SEMINAR OF ANAEMIA

(PHYSIOLOGY)

By Group 3

COMPOSITION OF BLOOD

1. Cellular Portion (45% of

total blood volume)

-Erythrocytes (RBCs)

-Leukocyes (WBCs)

-Thrombocytes

2. Fluid portion (Plasma, 55%

of total blood volume)

Erythrocytes

Biconcave Disk

Flattened

Flexible

Semi-permeable

membrane

Contains Antigen

(ABO & Rh) Blood

type

Anuclear

No Mitochondria

Erythrocytes

Life Span

100-120 days

FUNCTIONS

Transport O2

to tissues

Transport CO2

from tissues

Fate

Destroyed by

macrophage cells

(liver, spleen,

bone marrow)33% of RBC cell

mass consist of

hemoglobin

Normal Erythrocytes

Normal Value

Male : 4.32 – 5.72 X 1012 cells/L

Female : 3.90 – 5.03 X 1012 cells/L

Source : myoclinic.org/test-procedures/complete-blood-count/basics/results/prc-20014088

Hemoglobin

Consist of 4 Globin

Adult (HbA) : 2α & 2β

Fetal (HbF) : 2α & 2γ

1 Heme bound to each

globin

Hemoglobin Normal Values

Adults

Male

13.5 - 17.5 g/dL

Female

12.0 - 15.5 g/dL

Source : myoclinic.org/test-procedures/complete-blood-count/basics/results/prc-20014088

Children

Newborn

14 - 24 g/dL

Infant

9.5 – 13 g/dL

Pregnancy

11 – 12 g/dL

77% HbF (Newborn)

↓

23% HbF (after 4 month)

Hemoglobin Synthesis

Source : myoclinic.org/test-procedures/complete-blood-count/basics/results/prc-20014088

a and β genes

mRNAs

a and β globins chain

Haemoglobin

Succinyl CoA+ Glycine

Protophophyrins

Heme

Fe

Erythropoiesis

Primitive Hemopoietic Stem Cell (HSC)

Proerythroblast

Early normoblast

Late normoblast

Reticulocyte

Erythrocyte

Regulators of Erythropoiesis

• Erythropoietin (EPO)

Synthesis depends on the supply of

1. Iron

2. Folic Acid

3. Vitamin B12

Binds O2 in the Hb within PBC

For Thymine synthesis DNA formation

Normal cell division/maturation

Deficiency

↓Hb Production

↓Erythropoiesis

Stimulate proliferation of erythrocytes progenitor

cells & their differentiation into mature RBCs

Required for Folic acid function DNA formation

Normal cell division, maturation

Rate of Erythropoiesis

The Pathology: ANEMIA

By Group 1

Anaemia

Definition

WHO : ANAEMIA is a condition in which the number ofred blood cells or their oxygen carrying capacity isinsufficient to meet physiologic needs, which vary byage, sex, altitude, smoking and pregnancy status.

OXFORD : ANAEMIA is defined as low heamoglobin(Hb) concentration, and may be due either to a low redcell mass or increased plasma volume.

Source : www.who.int/topics/anaemia/en/

Reduction of Hb concentration below

normal

ANAEMIA

Female Adult : <11.5 g/dL

Male Adult : < 13.5 g/dL

2 years – puberty : < 11 g/dL

Newborn infants : < 14 g/dL

Types of Anemia

Based on Mean Cell Volume (MCV)

- Normal MCV : 76-96 fL (femtolitres)

Low MCV

MICROCYTIC

ANAEMIA

Normal MCV

NORMOCYTIC

ANAEMIA

High MCV

MACROCYTIC

ANAEMIA

Varying MCV

HAEMOLYTIC ANAEMIA

Low MCV

MCV < 80fLMCH <27pg

MICROCYTIC

ANAEMIA

Normal MCV

MCV 80 – 95 Fl

MCH > 27 pg

NORMOCYTIC

ANAEMIA

High MCV

MCV > 95 fL

MACROCYTIC

ANAEMIA

1. Iron-Deficiency

Anaemia

2. Thalassemia

3. Sideroblastic

Anaemia

1. Acute blood

loss

2. Anaemia of

Chronic Disease

3. Bone marrow

failure

4. Renal failure

5. Hypothyroidism

6. Haemolysis

7. Pregnancy

1. B12 / Folate

Deficiency

2. Alcohol excess /

Liver Disease

3. Reticulocytosis

4. Cytotoxics

5. Marrow

infiltration

6. Hypothyroidism

7. Antifolate drugs

(Phenytoin)

Source : Murray Longmore, Oxford Handbook of Clinical Medicine, 9th Edition, 2014.

MCV: 80 to 100fL

MCH: 27 to 31

picograms/cell.

CLASSICAL SIGN AND SYMPTOMS

SIGNS SYMPTOMS

Pallor Shortness of breath

Tachycardia (Compensatory Mechanism) Lethargic

Cardiac failure Weakness

Palpitation

Headaches

Angina pectoris

Confusion

MICROCYTIC ANAEMIA

Iron Deficiency Anemia (IDA)

Group 3

• Most common and widespread of nutritional disorder in the world

• Affecting large number of women and children in non-industrialized

country and virtually all industrialized nations.

• Half of pregnant women in the world estimated to be anemic (52% non

industrialized, 23% industrialized.)

Prevalence

Classification

based on WHO

Malay

N=135

Chinese

N=130

Indian

N=123

All

N=388

Anemia

(Hb < 12g/L)

16.4 20.6 26.4 20.9

Depleted iron

storage (ferritin <15

22.9 25.2 53.9 33.0

IDA

(Hb<12g/L+ferritin

<15 + MCV <80 fl

4.3 9.9 18.0 10.3

The prevalence of anaemia and IDA

among urban Malaysian women

Prevalence of anaemia, depleted iron stores and IDA

(Medicine UPM 2010)

WHO regions Children

(0-4years)

Children

(5- 14 years)

Pregnant

women

All

women

(15-

59years)

Men

(15-

59years)

Elderly

Africa 45 228 85 212 10 800 57 780 41 925 13 435

America 14 220 40 633 4 500 53 787 19 443 12 617

South East Asia 111 426 207 802 24 800 214 991 184 752 60 206

Europe 12 475 12 867 2 400 27 119 13 318 18 095

Eastern

mediteranian

33 264 37 931 7 700 60 196 41 462 11 463

Western pacific 29 793 156 839 9 700 158 667 174 400 78 211

Overall 245 386 541 284 59 900 572 540 475 300 194 029

Estimated prevalence of anaemia (1990-1995) by WHO Region based on

blood haemoglobin concentration (WHO)

Mariah a 17 year old student who has recently migrated from Australia to

Malta with her parents. She comes to you complaining of general fatigue and

occasional dizziness. Mariah has no significant past medical history and is not

any regular medicine. She does not drink alcohol or smoke. Her parents are

both healthy. On examination, she has strong peripheral pulses, and her

cardiovascular system examination is normal. BP is 115/75mmHg, pulse

90/min and BMI 19.5kg/m2. Mariah has pale skin, conjunctiva and nail beds.

