Anaemia in pregnancy

Introduction:
Anaemia is the commonest medical disorder to occur in pregnancy.
The incidence varies in different countries and depending on:
- State of nutrition.
- Parasitic infestation (intestinal worms, malaria).
- Bacterial infection (T.B., UTI).
- Genetically transmitted disorders of haemoglobin
synthesis.

Definition
a) Physiologically, anaemia can be defined as condition in which the
oxygen-carrying capacity of the blood is decreased.
b) Anaemia in pregnancy can be defined as a haemoglobine level less
than 10.5% gram /dl or a haematocrit less than 30%.
The normal female haemoglobin reference range changes from 13 15
g /dl, in non pregnant state to 10.5 12 g /dl with pregnancy.

Physiological changes in pregnancy(the haemodilution of pregnancy)

1. plasma volume increase by 50% (increase is greater in twin).
2. red blood cell mass(RBC) increases by 30% (needed increase in iron
demands).
The smaller increase in RBC than plasma volume results in a 15% dilution
effect on normal haemoglobin levels. (this explain the physiologic
anaemia).

Classification of anaemias
1. nutritional anaemias : involve the haeme part of haemoglobin
molecule and include :
a. iron deficiency.
b. Folate deficiency.
c.Vitamin B12 deficiency.
2 .lack of production of blood haemopoetic, Aplastic varieties.
3 .inherited anaemia involve the globin portion of haemoglobin molecule
and include haemoglobinopathies and thalassaemias.
4 .blood loss haemorrhagic.

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 Iron deficiency anaemia

This is the most common form of anaemia in pregnancy.

More than 90%of all cases of anaemia in women are caused by iron
deficiency.
This type of anaemia is ten times more common in women than in men
and is related to menstrual losses and pregnancy requirements.
Aetiology:
Iron deficiency anaemia may be due to :
a) Decrease intake of iron {poor diet, vomiting in pregnancy}.
b) Decrease absorption e.g.:
Malabsorption syndrome.
Phytic acid of brown bread.
Copious intake of alkalies.
Ferric iron in gut instead of ferrous.
Lack of vitamin C.
c) Increased demands:
Too many pregnancies.
Pregnancies close together.
Breast feeding.
Multiple pregnancy.
Chronic blood loss- heavy period, haemorrhoids.
d) Decreased utilization e.g. infection {UTI}.
Pathophysiology:
Formation of RBCs occurs in bone marrow from the erythroblast.
Normally the RBCs survive in circulation for 120 days, when the are
removed by the reticuloendothelial cells and broken up into haem and

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globin. Iron is an essential component of haemoglobin and respiratory
enzymes.
The body of the normal adult contains approximately(3 5gm).
Ingested iron must be reduced to ferrous before it can be absorbed and the
major part of this absorption occurs in the upper small intestine .the
normal daily intake of iron from the diet is (15 20mg ),and of this (1
2mg) is absorbed through the intestine. The intestinal mucosa absorbs
more in iron deficiency (3 4gm per day). Iron is transported from the
mucosal cells attached to a protein called transferrin, average plasma iron
levels associated with transferrin are between 110 - 125g/100ml.

Erythroblast
(folic acid)
promormoblast
(iron + copper)

polychromatic
normoblast

reticulocytes lose
their nucleus

mature
erythroblast

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 The normal amount of iron lost daily is about 1mg, and thus the daily loss
well balanced:
Daily iron intake in food Absorption plasma
15 20mg Upper small intestine absorbed via Iron with the transferrin
transferrin (1 2mg). (110 - 125g).
(3 4mg)in iron deficiency.

During pregnancy the total extra iron required is approximately 1400mg.

Balance of iron in pregnancy:
Maternal Hb 500mg - {saving due to cessation fetus &
placenta 500mg - of menstruation (400mg) }
Blood loss at delivery 200mg
Lactation 200mg
1400
Therefore extra absorption occurs from the diet = 1000mg.
still supplements are required.
Diagnosis:
Symptoms:
Symptoms of anemia are due to lack of Hb, resulting in deficient oxygen
carrying power of blood. The lack of iron resulting in reduced formation
of tissue enzymes leading to deficiency tissue utilization of oxygen. The
deficient utilization of oxygen combined with deficient oxygen carrying
power of blood result and will depend on the severity and duration of
anaemia will include:
* Lassitude * Tiredness
* Fatique * Weakness
* Griddiness * Loss of appetite
* Fainting * Dyspnea
* Parasthesia * Palpitation

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Signs:
Pallor of the mucous membranes, and palmar creases.
Smooth and pale tongue due to atrophy of papillae.
In sever cases dependent oedema.
Sign of congestive heart failure may be present.
Koilonychia (spoon shaped).

