJ Kidney Dis. 2001;38(5):988-91.


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Acknowledgment Dr.Yousuf Baig

Resident 2 Medical IV


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The noble professionMedicine, the only profession that laboursincessantly to destroy the reason for its existence.

James Bryce (1838-1922), English diplomat andauthor; ambassador to the United states, 1907-13


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Documents

An Approach to Anemic Patient