Scenario

Poor Diet Intake

Pathophysiology& Causes of IDA

Loss Of IRON Stores (Depletion Of Hemoglobin Recourse)

Malabsorption

Increased demands

Chronic blood loss

• GIT : peptic ulcer, esophageal varices, aspirin ingestion,

stomach/caecum/colon carcinoma, hookworm, angiodysplasia etc.

• Uterine menstrual loss (Menorrhagia)

• Prolonged hematuria, hemoglobinuria,, pulmonary haemosiderosis ,self

inflicted blood loss (rare)

Chronic blood loss

• Prematurity

• Growth

• Pregnancy

• Erythropoietin therapy

Increased demands

• Gluten-induced enteropathy

• Gastrectomy

• Autoimmune (atrophic) gastritis

Malabsoprtion

• A major factor in many developing countries but rarely the sole cause in

developed country

Poor diet intake

• Brittle nails

• Koilonychia

• Atrophy of papillae of the tongue, painless glossitis

• Angular stomatitis

• Dysphagia ( Plummer Vinson syndrome)

• Pica

Sign and Symptoms of IDA

• Blood count and film

- microcytic (MCV< 80 fl) and hypochromic (MCH < 27pg) anemia

- Poilocytosis

- Anisocytosis

Investigation

Iron deficiency anemia, severe. Blood film.

The field displays virtually all hypochromic

cells with an exaggerated pale center (arrow)

Test Findings

MCV Reduced

Serum iron Reduced

Serum TIBC Raised

Serum ferritin Reduced

Serum soluble transfer receptor Increased

Iron in marrow Absent

Iron in erythroblast Absent

Investigation cont.

• Treat the underlying causes

• Oral iron – ferrous sulphate ( 200mg three times daily, a total of 180mg

ferrous iron ) /- ferrous gluconate (300mg twice daily , only 70mg ferrous

iron)

• Parenteral iron (for high iron requirement)– ferric hydroxide sucrose (

200mg )/ iron dextran/ ferric carboxymaltose

Management

THALASSEMIA

Group 1

DEFINITION & EPIDEMIOLOGY

DEFINITION

Hereditary disease (autosomal recessive) ;

Defective in synthesis of globin chain in thalassemia -> imbalance globin

chain production-> precipitation of globin chain within red cell precursor->

ineffective erythropoiesis.

CAUSES

Thalassemia is caused by

mutations in the DNA of cells that

make hemoglobin .

The mutations associated with

thalassemia are passed from

parents to children.

The mutations that cause

thalassemia disrupt the normal

production of hemoglobin and

cause low hemoglobin levels and a

high rate of red blood cell

destruction, causing anemia.

CLASSIFICATION

thalassemia

alpha

1 gene

deletion

2 gene

deletion

3 gene deletion

4 gene deletion

beta

major minor Intermedia

CASE SCENARIO

Adriana is a 7 –years-old who lives with her parents in a suburban community.

Her parents brought Adriana to the US from their homeland in Greece when

she was 1-year-old. At the age of 3, Adriana was in the 10th percentile for

height and weight, pale, and her Hb was 5.8 g/dl. Following further diagnostic

studies, she was diagnosed with beta thalassemia major. Over the cause of the

next 4 years, Adriana was hospitalized every 1 – 2 months, so she could be

transfused with pack red blood cell.

PATHOPHYSIOLOGY• α-thalassemia

primarily to gene deletion causing reduced α-globin chain synthesis

Since all adult haemoglobin are containing, α-thalassemia produces no change in

the percentage distribution of haemoglobin A, A2 and F. In severe form of α-

thalassemia, excess β chain may form a β4 tetramere called haemoglobin H.

• β-thalassemia

Defects that result in absent β globin chain is called as βᴼ

Reduced synthesis is termed β

SIGNS AND SYMPTOMSTYPES ( ALPHA THALASSEMIA) SIGNS AND SYMPTOMS

Four-gene deletion (Hb Barts) Pale, oedematous, enormous livers and

spleen (hydrops fetalis)

Three-gene deletion Moderate anaemia and splenomegally

Two-gene deletion Mild anaemia

One-gene deletion Normal

TYPES ( BETA THALASSEMIA) SIGN AND SYMPTOM

Thalassemia minor Anaemia is mild or absent

Thalaasemia intermedia -Moderate anaemia

- May varies depending on mutation

Thalassemia major -severe anaemia

-Failure to thrive

-recurrent bacteria infection

-hepatosplenomegaly

-bone expansion

-classical thalassemic facies

-jaundice

INVESTIGATIONS (Can Be Applied To Both Alpha & Beta)

• Complete blood count

– Hb, MCV, MCH low

– RBC increased

– Red cell distribution width (RDW) – normal

• Peripheral blood film

– Microcytic, hypochromic

– Target cells, basophilic stipling, ± nucleated RBC

Blood smear showing marked microcytosis, hypochromia, target cell, and anisocytosis.

Peripheral blood smear showing basophilic stippling

CONT

• Hb analysis

– HPLC – No Hb A at all, replaced by Hb F and A2

– Hb electrophoresis – will be further explain after

this

• DNA analysis – alpha and/or beta gene

• Family screening

CONT…

•Haemoglobin (Hb) electrophoresis test

• Blood test done to check the different types of Hb in the blood.

• It uses an electrical current to separate normal and abnormal types of Hb in the

blood. Hb types have different electrical charges and move at different speeds.

The amount of each Hb type in the current is measured.

• An abnormal amount of normal Hb or an abnormal type of Hb in the blood may

mean that a disease is present.

• Typical finding : HbA decreased or absent, HbF increase, HbA2 variable

CONT…

• The most common abnormal Hb are :

– Haemoglobin S. This type of haemoglobin is present in sickle cell

disease.

– Haemoglobin C. This type of haemoglobin does not carry oxygen

well.

– Haemoglobin E. This type of haemoglobin is found in people of

Southeast Asian descent.

– Haemoglobin D. This type of haemoglobin is present in some sickle

cell disorders.

COMPLICATIONS

•Iron overload.

People with thalassemia can get too much iron in their bodies, either from the disease

itself or from frequent blood transfusions.

Too much iron can result in damage to :

•Infection.

People with thalassemia have an

increased risk of infection,

especially to those who had

splenectomy.

• In cases of severe thalassemia:

• Bone deformities. Thalassemia can make bone marrow expand, which causes bones to

widen.

This can result in abnormal bone structure, especially in face and skull.

Bone marrow expansion also makes bones thin and brittle, increasing the chance of broken bones.

•Enlarged spleen (splenomegaly). Thalassemia is often accompanied by the destruction of a large number

of red blood cells, making spleen work harder than normal, causing it to enlarge.

Splenomegaly worsen anemia as it can reduce the life of transfused red blood cells.

If spleen grows too big, it may need to be removed.

•Slowed growth rates. Anemia can cause a child's growth to slow.

Puberty also may be delayed in children with thalassemia.

•Heart problems. Heart problems, such as congestive heart failure and abnormal heart rhythms

(arrhythmias), may be associated with severe thalassemia.

