Anemia Last Islam

7/21/2019 Anemia Last Islam

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Approach to Anemia

Dr Islam Noureldin ABFM , MRCGP-INT

Specialist & Faculty of Family Medicine



Objectives

• Introduction.

• Definition of Anemia.

• Criteria for Diagnosis of Anemia.• General Clinical Features

• Types & Classification of Anemia

• Approach and Management• Summary & Take Home Messages



Case



• A 56-year-old female presents for an office evaluation, inWBHC in November for follow up of her DM , HTN ,Dyslipidemia.

• During the consultation pt complaining of fatigue for 6

months, She reports feeling “dizzy” on and off for the pastyear; the dizziness is associated with weakness that hasbeen worsening for the past month. She has been feeling“too tired” to even walk her regular daily exercise

• She occasionally has an alcoholic drink and denies tobacco

or drug use.• She is married and is a retired.



• Her physical exam reveals a well-appearing

female with normal vital signs and no

discernible abnormalities. her blood pressure

is 150/85 mm Hg; her pulse is 98 beats/min;

her respiratory rate is 20 breaths/min; her

temperature is 37.1°C;

• What is your next step?







➤ What is the most likely diagnosis?

➤ What is your next step in her evaluation andwhy?



Introduction

• Anemia is a symptom and not a disease

• It is never normal and its cause should always

be sought.

• Look for the Primary Cause!

• The history, physical examination, and simple

laboratory testing are all useful in evaluatingthe anemic patient



Anemia

Definition

• a decrease in red blood cell (RBC) mass that

can be detected by hemoglobin (Hb)

concentration, hematocrit (Hct), and RBC

count

adult males: Hb < (13.5 gldL) or Hct <41%

adult femalc:s: Hb < (12 gldL) or Hct <36%



• World Health Organization (WHO) criteria for

anemia in men and women are <13 and

<12 g/dL , respectively.







Clinical Features of any Anemia

History symptoms of anemia:

fatigue, malaise, weakness, dyspnea, decreased exercisetolerance,palpitations, headache, dizziness, tinnitus, syncope

acute vs. chronic bleeding. systemic illness

Diet

Alcohol

family history

Menstural hx: menorrhagia, menometrorrhagia, dysfunctionaluterine bleeding

rule out pancytopenia (recurrent infection, mucosalbleeding/easy bruisability)



Physical signs

HEENT: pallor in mucous membranes and

conjunctiva

Cardiac: tachycardia, orthostatic hypotension,

systolic flow murmur, wide pulse pressure,

Signsof CHF

Dermatologic: pallor in palmar skin creases

,jaundice (if due to hemolysis)



Can Symptoms & Signs differentiate Cause ofAnemia?



InvestigationsCBC with differential ??



Iron Indices??

Blood film

Additional laboratory investigations asindicated







Approach to Anemia







History and Physical Examination

In addition to general Hx & PE in Anemia:

• Important history information includes nutritionalintake (especially whole milk intake in children)

• pica or cravings for ice - for IDA• occupational or residential exposure to toxins For

Lead

• family history of anemia or ethnicity suggestive of

hemoglobinopathy• systemic symptoms of an underlying chronic

infectious or inflammatory process



• A review of gastrointestinal symptoms,

including abdominal discomfort,

hematochezia, and bright red rectal bleeding,

in adults.

• Menstrual history should be obtained in

menstruating women.

•



How to Differentiate between Causes

of Microcytosis?



Laboratory Tests in the Differentiation of

Microcytosis

• CBC

• RDW

• serum iron levels

• serum ferritin levels

• TIBC

• Transferrin saturation

• Reticulocyte blood count

• Peripheral blood smears

• Hemoglobin electrophoresis



Laboratory Tests in the Differential Diagnosis of

Microcytosis



Iron Deficiency Anemia

• IDA is the most common nutritional disorder

worldwide and accounts for approximately

one-half of anemia cases.

• IDA result from inadequate iron intake,

decreased iron absorption, increased iron

demand, and increased iron loss.



Etiologies of Iron Deficiency Anemia

Increased iron loss Inadequate iron intake

Decreased iron absorption

Increased iron demand



Screening?

