Understanding Iron Deficiency Anaemia (IDA) Lab Test & management

with focus on Parenteral Iron therapy

Dr. Sharda Jain

ANAEMIA FREE INDIA

ANAEMIA FREE WOMEN & GIRLS

is our AIM

Objectives

• Basic of Anemia in India

• key aspects of lab evaluation

• Systematic approach to Parenteral

Iron therapy in anemia

India has largest no of

• Anaemic women • Anaemic girls • Anaemic children

Anaemic MOTHERS make Anaemic BABIES

Few factsHard to swallow

8 out of 10

Children, adolescent and women

are anaemic.

BUT

The silver lining is

50% are only mildly anaemic

Anaemia drains all our energy &

makes us “Lazy Race”

Lets Pledge in 2015 to make

• Anaemia Free India• Anamia Free School• Anaemia Free Family• Anaemia Free Children

Hb of GIRLS AND WOMEN should not be less than 12gm%

In India our AIM is

12gm by 12 yrs

where as

in West AIM is for Hb 14-15gm

It is doable

&

we can do it

CHINA Role Model

• Once they brought one child norm, they concentrated on saving this child and making him/her healthy.

• Their incidence of anaemia in children, adolescent has markedly decreased.

• They have increased the height of their

children by 4-6 inc.

If they can do it, why can’t we do it.

• There are 1 million GOOD TEACHERS and 20 million highly placed WORKING WOMEN in India.

Each should work hard to make their class

Student’s and co workers :Anaemia Free”.

• Every parent should take pledge to make their family “Anaemia Free”

There are 8 lacs Doctors & 8 lacs nurses

• Bone MarrowPluripotent stem cells– Life span

•Reticulocyte- 4 days•RBC –120 days

Few facts about lab tests

The Important Players

• Hemoglobin

–Transports 02 from lungs to tissues

– 4 globin chains & iron

The important players • IRON

– key element in the production of hemoglobin

– absorption is poor

• TRANSFERRIN– iron transporter

• FERRITIN– iron binder, measure of iron stores,

Definitions

• Anemia-values of Anemia-values of HEMOGLOBIN, HEMATOCRIT or RBC counts which are more or RBC counts which are more than 2 standard deviations below the meanthan 2 standard deviations below the mean

– HGB<13.5 g/dL (men)HGB<13.5 g/dL (men) <12 (women)<12 (women)

– HCT<41% (men)HCT<41% (men) <36 (women)<36 (women)

Infants 6-12 months & children 1-2 years < 11 gm%

Adolescent girls < 12 gm%

Pregnant women < 11 gm%

Lactating women < 12 gm%

Women in reproductive age group < 12 gm%

Adult men < 13 gm%

Moderate anaemia 7 - 10.0 gm%

Severe anaemia < 7 gm%

WHO GUIDELINES HAEMOGLOBIN CUT OFF LEVELS

FOR DETERMINING ANAEMIA

ALGORITHM FOR EVALUATION OF ANEMIAALGORITHM FOR EVALUATION OF ANEMIA

ANEMIC PATIENT

Hyper-regenerative

Evaluate for hemolysisand bleeding

Hypo-regenerative

Rule out treatable nutritional deficiency (IDA , FA – B12)

endocrinopathy, etc

Low-EPO High-EPO

Trial of EPO Consider BMBxContinue EPO

Retic index

Epo level

Response No response

Laboratory Evaluation

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

Laboratory Evaluation • Bleeding *Iron Deficiency

– Serial HCT or HGB - Iron Studies

• Hemolysis– Serum LDH, – indirect bilirubin, – haptoglobin,– coombs,– coagulation studies

• Bone Marrow Examination

• Others-directed by clinical indicationhemoglobin

electrophoresisB12/folate levels

Information from CBC Parameters

1. HB/PCV : Degree of anaemia. Correlates with patient’s symptoms.

HB : PCV ----- 1 : 3

2. MCV, MCH, Peripheral Smear: allow Morphological Classification of anemia, guide workup and allow assessment of response to therapy

Peripheral smear: Shape, size, degree of pigmentation of cell types, presence of abnormal cells and blood parasites aid diagnosis of type of anemia

Reticulocyte count : An appropriate response (after correction) shows appropriate erythropoietin release, a marrow capable of producing red cell precursors, and sufficient iron stores.