Sideroblastic Anaemia

Group 4

Aetiology (Hereditary)

Structural defect of ALA-S gene

Impairment of heme synthesis

Accumulation of iron in mitochondria of erythroblasts

A ring of iron granules seen in Perls’ stain

Aetiology (Acquired)

Malignant diseases

Benign conditions

Signs & Symptoms

•Shortness of breath

•Weakness

•Lethargy

•Palpitation

•Headaches

•Visual disturbances – due to retinal

haemorrhages

•In older pt , symptoms of cardiac

failure , angina pectoris or

intermittent claudication or

confusion may be present.

•Pallor of mucous membranes

•Tachycardia

•Bounding pulse

•Systolic flow murmur at apex

SignsSymptoms

Laboratory investigations

Full blood count

Red cell indices

Peripheral blood film

Bone marrow iron

Iron studies

*Presence of 15% or more of ring sideroblasts in bone marrow

Basophilic stippling seen in lead poisoning

Sideroblastic anaemia

Hb Low

MCV Usually low in congenital type but MCV often raised in acquired type

MCH Usually low

Serum iron Raised

TIBC Normal

Serum transferrin receptor Normal

Serum ferritin Raised

Bone marrow iron stores Present

Erythroblast iron Ring forms

Haemoglobin electrophoresis Normal

Management

Pyridoxine therapy

Removal of toxic agents

Folic acid therapyBlood transfusion + iron chelating

agent

• Other factors that have been implicated:– Bone marrow toxins retained in renal failure

– BM fibrosis secondary to hyperthyroidism

– Haematinic deficiency– iron, vit B12, olate

– ↑ red cell distribution

– Abnormal red cell membranes causing ↑ osmotics fragility.

– ↑ blood loss– occult GIT bleeding, blood sampling, blood loss during haemodialysis or b’coz of platelet dysf(x).

– ACE inhibitors(by interfering w control of edogenous erythropoietin release)

11/18/2015

Macrocytic Anaemia

Megaloblastic Anaemia

Group 1

Epidemiology

• In developing countries, the deficiency of vitamin B12 is

significant in Africa, India, and South and Central America

due to low intakes of animal products.

• In western countries, severe deficiency is usually caused by

pernicious anaemia.

• B12 deficiency is more common in the elderly because B12

absorption decreases in atrophic gastritis patients which is

common in the elderly.

Case Scenario A 70-year-old woman presented with progressive weakness and fatigue.

The symptoms had begun about a month earlier, and she no longer felt well

enough to do her housework or take her daily walk. She experienced shortness

of breath on exertion. Complete blood cell count (CBC) was performed and the

results were, hemoglobin, 5.4 gm/dL; mean corpuscular volume (MCV), 103

µm3 (normal 76-96) ; red cell distribution width (RDW), 19.8% (normal, 12%-

15%),

She had no history of recent bleeding, jaundice, fever, anemia, or heart

disease. She had not been exposed to medications (other than occasional

vitamins and aspirin) or toxins.. Findings on the physical examination were

unremarkable except for mild tachycardia at rest (96 bpm), a blood pressure of

146/84 mm Hg recumbent and 142/78 mm Hg standing, pallor. Neither the liver

nor spleen were palpable. The stool was negative for occult blood. A chest x-ray

was normal, and an electrocardiogram showed only sinus tachycardia. The

blood urea nitrogen (BUN) level was 15 mg/dL; glucose, 108 mg/dL; and total

bilirubin, 1.2 mg/dL (normal, <1.2). Electrolyte levels were normal. A sickle

cell preparation was negative. Low serum B12 was notedBlood Film was

ordered

Causes of Megaloblastic Anaemias

• Vitamin B12 deficiency

• Folate deficiency

• Abnormalities of vitamin B12 or folate metabolism (eg transcobalamine deficiency , nitrous oxide, antifolate drugs)

Pathophysiology of Vitamin B12

Vitamin B12 is cofactor for:

1) Synthesis of thymidine

2) Normal methionine synthesis

In their absence:

Cause inadequate DNA synthesis

Defective nuclear maturation

(Nucleocytoplasmic Ansynchrony)

Blockade in cell division

Leads to:

• Abnormal large RBCs and erythroid precursors (megaloblasts).

• Affect granulocyte maturation.

• Neurologic complication:- attribute to abnormal myelin degradation.

Vitamin B12 Deficiency

Causes of severe vitamin B12 deficiency1. Nutritional

– Inadequate intake– Vegetarianism

2. Malabsorption– Gastric causes– Pernicious anemia– Congenital lack or abnormality of IF– Total or partial gastrectomy– Intestinal causes: chronic tropical sprue, intestinal stagnant loop

syndrome, ileal resection, Crohn’s disease, fish tapeworm

Causes of mild vitamin B12 deficiency

• Malabsorption of B12

• Elderly

• Atrophic gastritis

• Severe pancreatitis

• Gluten induced enteropathy

• HIV infection or therapy with metformin

Pathophysiology of Folate

• Folate enter plasma as methyl THF.

• Methyl THF is a required in synthesis of thymidine thus, for DNA synthesis.

• Lack of folate cause :

– Inadequate DNA synthesis thus, abnormal large RBC synthesis.

Folate Deficiency

Causes of folate deficiency• Nutritional

– Especially old age, institutions, poverty, famine, special diets

• Malabsorption– Tropical sprue, gluten induced enteropathy, partial gastrectomy, extensive jejunal resection or

Crohn’s disease

• Excess urinary folate loss– Active liver disease, CCF

• Drugs– Anticonvulsants, sulfasalazine

• Excess utilization– Physiological

• Pregnancy, lactation, prematurity

– Pathological• Haematological disease (haemolytic anaemias, myelofibrosis)• Malignant disease: carcinoma, lymphoma, myeloma• Inflammatory diseases: Crohn’s disease, tb , RA, psoriasis, malaria

• Mixed– Liver disease, alcoholism, ICU

Clinical Features

• Onset – insidious/ gradually progressive sign and symptoms of anemia

• Mildly jaundice- excess breakdown of hb due to increase ineffective erythropoiesis

• Glossitis, angular stomatitis, mild symptoms of malabsorption with loss of weight

• Neuropathy (severe B12 deficiency)

• Neural tube defect in fetus (eg : encephaly, spinabifida)

• Increased melanin pigmentation

Glossitis : beefy-red and painful tongue

Angular stomatitis

Baby with neural tube defect (spina bifida)

From : Essential Haematology , 6th Edition

Investigation

• FBC: MCV > 98fL

• FBP : Oval macrocytic rbcs, hypersegmented neutrophils, pancytopenia

• BMA : hypercellular, large erythroblast, failure of nuclear maturation, giant

metamyelocytes (BMA is not mandatory in B12/folate deficiency)

• Increased serum unconjugated bilirubin, LDH

• Reduced serum/ red cell folate and B12 (mandatory test)

Treatment of Megaloblastic AnaemiaVitamin B12 deficiency Folate deficiency

Compound Hydroxocobalamin (B12) Folic acid

Route Intramuscular Oral

Dose 1000ug 5mg

Initial dose 6x1000ug over 2-3 weeks Daily for 4 months

Maintenance 1000ug every 3 months Depend on underlying

disease; lifelong theraphy

may be needed in chronic

inherited haemolytic

anaemias, myelofibrosis,

renal dialysis

Prophylactic Treatment

Given To:

Total gastrectomy

Ileal resection

Pregnancy, severe

haemolytic anaemias,

dialysis, prematurity

From : Essential Haematology, 6th Edition

Normochromic & Normocytic

Anemia

Group 1

Acute of Chronic Disease (ACD)• Common type of anaemia among pt with chronic inflammatory and malignant dz

• Causes of ACD :

– Chronic iflammatory disease

• Infections (pulmonary abcess, tb, osteomyelitis, pneumonia)

• Non infectious (RA, SE, CTD, sarcoidosis )

– Malignant disease ( ca, lymphoma, sarcoma )

• Sign and symptoms depends on underlying causes

• Not related to bleeding, haemolysis or marrow infiltration

• EPIDEMIOLOGY

Most common anemia amongst patients with chronic inflammatory and malignant disease.

