Anaemias in pregnancy

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Anaemias in Pregnancy
By
Ahmed Elbohoty MD, MRCOG
Assistant professor of obstetrics and gynecology
Ain Shams University
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Definition
— TheWorld Health Organization uses haemoglobin
concentration to define anaemia, with diagnosis
made at levels below 120 g/l in nonpregnant
women and 110 g/l in pregnancy.
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Physiological changes in pregnancy
—Both red cell mass and plasma volume expand from the
first trimester of pregnancy.
—The expansion of 30 – 40% in plasma volume exceeds
the 20 – 25% increase in red cell mass
—As a consequence, there is a dilutional drop in
haemoglobin concentration.This creates a low viscosity
state, which promotes oxygen transport to the tissues
including the placenta.
—This is associated with a physiological increase in mean
corpuscular volume (MCV) increasing on average 4 fl at
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Haemopoesis
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The hemoglobin molecule is an
assembly of four globular protein
subunits.
Each subunit is composed of
A. a protein chain
B. a non-protein heme group.
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IRON
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Location Form Distribution
Hb Fe 70%
Tissue Fe 30%
Storage Fe Hemosiderin
Ferritin
Essential Fe Myoglobin
Enzymes
Plasma transport Fe Transferrin 0.19%
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Pharmaco-kinetics of Iron
— Normal diet contain about 14 mg of iron
— Absorption of iron is 5-10%
— Additional daily iron demand in early pregnancy 2-3 mg/day
— In late pregnancy 6-7 mg/day
— So daily supplement of 40-60 mg of elemental iron is required
during pregnancy
— Pregnancy results in an increased iron requirement of 1200 mg for
the entirety of pregnancy and this must be met through nutritional
changes and supplementation, where necessary.
— Iron is required by the fetus and the mother as the maternal
erythrocyte mass increases from 350 ml to 450 ml
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Iron intake
— The recommended daily intake of iron for women in their
reproductive years is 18 mg/day, although the median is 12
mg to combat loss due to menstruation.
— This compares to a recommended daily intake of just 8 mg
for adult men.
— Red meat, poultry, fish and wholegrain cereals are the
major contributors of iron to the average diet, with the
haem form more bioavailable than non-haem iron.
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Iron absorption & distribution
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Regulation of iron absorption by
hepcidin
— During normal physiological functioning, iron levels are regulated by a
homeostatic system which is controlled by hepcidin, a peptide hormone
mainly synthesised in the liver.
— Hepcidin expression increases in
— high circulating and tissue levels of iron.
— Hepcidin levels decrease in
— tissue hypoxia
— iron deficiency
— increased erythropoietic activity as a result of inhibited transcription.
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Fe from
intestine
(1 mg/day)
Erythroid precursors
in bone marrow
produce hemoglobin
(18 mg Fe/day)
Macrophages in spleen
remove and break down
senescent RBCs
(18 mg Fe/day)
Transferrin in plasma carries Fe back
to bone marrow
(17 mg/day)
Losses (1 mg Fe/day)
Ferroportin 1
Macrophages
Fe+2
Ferro-
portin 1
Macrophage
Fe+2
Senescent
RBC
Hb
Fe
Fe+3 Tf
Cerulo-
plasmin
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Iron recycling
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About 80% of iron passing through the plasma transferrin pool is recycled from
broken RBCs
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Key components in the metabolism of iron
Hepcidin: 25-amino acid peptide hormone that regulates iron uptake
and release from stores in response to circulating and tissue levels of
iron.
Ferroportin: transmembrane protein which exports iron into the blood
from enterocytes and macrophages.
Ferritin: main storage protein for iron. Found in all cells and bodily
fluids, the highest concentration being found in hepatocytes.
Serum ferritin is a marker of total iron stores in those with no chronic
illness.
Transferrin: iron-binding protein mostly produced by the liver which
acts as an intercellular transporter for iron. Approximately 3 mg total
body iron is bound to transferrin at any one time.
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Andrews N, NEJM 1999;341:1986
Receptor-Mediated Endocytosis
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IRON METABOLISM
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hemoglobin
globinheme
free amino acidsdegraded
(bilirubin)
Fe (reutilized)
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Heme
Biliverdin
Unconjugated bilirubin
Reticuloendothelial system
Unconj.bilirubin/album
in complex
Systemic circulation
HepatocytesUnconj. bilirubin
Bilirubin diglucuronide
Small intestineLarge intestine
Bilirubin diglucuronide
BilirubinUrobilinogenStercobilins
Kidney
urine
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Heme Catabolism
— Heme to Bilirubin in liver to gall bladder to small intestine
— Converted to urobilinogen reabsorbed to blood, liver, kidney
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Optimisation of haemoglobin in the
antenatal period
1. Screening of anaemia
2. Diagnosis of anaemia
3. Management of normocytic or
microcytic anaemia
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Screening
— At booking
— At 28 weeks.
— Women with multiple pregnancies should have an additional full blood
count done at 20–24 weeks.
— Women with additional risks for anemia should have individualized plans
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— Anaemia in pregnancy is defined as
— first trimester haemoglobin (Hb) less than 110 g/l
—second/third trimester Hb less than 105 g/l
—postpartum Hb less than 100 g/l
Diagnosis of anaemia
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Types of Anaemia during Pregnancy
— 1 . Hereditary causesà Thalassaemias , Sickle Cell
Haemoglobinopathies , Haemolytic anaemias , other type of
Haemgobinopathies.
— 2 .Acquired Causes à
A . Nutritional---Iron deficiency anaemia ( microcytic hypocromic
anaaemia , Folate deficiency anaemia ( megaloblastic anaemia ) , Vit B
12 Deficiency anaemia ( Megaloblastic anaemia )
B .Anaemia due to bone marrow failure ( aplstic / hypo plastic
anaemia ).
C .Anaemia secondary to inflammation , chronic disease ,
malignancy.
D .Anemia due to acute / chronic blood loss.
E .Acquire hemolytic anemia.
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Management of normocytic or microcytic
anaemia
— Iron deficiency is the most common cause
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If the history and examination don’t
suggest other causes of anemia
— Iron deficiency anaemia should be considered
— Iron deficiency can be difficult to diagnose.
— The signs and symptoms are generally nonspecific.
— The first step: A trial of oral iron should be considered
— Women should receive information on improvement of dietary
iron intake and factors affecting absorption of dietary iron.
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Iron Deficiency anaemia
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Amplitude of the problem
— almost 33% of the population globally and accounted for 8.8% of total
disability.
— 29% of nonpregnant women and 38% of pregnant women experience
anaemia.
— The most common cause of anaemia worldwide is iron deficiency,
accounting for at least 50% of cases.
— Iron deficiency can occur in the absence of anaemia (It is the most
common micronutrient deficiency worldwide).
— Iron deficiency is purported to affect at least double the number of
people who suffer from iron-deficiency anaemia, with both adversely
affecting a person’s quality of life.
— Worldwide:
— 27% of women with heavy menstrual bleeding (HMB) having iron- deficiency anaemia
and a further 60% having severe iron deficiency
— uterine fibroids are the 13th most common cause of anaemia
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Causes of iron deficiency anaemia
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Women at risk of iron deficiency:
— Teenage mothers
— previously anaemic
— Multiparous
— a consecutive pregnancy less than 1 year following a
delivery
— recent history of bleeding
— Obese
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Effect of blood lose
— Blood loss is an important cause of iron deficiency. For every millilitre of
blood lost, 0.5 mg iron is lost.
— Although compensatory mechanisms exist to increase iron absorption, a
daily iron loss of 5 mg or more exceeds these mechanisms, resulting in a
reduced iron supply, an increased iron demand for erythrocyte
production and therefore iron deficiency
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Common Sources of blood loss in women
— Menstrual blood loss is the most common cause of iron deficiency and
iron-deficiency anaemia in premenopausal women from high-income
countries
— HMB is thought to account for 20–30% of cases of iron-deficiency
anaemia worldwide.
— In postmenopausal women, the most common cause of anaemia is blood
loss from the gastrointestinal tract
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Obesity and anaemia
— Obese women may be at risk of iron deficiency and iron-
deficiency anaemia through locally produced
proinflammatory cytokines from obese adipose tissue.
— This obesity-related inflammation elevates hepcidin levels
resulting in reduced iron absorption and impaired
mitochondrial and cellular energy production, leading to
further inactivity and fatigue.
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Classic Symptoms
— Fatigue
— Weakness
— Irritability
— hair loss
— poor concentration
— shortness of breath on exertion and palpitations
— tongue discomfort, disturbance of taste
— Pruritus
— headaches and tinnitus
— Deficiency may result in pica, the craving for non-nutritive substances such as
ice or soil.
— Affection of Cognition , work performance and capacity to work..
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Symptoms of severe deficiency
— shortness of breath at rest
— angina and ankle oedema
— typically occur when haemoglobin is less than 70 g/l, unless there
is coexisting cardiorespiratory disease.
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Signs of iron-deficiency anaemia
— pallor (best seen in the tongue and mucosa of the mouth, particularly in
non- Caucasians)
— koilonychia (spoon-shaped nails with longitudinal ridges)
— angular cheilitis (ulceration at the corners of the mouth)
— atrophic glossitis (loss of tongue papillae, tongue typically appears dark
red).
— In severe cases tachycardia, cardiac murmur, cardiac enlargement, ankle
oedema and heart failure may be detected
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In pregnancy anaemia
— It is associated with morbidity for both mother and neonate. It is thought
that there is an increased risk of
— Prematurity
— low birthweight
— peripartum blood loss
— increased maternal susceptibility to infection
— maternal depression
— reduced brain maturation in the fetus
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Investigations
— A low haemoglobin is diagnostic of anaemia
— It is useful to look at the red cell morphology in determining the cause of the
anaemia.
— Iron deficiency is associated with microcytic, hypochromic red cells with a reduced
mean corpuscular volume and reduced mean corpuscular haemoglobin.(can
present in haemoglobinopathies).
