CHẨN ĐOÁN VÀ ĐIỀU TRỊ

THIẾU MÁU THIẾU SẮT

TS BS Nguyễn Minh TuấnBệnh viện Nhi Đồng 1

Khoa Y – Đại học Quốc gia TPHCMĐơn vị Nghiên cứu Lâm sàng Đại học Oxford

Hội nghị Khoa học Nhi khoa Bệnh viện Nhi Đồng 1TPHCM, 20-21/9/2019

Contents

• Definition of iron deficiency anemia

• Epidemiology

• Iron metabolism

• Etiology

• Diagnosis

• Management

Contents

• Definition of iron deficiency anemia

• Epidemiology

• Iron metabolism

• Etiology

• Diagnosis

• Management

ANEMIA

Defined as an insufficient RBC mass to adequately deliver oxygen to peripheral tissues.

-- Wintrobes

Defined as a decrease in the amount of red blood cells (RBCs) or the amount of hemoglobin in the blood. It can also be defined as a lowered ability of the blood to carry oxygen.

-- Wikipedia

Anemia is defined as a reduction of the total circulating red cell mass below normal limits

-- Robbins

ANEMIATheo Tổ chức Y tế thế giới, gọi là thiếu máu khi lượng hemoglobin (Hb) dưới giới hạn sau đây:

Tuổi / giới tínhHb bình thường

(g/dL)

Thiếu máu

(Hb ≤ giới hạn)

Trẻ sơ sinh (đủ tháng)

Trẻ từ 2 – 6 tháng

Trẻ từ 6 tháng đến 2 tuổi

Trẻ từ 2 – 6 tuổi

Trẻ từ 6 – 12 tuổi

Nam trưởng thành

Nữ trưởng thành (không mang

thai)

13.5 – 18.5

9.5 – 13.5

10.5-13.5

11.0 – 14.4

11.5 – 15.5

13.0 – 17.0

12.0 – 15.0

13.5 (Hct 34%)

9.5 (Hct 28%)

10.5 (Hct 33%)

11.0 (Hct 33%)

11.5 (Hct 34%)

13.0 (Hct 39%)

12.0 (Hct 36%)

IRON DEFICIENCY ANEMIA

Anemia with biochemical evidence of iron deficiency based on following laboratory findings:

• serum ferritin,

• total iron binding capacity (TIBC),

• transferrin saturation,

• or transferrin receptor

Contents

• Definition of iron deficiency anemia

• Epidemiology

• Iron metabolism

• Etiology

• Diagnosis

• Management

EPIDEMIOLOGY

• Globally, anemia affects 1.62 billion people , which corresponds to 24.8% of the population

• IDA occurs across all populations and is associated with

✓ Diminished QOL

✓ Physical and cognitive performance, and

✓ Unfavorable clinical outcomes

Classification of anemia as a problem of public health significant

Anemia prevalence

Contents

• Definition of iron deficiency anemia

• Epidemiology

• Iron metabolism

• Etiology

• Diagnosis

• Management

IRON DISTRIBUTION

IRON DISTRIBUTION

• Most body iron is present in haemoglobin in circulating red cells

• The macrophages of the reticuloendotelialsystem store iron released from haemoglobinas ferritin and hemosiderin

• Small loss of iron each day in urine, faeces, skin and nails and in menstruating females as blood (1-2 mg daily)

IRON ABSORPTION

• Food sources supply: 10 - 25 mg / day

• Absorbed in the brush border of the upper small intestine– Enhanced by gastric acid

– Inhibited by tannins, systemic inflammation

• Most dietary iron is nonheme form, <5% bioavailability

• < 10% dietary iron is heme form, >25% bioavailability

IRON ABSORPTION

Iron absorption from food

Iron Absorption (% of dose)

0 5 10 15 20 25

Veal muscle

Hemoglobin

Fish muscle

Veal liver

Ferritin

Soy beans

Wheat

Lettuce

Corn

Black beans

Spinach

Rice

Non-heme

iron

Heme

iron

Contents

• Definition of iron deficiency anemia

• Epidemiology

• Iron metabolism

• Etiology

• Diagnosis

• Management

ETIOLOGY

• IDA results from prolonged negative iron balance

• Mainly due to following factors:

1. Inadequate iron intake: infancy, inappropriate diet

2. Decreased iron absorption:

3. Increased iron demand or hematopoiesis: prematurity, low-birth weight, cyanotic congenital heart diseases, polycythemia

4. Increased iron loss: GI bleeding, menorrhagia, recurrent bleeding of hematologic diseases, etc.

Matthew W. et al. Am Fam Physician. 2013;87(2):98-104

PROGNOSIS

IDA adversely effects:• Cognitive performance, behavior, and physical

growth of infants, preschool, and school-agedchildren

• The immune status and morbidity from infections of all age groups

• The use of energy sources by muscle and thus the physical capacity and work performance of adolescents and adults of all age groups

• Increase perinatal risks for mothers and neonates and overall infant mortality during pregnancy

Contents

• Definition of iron deficiency anemia

• Epidemiology

• Iron metabolism

• Etiology

• Diagnosis

• Management

Preliminary findingsChief ComplaintsFatigue, lassitude, palpitation, and generalized weakness

HistoryChronic blood loss, deficient diet

Clinical Features1. Palor: skin, nailbed, conjunctiva2. Koilonychia (brittle, spoon shaped nails)3. Atrophic glossitis (atrophy of tongue papilla;

making the tongue smooth and shiny)4. Pica (compulsive eating of nonfood items)

or pagophagia (compulsive eating of ice)

Symptoms and SignsSymptoms Signs

Decreased exercise tolerance

Tachycardia

Fatigue Pale appearance (most prominent inconjunctiva)

Dizziness Decreased mental acuity

Irritability Increased intensity of some cardiac valvular murmurs

Weakness

Palpitations

Vertigo

Shortness of breath

Chest pain

Laboratory evaluation

• Complete blood count (CBC), erythrocyte sedimentation rate (ESR), and peripheral blood film (PBF)

• Serum Iron profile

• Bone marrow study (if needed)

• Investigations to determine other causes of IDA (e.g. fecal occult blood test, colonoscopy, gastroscopy, etc.)