MEN AND POSTMENOPAUSAL WOMEN• Asymptomatic men and postmenopausal women should not be screened

for iron deficiency anemia.

• Testing should be performed in patients with signs and symptoms of

anemia.

• All adult men and postmenopausal women with iron deficiency anemia

should be screened for gastrointestinal malignancy.



PREGNANT WOMEN The American Academy of Family Physicians, U.S. Preventive Services Task

Force, and Centers for Disease Control and Prevention recommend routine

screening of asymptomatic pregnant women for iron deficiency anemia.

The defined values consistent with anemia in pregnancy are hemoglobin

levels less than 11 g in the first or third trimester, or less than 10.5 g in the

second trimester.

CHILDREN The American Academy of Pediatrics recommends universal hemoglobin

screening and evaluation of risk factors for iron deficiency anemia in allchildren at one year of age.



Diagnosis

• laboratory-confirmed evidence of anemia, as wellas evidence of low iron stores.

• Although IDA is the most common cause ofmicrocytic anemia, up to 40 percent of patientswith iron deficiency anemia will have normocytic erythrocytes

• IDA should still be considered in all cases ofanemia unless the mean corpuscular volume isgreater than 95 μm



Diagnostic approach



• Values consistent with iron deficiency include

a low serum iron leveL , low transferrin

saturation, and a high total iron-binding

capacity



Iron Therapy

Lifestyle Management – dietary advice

The dosage of elemental iron required to treat iron deficiency anemia

in adults is 120 – 200 mg per day for three months

the dosage for children is 3 mg per kg per day, up to 60 mg per day

Monthly CBC for follow up

An increase in hemoglobin of 1 g per dL after one month of treatment

shows an adequate response to treatment and confirms the diagnosis.

In adults, therapy should be continued for three months after theanemia is corrected (hematocrit and ferritin levels normalize ) to allow

iron stores to become replenished then discontinue oral iron .



Adherence to oral iron therapy can be a barrier to treatment because of GIadverse effects such as epigastric discomfort, nausea, diarrhea, andconstipation.

Medication : such as proton pump inhibitors and factors that induce gastricacid hyposecretion (e.g., chronic atrophic gastritis, recent gastrectomy orvagotomy) are associated with reduced absorption of dietary iron and irontablets

Oral iron replacement is preferred to intravenous (IV) therapy. • It is safer, more cost-effective, and convenient when compared to IV

therapy.

• However, intravenous therapy may be substituted when there is:• inadequate iron absorption, continued blood loss, noncompliance or intolerance to

oral iron therapy.

• Internal medicine/hematologist consultation is recommended. Intramuscular (IM) iron therapy is not recommended • except in institutions with facility for treating anaphylactic reactions.

• Additional risks of IM iron therapy include unpredictable absorption and localcomplications (e.g. pain, staining of the skin, sarcoma formation).



Iron Therapy: Formulations and Dosing

Oral in PHCC: doses according

Other Doses and forms are available in private &

Hamad

Form Formulation Elemental iron Adult dosage

Ferrous fumarate 200-mg tablet 66 mg One tablet twice - 3

per day

Ferrous gluconateNot in phcc

300-mg tablet 38 mg One to three tabletstwo or three timesper day

Ferrous sulfate 190-mg tablet 60 mg One tablet three

times per day



PARENTERAL IRON THERAPY

Used in patients who cannot tolerate or absorb oral

preparations, such as those who have undergone

gastrectomy, bariatric surgery, or other small bowelsurgeries.

Not Available in PHCC





Interpret lab



Thalassemia

Definition

• defects in production of the alpha or beta chains of

hemoglobin

• clinical manifestations and treatment depends on specific:

gene and number of alleles affected

Common features:

• increasing severity with increasing number of alleles involved

• hypochromic microcytic anemia• basophilic stippling, abnormally shaped RBCs on blood film



Pathophysiology:

• Defect may be in any of the Hb genes

normally 4 Alpha genes in total

normally 2B genes in total

• Fetal hemoglobin, HbF switches to adult forms HbA and HbA2

at 3-6 months of life

• HbA constitutes 97% of adult hemoglobin

• HbA2 constitutes 3% of adult hemoglobin



Beta-Thalassemia Minor (Thalassemia Trait)

Definition• defect in single allele of beta gene (heterozygous)

• common in people of Mediterranean and Asian descent

Investigations • Hb 9-14 gldL , increase RBC ? , MCV<70 much lower levels than with IDA alone ,

normal Fe• peripheral blood film - microcytosis basophilic stippling ,

• Hb electrophoresis

specific: HbA2 increased to 3.5-5% (normall.S-3.5%)

Coexisting iron deficiency anemia can lower hemoglobin A2 levels.

iron deficiency anemia must be corrected before Hb electrophoresis results can beappropriately evaluated.