— It can be Normocytic anaemia at earlier stages
— Serum ferritin is the most reliable indicator of iron deficiency, in the absence
of inflammation or chronic disease.
— Serum ferritin levels below 15 ng/ml (33.70 pmol/l) are consistent with a
diagnosis of iron deficiency.
— Transferrin saturation :When acute or chronic inflammation, hepatocellular
damage and some malignancies are present
— A transferrin saturation of less than 16% is indicative of insufficient iron supply for
erythropoiesis
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Indications for assessment of serum
ferritin.
— Anaemic women where estimation of iron stores is necessary
— Known haemoglobinopathy
— Prior to parenteral iron replacement
— Non-anaemic women with high risk of iron depletion
— Previous anaemia
— Multiparity >P3
— Consecutive pregnancy <1 year following delivery
— Vegetarians
— Teenage pregnancies
— Recent history of bleeding
— Non-anaemic women where estimation of iron stores is necessary
— High risk of bleeding
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Treatment
— Correct risk factors: Search for the cause, Diet modification,….
— Oral Iron
— Parenteral Iron
— Packed Red Blood cells
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Dose and elemental iron content per
tablet.
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Preparation Dose per tablet Elemental Iron
No of tablets per
day
Ferrous Sulphate 300mg 65mg 3
ferrous sulfate,
dried 200 mg 65 mg 3
Ferrous Gluconate 300mg 35mg 6
Ferrous Fumarate 210mg 68mg 3
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— Compliance and intolerance of oral iron preparations can limit efficacy.
Iron salts may cause gastric irritation and up to a third of patients may
develop dose limiting side effects, including nausea and epigastric
discomfort.
— Titration of dose to a level where side effects are acceptable or a trial
of an alternative preparation may be necessary.
— Enteric- coated or sustained release preparations should be avoided as
the majority of the iron is carried past the duodenum, limiting
absorption.
— The relationship between dose and altered bowel habit (diarrhoea and
constipation) is less clear and other strategies, such as use of laxatives
are helpful. 3/23/20ELBOHOTY
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Modified-release preparations
— Modified-release preparations of iron are licensed for once- daily dosage,
but have no therapeutic advantage and should not be used.
— These preparations are formulated to release iron gradually; the low
incidence of side-effects may reflect the small amounts of iron available
for absorption as the iron is carried past the first part of the duodenum
into an area of the gut where absorption may be poor.
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— To maximise absorption, iron tablets should be at empty stomach at least
1 hour prior to food.
— Furthermore, substances that inhibit absorption such as tannins and milk
should be avoided, but fruit juice containing ascorbic acid taken in
conjunction with iron supplements increases their absorption.
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The adverse effects of oral iron
therapy
— Nausea
— Vomiting
— Constipation
— dark stools
— abdominal discomfort
— as a result of free radical-mediated mucosal luminal damage
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— Following commencement of oral iron therapy a further full blood count
and serum ferritin level should be undertaken three to four weeks later
(2 weeks in pregnancy) to assess response to treatment.
— Haemoglobin should rise by 20 g/l every three to four weeks or 1.2
g/l/day.
— Once haemoglobin and serum ferritin levels are normal treatment
should be continued for three months.
— If haemaglobin falls below normal reinvestigation should be considered
along with re-provision of iron supplementation.
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Inadequate response
— The most common reason for an inadequate response is non-compliance.
However, it is important to determine if continuing loss or inadequate
iron absorption resulting from an inflammatory or malabsorption
condition such as coeliac disease are responsible for failure to respond to
therapy.
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Parenteral iron therapy
— During pregnancy its use is contraindicated in the first trimester.
— Parenteral iron results in rapid repletion of iron levels (up to 20 g/l in
seven days) making it an appropriate choice before major surgery.
— Within bone marrow, parenteral iron results in 4.5–7.8 times the
normal production of erythrocytes compared with the 2.5–3.5 times
normal production associated with oral iron therapy.
— It is generally safe and associated with fewer adverse effects than oral
preparations, although anaphylaxis has been reported.Therefore, during
an infusion and for 30 minutes afterwards, patients must be monitored
for signs of hypersensitivity
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Indications
—oral iron is not tolerated
—or absorbed
—or patient compliance is in doubt
—or if the woman is approaching term and there is
insufficient time for oral supplementation to be
effective.
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— Severe allergic reactions are possible with all iron preparations.
— Intravenous iron products should only be administered when staff trained to
evaluate and manage anaphylactic or anaphylactoid reactions, as well as
resuscitation facilities, are immediately available.
— Long-lasting brown discoloration (staining) of the skin may occur due to
leakage of IV iron into the tissues around the injection site.This may be
permanent. Ensure injection site is monitored and women receiving IV iron
are educated to report any discomfort, burning, redness or swelling. In case of
paravenous leakage STOP infusion immediately.The infusion should be
completed after intravenous access is resited
Disadvantages
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Forms
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Iron dextran
— 50 mg elemental iron/mL, given either IM or IV
— Side effects: Usually in ~ 5% patients
— Local rxns: Pain, muscle necrosis, phlebitis
— Systemic:Anaphylaxis seen in 1%, fever, urticaria, arthritic flares
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Iron sucrose (20 mg iron/mL)
— Iron sucrose also has less side effects, even if there is a prior
history of Iron dextran
Faich, G. Am J Kidney Dis 1999; 33:464
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Administration
— Option 1: 500 mg Iron Sucrose in NS 250 ml administered over three
(3) hours; repeat in 3-7 days to reach 1 gm.
— Option 2: 200 mg in NS 100 ml administered over 20-30 minutes; may
repeat every other day to reach target. Fe need; see below.
— Calculate Fe (Iron sucrose) need: Fe need = wt (kg) x 0.24 x Hgb
(target – current)(gm/L) + 500mg
— Example: 70 kg woman with Hgb of 7.0 gm/dL and a target of 11 gm/L
= 70 kg x 0.24 x (target: 110 gm/L — actual: 70 gm/L) + 500 mg
Remember: 7 gm/dL = 70 gm/L
— Remember: Use pre-pregnancy weight (kg) = 672 mg + 500 mg =
1172 mg (This is usually rounded off to 100 or 200 mg increments)
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IM Iron (NOT TO BE USED)
— Usually slow iron mobilization and occasionally incomplete
— Therefore usually not used, even though available in the Iron
dextran form
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Blood transfusion
— The final treatment option is blood transfusion.
— Given the adverse outcomes associated with transfusion, including fluid
overload, anaphylaxis, allergic reaction, acute lung injury, infection and,
in women of childbearing age, potential sensitisation of red cell antigens,
its use should be limited to the management of major obstetric
haemorrhage, those who are haemodynamically unstable or with organ
function compromise.
— Each unit of packed red blood cells transfused should raise the
haemoglobin by 10 g/l.
— The need for additional iron supplementation can be determined once
the woman has been stabilised.
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Evidence on PRC transfusion in women who are not actively
bleeding, with a:
— Haemoglobin >90 g/L, red cell transfusion is usually inappropriate
— Haemoglobin 70-90 g/L, red cell transfusion is not associated with reduced mortality.The
decision to transfuse peripartum women (with a single unit followed by reassessment) should
be based on the need to relieve clinical signs and symptoms of anaemia, the availability of other
therapies for the treatment of anaemia, the expected timeframe to delivery and the presence of
risk factors for haemorrhage
— Haemoglobin <70 g/L, red cell transfusion may be associated with reduced mortality and
may be appropriate. However, transfusion may not be required in well- compensated patients,
or where other specific therapy is available
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— If there is no demonstrable rise in Hb at 2 weeks and compliance
has been checked: Further tests should be undertaken.
— Serum ferritin is the most useful test for diagnosing iron
deficiency.
Blood tests
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— The recombinant human erythropoietin (rHuEPO) for non-end-
stage renal anaemia should only be used in the context of a controlled
clinical trial or on the expert advice of the haematologist.
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Anaemia not due to haematinic
deficiency
(for example, haemoglobinopathies and
bone marrow failure syndromes)
— should be managed by blood transfusion where appropriate in
close conjunction with a haematologist.
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Megaloblastic anaemia
— It is the second most common nutritional anaemia seen during pregnancy
— Folate deficiency is a more common cause of megaloblastic anaemia than
vitamin B12 deficiency
— During pregnancy, requirements are increased approximately 5-10 fold and
stores may be exhausted if increased folate intake does not occur
— Except in strict vegans, true vitamin B12 deficiency is uncommon, despite the
increased requirements of pregnancy, due to the extent of vitamin B12 stores.
Other causes of vitamin B12 deficiency include conditions affecting the
stomach (e.g. hypochlorhydria, gastrectomy, pernicious anaemia –
autoimmune, rare in women of childbearing age), conditions affecting the
intestines (e.g. Crohn’s disease) and some medications
— Folate stores are much smaller and more easily exhausted
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— Women with anaemia in the presence of a normal MCV should
have further testing to exclude folate, vitamin B12 deficiency or
thalassaemia / haemoglobinopathy
— Vitamin B12 and folate measurements should be undertaken to
exclude deficiencies of both haematinics.The metabolic roles of
folate and vitamin B12 are closely linked, and deficiency of either
vitamin can result in the same clinical manifestations.
— In addition, a low serum folate may be associated with a low
serum B12, in which case treatment is initiated with B12 therapy
before adding in folate therapy
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Folate deficiency
— Pregnancy and lactation are associated with increased folate requirements, and preferential delivery of
folate to the fetus may result in severe maternal deficiency in the presence of normal folate status in the
baby.