2nd commonest anemia after IDA, worldwide.

CASE SCENARIO 1

A 72 - year – old man, previously healthy, presents with fever, chills, cough

and SOB. CXR shows a right – middle – lobe infiltrate. He is diagnosed

with pneumonia and admitted for iv antibiotics. Blood cultures

eventually grow Strep. Pneumoniae. By hospital day 3, he is afebrile but his

Hb is 10.5 g/dl, down from 12.4 g/dl on admission and 13.5 g/ dl 1 month

ago. He has no evidence of GI blood loss or overt haemolysis. Red cell indices

revealed a normocytic normochromic anaemia.

CHARACTERISTIC FEATURES

Anemia in chronic disease

MCV/MCH Normochromic normocytic anaemia or mildly

hypochromic (MCV rarely <75fL)

Serum iron Reduced

TIBC Reduced

Serum ferritin Normal/ raised

Bone marrow iron stores Present

Eryhtroblast iron Absent

Hb electropheresis Normal

• Pathogenesis-Key regulatory protein – hepcidin which is produced by liver

High levels of production are encouraged by pro-inflammatory cytokines, especially IL- 6.

Hepcidin binds to ferroportin on the membrane of iron exporting cells, and thereby inhibiting the export of iron from these cells into the blood

Iron remain trapped inside the cells in the form of ferritin, levels of which are therefore normal or high in the face of significant anaemia

• Treatment- treat underlying cause (eg. 60% RA patients).• Inhibition hepcidin and inflammatory modulator → block the inhibition of iron

transfer.

EXAMPLE- ANEMIA IN CHRONIC KIDNEY DISEASE(CKD)

• Anaemia is a complication of CKD whereby erythropoietin deficiency is the most significant cause.

• Insufficient or absent erythropoietin secretion results in normochromic, normocytic anaemia.

• The anaemia becomes more severe as the glomerular filtration rate progressively decreases.

Haemolytic Anaemia

HERIDATARY ACQUIRED

Loss Of Elasticity:Sickle Cell

Anaemiao Sickle cell disease is a group of haemoglobin disorder in which the

sickle β-globin gene is inherited.

o Homozygous sickle cell anaemia (Hb SS) is the MOST COMMON

o Doubly the doubly heterozygote conditions if Hb SC and Hb

Sβthal also cause sickling disease

o The abnormal red blood cells are rigid and crescent- like shaped

that can stuck in the blood vessels resulting in blocking of the

blood flow. Hence, distribution of the blood to supply oxygen to

all parts of the body might be impaired.

Hoffbrand, A., & Moss, P. (2006). Essential haematology (5th ed., p. 85). Malden, Mass.: Blackwell Pub.

Epidemiology

o It is believed that the sickle cell abnormal hemoglobin originated in

Africa, where it is most commonly encountered, while India is

considered as an additional place of origin. HbS is prevalent in

Middle East and Mediterranean countries, while population migration

has taken the gene to almost all regions of the world, including

Western and Northern Europe.

o About 7% of the global population carry non-functional hemoglobin

gene, with more than 500 000 affected children born annually. More

than 80% of these are born and live in the developing countries in the

world.

o More than 70% of them have a sickle disorder. A number of affected

children born in developing countries might be died, misdiagnosed,

receiving treatment or left untreated.

Causes Point mutation at 6th codon of β globin (Glutamate valine)

Pathophysiology

Clinical Features

1. Vaso-occlusive crises

The earliest presentation in the first few years of life is acute pain in

hand, and feet (dactylitis) dt vaso-occlusion of the small vessels.

Severe pain in the other bones occur in older children/adult. Fever often

accompanies the pain.

2. Anaemia

Hb range from 6-8 g/dL but acute fall in Hb level can occur owing

to :

• Splenic sequestration

• Bone marrow aplasia

• Further haemolysis

Kumar, P. (n.d.). Kumar & Clark’s clinical medicine (Seventh ed., p. 409, 410)

3. Splenic Sequestration

• Vaso-occlusion causes acute painful enlargement of the spleen

• Causing splenic pooling of RBC hypovolaemia circulatory

collapse death

4. Aplastic Crises

Caused by infection with Parvovirus B19 or Folate deficiency

Clinical Features (cont)

Long-term Complications

• AFFECT GROWTH AND DEVELOPMENT OF CHILD

– Short statue in young children (regain height by adulthood)

– weight not appropriate with age (below normal weight)

– Delayed sexual maturation (boy- no increase in testicular volume

by 14 years; girl- no breast development by 13 and a half years)

• BONE

– Common site for vaso-occlusive of small vessels.

• Avascular necrosis of hips and shoulders

• Compression of vertebrae

• Shortening of bones in the hands and feet.

• Osteomyelitis (by Staphylococcus aureus, Staphylococcus

pneumoniae, Salmonella)

Kumar, P. (n.d.). Kumar & Clark’s clinical medicine (Seventh ed., p. 410)

INFECTIONS

• Tissue susceptible to vaso-occlusive (Bones , lungs, kidneys)

LEG ULCERS

• Occur spontaneously (vaso-occlusive) or following trauma. Then become infected and resistant to treatment.

CARDIAC PROBLEMS

• Cardiomegaly, arrthymias, iron overload cardiomyopathy.

• Myocardial infarction due to thrombotic episodes.

NEUROLOGICAL COMPLICATIONS

• 25% of patient

• Transient ischemic attacks, fits, cerebral infarction, cerebral haemorrhage, coma.

• Strokes occur in about 11% of patient under 20 years of age.

• Most common finding is obstrustion of a distal intracranial internal carotid artery or a proximal middle cerebral artery.

Cholelithiasis

– Pigment stone as a result of chronic haemolysis

Liver problems

– Chronic hepatomegaly and liver dysfuction caused by trapping of sickle cells.

Renal. Chronic tubulointestitial nephritis.

Priapism.

– Unwanted painful erection as a result of vaso-acclusion.

– Impotence

Eye

– Background retinopathy, proliferative retinopathy, vitreous haemorrhages and retinal

detachment all occur

Pregnancy

– Impaired placental blood flow causes

• Spontaneous abortion

• Intrauterine growth impairment

• Pre-eclampsia

• Fetal death

Investigations 1. Complete blood count (CBC)

Anaemia (Hb range 6-8 g/dL)

High reticulocyte count (10-20%)

2. Blood films (feature of hyposplenic

and sickling

Sickle cells(arrowed) and

target cells.