Lưu đồ chẩn đoán thiếu máu

DIFFERENTIAL DIAGNOSIS

Ferritin Serum iron RDW

IDA Reduced Reduced Raised

Thalassemia Raised Raised or

Normal

Normal

Chronic disease Raised or

Normal

Reduced Normal

IDA Thalassemia trait

Mentzer index

MCV : RBC

> 13 < 13

Srivastava index

MCH : RBC

> 3,8 < 3,8

Shine and Lal index

(MCV2 x MCH) x 0.01

> 1530 < 1530

MCV – RBC – (Hb x 5) – 3.4 > 0 < 0

Green and King index

(MCV2 x RDW) x Hb x 0.01

> 65 < 65

RDW – CV% > 14,6 < 14,6

RDW index

MCV x RDW : RBC

> 220 < 220

DIFFERENTIAL DIAGNOSIS

Contents

• Definition of iron deficiency anemia

• Epidemiology

• Iron metabolism

• Etiology

• Diagnosis

• Management

Therapeutic goals

Short term

• Resolution of symptoms

• Replenish iron stores

Long term

• Improve quality of life (QOL)

• Prevention of recurrences

• Better growth and development (children)

MANAGEMENT

Treatment options

Pharmacological management

• Oral/parenteral iron therapy

Non-pharmacological

• Blood transfusion

MANAGEMENT

Matthew W. et al. Am Fam Physician. 2013;87(2):98-104

Dosage of oral iron therapy:

4-6mg/kg/d, t.i.d

Forms:

• Tablets, capsules

• Sugar coated & uncoated tablets

• Slow release tabs & chewable tabs

• Drops & syrups—used by children

MANAGEMENT

AVAILABLE PRODUCTS

DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011

AVAILABLE PRODUCTS

Forms:

• Tablets, capsules

• Sugar coated & uncoated tablets

• Slow release tabs & chewable tabs

• Drops & syrups—used by children

Response to oral therapy

• 12 – 24hrs: restore enzyme, improve appetite andirritability

• 48 – 72hrs: reticulocytes increase, peak after 1 – 2 weeks

• Considered as satisfactory if Hb ↑ by 1 % per day (0.15 g %), with at least 10 % (1.5 g % ) within 3 weeks

Factors influencing iron absorption

Important points to remember

• Elemental iron content and not quantity of iron compound per unit dose to be considered

• Sustained released preparations expensiveand irrational

• Liquid formulations should be put on back of tongue and swallowed

• Absorption better on empty stomach but sideeffects more

Common side effects

• Gastrointestinal (GI) intolerance

Nausea, vomiting, heartburn, and constipation or diarrhea

➢ Slow release or sustained release preparations may be used

➢ Combination products, e.g. Ferro-DDS (ferrousfumarate/docusate), may be advantageous for certain patient population

• Cause discoloration of stool

• Metallic taste

• Staining of teeth

Parenteral iron therapy

➢ Indications for therapy• Intolerance to oral route• Malabsorption• Long-term nonadherence• Patient with significant blood loss who refuse transfusion and are

intolerant to oral therapy• Chronic kidney disease (CKD) or malignancy

➢ Currently available formulations includeDextran, sodium ferric gluconate, iron sucrose, ferumoxytol➢ Formulations differ in their molecular size, degradation

kinetics, bioavailability, and side effects profile➢ All preparations carry a risk for anaphylactic reactions

but likely to a lesser extent than iron dextran

𝑙ượ𝑛𝑔 𝑠ắ𝑡 (𝑚𝑔) =𝑡ℎể 𝑡í𝑐ℎ 𝑚á𝑢 × 12,5 − 𝐻𝑏 𝑏𝑛 × 3,4 × 1,2

100

rải ra tiêm bắp hay tĩnh mạch cách ngày hay cách tuần

trong 2-3 tuần, ≤0,1 mg/kg/liều.

Thể tích máu: ml/kg

3,4: 1g Hb cần 3,4mg sắt

1,2: thêm 20% cho sắt dự trữ

Parenteral iron therapy

Iron supplementation to prevent IDA

TAKE-HOME MESSAGES

➢ IDA is the most common form of anemia

➢ Four main factors contributing to IDA:

• Inadequate iron intake

• Decreased iron absorption

• Increased iron demand or hematopoiesis

• Increased iron loss

➢ Complete patient history, physical exams, and laboratory investigations

➢ Abnormal laboratory investigations: low MCV, serum iron, and ferritin.

➢ Treatment of IDA consists of dietary supplementation and administration of oral iron preparations.

➢ Complete therapeutic response requires iron supplementation for 3 months after Hct and ferritin levels normalize.