— Multiparity and hyperemesis gravidarum increase the risk of developing deficiency in the mother
— Folate deficiency in pregnancy may be difficult to diagnose early. However it should be thought of and
excluded in the presence of:
— Increasing MCV ( greater than 96 fL but may be of the order of 120 fL)
— Large hyper-segmented neutrophils (these being a late sign in pregnancy)
— Falling platelet count (less than 100 x 109 / L)
— Isolated folate deficiency without malabsorption can be secondary to increased requirements in
pregnancy
— If serum folate confirmed to be low check CBE and film, ferritin, coeliac disease screen,Active
vitamin B12 level and start folate once vitamin B12 confirmed normal
— In the case of folate deficiency, supplemental folate is given at 5 mg per day and continued throughout
the pregnancy.
— Lack of reticulocytosis should raise the question of folate malabsorption
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An Important Point!
— Folic acid can partially reverse some of the hematologic
abnormalities ofVitamin B12 deficiency, although the neurologic
manifestations will progress.
— Thus, it is important to rule outVitamin B12 deficiency before
treating a patient with megaloblastic anemia with folic acid
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Folate deficiency
— Folic acid (1 to 5 mg/day PO) for one to four months, or until
complete hematologic recovery occurs.A dose of 1 mg/day is
usually sufficient, even if malabsorption is present.
— These doses are in excess of those recommended for disease
prevention (eg, recommended daily allowance in normal adults,
alcoholics, prevention of neural tube defects) 500mcg/day
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Vitamin B12 deficiency
— Vitamin B12 is essential for infant neurodevelopment.
— Undiagnosed maternal vitamin B12 deficiency may result in
irreversible neurological damage to the breastfed infant.
— Although maternal vitamin B12 deficiency is uncommon, the
majority of women with deficient vitamin B12 levels are
asymptomatic
— Those who have had gastric surgery have a high prevalence of
vitamin B12 deficiency, and more recently, treatments for obesity
including gastric banding and gastric bypass surgery also lead to
vitamin deficiency
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— Vitamin B12 absorption
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check the serum vitamin B12 level if:
— Increased MCV
— Vegetarian diet.Also consider referral to dietician
— GI pathology (coeliac disease, Crohn’s disease, gastric banding / bypass
etc.)
— Family history of vitamin B12 deficiency or pernicious anaemia
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— In pregnancyTotal vitamin B12 is reduced, however, this is not necessarily reflective of
deficiency even if the value is below the reference interval.
— Total vitamin B12 is made up of biologically active (10 - 30% ofTotal vitamin B12) and
biologically inert (70 - 90% ofTotal vitamin B12) complexes.This is determined by the protein
it is bound to.
— In normal pregnancy the protein that complexes with vitamin B12 to produce the biologically
inert complex (haptocorrin + vitamin B12 è holohaptocorrin) is‘naturally’ reduced,
whereas the protein that complexes with vitamin B12 to produce the biologically active
complex (transcobalamin + B12 è holotranscobalamin) remains unchanged
— if theTotal vitamin B12 concentration when assayed is low / equivocal, testing of Active
vitamin B12 is initiated automatically in both pregnant and non-pregnant women.
— This will determine whether a woman has normalActive vitamin B12 levels (no further testing
needed), indeterminate levels (measure homocysteine and methylmalonic acid and discuss
with a haematologist) or low levels (discuss with a haematologist)
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Treatment
— Hydroxocobalamin dose of 1000 µg (1 mg) IM every day for one
week, followed by 1 mg every week for four weeks and then, if
the underlying disorder persists, as in PA, 1 mg every 3 months
for life
— s/e allergic reactions; hypokalaemia
— high dose oral cobalamin is an alternative but requires much
greater patient compliance
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Anaemia management in 1ry health care
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Hemoglobin disorders in pregnancy
By
Ahmed Elbohoty MD, MRCOG
Assistant professor of obstetrics and gynecology
Ain Shams University
91
Basic knowledge
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The hemoglobin molecule is an
assembly of four globular protein
subunits.
Each subunit is composed of
A. a protein chain
B. a non-protein heme group.
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Hemoglobin A
— Fetal Hemoglobin (2 alpha, 2 gamma)
— HemoglobinA2 (2 alpha, 2 delta)
— Small amounts in body
α
αβ
β
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Time Hb type
8 Weeks Gower 1 (ζ2ε2), Gower 2 (α2ε2) and Hb
Portland (ζ2γ2) (more O2 affinity than HbF)
10-28 weeks Hb F (α2γ2)
28-34 weeks Conversion from the synthesis of Hb F
(α2γ2) to Hb A (α2β2 ) starts
At term Hb F (α2γ2) : Hb A (α2β2 ) = 80:20
At 6 months
postnatal
Hb A (α2β2 ): 95%
Hb A2 (α2δ2):3.5%
Hb F (α2γ2) : 1% 3/23/20ELBOHOTY
Normal variants of Hb through life
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Chromosomes
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Disorders of Haemoglobin
1. Quantity (Thalassemia)
2. Quality (Sickle cell)
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Thalassaemias in Pregnancy
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What is Thalassaemia ?
Thalassaemia is a group of inherited disorders of
hemoglobin synthesis characterized by a reduced
or absent one or more of the globin chains of adult
hemoglobin .
Genetic autosomal recessive blood disease.
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Thalassemia
—May be either homozygous defect or
heterozygous defect.
—Results in overall decrease in
amount of hemoglobin produced
and may induce hemolysis.
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Pathophysiology of the major types
— Reduced globin chain synthesis
— The resultant red cells having inadequate haemoglobin content.
— Extravascular haemolysis due to the release into the peripheral
circulation of damaged red blood cells and erythroid precursors
— Extra-medullary hematopoiesis
— SevereAnaemia
— Blood transfusion
— Iron Overload
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Genetics of Thalassemia
—Adult hemoglobin composed two alpha and
two beta chains.
—Alpha thalassemia usually caused by gene
deletion
—Beta thalassemia usually caused by mutation.
—Results in microcytic, hypochromic anemias of
varying severity.
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Alpha Thalassemia
—AlphaThalassemia: deficient/absent alpha
subunits
—Excess beta subunits
—Excess gamma subunits newborns
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Genetic basis of Alpha Thalassemia
— Encoding genes on chromosome 16 (short arm)
— Each cell has 4 copies of the alpha globin gene
— Each gene responsible for ¼ production of alpha globin
— 4 possible mutation states:
— Loss of ONE gene à silent carrier
— Loss ofTWO genes à thalassemia minor (trait)
— Loss ofTHREE genes à Hemoglobin H
— Accumulation of beta chains
— Association of beta chains in groups of 4 à Hemoglobin H
— Loss of FOUR genes à Hemoglobin Barts
— NO alpha chains produced ∴ only gamma chains present
— Association of 4 gamma chains à Hemoglobin Barts
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Classification & Terminology
Alpha Thalassemia
• Normal aa/aa
• Silent carrier - a/aa
• Minor -a/-a
--/aa
• Hb H disease --/-a
• Barts hydrops fetalis --/--
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Inheritance
— Carrier parents with different forms can result in different
inheritances
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Alleles
affected
Description
Chromosome 16 (short arm)
One asymptomatic
Two The condition is called alpha thalassemia trait. There is a mild
microcytic hypochromic anemia.
Three The condition is called Hemoglobin H disease.
The disease may first be noticed in childhood or in early adult life,
when the anemia and splenomegaly are noted.
Four The fetus cannot live without intrauterine transfusion and usually
presents dead at birth with hydrops fetalis(hemoglobin Barts).
Alpha thalassemia
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α Thalassemias result in decreased alpha-globin production, therefore fewer alpha-globin chains are
produced, resulting in an excess of β chains in adults and excess γ chains in newborns.
The excess β chains form unstable tetramers (called hemoglobin H or HbH of 4 beta chains), which have
abnormal oxygen dissociation curves.
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Clinical Types of Beta Thalassaemia :
There are 3 types of Beta thalassaemia :
1. Thalassaemia Minor
2. Thalassaemia Intermediate
3. Thalassaemia Major
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Beta Thalassemia
— BetaThalassemia: deficient/absent beta subunits
— Commonly found in Mediterranean, Middle East,Asia, andAfrica
— Three types:
— Minor
— Intermedia
— Major (Cooley anemia)
— May be asymptomatic at birth as HbF functions
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Prevalence
— TheAsian communities of India, Pakistan and Bangladesh account for
79% of thalassaemia births
— only 7% occurring in the Cypriot population who have taken advantage
of the availability of prenatal diagnosis.
— High incidence areas include Greater London, Birmingham and
Manchester.
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The NHS Sickle Cell and Thalassaemia
Screening Programme in England
— Sickle cell and thallassaemia are the two most common
haemoglobinopathies in the UK.
— Screening for should be offered to women as early as possible in
pregnancy (ideally by 10 weeks)
— It identified 16000 women as carriers of a haemoglobinopathy during
2009/10 and partner testing was offered.
— 59% of screen positive women had partner testing
— The majority of pregnancies affected by thalassaemia major were
terminated
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How is it done?
— For thalathemia: MCV is done as a part of CBC
— For sickle cell: Screening tests offered on it's prevalence within
that area
— high prevalence is more than 1.5 per 10,000 pregnancies
— InTrusts defined as covering high prevalence populations, laboratory sickle cell and
thalassaemia screening should be offered to all women.
— low prevalence is less than or equal to 1.5 per 10,000
pregnancies).
— The designation of high and low prevalence is kept under review based
on newborn screening carrier results.
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Further steps
• MCV
• below 27 picograms: laboratory screening (preferably high-performance liquid
chromatography) should be offered.
• More than 27 picogram: reassure
• Where prevalence of sickle cell disease is high (fetal prevalence above 1.5 cases
per 10,000 pregnancies)
• laboratory screening (preferably high-performance liquid chromatography) should be offered to
identify carriers of sickle cell disease and/or thalassaemia.
• Where prevalence of sickle cell disease is low fetal prevalence 1.5 cases per
10,000 pregnancies or below)
• the Family Origin Questionnaire is done:
• high risk of sickle cell disorders: laboratory screening (preferably high-performance
liquid chromatography) should be offered.