Investigations:
Blood:
a) Red blood indices include :
1- Microcytic, Hypochromic.
2- Low mean cell volume (MCV).
3- Low mean corpscular haemoglobin
concentration (MCHC).
4- Anisocytosis, poikilocytosis.
b) Serum iron studies are of minimal value because the normal change
of pregnancy mimic finding in iron deficiency anaemia such as:
Increase total iron binding capacity(TIBC).
Decrease serum iron and in-ferritin.
c) Bone marrow:
aspiration shows decreased iron stores.

Implication of anaemia in pregnancy:

Mother:
1. More prone to abortion and premature labour.
2. Less likely to stand APH and PPH of any degree.
3. More prone to infection in the puerperium.
4. A cardiac patient suffers from greatly increased dyspnea.

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5. Recovery of an anaemic patients retarded in the postnatal
period.
6. Peripartum: - increases risk of heamodynamic compromise.
- increased likelyhood of transfusion.
Baby: (possible)
1. Low birth weight.
2. Neonatal anaemia.
3. Cognitive impairment.
Management:
Routine haemoglobin checks should be carried out on all pregnant
patient at booking 28, 32, 36 weeks and third day postpartum.

Prevention:
a. A good balanced diet before and during pregnancy include
(liver, meat, peas, eggs, appricots, are good sources of iron).
b. Prophylactic oral iron in pregnancy.
The normal requirements of pregnancy are met with a daily
supplement of 300mg elemental iron. One tablet of ferrous
sulphate (325mg) has (60mg) elemental iron.
If the patient taking well balanced diet and her Hb within
normal no need for iron supplement.

Treatment:
If iron deficiency anaemia is diagnosed, the treatment will
depend on :
1. severity of the anaemia.
2. duration of pregnancy.
3. causes for iron deficiency.

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 N.B.:
Mild anaemia ---Hb below 10 g/dl.
Severe anaemia ---Hb below 7 g/dl.

* oral iron:
-any ferrous iron salt are effective :
ferrous sulphate (325mg) orally, administered three times daily will
achieve the maximum bone marrow response.
Ferrous gluconate and ferrous fumorate are alternative forms.
Treatment should be continued for (3 _ 6 months) to restore bone marrow
iron stores.

**during treatment make sure that:

1. The patient gets them.
2. She takes them.
3. See they are effective by:
o Improve the symptoms.
o Increase Reticulocytes account.
o Rise the haemoglobin level.

*parental iron:
is indicated only if there is no response to oral iron as in the compliance
cannot be secured:
o Not taking oral iron.
o Cannot tolerate oral iron because it causes gastric upset.
o Cannot absorb iron from the gut.
There is no difference in the rapidity of the bone marrow response
whether the iron is given orally or parentally.

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 a. Jectofer (iron sorbital) : contains 50mg of elemental iron
per ml, and is supplied in 2ml ampules to be given daily I.M.
.{jectofar 4ml (200gm) will raise the Hb level by
1gm/100ml., so a course of 10-20 injections required}.
b. Inferon (iron dextran complex): 1ml = 50mg, elemental
iron available as 2ml ampules.
The total requirement of iron is calculated by formula and given as a
whole in slow saline intravenous drip after an initial test dose.

No. of mls. Of inferon required

= 0.3 X wt of patient in lbs. X Hb%defecint
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side effect of inferno:
Local phlebitis.
Rigor.
Sever allergic reaction can occur during treatment.

Laboratory response parameters include:

- Increase reticulocytes count is the first indication; it should be with
in 3 days (2%).
- Increase Hb / haematocrit is slower taking 14 21 days.