Treatment• no treatment required

• genetic counselling for patient and family



Alpha-Thalassemia

Definition• defect(s) in alpha genes

• similar geographic distribution as beta-thalassemia but higher frequencyamong Asians and Africans

Investigations • 1 defective a gene: silent carrier ; normal Hb, normal MCV

• 2 defective a genes:alpha-thalassemia trait microcytosis without anemia

• 3 defective a genes: HbH disease; presents in adults, decreased MCV, decreasedHb, splenomegaly

• 4 defective a genes: (hydrops fetalis); not compatible with life

Treatment• depends on degree of anemia

• 1 or 2 defective a genes: no treatment required

Summary



Summary



Normocytic anemia



A 16-year-old male presents to your office with complaints of progressive fatigue

and dyspnea over the last few days. He also has some mild upper

respiratorysymptoms which are being treated with sTMP/SMX,On examination, you find a well-nourished male in no distress. He is afebrile but

slightly tachycardic. You note mild scleral icterus and pallor of the palmar creases,

but the remainder of the exam is unremarkable. A CBC shows normal WBC count

and platelets, with hemoglobin 10.2 g/dL. On peripheral smear, “bite cells” and rare

Heinz bodies are reported. The LDH and bilirubin are elevated and the serum

haptoglobin is low, but the other serum chemistries are normal.

Which of the following is the most likely diagnosis?

Which of the following is the most appropriate intervention for this patient

with G6PD deficiency at this point?

A) Admit to the hospital and observe.B) Admit to the hospital and transfuse 2 units of packed red cell

C) Recommend supportive care and follow-up in a few days.D) Recommend splenectomy and refer to a general surgeon.



Definition:

• The mean RBC volume is normal (ie, MCV between 80and 100 fL) in patients with normocytic anemia.

• The next step in evaluation of normocytic anemia isdetermination of the reticulocyte count , this will

differentiate causes.

• Anemia with a high RC reflects an increasederythropoietic response to hemolysis or blood loss.

• Anemia with a low or normal RC reflects deficient

production of RBCs (ie, a reduced marrow response tothe anemia)



Normocytic anemia1) High reticulocyte Count

– increased Destruction (retics >2-3%)

Hemolysis

• Inherited: – hemoglobinopathy: sickle cell, thalassemia,

– Membrane: spherocytic

• Acquired: – Immune – Coombs positive, drug-related, cold agglutinin

– Infection – malaria

– Microangiopathic hemolytic anemia – DIC, TTP, HUS, HELLP

– Oxidative / drug-related

Bleeding: Acute vs Chronic

GI, GU, other

• With blood loss, reticulocytes should increase 2-3x initially andthen 5-7x over the next week



2) Low reticulocyte count

– decreased production (Retics <2%) – a normal reticulocytes in anemia is interpreted as asign of ↓ reticulocytes production

Pancytopenia

• Aplastic anemia, MDS, myelofibrosis, Leukemia• TB

• Amyloidosis, sarcoidosis

• Drugs – chemotherapy

Non-pancytopenia • Anemia of chronic dz

• Renal / liver dz



• Don’t forget to rule out IDA :

As 40 percent of patients with iron deficiency

anemia will have normocytic erythrocytes



HEMOLYTIC ANEMIAS

Classification:

Hereditary: abnormal membrane (spherocytosis, elliptocytosis)

abnormal enzymes (pyruvate kinase defictency, G6PD defictency)

abnormal hemoglobin synthesis (thalassemias, hemoglobinopathies)