Post splenectomy film with Howell-Jolly

bodies(arrowed), target cells and irregular

contracted cells.

Kumar, P. (n.d.). Kumar & Clark’s clinical medicine (Seventh ed., p. 410)

Investigations (cont)

3. Sickle solubility test

A mixture of HbS in a reducing solution

(sodium dithionite) gives a turbid apperance

because of precipitation of HbS

Normal Hb gives clear solution

5. The parents of the affected child will

show features of sickle cell trait.

Normal

Sickle cell trait

Sickle cell anaemia

Hb electrophoresis

4. Hb electrophoresis to confirm

diagnosis

Results shows : no Hb A, 80-95% Hb SS,

and 2-20% Hb F

Treatment

o Prophylactic –to avoid those factors known to precipitate crises, esp dehydration,

anoxia, infections, stasis to the circulation and cooling of the cell surface

o Folic acid (5 mg once weekly)

o Pneumococcal, haemophilus, and meningococcal vaccination and Hepatitis B

vaccine if transfusion is needed.

o Regular oral penicillin (should start at dx and continue at least until puberty)

o Crises –treat by rest, warmth, rehydration by oral fluid and/or IV normal saline

(3L in 24H)

–blood transfusion is given in severe anaemia

o Hydroxyurea (15-20 mg/kg) can increase Hb F levels and have shown to improve

the clinical course children/adults who are having 3 or more painful crises each

year

o For pain –analgesia at appropriate level should be given (NSAID, opiates or

paracetamol)

Hoffbrand, A., & Moss, P. (2006). Essential haematology (5th ed., p. 89). Malden, Mass.: Blackwell Pub.

1. Membrane defects : Hereditary

Spherocytosis• Most common in northern Europeans

Pathogenesis :-

• Vertical interactions between the membrane skeleton and the lipid bilayer of the red cell

• Loss of membrane because release of parts of the lipid bilayer that are not supported by the skeleton

• Normal biconcave red cell but become increasingly spherical as loss of surface area relative to volume as they circulate through spleen and the rest of RE system

• Unable to pass through splenic microcirculation where they die prematurely

Blood film of HS

Membrane defects : Hereditary

SpherocytosisMolecular basis :-

• Ankyrin deficiency/ abnormalities

• Alpha or beta – spectrin deficiency / abnormalities

• Band 3 abnormalities

• Pallidin (protein 4.2) abnormalities

Clinical features :-

• Autosomal dominant rarely recessive

• Anemia can be present at any age

• Fluctuating jaundice (particularly marked if a/w Gilbert’s disease (a defect

of hepatic conjugation of bilirubin) ; splenomegaly occurs in most patients

• Frequent pigment gallstones

Membrane defects : Hereditary Spherocytosis

Investigation :-

• A rapid fluorescent flow analysis of eosin-maleimide bound to red cells

• Treatment :-

• Splenectomy : preferably laparoscopic but only if clinically indicated

;symptomatic anemia/gallstones/leg ulcers/growth retardation – risk of

post-splenectomy sepsis particularly in early childhood

• Cholecystectomy should be performed with splenectomy if symptomatic

gallstones are present

Membrane defects : Hereditary

Spherocytosis

2. Defective red cell metabolism : Glucose-

6-phosphate dehydrogenase deficiency

Epidemiology :-

• 400 million people worldwide are deficient in enzyme activity

• Sex-linked

• Affecting males

• Carried by females (advantage resitance to Falciparum Malaria

• Main races :- West Africa, the Mediterranean, the Middle East and SE Asia

• Mildly in black Africans, more severe in Orientals and most severe in Mediterranean

• Severe deficiency occurs occasionally in white people

Agents that may cause HA in G6PD deficiency (Things that induce

OXIDATIVE STRESS) :-

• Infections and other acute illnesses eg DKA

• Drugs – antimalarials eg primaquine, sulphonamides eg cotrimoxazole,

analgesics eg aspirin, antihelminths eg beta-napthol

• Fava beans or other vegetables

• Miscellaneous eg vit K analogues

Defective red cell metabolism : Glucose-6-

phosphate dehydrogenase deficiency

Defective red cell metabolism : Glucose-6-

phosphate dehydrogenase deficiency

Pathogenesis :-

• Function of G6PD is to reduce nicotinamide adenine dinucleotide

phosphate (NADP)

• The only source of NADPH for production of glutathione

• Defieciency of G6PD renders the red cell susceptible to oxidant stress

• Most common types are B (Western) and type A in Africans

Clinical features :-

• Usually asymptomatic

• Main syndromes :-

1. Acute HA in response to oxidant stress eg drugs, fava beans or infections –

caused by rapidly developing intravascular haemolysis with

haemoglobinuria, the anemia maybe self limiting as new young red cells

are made with near normal enzyme levels

2. Neonatal jaundice

3. Rarely, a congenital non-spherocytic haemolytic anemia

These syndromes may result from different types of severe enzyme deficiency

Defective red cell metabolism : Glucose-6-phosphate dehydrogenase deficiency

Diagnosis :-

• Between crises the blood count is normal

• By screening test or direct enzyme assay on red cells

• During crises – ‘bite’ cells/ ‘blister’ cells / contracted and fragmented cells which have had Heinz bodies removed by the spleen. Heinz bodies are oxidized, denatured Hb

• Higher enzyme level in young red cells, red cell enzyme assay may give a ‘false’ normal level in the phase of acute hemolysis with a reticulocyte response

• Subsequent assay after the acute phase reveals the low G6PD level when the red cell population is of normal age distribution

Defective red cell metabolism : Glucose-6-

phosphate dehydrogenase deficiency

Treatment :-

• Stop offending drugs

• Treat underlying infection

• Maintain high urine output

• Blood transfusion for severe anemia when necessary

• Photography and exchange transfusion might be needed in severe cases for neonates as they are prone to neonatal jaundice. The jaundice is usually not caused by excess haemolysis but by deficiency of G6PD affecting neonatal liver function

Defective red cell metabolism :

Glucose-6-phosphate dehydrogenase

deficiency

Haemolytic Anaemia

HERIDATARY ACQUIRED

Group 4

Autoimmune Hemolytic anemia

A 32-year-old man gradually noticed that he had yellow eyes and dark urine, felt continually tired, and was short of breath when climbing stairs.

He had no other symptoms; in particular there was no itching, fever or bleeding, and he was not taking any drugs. On examination, he was anaemic and jaundiced.

He was afebrile and had no palpable lymphadenopathy, but evident of splenomegaly

Possible Diagnosis?

Possible causes Points

Liver disease JaundiceDark urineSplenomegaly

Hemolytic anemia JaundiceDark urineShortness of breathTired Splenomegaly

INVESTIGATION

FBC

• Haemoglobin 54g/l (130- 180 g/l)

• WBC 9.4 x 109/L

• Platelets 192 x 109/L

• MCV 120 fl (76-96 fl)

• Reticulocyte count 9% (<2%)

• The blood film shows gross polychromasia and spherocytes; Suspected :Hereditary spherocytosis

AIHA

FURTHER INVESTIGATION

• LFTs

Serum bilirubin 47 umol/L ( 3-17umol/L)

• LDH 5721 iu/L (105-333iu/L)

• DAT 3+ positive with IgG

.