• Low risk: reasure
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FOQ
— you need to ask for the family origins of both the
woman AND the baby's father going back at least 2
generations (or more if possible).
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”Low risk“ Family Origins
— United Kingdom (White)
— England, Scotland, Northern Ireland,Wales.
— Northern European (White)
— Austria, Belgium, Denmark, Greenland, Iceland, Ireland (Eire), Finland,
France, Germany, Luxembourg, Netherlands, Norway, Sweden,
Switzerland.
— Some populations of the following countries have Northern European
origin (countries listed above) and are also at low risk for haemoglobin
variants:
— Northern European Origin (White)
— Australia, NorthAmerica (USA, Canada), SouthAfrica, New Zealand.
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123
Further testing and counselling
— if the pregnant woman is identified as, or known to
be a carrier: offer screening to the baby’s father as
soon as possible
— if the pregnant woman and baby’s father are
identified as carriers or affected: refer for
counselling and offer prenatal diagnosis by 12+ 6
weeks of pregnancy
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Family origin questionnaire is not useful
— Adoption
— If either parent has been adopted, the FOQ information may not accurately
reflect the true family origins. Such cases should be treated as high risk and
have full laboratory screening.
— Fertility treatment – donor gametes
— If the pregnancy has been achieved by the use of a donor egg then the
screening results on the woman will not be informative so the baby’s father
should always be tested to ensure that this is not a high risk pregnancy.
— If donor sperm has been used then it may be appropriate to refer back to the
fertility clinic if the screening results on the woman show that she is a
carrier for a haemoglobinopathy.
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125
Bone marrow transplants
— In women who have received a bone marrow transplant, the
haemoglobin results on her blood specimen will not necessarily
indicate the genetic make up of the fetus.
— The baby’s father should always be tested to ensure that this is not
a high risk pregnancy.
— Caution should be exercised in the interpretation of any
haematology results in this instance.
— If DNA confirmation of mother’s status is required then pre-
transplant DNA or DNA obtained from hair follicles should be
used.
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Testing algorithm for laboratory screening in LOW
PREVALENCE area
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Testing algorithm for laboratory screening in HIGH
PREVALENCE areas
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Genetic basis of Beta Thalassemia
¢Encoding genes on chromosome 11 (short arm)
¢Each cell contains 2 copies of beta globin gene
— beta globin protein level = alpha globin protein level
¢Suppression of gene more likely than deletion
— 2 mutations: beta-+-thal / beta-0-thal
¢“Loss” of ONE gene à thalassemia minor (trait)
¢“Loss” of BOTH gene à complex picture
— 2 beta-+-thal à thalassemia intermedia / thalassemia major
— 2 beta-0-thal à thalassemia major
— beta-+-thal / beta-0-thal à thalassemia major
¢Excess of alpha globin chains
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Classification & Terminology
Beta Thalassemia
• Normal b/b
• Minor b/b0
b/b+
• Intermedia b0/b+
b+/b+
• Major b0
/b0
b+/b+
b0/b+
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Name Description
Chromosome 11 (short arm)
β thalassemia
minor (β
thalassemia
trait)
If only one β globin allele bears a mutation. This is a mild microcytic anemia.
The patient will have an increased fraction of Hemoglobin A2 (>3.5%) and a
decreased fraction of Hemoglobin A (<97.5%).
do not require transfusion.
Thalassemia
intermedia
Either both alleles have suppressed gene or one absent and the other is suppressed
less severe
needing seven or fewer transfusion episodes per year or those who are not transfused
β thalassemia
major or Cooley's
anemia
• most severe form
• moderate to severe anemia
• intramedullary hemolysis (RBC die before full development)
• peripheral hemolysis & splenomegaly
• skeletal abnormalities (overcompensation by bone marrow)
• increased risk of thromboses
• pulmonary hypertension & congestive heart failure
• require more than seven transfusion episodes per year
Clinical outcomes of β thalassemia
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Laboratory Diagnosis
of Thalassemia
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Laboratory Diagnosis
ØHaemoglobin : Haemoglobin level is usually normal or mildly
reduced inThalassemia minor but markedly affected in major.
ØPeripheral blood film : Hypochromia and Microcytosis
(similar to Iron DeficiencyAnemia).
ØMCV< 75 fl, RDW < 14%.
ØReticulocyte Count increases
ØHaemoglobin electrophoresis
ØHPLC (High Performance liquid chromatography)
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Trait management
— Diagnosis:
— red cell indices (indicating hypochromia and microcytosis)
— quantification of the different haemoglobin types in the individual (with an
increased percentage of fetal haemoglobin and haemoglobin A2).
— Presentation:
— Many women will already know, prior to pregnancy, that they are carriers of b-
thalassaemia, and their partner’s haemoglobinopathy status will also be known.
— Otherwise, testing in the national Antenatal Screening Programme should be
undertaken as early as possible in the pregnancy.
— Reliable diagnosis of a-thalassaemia trait may be more problematic, as the
haematological picture can be difficult to differentiate from iron deficiency
anaemia.
— Once the diagnosis has been clarified, there is the need to recognise the
development of concurrent iron deficiency.
— This will require measurement of serum ferritin levels, which should be
undertaken in each trimester of the pregnancy.
— Conversely, it is important to avoid giving unnecessary iron supplements to the
patient, if the cause of her microcytic anaemia has been misunderstood.
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Intermediate & Major
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Treatments for Alpha Thalassemia
— Silent Carrier – no treatment required
— Trait (Minor) – no treatment required
— Hemoglobin H Disease – Folate
— avoid iron supplements
— Major (Hemoglobin Bart’s) –It is usualy presented with early
hydrops os SB but it can be managed with early intrauterine
RBC transfusion
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Treatment for Beta Thalassemia
— Trait – no treatment required
— Intermedia
— Major (Cooley anemia)
— Regular folate supplementation
— RBC transfusion (Splenectomy may decrease need for transfusions)
— to maintain [Hgb] ~9-10g/dL
— Blood transfusions à iron accumulation à iron overload
— Iron chelators (diferroxamin)
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splenectomy
— Splenectomy is no longer the mainstay of treatment for thalassaemia
major and intermedia patients.
— It was previously offered splenectomy to help reduce transfusion requirements.
— Women who have undergone splenectomy are at risk of infection from
encapsulated bacteria such as Neisseria meningitidis, Streptococcus
pneumoniae and Haemophilus influenzae type b.
— So theses measures should be taken:
— daily penicillin prophylaxis and who are allergic to penicillin should be recive erythromycin.
— Haemophilus influenzae type b and the conjugated meningococcal C vaccine
as a single dose if they have not received it as part of primary vaccination.
— The pneumococcal vaccine every 5 years.
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blood transfusion
— These are the cornerstones of β thalassaemia treatment are therapy.
— All women with thalassaemia major should be receiving blood
transfusions on a regular basis aiming for a pretransfusion haemoglobin
of 100 g/l.
— Improved transfusion techniques and effective chelation protocols have
improved the quality of life and survival of individuals with thalassaemia.
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iron chelation
— Multiple transfusions cause iron overload resulting in hepatic, cardiac
and endocrine dysfunction.
— The anterior pituitary is very sensitive to iron overload and evidence of
dysfunction is common.
— Puberty is often delayed and incomplete, resulting in low bone mass.
— Most of these women are subfertile due to hypogonadotrophic
hypogonadism and therefore require ovulation induction therapy with
gonadotrophins to achieve a pregnancy.
— Cardiac failure is the primary cause of death in over 50% of cases.
— The mortality from cardiac iron overload has reduced significantly since
the development of magnetic resonance imaging (MRI) methods for
monitoring cardiac (cardiacT2*) and hepatic iron overload (liverT2*)
and FerriScan® liver iron assessment (FerriScan®, Resonance
Health,Australia).
— These methods are now available in most large centres looking after
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Preconception care
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additional risks to the woman and baby
— Iron overload
— cardiomyopathy
— with around 9 months of little or no
chelation, women with thalassaemia
major may develop new
endocrinopathies: in particular,
diabetes mellitus, hypothyroidism and
hypoparathyroidism due to the
increasing iron burden
— FGR
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optimum preconceptual care for women
with thalassaemia
— MDT (thalassaemia team)
— At each visit, there should be a discussion and documentation of
intentions regarding pregnancy.
— prior to embarking on any pregnancy
— Screening for end-organ damage
— optimisation of complications.
— Aggressive chelation reduce and optimise body iron burden and reduce end-
organ damage.
— Not suitable to pregnancy: use contraception despite the reduced
fertility associated with thalassaemia.
— Hypogonadotrophic hypogonadism may occur and ovulation induction
using injectable gonadotrophins is required to conceive
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Different organ affection
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Heart
— All women should be assessed by a cardiologist with expertise in
thalassaemia and/or iron overload
— An echocardiogram and an electrocardiogram (ECG) should be
performed as well asT2 cardiac MRI.
— The aim is for no cardiac iron, but this can take years to achieve so care
should be individualised to the woman.
— Otherwise, aim for cardiacT2 > 20 ms wherever possible as this reflects
minimal iron in the heart.
— AT2 < 10 ms is associated with an increased risk of cardiac failure.
— A reduced ejection fraction is a relative contraindication to pregnancy
and the management should be the subject of multidisciplinary
discussions
— Cardiac arrhythmias are more likely in older patients who have
previously had severe myocardial iron overload and are now clear of
cardiac iron.
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Management of women with myocardial iron
— Regular cardiology review with careful monitoring of ejection fraction
during the pregnancy
— Indication for chelation therapy: signs of cardiac decompensation
— Those women at highest risk of cardiac decompensation should
commence low-dose subcutaneous desferrioxamine (20 mg/kg/day) on
a minimum of 4–5 days a week under joint haematology and cardiology
guidance from 20–24 weeks of gestation.
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Diabetes
— Diabetes is common in women with thalassaemia.
— They should be referred to a diabetologist.
— Good glycaemic control is essential prepregnancy.