Acquired: Immune :hemolytic transfusion reaction, autoimmune HA (AIHA), drugs (e.g. penicillin),

cold agglutinins

non-immune: - (MAHA) , - PNH, hypersplenism , infection (e.g. malaria)

intravascular: G6PD deficiency, TTP, DIC and PNH

extravascular: AIHA and hereditary spherocytosis



Clinical Features Specific to HA

• jaundice

• dark urine

• cholelithiasis (pigment stones)

• potential for an aplastic crisis (ie. BM

suppression in overwhelming infection)

• iron overload• iron deficiency



laboratory signs

• The laboratory signs of hemolytic anemias

include:

1. Increased LDH

2. Increased indirect bilirubin.

3. Increased reticulocyte count

4. Decreased haptoglobin5. Urine hemosiderin-presence.



Aplastic Anemia

Definitiondestruction of hematopoietic cells of the bone marrow leading to

pancytopenia and hypocellular bone marrow

Etiology

Congenital

Acquired :T-cell mediated, drugs , toxins , ionizing radiation ,

post-viral infection , autoimmune

Clinical Features:

can present acutely or insidiously

symptoms of anemia, thrombocytopenia

absence of splenomegaly and lymphadenopathy



Investigations:

CBC

• anemia or neutropenia or thrombocytopenia (anycombination) ±pancytopenia ,

• decreased reticulocytes ( < 1% of the total RBCcount)

Bloodfilm

• decreased number of normal RBCs

bone marrow

• aplasia or hypoplasia of marrow cells with fatreplacement

• decreased cellularity

T t t



Treatment:

Referral to Emergency for Admission• remove offending agents

• supportive care (red cell and platelet transfusions,

antibiotics)

• Immunosuppression: anti-thymocyte globulin- 50-60% ofpatients respond , cyclosporine

• allogenic bone marrow transplant



G6PD Deficiency

Definition : deficiency in glucose-6-phosphatedehydrogenase ( G6PD) leads to a sensitivityof RBC to oxidative stress

X-linked recessiveClinical Features: frequently presents as episodic

hemolysis precipitated by:

oxidative stress

drugs (e.g. sulfonamide, antimalarials, nitrofurantoin)

infection

food (fava beans)



Investigations

• neonatal screening

• G6PD assay : should not be done in acute

crisis when reticulocyte count is high

(reticulocytes have high G6PD levels)

• Blood film





Macrocytosis



61 yrs old female DM controlled on OHA ,

Complaining of Tingling & parathesia in both hands

and feet ?



Next Step



Macrocytosis

Definition• defined as a mean corpuscular volume greater than 100 fL

• occurs in approximately 3 percent of the general population

Classified as megaloblastic and nonmegaloblastic

Pathophysiology

• Megaloblastic processes are characterized on the peripheral smear bymacro-ovalocytes and hypersegmented neutrophils, which are absent in

nonmegaloblastic.• folate and vitamin B12 deficienciesresult in defective RNAand DNA

syntheses



Macrocytosis

Causes:

1 - Megaloblastic (involving Abnormalities of DNAmetabolism B12 and/or folate deficiency in: Atrophic gastritis Enteral

malabsorption

Drugs that impair DNA synthesis (methotrexate, sulfa, chemotherapy)

2 - Non-megaloblastic• Liver dz

• hypothyroidism

• Alcoholism• Myelodysplasia

• Reticulocytosis





Vitamin B12 Deficiency

• Vitamin B12 is crucial to normal neurologic

function, red blood cell production, and DNA

synthesis.

• Vitamin B12 (cobalamin) deficiency is a commoncause of megaloblastic anemia.



Causes of vitamin B12 deficiency Decreased ileal absorption

• Crohn disease

• Ileal resection

• Tapeworm infestation

Decreased intrinsic factor

• Atrophic gastritis

• Pernicious anemia• Postgastrectomy syndrome (includes Roux-en-Y gastric bypass)

Inadequate intake

• Alcohol abuse

• Older persons

• Vegetarians (includes exclusively breastfed children of vegetarianmothers)

Prolonged medication use

• Histamine H2blockers

• Metformin (Glucophage)

• Proton pump inhibitors



Suspect Vitamin B12 in the following

• Oval macrocytic red blood cells (ie, mean corpuscular volume >100fL) on the peripheral blood smear, with or without anemia

• The presence of hypersegmented neutrophils on the peripheralblood smear

• Unexplained neurologic signs and symptoms, especially dementia

or weakness, sensory ataxia, and paresthesias• High Risk populations, such as older adults, alcoholics, and patientswith malnutrition

• Strict vegans are at risk of vitamin B12 deficiency.