PROVISIONAL DIAGNOSIS

Warm AIHA +ve DAT with IgG

Autoimmune hemolytic anemia

• Acquired disorder resulting from increased red cell destruction d/t red cell autoantibodies.

• Classification :• Warm AIHA

• Cold AIHA

• Paroxysmal cold haemoglobinuria (PNH)

Warm AIHA

• Autoantibodies predominantly IgG

• Possess relatively high affinity for RBCs at 37ºc

• Clinical Features• Occur at any age either sex

• Short episode of anemia and jaundice.

• Generalised symptoms –fatigue, weakness, malaise, fever

• Splenomegaly & hepatomegaly common

Cold AIHA

Autoimmune predominantly IgM

Antibody attach to red cells and cause agglutination – at lower temperature <4◦C

• Infection related : Mycoplasma. pneumonia, EBV

• Clinical Features

• Exacerbation in winter

• Cold, painful, often blue fingers, toes, ears or nose (Acrocynosis)

Paroxysmal cold haemoglobinuria (PNH)

• Due to a biphase IgG antibodyAttaches with complement to RCs in the cold extremities

• Causes lysis when the cell is warmed later from the complement which remains attached

• Post-viral phenomenon

• Typically an acute self-limiting disease

Clinical features PCH

• Presents acutely with leg and back pain, abdominal pain with cramps, nausea/vomiting/diarrhoea and

• dark urine (haemoglobinuria)

• following exposure to the cold

Investigation for suspected AIHA

• FBC and reticulocyte count

• Blood film

• DAT (Direct Agglutination Test)

• Donath Landsteiner Ab (test for PNH)

• Blood group specificity

• Cold agglutinin titre

• Tests for associated infection or disease

Treatment

• Corticosteroid (induced remission)

• Splenectomy (if fail to respond well to corticosteroid)

• Immunosuppressive drugs ( rituximab)

• Blood transfusion (if necessary)

• Avoidance of Cold ( Cold AIHA & PNH)

• Folic acid – as active hemolysis consume folate

Alloimmune Haemolytic

Anaemia

Classification(source : Essential Haematology Hoffbrand Moss)

Induced by red cell antigens

• Haemolytictransfusion reactions

• Haemolytic disease of the newborn

• Post stem cell grafts

Drug-induced

• Drug-red cell membrane complex

• Immune complex

Haemolytic transfusion reactions(source : Essential Haematology Hoffbrand Moss)

Immediate Delayed

Clinical features of a major haemolytictransfusion reaction

(source : Essential Haematology Hoffbrand Moss)

Haemolyticshock phase

Oliguric phaseDiuretic phase

Investigations (source : Essential Haematology Hoffbrand Moss)

Check for blood compatibility and

bacterial contamination of

the blood

Management(source : Essential Haematology Hoffbrand Moss)

To maintain blood

pressure and renal

perfusion

IV dextran, plasma or saline &

frusemide

IV hydrocortisone

& antihistamine

IV adrenaline

Compatibletransfusion

Drug-induced immune haemolytic anemia

Drug-induced immune haemolyticanemia

• Drug-induced immune hemolytic anemia is a blood disorder that occurs when a medicine triggers the body's defense (immune) system to attack its own red blood cells.

• Drugs can cause HA by 3 mechanisms.1)Antibody directed against a drug red-red cell membrane

complex – Penicillin, ampicillin2)Deposition of complement via a drug protein(antigen)-

antibody complex onto the red cell surface – Quinidine, Rifampicin

3)A true autoimmune hemolytic anemia with unclear role of the drug – methyldopa

Symptoms

• Dark urine

• Fatigue

• Pale skin color

• Rapid heart rate

• Shortness of breath

• Yellow skin color (jaundice)

InvestigationsPhysical examination : enlarged spleenTests : blood/ urine test- Absolute reticulocyte count- Direct or indirect Coombs test- Indirect bilirubin levels- Red blood cell count- Serum haptoglobin

Treatment

- Stop taking the drugs

-Take a prednisone to suppress

the immune response against

the red blood cells. Special

blood transfusions may be

needed to treat severe

symptoms.

Red Cell Fragmentation syndromes.

DEFINITION

• Form of haemolytic anaemia caused by intravascular mechanical trauma resulting in destruction of red cells, related to cardiovascular defects and haemolytic anaemia.

• Caused by red blood cells passing through abnormal small vessels with also fibrin deposition.

• Also known as microangiopathic hemolytic anemia.

• Also associated with disseminated intravascular coagulation or platelet adherence.

Infection-induced hemolytic anemia

Microorganisms may cause injury to red cells through different

mechanisms such as:

(1) physical invasion of red cells (e.g. malaria)

(2) hemolysin secretions(alpha toxin) to damage the red cells directly

(e.g. Clostridium perfringen)

(3) infection that triggers formation of antibody (anti-I) against red

cells (e.g. mycoplasma)

(4) microangiopathic hemolysis caused by disseminated intravascular

coagulation associated with infection.

(5) may precipitate haemolytic crisis in G6PD deficiency.

Anaemia in

infant & children

PAEDIATRICS TEAM:

Muhammad Faiz Bin Nordin

Bibi Afzarina Binti Mohamed Hanafee

Hanis Zahirah Binti Baharudin

Definition

Anaemia is defined as an Hb level below the normal range.

The normal range varies with age, so anemia can be defined as:

• Neonate : Hb < 14 g/dl

• 1-12 months : Hb < 10 g/dl

• 1-12 years : Hb < 11 g/dl

Causes of anaemia in infant & children

• Impaired red cell production

• Increased red cell destruction (haemolysis)

• Blood loss

• Anaemia of prematurity

Impaired red cell production

May be due to

Infective erythropoiesis- iron deficiency

red cell aplasia- Fanconi anemia

Infective erythropoiesis:Iron deficiency

• Main cause

- inadequate intake

- malabsorption

- blood loss

• Common in infants because additional iron is required for ↑ blood volume accompanying growth & to build up

• Diagnostic clue for infective erythropoiesis

- normal reticulocyte count

- abnormal MCV of RBC :

*low in iron deficiency

*raised in folic acid deficiency

• Iron may come from

- breast milk

*low iron content but 50% of iron is absorbed

- infant formula: supplement

- cow’s milk

*higher iron content than breast milk but only

10% is absorbed.

- solid introduced at weaning

Dietary sources of iron

Iron requirement during childhood

• Clinical feature- most infant & children are asymptomaticuntil Hb drop below 6-7 g/dl

- When it become worsen, children tire easily& young infant feed more slowly than usual.

- appear pale but pallor is an unreliable signunless confirmed by pallor of conjuctiva, tongueor palmar creases.

- children have ‘pica’

• Management- dietary advice and supplementation with oral

iron.*except for malabsorption (celiac disease) & chronic

blood loss patient (Meckel diverticulum)- should be continue until Hb is normal and then

for a minimum of a further 3 months toreplenish the iron stores.