— Level of control:
— serum fructosamine concentrations < 300 nmol/l for at least 3 months
prior to conception.
— This is equivalent to an HbA1c of 43 mmol/mol.
— This level is associated with a reduced risk of congenital abnormalities.
— HbA1c is not a reliable marker of glycaemic control as this is diluted by
transfused blood and results in underestimation, so serum fructosamine
is preferred for monitoring
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Thyroid
— Thyroid function should be determined.
— The woman should be euthyroid prepregnancy.
— Hypothyroidism is frequently found in patients with thalassaemia.
— Untreated hypothyroidism can result in maternal morbidity, as well as
perinatal morbidity and mortality.
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Liver
— Women should be assessed for liver iron concentration using a
FerriScan® or liverT2*.
— Ideally the liver iron should be < 7 mg/g (dry weight).
— Liver and gall bladder (and spleen if present) ultrasound should be used
to detect cholelithiasis and evidence of liver cirrhosis due to iron
overload or transfusion-related viral hepatitis.
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hepatic iron
— Women with severe hepatic iron loading should be carefully
reviewed and consideration given to low- dose desferrioxamine iron
chelation from 20 weeks.
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Bone density scan
— Osteoporosis is a common finding in adults with thalassaemia due to:
— thalassaemic bone disease
— chelation of calcium by chelation drugs
— hypogonadism
— vitamin D deficiency.
— All women should have vitamin D levels optimised before pregnancy and
thereafter maintained in the normal range
— All women should be offered a bone density scan to document pre-
existing osteoporosis.
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Red cell antibodies
— Alloimmunity occurs in 16.5% of individuals with thalassaemia.
— Red cell antibodies may indicate a risk of haemolytic disease of the fetus
and newborn.
— If antibodies are present there may be challenges in obtaining suitable
blood for transfusion
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medication
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—Long acting:
— Deferasirox and deferiprone should ideally be discontinued 3
months before conception and women converted to
desferrioxamine iron chelation.
—Short acting:
— Desferrioxamine has a short half-life and is safe for infusion
during ovulation induction therapy.
— Desferrioxamine should be avoided in the first trimester
owing to lack of safety data.
— It has been used safely after 20 weeks of gestation at low
doses.
Iron Chelators
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For osteoporosis
— All bisphosphonates are contraindicated in pregnancy and should ideally
be discontinued 3 months prior to conception in accordance with the
product safety information sheet.
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Vaccination and antibiotics
— Hepatitis B vaccination is recommended in HBsAg negative women who
are transfused or may be transfused.
— Hepatitis C status should be determined.
— All women who have undergone a splenectomy should take penicillin
prophylaxis or equivalent.
— All women who have undergone a splenectomy should be vaccinated for
pneumococcus and Haemophilus influenzae type b if this has not been done
before.
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Folic acid
— Women with thalassaemia have a much higher demand for folic acid so
high-dose supplementation
is needed.
— Folic acid 5 mg daily should be commenced 3 months prior to
conception
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Genetic consideration
— Genetic counselling should be offered if the partner is a carrier of a
haemoglobinopathy
— In vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) with a
pre-implantation genetic diagnosis (PGD) should be considered so that a
homozygous or compound heterozygous pregnancy can be avoided.
— Egg and sperm donors considering IVF should be screened for
haemoglobinopathies.
— Preconception counselling for women with thalassaemia includes partner
screening and genetic counselling as well as the methods and risks of
prenatal diagnosis and termination of pregnancy.
— If the partner is unavailable, an offer of prenatal testing is appropriate.
— Egg and sperm donors should be screened for haemoglobinopathies.
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Booking appointment
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— Offer information, advice and support in relation to optimising general health.
— Discuss information, education and advice about how thalassaemia will affect
pregnancy.
— Primary care or hospital appointment – offer partner testing if not already done,
review partner results if available and discuss prenatal diagnosis (chorionic villus
sampling, amniocentesis or cell-free fetal DNA) if appropriate.
— Take a clinical history to establish the extent of thalassaemia complications.
— Women with diabetes to be referred to joint diabetes pregnancy clinic with
haematology input.
— Review medications
— e.g. chelators such as deferiprone or deferasirox.
— Women should be taking 5 mg folic acid.
— Women who have had a splenectomy
— should receive antibiotic prophylaxis.
— vaccinations with those women who have had a splenectomy.
— Offer MRI heart and liver (T2* and FerriScan®) if these have not been performed in
the previous year for thalassaemia major patients only. Determine presence of any red
cell antibodies.
— Document blood pressure.
— Send midstream specimen of urine for culture.
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Transfusion
— The decision to initiate a transfusion regimen is a clinical one based on
the woman’s symptoms and fetal growth.
— If a woman with thalassaemia intermedia starts transfusion, haemoglobin
targets are managed as for thalassaemia major.
— Women with thalassaemia intermedia who are asymptomatic with
normal fetal growth and low haemoglobin should have a formal plan
outlined in the notes with regard to blood transfusion in late pregnancy.
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— Regular transfusions should be started in
— there is worsening maternal anaemia
— evidence of FGR regular transfusions should be started
— Aim: maintenance of pretransfusion haemoglobin concentration above 100 g/l.
— Dose:
— Initially a 2–3 unit transfusion should be administered with additional top-up
transfusion if necessary
— the following week until the haemoglobin reaches 120 g/l.
— Monitoring of haemoglobin: after 2 to 3 weeks
— If the haemoglobin has fallen below 100 g/l: a 2-unit transfusion administered.
— Each woman’s haemoglobin falls at different rates after transfusion so close
surveillance of pretransfusion haemoglobin concentrations is required.
— Generally, in nontransfused patients, if the haemoglobin is above 80 g/l at 36
weeks of gestation, transfusion can be avoided prior to delivery.
— If the haemoglobin is less than 80 g/l then aim for a top-up transfusion of 2
units at 37–38 weeks of gestation.
— Postnatal transfusion can be provided as necessary.
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antenatal thromboprophylaxis
— commence or continue taking low-dose aspirin (75 mg/day):
— Women with thalassaemia who have undergone splenectomy
— have a platelet count greater than 600 x 109/l should
— low-molecular-weight heparin thromboprophylaxis + low-dose aspirin
(75 mg/day):
— Women with thalassaemia who have undergone splenectomy and have a
platelet count above 600 x 109/l should be offered.
— antenatal hospital admissions.
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Schedule of antenatal appointments
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11–14 weeks
— Midwife with high-risk obstetric experience. Review partner results and
discuss prenatal diagnosis if appropriate.
— Confirm that all actions from first visit are complete.
— Continue folic acid 5 mg.
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16 weeks
— Midwife and multidisciplinary review (haematologist, obstetrician and
diabetologist if diabetic).
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20 weeks
— Midwife and multidisciplinary review.
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20–24 weeks
— Women assessed with risks of cardiac decompensation should start on
low-dose subcutaneous desferrioxamine (20 mg/kg/day) on a
— minimum of 4 to 5 days a week under guidance of a haematologist with
experience in iron chelation.
— Women withT2* > 10 but < 20 ms should be assessed for risks and
consideration given to starting desferrioxamine infusions if there are
concerns.
— Women withT2* > 20 ms (optimal preconception result) should not be
given any desferrioxamine chelation during pregnancy unless there is
severe hepatic iron overload.
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24 weeks
— Midwife and multidisciplinary review. Ultrasound for fetal
biometry.
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28 weeks
— Ultrasound for fetal biometry.
— Specialist cardiology review and formulation of delivery plan
based on cardiac function.
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30 weeks
— Midwife for routine assessment.
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32 weeks
— Ultrasound for biometry.
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34 weeks
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36 weeks
— A care plan regarding the delivery should be formulated by the team and
documented in the notes.
— Ultrasound for fetal biometry.
Offer information and advice about:
— Timing, mode and management of the birth
Analgesia and anaesthesia; arrange anaesthetic assessment if cardiac
dysfunction Care of baby after birth.
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38 weeks
— Midwife and obstetrician for routine assessment.
— Offer induction of labour if the woman has diabetes.
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39 weeks
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40 weeks
— Obstetrician for routine assessment.
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41 weeks
— Obstetrician for routine assessment.
For a nondiabetic woman with normal fetal growth and no
complications, offer induction of labour in accordance with the NICE
guideline for
— Thalassaemia in itself is not an indication for caesarean section.
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Intrapartum care— Indications of timed delivery can be found e.g. diabetes or FGR
— Senior midwifery, obstetric, anaesthetic and haematology staff should be
informed as soon as the woman is admitted to the delivery suite.
— If there are medical complications such as cardiomyopathy, a detailed
management plan formulated during the pregnancy should be in the woman’s
notes.
— In the presence of red cell antibodies, blood should be cross-matched for
delivery since this may delay the availability of blood. Otherwise a group and
save will suffice.
— Depending on the timing of the last blood transfusion, the woman may well
have a low haemoglobin. If the haemoglobin is less than 100 g/l, cross-match 2
units on admission to the labour ward.
— In women with thalassaemia major intravenous desferrioxamine 2 g over 24
hours should be administered for the duration of labour.
— Continuous intrapartum electronic fetal monitoring should be instituted.
— Active management of the third stage of labour is recommended to minimise
blood loss.
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Importance of peripartum chelating
therapy
— Women who are transfusion-dependent and not on a chelating agent will
have high serum concentrations of a toxic iron species known as non-
transferrin bound iron.
— These may cause free radical damage and cardiac dysrhythmia when the
woman is subjected to the stress of labour.
— Peripartum chelation therapy is therefore recommended.
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post delivery
— Women with thalassaemia should be considered at high risk for venous
thromboembolism.
— Breastfeeding is safe and should be encouraged.
— Desferrioxamine is secreted in breast milk but is not orally absorbed and
therefore not harmful to the newborn.
— There is a high risk of venous thromboembolism due to the presence of
abnormal red cells in the circulation.