Blood transfusion:
is reserved for Hb 4gm%, if there is evidence of cardiac
decomposition as a result of anaemia then it may be necessary
to give packed cell ( to reduce the load on the heart).

Folic acid: should be given to all the cases.

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 Folate deficiency anaemia
This is due to deficiency of dietary folic acid, which has limited stores in
the body. There is a marked increase in demand in pregnancy (especially
twins) due to rapid cell divisions.
Incidence:

Folate deficiency anaemia is the second most common form of nutritional

anaemia in women, occurring with an incidence of (0.5% - 15%).
Pathophysiology:

Folate is requisite for single-carbon transfer during the building of

molecular carbon skeletons.
Normal body store last 90 days, folate is found in green leafy vegetables.
Lack of folate, results in decreased production of haem molecular carbon
skeleton.
Risk factors:

1- Obstetric factors:
Frequent pregnancies.
Multiple gestations.
2- seizures medications:
Phenobarbital.
Phenyton.
3- antibiotic medications:
Pyrimethamine.
Trimethoprim.
Sulfamethoxazol.
4- chronic haemolytic anaemia:
Sickle cell disease.

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 Hereditary spherocytosis.
Diagnosis:
Symptoms:
- tiredness.
- Weakness.
- Lassitude.
Signs:

- Pallor of the mucous membranes.

- Smooth tongue, sore and red.
- Spleen may be palpable in some cases.

Investigations:

- RBC indices include macrocytic RBC with high MCV >100fl,

AND >MCHC.
- Peripheral smear include hypersegmented neutrophils.
- Serum folate levels are low.
- Bone marrow megaloblastic.

Effects:

1. low birth weight.

2. more prone to miscarriage.
3. more prone to abruption placenta.
4. neural tube defects (if the deficiency was present during early
embryogenesis).

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Management:

a. once folate deficiency is diagnosed, treatment with folic acid

is required throughout pregnancy and should be continued
for several weeks postpartum or until the cessation of
lactation.
b. Folic acid (1 3 mg daily) produce the maximum
haematologic response and replace stores.
c. In those who is not respond to oral therapy and in severe
cases parentral folic acid is recommended (10mg daily I.M.).

Response to treatment:
Reticulocyte count it should increase within 3
days.
The haemoglobin / haematocrit increase is slower,
taking 10 14 days.
Prophylaxis:
Generally unnecessary in communities with reasonable mixed diets, the
normal requirements of pregnancy are met with a daily supplement of
0.4mg folic acid.
**in high risk population routine prophylaxis may be desirable these
include:
1) High parity.
2) Multiple pregnancies.
3) Previous H/O folate deficiency.
4) Anticonvulsant therapy.
5) Malabsorption disorders, past or present haemoglobinopathies.

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6) History of complications of pregnancy known to be associated with
a high incidence of folate deficiency.
* the recommended dose to prevent neural tube defects is 4mg/ day
starting 3 months before pregnancy and during early embryogenesis.

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 Haemoglobinopathies
Haemoglobinopathies are inherited disorders of haemoglobin synthesis
affecting the polypeptide chain of the globin fraction.

HB A= HB 2, 2

The defect of haemoglobin synthesis may be either:

A- Qualitative: when there is substitution of an amino acid in the

polypeptide chain, as in HBS (sickle) HB 2 2 S6 val, in which
glutamic radical normally present at position 6 is replaced by valine.

HB = 2 2
Glutamic radical at position 6 replaced by valine.

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B- Quantitative: when there is defective production of one type of
polypeptide chain and replacement with another, as in thalassemia e.g.
-thalassemia (HB bart's HB 4)

HB Bart's 4
Inability to synthesize chain --- -thalassemia.

Diagnosis:
Is by haemoglobin electrophoresis
- The difference in electrical charge resulting from different amino
acids in the chain.
- Haemoglobin typing should always be performed in clinically
suspicious circumstances including:
1. Ethnic origin of known high risk.
2. haematocrit <30%.
3. low haemoglobin concentration and haematocrit in spite of full
therapy.