- Blood transfusion should never be necessary fordietary IDA

Red cell aplasia

• Causes

- congenital red cell aplasia

*Fanconi anaemia

- transient erythroblastopenia of childhood

- parvovirus B19

• Diagnostic clue

- low reticulocyte count despite low Hb

- normal bilirubin

- negative direct antiglobulin test

(Coombs test)

- absent red cell precursors on bone marrow

examination.

Aplastic anaemia: Fanconi anemia

• Most common inherited type

• Autosomal recessive diorder due to genetic defect DNA repair.

• Usually oocur among 5 to 10 years old children.

• 10% developed acute myeloblastic anemia

• Clinical feature

- Growth retardation & congenital effect of

skeleton

- short stature, abnormal thumb and radii,

microcephaly, micropthalmia, café au lait &

hypopigmented spot, renal structural

abnormality

• Management

- bone marrow transplantation using normal

donor bone marrow from unaffected siblings

or matched unrelated marrow donor.

Causes of anaemia in infant & children

• Impaired red cell production

• Increased red cell destruction (haemolysis)

• Blood loss

• Anaemia of prematurity

Increased red cell destruction(haemolytic anemia)

• Causes

- red cell membrane disorders

*Hereditary spherocytosis

- red cell enzyme disorder

*G6PD deficiency

- haemoglobinopathies

*Sickle cell disease, B-thalassaemia major

red cell membrane disorders:Hereditary spherocytosis

• Autosomal dominant inheritance but 25% of cases there is no family history

• May cause early, severe jaundice in newborn infants.

• Clinical feature- usually asymptomatic- jaundice, anemia, mild to moderatesplnomegaly, aplastic crisis & gallstones

• Management - oral folic acid, splenectomy if symptomatic

red cell enzyme disorder:G6PD deficiency

• Commonest red cell enzymopathy

• Is x-linked recessive (predominantly affect male)

• May present with neonatal jaundice

• Causes acute intermittent hemolysis precipatated by infection, certain drugs, fava bean & naphthalene.

• Associated with jaundice, dark urine, fever, malaise

• Management

- parents should be given advice about the sign of acute

hemolysis and give a list of drugs, chemicals and food

to avoid.

Haemoglobinopathies:Sickle cell disease

• Autosomal recessive• SCD result in ischemia in organ• Clinical feature- anemia, infection, painful crises, squestration crises,

splenomegaly, growth failure, gallstone- Serious complication are bacterial infection, acute chest

syndrome, stroke and priapism.• Management - Treatment of acute crisis- oral or IV analgesia and good

hydration- Treatment of chronic problem- hydroxyurea to increase

HbF, bone marrow transplant

haemoglobinopathies:B-thalassaemia major

• Mutation of B-globin gene result in an inability to prodece HbA

• Clinical feature

- severe anemia, growth failure, pallor,

jaundice, bossing of skull, maxillary

overgrowth, splenomegaly, hepatomegaly,

need for repeated blood transfusion

• Management

- life long blood transfusion

• Complication of long rem-blood transfusion in children

- iron deposition

- antibody formation

- infection

Anaemia in the newborn

• Reduced RBC production

• Increased RBC destruction

• Blood loss

• Anaemia of prematurity

Blood loss

• Main causes

- feto-maternal haemorrhage

- twin-to-twin transfussion

- blood loss around the time of delivery

• Main diagnostic clue

- severe anemia with a raised reticulocyte

count and normal bilirubin

Anaemia of prematurity

• Main causes

- inadequate erythropoietin production

- reduced red cell lifespan

- frequent blood sampling whilst in hospital

- iron and folic acid deficiency (after 2-3

months)

Thank You

PHYSIOLOGICAL CHANGES IN PREGNANCY

ESSENTIAL FOR:

Support and protection to developing fetus

To prepare the mother for labour and delivery

CHANGES ARE DUE TO:

Hormonal alteration

Increased metabolic

Mechanical factor of gravid uterus

WHY STUDY THE CHANGES???

To differentiate normal from abnormal

To make the process of delivery smooth

To anticipate and manage complications

HEMATOLOGICAL SYSTEM

1) Plasma volume

o Begin to ↑ to 10% at 7 weeks and increasing rapidly, then plateauing at 40-50% by 32 weeks.

o At the same time,red cell volume also ↑ by 15-20% → help to improve utero-placental perfusion

2) Red cell mass

Red cell mass expansion < blood volume expansion

Total net of blood conc./viscosity ↓ by 20% (condition known as hemodilution)

Dilutional anemia(physiological anemia)

Oedema in pregnancy d/t drop colloid oncotic

pressure

3) Blood component

o ↑ total vol. RBC up to 25% d/t elevated level erythropoeitin →provide extra O₂ demand

o WBC can go up to 15,000-16,000/mm3

o Platelet slightly fall d/t dilutional effect

o ↑ clotting factors(VII,VIII,IX,X) and fibrinogen→protect from hemorrhage at delivery

• Severe anemia may weaken the uterine muscle strength which leads to uterine atony, that leads to post partum hemorrhage

• Anemia can also lower resistance to infectious disease

• However, the impact of anaemia on the extent of blood lost at childbirth and postpartum is not well-understood.

How ‘anemia’ cause increased risk of PPH ?

• Check ferritin in early pregnancy: give iron supplements only if iron deficient

• Folic acid 5mg daily is required.

• Parenteral iron should be avoided

• The aim during pregnancy is to maintain pre-transfusion Hb concentration level above 10g/dL

How do you manage a patient with thalassemia during pregnancy ?

• Thalassemia screening of the partner; If both positive, the couple need counselling on the risk of pregnancy with thalassemia major.

• Evaluation of cardiac function by ECHO, and of liver and thyroid functions, in each trimester (Main risk to the mother is cardiac complications).

• Iron chelation therapy is complex and should be tailored to the needs of the individual woman.

Others

Anemia in Pregnancy

Contents

Definition of anaemia in pregnancy

Prevalence of anaemia in pregnancy

Causes of anaemia in pregnancy

Iron-deficiency anaemia

- factors affecting Iron absorption

- types (Prepartum anaemia, IDA during Pregnancy, Anemia + Post partum hemorrhage)

- signs & symptoms of IDA

- advice on how to take Iron tablet

Definition of anaemia in pregnancy

During Pregnancy

Haemoglobin(g/dL)

WHO < 11

CDC < 11 (1ST trimester)

< 10.5 (2nd trimester)

< 11 (3rd trimester)

Post partum

Haemoglobin (g/dL) <10

Prevalence of anemia in pregnancy

World 47% 42% 30%

Malaysia 32% 38% 30%

Pre-school children Pregnant women

Non-pregnant women during

child bearing age

WHO Global Database on Anemia

Prevalence (contd.)

• Developing countries

– Africa 35% to 56%

– Asia 37% to 75%

– Latin America 37% to 52%

• Industralised countries- mean prevalence 18%

• HSNZ- 70.8%

Insufficient intake/insufficient production : nutrition, blood disease

Increase loss : bleeding, renal disease, infestation of parasites

Increase demand : placenta, fetus, red blood cells expansion

Causes of anaemia in pregnancy

Iron-deficiency Anaemia (commonest cause)

The most frequent nutritional disorder

How many suffer from iron deficiency anemia?