— Women should receive low-molecular-weight heparin prophylaxis while
in hospital.
— In addition, low-molecular-weight heparin should be administered for 10
days post discharge following vaginal delivery or for 6 weeks following
caesarean section
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3/23/20ELBOHOTY
Maternal Medical complications for thathemia major Technical complications/Management
Pre-
pregnancy
Endocrinopathies (hypogonadotrophic
hypogonadism), Hepatic , cardiac, Diabetes
splenomegaly,.
Hepatitic C,B _____screening
Splenectomy.___vaccination+ AB
screening for end-organ damage
Aggressive chelation discontinued 3 months
before conception
Good glycaemic control (fructosamine
concentrations
< 300 nmol/l)
ovulation induction using injectable
gonadotrophins
Screen the partner & (IVF/ICSI) with a pre-
implantation genetic diagnosis (PGD)
Thyroid function
Antenatal Miscarriage, fetal anomalies
splenectomy or have a platelet count
greater than
600 x 109/l
Gestational diabetes
Venous thromboembolic disease
Anaemia
FGR
early scan at 7–9 weeks
routine first trimester scan (11–14 weeks of
gestation) and a detailed anomaly scan at
18–20+6 weeks of gestation, serial biometry
scans every 4 weeks from 24weeks
Folic acid 5 mg/day
low-dose aspirin (75 mg/day)+- LMWH.
OGTT at 24-28 weeks
Intrapartum Desferoxamine
EFM
Postpartum Venous thromboembolic disease Prophylaxis
191
Some other mutations
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Hemoglobin C— It is an abnormal hemoglobin in which substitution of a glutamic acid
residue with a lysine residue at the 6th position of the β-globin chain has
occurred.
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• Hemoglobin C disease is not a form of sickle cell disease.
— Most people do not have symptoms.
— Too much hemoglobin C can reduce the number and size of red blood
cells in the body, causing mild anemia.
— It can cause
— a mild to moderate splenomegaly
— hemolytic anemia
— jaundice
— gallstones
Hemoglobin C disease
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HbSC:
— have the gene for HbS inherited from one parent and the gene for HbC is
inherited from the other parent
— HbC does not polymerize as readily as HbS, there is less sickling (fewer
sickle cells).
— There are fewer acute vaso-occlusive events.
— Persons with hemoglobin SC disease (HbSC) have more
— significant retinopathy
— ischemic necrosis of bone than those with pure SS disease.
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Risks with HbSC
— Painful crises.
— FGR.
— Antepartum hospitalisation.
— Postpartum infection.
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hemoglobin C trait
— Some red blood cells that have normal hemoglobinA and an abnormal
hemoglobin (Hb C).
— They do not have health problems related to having the trait.
— People with hemoglobin C do not have Hemoglobin C disease or sickle cell
disease.
— Individuals who carry the hemoglobin C trait can have a child with
Hemoglobin C disease or Hemoglobin SC disease.
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Hemoglobin E
— It is an abnormal hemoglobin with a single point mutation in the β
chain.
— At position 26 there is a change in the amino acid, from glutamic
acid to lysine.
— It has been one of the less well known variants of normal hemoglobin
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Hemoglobin E/β-thalassaemia
— People who have hemoglobin E/β-thalassemia have inherited one gene
for hemoglobin E from one parent and one gene for β-thalassemia from
the other parent.
— Hemoglobin E/β-thalassemia is a severe disease, and it still has no
universal cure.
— It affects more than a million people in the world.
— The consequences of hemoglobin E/β-thalassemia when it is not treated
can be heart failure, enlargement of the liver, problems in the bones,
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Sickle Cell Disease
201
Sickle Cell Disease (SCD)
— SCD is the most common inherited condition worldwide.
— Single-gene autosomal recessive disorders.
— The sickle cell syndromes are associated with a qualitative globin gene
defect.
— It is the structure of the globin chains rather than the production that is
abnormal.
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It is most prevalent in individuals of
— Caribbeans
— Middle East
— Parts of India & Mediterranean
— South & CentralAmerica
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Genetic mutation
— The most common and important is HbS is a single amino acid
substitution (from glutamic acid to valine) in the beta-globin chain
— This alters the shape of the red blood cell into a sickle shape
renders Hb insoluble in the deoxygenated state.
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Effects
— These cells are prone to increased breakdown and adherence,
which causes
1. The haemolytic anaemia
— These sickled red cells are permanently removed from the
circulation (haemolytic anaemia).
— The life expectancy of a normal red blood cell is 120 days and of a sickled
cell 5–30 days.
2. Vaso-occlusion in the small blood vessels
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Genotypes
— Homozygous (HbSS) = Sickle cell anaemia
— Heterozygous
— Combination with HbC (HbSC)
— Combination with b-thalassaemia = (HbSB thalass)
— Other rare combinations
— With HbD (HbSD)
— HbE (HbSE)
— HbO-Arab (HbSO-Arab)
………………………………………………………………………………………………………….
…………………………………………..
— HbS combined with normal HbA gives rise to sickle cell trait (HbAS)
All give similar clinical
phenotype of varying
severity
Most Severe Form
Asymptomatic except for a possible increased risk of
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Sickle Cell Trait
— Sickle cell trait (HbAS) is much more common than sickle cell disease
(HbSS).
— Other haemoglobin variants exist (e.g. HbC, HbE), but are less common.
— If both partners carry a haemoglobin variant (i.e. trait), there is a 1:4
chance of the child inheriting both the abnormal genes, and thus sickle
cell disease.
— This risk increases to 1:2 if one partner has two abnormal genes (i.e.
disease) and the other has trait.
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Sickle cell trait
— Pregnancy in women with sickle cell trait has few additional complication rates
compared with other women of the same ethnic and obstetric background, the
only issue of significance being a susceptibility to urinary infections.
— Recurrent urinary tract infections
— seen in 6% of women during pregnancy
— 16% showing microscopic haematuria (a reflection of micro-infarcts from localised
sickling in the peculiarly challenging renal environment, which may be sufficient to
provoke sickling of red blood cells)
— Anemia
— It is important to diagnose concurrent iron deficiency correctly, and serum ferritin
measurements should therefore be made in each trimester, in order to guide the
appropriate prescription of iron supplements.
— An increased incidence of venous thromboembolism in individuals with sickle
cell trait
— similar to those of individuals carrying the FactorV Leiden mutation
— doubled incidence of venous thrombosis and four-fold greater incidence of
pulmonary embolism, compared with similar individuals without sickle
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Sickle Cell Disease (SCD)
— Most common inherited condition worldwide.
— About 300,000 children with SCD are born each year.
— Two-thirds of these are inAfrica.
— In the UK, it is estimated that there are 12,000 – 15,000 affected
individuals.
— Over 300 infants are born with SCD in the UK each year, who are
diagnosed as part of the neonatal screening programme.
— There are approximately 100 – 200 pregnancies in women with SCD per
year in the UK.
— Average life expectancy now is around mid 50s.
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Pathophysiology
— It is consequence of the polymerisation of the abnormal Hb in low-
oxygen conditions, leading to formation of rigid & fragile sickle-shaped
red cells.
— These cells are prone to breakdown, resulting in haemolytic anaemia &
vaso-occlusion in small blood vessels, which cause most of the other
clinical picture.
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Clinical Picture
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Sickle cell disease: clinical
problems
— Anaemia
— Infections
— Stroke
— Leg ulcers
— Acute painful crises.
— Chronic organ damage
— Stroke.
— Pulmonary hypertension.
— Renal dysfunction.
— Retinal disease.
— Leg ulcers.
— Cholelithiasis.
— Avascular necrosis (commonly femoral head).
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Risks of SCD (HbSS) during pregnanacy
— Increased perinatal mortality.
— Premature labour. (in 16–24%)
— FGR. (in 18–23%)
— Acute painful crises.
— Spontaneous miscarriage.
— Antenatal hospitalisation.
— Maternal mortality.
— Delivery by CS.
— Infection.
— Thromboembolism.
— Antepartum haemorrhage.
— Pre-eclampsia 9 % 3/23/20ELBOHOTY
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Acute sickling crises
— That are sufficiently severe to require hospital admission, occur in about
37% of pregnancies before delivery and in about 12% of pregnancies
during the puerperium.
— Episodes of infection are often compounded by acute sickling, with a
particular propensity to urinary tract infections (seen in about 13% of
pregnancies).
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Acute Chest syndrome
— The acute chest syndrome is a vaso-occlusive crisis of
the pulmonary vasculature
— This condition commonly manifests with pulmonary infiltrate on a
chest x-ray.
— It is seen in about 12% of pregnancies.
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Pre-conception Planning of Pregnancy
— Desire to get pregnant should be documented in the notes with the
sickle cell team caring for the woman.
— Woman seen by sickle specialist to provide her with information
regarding:
— How SCD affects pregnancy.
— How pregnancy affects SCD.
— How to improve outcome
— This consultation should aim at optimisation of management & screening
for end organ damage.
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Pre-conception Planning of Pregnancy
— The woman should be given advice regarding:
— Vaccination.
— Medications.
— Crises avoidance.
— The woman should be advised to have a low threshold for
seeking medical help.
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Most Important Information
— Role of dehydration, cold exposure, hypoxia, over-exertion & stress in
the frequency of sickle crises.
— Nausea & vomiting can cause hydration & crises precipitation.
— Risk of worsening of anaemia (which might be already present).
— Increased risk of crises & acute chest syndrome (ACS).
— Increased risk of infection, especially UTI.
— Increased risk of having a baby with FGR, which increases risk of fetal
distress, induction of labour & CS.
— The chance that the baby may inherit SCD.
— Up-date proper assessment of chronic disease complications.
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Chronic Disease Complications
— Screening for pulmonary hypertension with echocardiography (ideally
annually):
— A tricuspid regurgitant jet velocity of more than 2.5 m/sec is associated
with high risk of pulmonary hypertension.