Normal Polychromasia

PBS

Normal rbc Microcytosis, hypochromia

NormalMacrocytic/megaloblastic

Microangiopathic hemolytic anemia

Spur cell anemia (liver disease)

Hereditary spherocytosis

CBC PARAMETERS IDA THALASSEMIA

RBC count < 5 million/ml >5 million /ml

RDW >14 <14

Mentzer’s Index >14 <14

MCV

MCH

MCHC NORMAL

IDA / THALASSEMIA

IDA VERSUS THALASEMIA

MENTZER’S INDEX

MCV/ RBC < 14 THALASEMMIA

> 14 IDA

SPECIFIC INVESTIGATIONS

• SERUM FERRITIN

• HPLC --- if needed

UK Guidelines on the management of iron deficiency in pregnancy 2012

NOT ROUTINELY RECOMMENDED

• SERUM IRON• TIBC• % TRANSFERRIN SATURATION

Only when serum Ferritin is normal but clinical and morphological picture strongly suggestive of Iron Deficiency Anaemia

SERUM FERRITIN

• Serum ferritin is the best single indicator of storage iron.

Adults (ug/L)– less than 12→ diagnostic of iron deficiency– 15 - 50 → probable iron deficiency– 50 - 100 → possible iron deficiency– more than 100 → iron deficiency unlikely– persistently more than 1000 → consider test for iron

overload

TESTS OF IRON STATUSPractical aspectsPractical aspects

• Low serum ferritin almost always indicates iron deficiency

• Low serum iron and high TIBC almost always indicate iron deficiency

• Ferritin > 100 rarely found in iron deficiency– Exception - liver inflammation/necrosis

• Normal serum iron rarely found in iron deficiency– Exception - iron deficiency recently treated

with oral iron

TESTS OF IRON STATUSPractical aspectsPractical aspects

• When TIBC is low or normal, low serum iron not a reliable indicator of iron deficiency!

• IRON DEFICIENCY may be HARD TO DIAGNOSE via blood tests in setting of INFLAMMATION (eg, low iron, low TIBC, intermediate ferritin level)– Therapeutic trial of iron +/- EPO a reasonable alternative to

marrow biopsy

Treatment PlansTreatment Plans

Remember 5 A’s

• Ask what is your Hb• Ask when was it done last • Ask what is the normal Hb • Ask to get it done right away • Advise : Diet : Tablet : Deworming

DIET --- IRON AND PROTEINS

SOURCES OF IRON

Green leafy vegetables

Legumes, Nuts

Jaggery , Dried Fruits

Meat , Liver ,

Poultry , Fish

SOURCES OF FOLIC ACID

Green leafy vegetables

Legumes, Nuts

Milk , Fruits

Meat , Liver , Eggs

WHO (deworming)

•Drug of choice is Mebendazole 100mg BD for 3 days

OR Albendazole 400mg

•In pregnant women with anaemia after 12 weeks of pregnancy

REASONS FOR FAILURE TO ORAL IRON REASONS FOR FAILURE TO ORAL IRON THERAPYTHERAPY

Reasons for failure to oral iron therapyReasons for failure to oral iron therapy

44

Ferric Carboxymaltose Injection

For the use of a Registered Medical Practitioner or a Hospital or a Laboratory only

Parenteral Iron Therapy &

medical@

emcure.co.in

Parenteral Introduction of Iron

• in severe iron deficiency anemiain severe iron deficiency anemia• intolerance of oral preparations intolerance of oral preparations • Gynae Conditions - before surgery ,Gynae Conditions - before surgery , After Delivery , After Delivery , AUB/ DUB with moderate anamia AUB/ DUB with moderate anamia Pregnancy Anamia Pregnancy Anamia

• diseases of gastro-intestinal tractdiseases of gastro-intestinal tract• continuous blood losscontinuous blood loss• not compensated by oral method not compensated by oral method

Recent Advance in Parenteral Iron -Ferric Carboxymaltose Injection

Injection Iron Sucrose

Properties of an ideal parenteral iron

Property

Type

Molecular weight

Complex stability

Half life

pH

Osmolality

Antigenicity

Test dose

Time for inj.