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 Sickle cell haemoglobinopathies

This group of disorders in which there are qualitative changes in

globin synthesis, is characterized by sickle shaped which affect the
erythrocytes, in an environment of low oxygen tension or acidosis.

the essential features for HBS disease are:

1. Reduced solubility at low oxygen tension.

2. Rigid and deformed cells which do not easily pass through the
microcirculation.
3. Reduced erythrocyte life span resulting in anaemia.
4. Reticulocytosis.
5. Bone marrow hyperplasia and siderosis.
6. folate deficiency.
7. megaloblastosis erythropoiesis.

Homozygous sickle cell disease (s/s):

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 - Symptoms are rarely present at birth but developed when HB F (2
2) is replaced by HBS (2 2 S).
- Death by age of ten years is common. For those who survive and
get pregnant, the maternal and perinatal mortality and morbidity is
high.

Clinical features:

1- anaemia: - decrease life span.

- folate deficiency.
- HB 6-7g/dl.
- Reticulocytosis.
- Bone marrow hyperplasia.
2- Multiple infarcts:
Obstruction of small blood vessels in the lungs, bone, and cerebral
circulation.
3-Indulent leg ulcer.

Crisis:

Haemolytic.
Thrombotic.
Precipitated by stress, characterized by shock, prostration, and
abdominal pain.

Effect of pregnancy:

Anaemia sudden deterioration.

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 Crisis more frequent, more sever.
Pulmonary complication infection, infarction.
Cardiac disease cardiomyopathy, high cardiac output failure.
Other infections especially UTI.
Thromboembolism.
Increased fetal wastage from abortion, preterm labour, and
growth deficiency.
Pre-eclampsia and HELLP syndrome.

Management:
General:

Prophylactic folic acid is indicated in all cases.

Iron supplementation in some cases.
Blood transfusion only in severe anaemia.
Full antibiotic therapy in infection.

In labour:

Avoid hypoxia, dehydration and acidosis.

Blood transfusion if HB below 6g/dl.
Treat crisis by Rehydration, bicarbonate, analgesics.

Heterozygous sickle cell anaemia (A/S) sickle cell trait:

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 - Pregnancy is usually well tolerated and clinical manifestations are
rare.
- The management of clinical problems and prevention of crisis is as
for homozygous disease.

Thalassemia

Thalassemia are the result of failure of production of either and

chains and their replacement with other polypeptide chain. They are
inherited and occur in both homozygotic and heterozygotic forms.

-thalassemia:

thalassemia are found most commonly in SE Asia and are characterized

by inability to synthesize chain. In the majority of cases the chain are
replaced by chain (HBH HB 4) or by chain (HB Bart's HB 4).

*Homozygous( thalassemia major):

- rarely survive.
- the fetus affected in utero, polyhydramnios, erythroblastosis, anaemia,
hydrops.
- clinical picture of haemolytic disease of the new born occur.

*Hetrozygous ( Thalassemia minor):

varying degrees, with a clinical picture similar to that seen in -
thalassemia.

-thalassemia:

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-thalassemia are found most commonly in those of Mediterranean
stock and are characterized by inability to synthesize chain whilst
chain synthesis is normal.
The chain may be replaced by additional chain, o chain (HB A2)
and /or persistence of chain HBF.
HBF is normally the predominant haemoglobin type at birth, -
thalassemia dose not manifest itself until late in infancy or even in adult
life.

Homozygous (-thalassemia major):

Usually die in second or third decade and few achieve pregnancy.

Heterozygous (-thalassemia minor):

Tends to develop mild progressive anaemia during pregnancy.

Clinical feature:

1. Anaemia.
2. Jaundice.
3. Hepatosplenomegally.
4. Stunting growth.
5. Failure of development of secondary sexual characters.
6. Amenorrhea.
7. Infertility.

Effects on pregnancy:

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 -thalassemia major is rarely encountered in pregnant
women usually there are multiple complication and poor
prognosis.
-thalassemia minor is often first detected during
pregnancy as a result of screening of anaemia refractory to
treatment with haematonics.
Anaemia may become sever and occasionally result in
cardiac failure.

Treatment:
Folate supplementation.
Iron should only be given if iron deficiency is
demonstrated.
Blood transfusion in severe cases.
Husband's haemoglobin type should be determined.
Patients with thalassemia major are transfusion
dependent.

Screening:

- haemoglobin electrophoresis.
- DNA techniques.

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