— Blood pressure & urinalysis (to check for hypertension & proteinuria).
— Liver & kidney function should be done annually to identify sickle cell
nephropathy &/or hepatic dysfunction.
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Chronic Disease Complications
— Retinal screening
— Proliferative retinopathy is common with SCD (especially
HbSC) & can lead to loss of vision.
— Screening for iron overload
— Ferritin level
— T2 cardiac magnetic resonance imaging
— Aggressive iron chelation pre-conception is advisable.
— Screening for red cell antibodies
— Increases risk of haemolytic disease of the newborn.
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Genetic Screening
— Women & men with SCD should be encouraged to have the
haematological status of her/his partner determined before embarking
into pregnancy.
— If identified as‘at-risk couple’, (as per National Screening Committee
guidance), they should be offered counselling & advice about
reproductive options.
— The methods & risks of prenatal diagnosis &TOP should be discussed
with the couple.
— They should receive counselling about the availability of pre-
implantation genetic diagnosis.
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Conditions requiring counselling when
the woman is affected by SCD
— HbS, b-thalassaemia, O-Arab, HbC & D-Punjab
— Carrier status of partner determined
— Requires referral for counselling & offer of prenatal diagnsois
— DB-thalass, Lepore, HbE & Hereditary Persistence of Fetal
Haemoglobin (HPFH)
— Carrier status of partner determined
— Requires referral for counselling & further investigation
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Prophylaxis against infections
— Penicillin prophylaxis (daily) or an equivalent should be prescribed.
— Erythromycin in women allergic to penicillin.
— Vaccination status should be determined & updated before pregnancy.
— H influenza type b – once
— Conjugated meningococcal C vaccine – once
— Pneumococcal vaccine – every 5 years
— Hepatitis B vaccination is recommended with immune status determined
before pregnancy
— Influenza & swine flu vaccine – annually
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Folic Acid
— 5mg/day folic acid should be prescribed both pre-pregnancy &
throughout the whole pregnancy.
— Women with SCD should receive 1mg/day outside pregnancy in view of
their haemolytic anaemia state.
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Medications
— Hydroxycarbamide (hydroxyurea) should be stopped at least
3 months before conception.
— Used to decrease incidence of painful crises.
— ACE-inhibitors & ARBs should be stopped before
conception.
— Used to reduce proteinuria & microalbuminuria.
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ANC
— General aspects
— MDT (obstetrician & midwife with experience in high-riskANC +
haematologist with interest in SCD)
— Medical review by haematologist plus screening for end organ damage (if
not done pre-conception)
— Advice to avoid participation factors of sickle cell crises such as exposure to
extreme temperature, dehydration & over-exertion
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ANC
— General aspects
— Persistent vomiting can cause dehydration, thus precipitating sickle cell
crises & women should seek medical help early
— Influenza vaccine given, if not already given in the previous year
— Live-attenuated vaccines should be deferred until after pregnancy
— Women with HbSc should be monitored as those with HbSS because of
increased risk of painful crises, FGR, antepartum hospital admission &
postpartum infection
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Detailed ANC
— First appointment:
— Offer information, advice & support in relation to optimisation
of general health.
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Detailed ANC
— Primary care or hospital appointment:
— Offer partner testing, if not already done.
— Review partner results & discuss PND if appropriate.
— Take clinical history to establish extent of SCD & its complications.
— Review medications & its complications:
— Hydroxycarbamide,ACE-I &ARBs stopped.
— Folic acid 5mg/day.
— Penicillin daily prophylaxis (if not contraindicated).
— Discuss vaccinations.
— Offer retinal/renal/cardiac assessment if this has not been
performed in the previous year.
— Document baseline oxygen saturation & BP.
— Send MSU for culture.
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Detailed ANC
— 7 – 9 weeks:
— Confirm viability in view of increased risk of miscarriage.
— Booking appointment (10 weeks):
— Discuss information, education & advice about how SCD will affect
pregnancy.
— See midwife with experience in high-risk obstetrics:
— Review partner results & discuss PND if appropriate.
— Baseline renal function, urine protein/creatinine ratio, liven function
test & ferritin performed.
— Extended red cell phenotype if not previously performed.
— Confirm that all actions from 1st visit completed.
— Confirm low-dose aspirin from 12 weeks gestation.
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Detailed ANC
— 16 weeks (midwife + MDT):
— Routine as NICE guidelines.
— Repeat MSU.
— MDT review (consultant obstetrician & haematologist).
— 20 weeks (midwife + MDT):
— Detailed USS as per NICE Guidelines.
— Repeat MSU.
— Repeat FBC.
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Detailed ANC
— 24 weeks (MDT):
— Ultrasound monitoring of fetal growth & amniotic fluid
volume.
— Repeat MDU.
— 26 weeks (midwife):
— Routine check including BP & urinalysis.
— 28 weeks (MDT):
— USS monitoring of fetal growth & amniotic fluid volume.
— Repeat MSU.
— Repeat FBC & group & antibody screen.
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Detailed ANC
— 30 weeks (midwife + offer antenatal classes):
— 32 weeks (MDT):
— Routine check.
— USS monitoring for fetal growth & amniotic fluid volume.
— Repeat MSU & FBC.
— 34 weeks (midwife)
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Detailed ANC
— 36 weeks (MDT):
— Routine check.
— USS monitoring of fetal growth & amniotic fluid volume.
— Offer information & advice about:
— Timing, mode & management of birth.
— Analgesia & anaesthesia; arrange anaesthetic assessment.
— Care of baby after birth.
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Detailed ANC
— 38 weeks (midwife + obstetrician):
— Routine check.
— Recommend IOL or CS between 38wks – 40wks.
— 39 weeks (midwife):
— Routine check & recommend delivery by 40wks.
— 40 weeks (obstetrician):
— Routine check & offer fetal monitoring if the woman declines
delivery by 40wks gestation.
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Antenatal Haemoglobinopathy Screening
— If the woman has not been seen preconceptionally, she should be offered
partner testing.
— If the partner is a carrier, appropriate counselling should be offered as
early as possible in pregnancy (ideally by 10wks gestation) to allow 1st
trimester diagnosis &TOP if chosen by the woman.
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Medications During Pregnancy
— If not seen before pregnancy, a woman with SCD should be advised to
take folic acid 5mg/day all through her pregnancy.
— Daily penicillin (or erythromycin if allergic to penicillin) if not
contraindicated.
— Drugs which are unsafe in pregnancy should be stopped (Hydroxyurea,
ACE-I & ARBs).
— Iron given ONLY when there is evidence of iron deficiency.
— Iron status should be assessed.
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Medications During Pregnancy
— Low-dose aspirin considered (75mg/day) from 12wks gestation to
reduce risk of PE.
— Prophylactic LMWH during antenatal hospital admissions.
— NSAIDs should be prescribed only between 12 – 28 weeks of gestation
owing to concerns regarding adverse effects on fetal development.
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Additional Care
— Antenatal appointments should meet individual needs of the woman with
SCD according to her disease severity.
— Blood pressure & urinalysis should be performed at each consultation, &
midstream urine for culture performed monthly.
— Women with SCD usually have low blood pressure, so even a modest rise in
blood pressure should be monitored carefully.
— Women with known renal impairment or pre-existing proteinuria will
require more frequent monitoring.
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Recommended Ultrasound Schedule
— Viability scan at 7 – 9 weeks gestation.
— Routine 1st trimester scan (11 – 14 weeks).
— Detailed anomaly scan (18 – 21 weeks).
— In addition, women should be offered serial fetal biometry
scans (growth scans) every 4 weeks from 24 weeks gestation.
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Role of Blood Transfusion in Pregnancy
— Routine prophylactic blood transfusion is not recommended during
pregnancy for women with SCD.
— If acute exchange transfusion is required for treatment of sickle
complications, it should be appropriate to continue the transfusion
regimen for the remainder of pregnancy.
— Blood should be matched for an extended phenotype including full
rhesus typing (C, D & E) as well as Kell typing.
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— Blood used for transfusion in pregnancy should be CMV-negative.
— Top-up transfusion is indicated for women with acute anaemia
attributable to:
— Transient red cell aplasia.
— Acute splenic sequestration.
— Increased haemolysis.
— Volume expansion.
— No absolute level; but Hb < 6 g/dl or a fall of > 2 g/dl from baseline is often an
indication for transfusion.
— Exchange transfusion is also indicated in acute stroke.
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— Alloimmunisation is common in SCD, occurring in 18 – 36% of patients.
— Alloimmunisation may lead to delayed haemolytic transfusion reaction or
haemolytic disease of the newborn, rendering patients untransfusable.
— The most common antibodies are to the C, E & Kell antigens.
— The risk of alloimmunisation is much reduced by giving red cells
matched for the C, E & Kell antigens.
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Management of Sickle Crises
— Sickle crises is the most frequent complication of SCD
during pregnancy.
— It occurs between 27% – 50% of women with SCD during
pregnancy.
— It is the most common frequent cause for admission to
hospital.
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— History should ascertain if this typical crises pain or not:
— Site of pain, any atypical features, any precipitating factors
(particularly signs of infection).
— Initial investigations should include:
— FBC, reticulocytic count & renal function.
— Other investigations will depend on the clinical scenario, &
could include:
— Blood culture, CXR, urine culture & liver function.
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— Women with SCD who become unwell, should have sickle cell crises
excluded as a matter of urgency.
— Women presenting with sickle cell crises should be managed by the
MDT involving obstetrician, midwives, haematologists & anaesthetists.
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— Appropriate analgesia administered.
— Pethidine should NOT be used because of increased risk of seizures in
women with SCD.
— Opiates are not associated with teratogenicity or malformations.
— They may be associated with transient depression of fetal movements &
reduced baseline variability of the fetal heart rate.
— If opiates have been given for long time in 3rd trimester, the newborn should
be observed for signs of withdrawal.