Max dose

Ideal

I (robust)

>100 kD

High

Long

Neutral

Isotonic

Low

No

Short

High

Iron dextran

I (robust)

>100 kD

High

3-4 days

Neutral

Isotonic

High

Yes

4 - 6 h for 20mg/kg

20mg/kg

Iron sucrose

II (semi-robust)

34-60 kD

Moderate

6 hours

High

High

Low

No

15 min for100mg

600 mg/week

Ferric carboxymaltoseI (robust)

150 kD

High

16 hours

Near-Neutral

Isotonic

Low

No

15 min for 1000mg

1000 mg/infusion /week

Iron usage over years

Dosage• For IV use only• Conventionally calculated using Ganzoni formula: Cumulative iron deficit

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

• Use simpler regimen as used in FERGIcor study [Gastroenterology 2011]

Cumulative iron dose of 500 mg should not be exceeded for patients with body weight < 35 kg

Dilution for Infusion • In case of drip infusion Ferric Carboxymaltose Injection must be diluted only in

sterile 0.9% sodium chloride solution as follows:

Iron Maximum volume of normal saline

Minimum time for

administration

200 to < 500 mg 100 ml 6 min

500 to <1000 mg

250 ml 15 min

How critical is speed of infusion?What could be the consequence of excessive dilution (<2mg/ml)?

FERRIC CARBOXYMALTOSE INJECTIONFERIUM INJECTION

Allaying the fear of an injectable iron…..

Adverse effects*System Common

(>1%- <10%)Uncommon

(>0.1% - <1%)Immune system hypersensitivity

Nervous system headache (3.3%); dizziness paraesthesia

Vascular hypotension, flushing

Gastrointestinal nausea, abdominal pain, constipation, diarrhoea

dysgeusia, vomiting, dyspepsia, flatulence

Skin rash pruritus, urticaria

Musculoskeletal myalgia, back pain, arthralgia

General injection site reactions pyrexia, fatigue, chest pain, rigors, malaise, oedema peripheral

Investigational transient blood phosphorus decreased, alanine

aminotransferase increased

aspartate aminotransferase increased, gamma-glutamyltransferase increased, blood lactate dehydrogenase increased

* UK-MHRA approved Prescribing Information

FERRIC CARBOXYMALTOSE INJECTIONFERIUM INJECTION

Allaying the fear of an injectable iron…..

Contraindications

• Known hypersensitivity to Ferric Carboxymaltose Injection or to any of its excipients

• Anaemia not attributed to iron deficiency• Evidence of iron overload or disturbances in

iron utilization of iron• First trimester pregnancy • Children below 14 yrs

Comparative Efficacy of 3 Parenteral Irons

Journal of Blood Transfusion Volume 2012, Article ID 473514 Adobe Acrobat

Docum ent

Perioperative anemia

• There is a high incidence of preoperative and postoperative anemia in surgical patients, with a coincident increase in blood utilization.

• These factors are associated with increased risk for perioperative infection and adverse outcome (mortality) in surgical patients.

Journal of Surgical Research 102, 237–244 (2002)

LIFECARE EXPERIENCE

IRON SUCROSE

• USED IN OVER 500 CASES• ALL PREGNANT WOMEN• 6 PATIENTS HAD REACTIONS• THOUGH NOT MAJOR BUT SCARY ENOUGH

• DEFINITE RISE IN HB IS NOT ASSURED Severe Reaction if Occurs Recovery is Difficult

Company itself is withdrawing

FERRIC CARBOXYMALTOSE

• USED IN 304 CASES• 256 NON PREGNANT AND 48 *PREGNANT• 3 PATIENTS HAD REACTIONS (Rashe 2 , swollen lips 1)

• AGAIN THOUGH NOT MAJOR BUT SCARY ENOUGH

• RISE IN 2 gm HB SEEN IN 1 MONTH IN 90% OF CASES

*Pregnancy not approved by drug controller of India

Our Protocol

• COUNSELING AND CONSENT

• EMERGENCY TRAY

• RESUSCITATION FACILTIES

• ENOUGH EXPERIENCED MANPOWER – DOCTORS, NURSES

Conclusion

• Major benefits of FCM inj over iron sucrose Inj.

• Safe

• Rapid infusion rate – 1000 mg in 15 minutes

• Low antigenicity

• No test dose required

Thank You

Thank You