• Patients who have undergone bariatric surgery are also at risk ofdeveloping folate and vitamin B12 deficiency.

• Vitamin B12 and folate deficiency often coexist and are not easilydifferentiated on a clinical basis. such patients should be evaluatedfor both deficiencies.

Manifestations:



Manifestations:

Cutaneous

• Hyperpigmentation

• Vitiligo

Gastrointestinal

• Glossitis

•Jaundice

Hematologic

• Anemia (macrocytic, megaloblastic)

• Thrombocytopenia

Neuropsychiatric

• Cognitive impairment• Gait abnormalities

• Irritability

• Peripheral neuropathy

• Weakness



• up to 28 percent of affected patients may have

a normal hemoglobin level, and up to 17percent may have a normal MCV.

• No major medical organizations, including the

U.S. Preventive Services Task Force, havepublished guidelines on screening

asymptomatic or low-risk adults for vitamin B12

deficiency, but high-risk patients, such as thosewith malabsorptive disorders, prolonged use of

metformin and proton pump inhibitors may

warrant screening.



• The initial laboratory assessment of a patient with

suspected vitamin B12 deficiency should include a CBC

and a serum vitamin B12 level.• Measurements of serum vitamin B12 may not reliably

detect deficiency, and measurement of serum

homocysteine and/or methylmalonic acid should be used

to confirm deficiency in asymptomatic high-risk patients

with low normal levels of vitamin B12.

• In patients with clinical symptoms of vitamin B12

deficiency and low levels of serum vitamin B12, nofurther confirmatory testing is generally needed





Treatment

• IM injection of vitamin B12 at a dosage of

1 mg weekly for eight weeks, followed by 1 mg

monthly for life.

Or

• Oral vitamin B12 (1 to 2 mg daily)



Treatment

• In a 2005 Cochrane review, patients who received

high dosages of oral vitamin B12 (1 to 2 mg daily)

for 90 to 120 days had an improvement in serum

vitamin B12 similar to patients who receivedintramuscular injections of vitamin B12.

• These results were consistent in patients

regardless of the etiology of their vitamin B12

deficiency, including malabsorption & states and

pernicious anemia



• Because of the high incidence of vitamin B12deficiency in patients undergoing gastricbypass surgery, daily prophylactic

supplementation with 1 mg is recommended.

• Never give folate alone to an individual withmegaloblastic anemia because it will maskB12 deficiency and neurological degenerationwill continue



Summary





Questions

You have prescribed oral iron replacement for a 46-year-old female with iron deficiency anemia

related to heavy menses. She wants to be sure thatthe iron she takes will be absorbed well.

Which one of the following would you suggest forimproving iron absorption?

A) Calcium

B) Vitamin C

C) Coffee

D) Tea



After you started Iron

Which of the tests will be the first to indicate that

you have instituted appropriate therapy?



How long should you continue iron

supplementation?



• The patient returns to your office in 2 months

but her labs are worse than at first presentation.

• The patient swears that she has been taking the

iron faithfully.

Which can lead to a failure of iron therapy for

iron deficiency anemia?

Lab Interpretation



Lab Interpretation

Next Step ?



First Hg electrophoresis report

Second Hg electrophoresis report

Lab Interpretation



Lab Interpretation

The Physician orded Hb electrophoresis

What do you expect the results?



Interpret the Hb electrophoresis?



• A 67-year-old male with moderate macrocytosiscomplains of paresthesias of his feet. If thepatient has a borderline low vitamin B12 level,elevated levels of which one of the following

would suggest vitamin B12 deficiency?A) Serum gastrin

B) Reticulocytes

C) Methylmalonic acid

D) Serum ferritinE) Serum folate



Any Questions?

R f



References

• AAFP, American Academy of Family Physicians.

• Medscape.

• Up-to-date.



Anemia Last Islam

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