2 billion peoples

1/3rd of the world’s population

Factors affecting Iron absorption

Iron Absorption Enhancers

- Vitamin C; citrus fruit and juice, kiwi, strawberries, tomatoes, etc

Iron Absorption Inhibitors- Iron binding polyphenol: red wine- Coffee & tea- Eggs- Milk

Prepartum anemia

• Among fertile, non-pregnant women, ∼40% have ferritin of ≤30 μg/L(low iron status)

• Prepartum IDA predisposes to postpartum IDA- some amt blood loss during labour, lactation, dilutional effect of pregnancy

Test Level Remarks

Serum Ferritin (ug/L) < 30 Low iron status

< 15 Iron deficiency

IDA During pregnancy

Iron requirement in pregnancy

100mg/day iron for all

women*

9x higher

Iron requirement during pregnancy

Anemia and Post Partum Hemorrhage

• Anaemia increase the risk of PPH

• Unability of uterus to contract

• Risk of DIVC higher

• Risk of post partum hysterectomy higher

Post-partum Anemia

“More than 80 percent of maternal deaths are caused by haemorrhage,…… Most of these deaths are preventable when there is access to adequate reproductive health service”

Post partum anemia

• Severe postpartum anemia is a complication of 5% of deliveries

• Following delivery, women lose some amount of iron through breastfeeding and lactation

• IDA has been associated with impaired cognitive function and behavioral disturbances in postpartum women

• Mother’s iron status should be evaluated prior to discharge to monitor postpartum anemia

Post partum anemia

• Iron deficiency persists beyond the 4-6 weeks postpartum period

– 12% of women are iron deficient up to 12 months after delivery

– 8% of women are iron deficient 13-24 months after delivery

• Iron supplementation should continue after delivery if iron status remains low or while the mother is breastfeeding

Sign & Symptoms of IDA

HEADACHESCOLD HANDS

& FEET

WEAKNESS, FATIGUE,

SHORTNESS OF BREATH

DIZZINESSPALE SKIN

PALLOR

KOilonychia

ANGULAR STOMATITIS

ATROPHIC GLOSSITIS

CHEALITIS

Clinical sign of anaemia

Management of Anemia in pregnancy

Method Pros Cons

Oral Iron Cheap, Easy to take, Hardly any serious side effects

Slow to act, Compliance issue

Parenteral Iron Faster action, ensure compliance

Cause anaphylactic reaction, Pain and skin discoloration at injection.

Blood Transfusion Treat anemia almost instantly

Mismatch, Blood reaction, Disease(Hepatitis, HIV), Fluid Overload

• IDA is treated mainly with iron supplements

• Iron supplements have 2 forms, oral and parenteral. Oral iron is most commonly used

• Use of iron supplements helps in improving the iron status of the mother during pregnancy and during the postpartum period, even in women who enter pregnancy with reasonable iron stores

Iron Supplements

• Oral Iron (200 – 300 mg of elemental iron) with folic acid (500 microgram) prescribed in divided dose

• Type of oral supplement available :- Ferrous fumarate- Ferrous gluconate (If the above is not tolerated)- Ferrous glycine sulphate- Ferrous sulphate (dry)- Iron polysaccharide• Why Ferrous fumarate ?- Least expensive and best absorbed form of iron- Newer drugs ? Not proven yet

Oral Iron Supplements

• Anorexia

• Diarrhea

• Epigastric Discomfort (Combination with Vit C supplements)

• Nausea, Vomiting

• Constipation and Dark colored stool

• Temporary staining of teeth

*Oral Iron therapy must be continued for at least 12 months after the anemia has been corrected in order to replenish the depleted iron stores

Side Effects

• Start with one tablet daily first, then increase gradually until three times daily dosing

• Avoid use of high-dose Vit C supplements

• Taking with meals (But can also reduced iron absorption) – One hour before meal

• Administer at bed time

Methods of reducing side effects

• Daily oral iron and folic acid supplementation is recommended as part of the antenatal care to reduce the risk of low birth weight, maternal anaemia and iron deficiency (strong recommendation)

WHO Recommendation

• a 30 mg of elemental iron equals 150 mg of ferrous sulfate heptahydrate, 90 mg of ferrous fumarate or 250 mg of ferrous gluconate.

Suggested scheme Supplement composition Iron: 30–60 mg of elemental

ironFolic acid: 400 μg (0.4 mg)

Frequency One supplement daily

Duration Throughout pregnancy. Iron and folic acid supplementation should begin as early as possible

Target group All pregnant adolescents and adult women

Settings All settings

• An agent that increase the hemoglobin level and the number of erythrocytes in the blood

• Drug to stimulate RBC formation

• Primarily used in treatment of anemia

• Example –

- Iron (Oral, Parenteral)

- Folic Acid

- Vit B12

What is ‘hematinic’

According to period of gestation :

Less than 30 Weeks – Oral iron with folic acid

30 – 36 weeks – Parenteral Iron Therapy

Greater than 36 weeks – Blood Transfusion

Management of IDA in pregnancy

Advice on how to take iron tablet:

take several times a day on an empty stomach.

best to be taken at;

-bedtime

-or about an hour before a meal and at the same time drink juice that's rich in vitamin C, such as a glass of orange juice for optimum absorption of iron.

• Increased in reticulocytes- Increased 2 – 16%, by 4 – 6 days (earliest), pekas at 9 –

12 days.• Increased in hemoglobin levels (Rising at rate of 2 g/dl

after 3 weeks)• Total Plasma Iron will gradually increase and TIBC will

return to normal in about a month• Blood ferritin levels return to normal in about 4 – 6

months• Epithelial Changes (eg. Tongue and nails) revert to

normal

Increased in Hb in oral therapy

*Given over 6 – 8 hours under constant observation

Parenteral forms of IronIron preparation Route Elemental Iron Content

Iron Dextran(Imferon)

IM or IV 1ml = 50 mg FerricHydroxide +

Dextran

Iron sorbitolcitrate complex (Jectofer)

IV 1ml = 50mg Ferric Iron, sorbitol and

citric acid

Iron sucrose IV 1ml = 2mg Iron-ferrichydroxide in

sucrose

• Intolerance to oral form of iron• When iron deficiency is not correctable with oral

treatment• Non-compliance on part of the patient (Repeatly

fails to heed instructions/incapable of following them)

• Patient suffering from Inflammatory Bowel Disease (Aggravated by oral iron therapy)

• Patient is unable to absorb iron orally• Patients near term (32 – 36 weeks of pregnancy)

Indication of use of parenteral iron therapy

• IM - Pain and staining of the skin at the site of injection + Development of fever, chills, myalgia, athralgia, injection abscess

• IV - Serious side effect like anaphylaxis reactions (0.7%)

• Both – Systemic reactions

Immediate : Hypotension, headache, malaise

Delayed : Lymphadenopathy, myalgia, athralgia

Side Effects

• There is not enough time to achieve a reasonable Hb level before delivery. (For example, patient presents with severe anemia beyond 36 weeks)

• There is acute blood loss or associated infections

• Anemia is refractory to iron therapy

Indication for blood transfusion