— TheWHO analgesic ladder should be used:
— Paracetamol for mild pain;
— NSAIDs for mild to moderate pain between 12 & 28 weeks gestation;
— Weak opioids (do-dydramol, co-codamol & dihydrocodein) for moderate pain;
— Strong opiates (morphine) for severe pain.
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— Requirements for fluids & oxygen assessed, & fluids & oxygen administered
accordingly.
— Fluid intake of at least 60ml/kg/day should be ensured.
— Oxygen saturation should be monitored & facial oxygen prescribed if saturation falls
below 95% or below the woman’s baseline.
— Early recourse to critical care if satisfactory saturation cannot be maintained by facial
prong oxygen administration.
— Thromboprophylaxis should be given to women admitted with acute painful
crises.
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Other acute complications of SCD
— All patients, carers & nursing staff should be aware of the other SCD
complications in pregnancy:
— Acute chest syndrome (ACS)
— Acute stroke
— Acute anaemia
— Each hospital should have a protocol for the management of SCD in
pregnancy, including the use of transfusion therapy.
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Acute Chest Syndrome (ACS)— The second most common complication of SCD in pregnancy (after pain
crises).
— Reported in 7% – 20% of pregnancies.
— Characterised by respiratory symptoms such as dyspnoea, chest pain,
cough & shortness of breath.
— Presence of new infiltrate in CXR.
— Symptoms & signs are similar to those of pneumonia, so both should be
treated simultaneously.
— Acute severe H1N1 viral infection (swine flu) in pregnancy can cause a
similar clinical picture, so investigation & treatment for this should be
instituted.
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Acute Chest Syndrome (ACS)
— Early recognition is the key.
— Treatment is with:
— Intravenous antibiotics
— Oxygen
— Blood transfusion (new or top-up)
— Hb < 6 g / dL
— Review by haematologist to advice on transfusion
— Review by critical care physician to advice on need for admission for
ventilatory support
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Acute Chest Syndrome (ACS)
— There should be low threshold for considering pulmonary embolism.
— In this situation, LMWH should be started & the woman is reviewed by a
senior member of staff &VTE is objectively excluded by proper
investigation.
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Acute Stroke
— Both infarctive & haemorrhagic are associated with SCD.
— Diagnosis should be suspected when a pregnant women with SCD is
presenting with acute neurological impairment.
— It is an acute emergency & rapid exchange-transfusion can decrease long-
term neurological damage.
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Acute Anaemia— Acute anaemia associated with SCD is attributable to erythrovirus
infection.
— Erythrovirus causes arrest of red cell maturation & aplastic crises
characterised by reticulocytopenia.
— So, reticulocytic count should be requested in any woman with SCD
presenting with acute anaemia, if low, this indicated infection with
erythrovirus.
— Treatment is by blood transfusion & isolation.
— With erythrovirus infection there is increased risk of vertical
transmission, which can result in hydrops fetalis.
— Hence, review by fetal medicine specialist is indicated.
— Rare causes of acute anaemia are malaria & splenic sequestration.
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Intrapartum Care— Place:
— Hospital with facilities to manage both high-risk pregnancies &
complications of SCD.
— Timing of delivery:
— With a normally growing fetus after 38+0
weeks.
— Mode of delivery:
— IOL or elective CS.
— SCD by itself is not a contraindication for vaginal delivery orVBAC.
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Intrapartum Care
— Blood should be cross-matched for delivery if there is atypical antibodies
present (as this would delay the availability of blood), otherwise a‘group
& save’ will suffice.
— In women who have had hip replacement (because of avascular necrosis)
it is important to discuss suitable position for delivery.
— Relevant MDT (senior midwife, senior obstetrician, anaesthetist, &
haematologist) should be informed as soon as labour is confirmed.
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Intrapartum Care— Woman should be kept warm.
— The woman should be given adequate fluid during labour.
— Continuous intrapartum EFM is recommended owing to the increased
risk of fetal distress which necessitates operative delivery;
— Also there is increased risk of stillbirth, placental abruption, & compromised
placental reserve.
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Intrapartum Care
— Routine antibiotic prophylaxis in labour is currently NOT supported by
evidence, but hourly observations of vital signs should be performed.
— A raised temperature over (37.5°C) require investigation.
— The clinician should have a low threshold to commence broad-spectrum
antibiotics.
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Optimum Analgesia & Anaesthesia
— Anaesthetic assessment in the 3rd trimester should be offered to all
women with SCD.
— Regional anaesthesia may reduce the need for general anaesthesia & the need
for high-dose opiates.
— Avoid use of pethidine, but other opiates can be used.
— Regional analgesia is recommended for CS.
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Postpartum Care
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— pregnant women where the baby is at high risk of SCD (i.e. the partner
is a carrier or affected), early testing for SCD should be offered.
— Capillary samples should be sent to laboratories where there is
experience in the routine analysis of SCD in newborn samples.
— Maintain maternal oxygen saturation above 94% and adequate hydration
based on fluid balance until discharge.
— Low-molecular-weight heparin should be administered while in hospital
and for a period of 6 weeks following delivery even if it is vaginal
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contraception— Progestogen-containing contraceptives such as
— the progesterone only pill (Cerazette®, Organon Laboratories Ltd,
Hoddesdon, UK)
— injectable contraceptives (Depo-Provera®, Pfizer Ltd, NewYork, USA)
— the levenorgestrel intrauterine system (Mirena®, Bayer Schering Pharma
AG, Berlin, Germany) are safe and effective in SCD.
— Estrogen-containing contraceptives should be used as second-line agents
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BLOOD TRANSFUSION
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How to reduce blood transfusion
1. Optimisation of haemoglobin in
the antenatal period
2. Mmanagement of pregnant women at
high risk of hemorrhage
3. Active managemnt of the 3rd stage of
labour
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Management of the 3rd stage
and high risk cases
—Active management of the third stage of
labour is recommended to minimize blood
loss.
—Women at high risk of hemorrhage should
be advised to deliver in hospital.
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Alternatives to blood transfusion for
patients having surgery
— Intravenous and oral iron
Offer oral iron before and after surgery to patients with iron-defeciency
anaemia.
— Cell salvage and tranexamic acid
— Offer tranexamic acid to adults undergoing surgery who are expected to
have at least moderate blood loss (greater than 500 ml).
— Consider intra-operative cell salvage with tranexamic acid for patients
who are expected to lose a very high volume of blood (for example in
cardiac and complex vascular surgery, major obstetric procedures, and
pelvic reconstruction and scoliosis surgery)
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General principles of blood transfusion
— Consent for blood transfusion
— Valid consent should be obtained where possible prior to administering a blood
transfusion.
— In an emergency, where it is not feasible to get consent, information on blood
transfusion should be provided retrospectively.
— Documentation
— The reason for transfusion and a note of the consent discussion should be
documented in the patient’s case notes.
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Provide verbal and written information to
patients
— the reason for the transfusion
— the risks and benefits
— the transfusion process
— any transfusion needs specific to them
— any alternatives that are available, and how they might reduce their need
for a transfusion
— that they are no longer eligible to donate blood that they are encouraged
to ask questions.
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Blood Transfusion in obstetrics:
:
1-CHRONIC ANEMIA (Thalathemia, SCD)
or (hematinic deficiency but need rapid
correction)
2- MAJOR OBSTETRIC HAEMORRHAGE
3- Other conditions that need specific
components
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To transfuse or not
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Women with intrapartum or postpartum
anaemia?
— If the Hb is less than 70 g/l where there is no ongoing or threat of
bleeding, the decision to transfuse should be made on an informed
individual basis according to the individual’s medical history and
symptoms.
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When should red cells be used?
— There are no firm criteria for initiating red cell transfusion.
— It should be made on clinical and haematological grounds.
— In an extreme situation and when the blood group is
unknown, group O RhD-negative red cells should be given
(although they may be incompatible for patients with
irregular antibodies).
— Staff working in obstetric units should be aware of the
location of the satellite blood fridge (where available) and
should ensure that access is possible for blood collection.
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it is not only volume !
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— ! Consideration of body weight Blood volume=100
ml /KG
— ! Rapidity of blood loss severe > 150 ml/min
— ! Consideration of current anaemia during
pregnancy
— ! Malfunctioning heart
277
Small women have small blood volumes
Weight (kg) Total blood
volume (mls)*
15% loss
(mls)
30% loss 40% loss
50 5000 750 1500 2000
55 5500 825 1650 2200
60 6000 900 1800 2400
65 6500 975 1950 2600
70 7000 1050 2100 2800
*Based on 100mls/kg blood volume in pregnancy (RCOG
2011) but may overestimate blood volume in obese women
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Blood components
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Red blood cells
— Thresholds and targets
— When using a restrictive red blood cell transfusion threshold, consider a
threshold of 70 g/litre and a haemoglobin concentration target of 70–90
g/litre after transfusion.
— Doses
— Consider single-unit red blood cell transfusions for adults (or equivalent
volumes calculated based on body weight for children or adults with low
body weight) who do not have active bleeding.
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When should fresh frozen plasma (FFP)
and cryoprecipitate be used?
— During major obstetric haemorrhage:
— FFP at a dose of 12–15 ml/kg should be administered for every 6 units of red cells
— Subsequent FFP transfusion should be guided by the results of clotting tests if they are available
in a timely manner, aiming to maintain prothrombin time (PT) and activated partial
thromboplastin time (APTT) ratios at less than 1.5 x normal.
— It is essential that regular full blood counts and coagulation screens (PT,APTT and fibrinogen)
are performed during the bleeding episode.
— Cryoprecipitate at a standard dose of two 5-unit pools should be administered early in major
obstetric haemorrhage. Subsequent cryoprecipitate transfusion should be guided by fibrinogen
results, aiming to keep levels above 1.5 g/l.
— The FFP and cryoprecipitate should ideally be of the same group as the recipient. If
unavailable, FFP of a different ABO group is acceptable providing that it does not have a high
titre of anti-A or anti-B activity.
— No anti-D prophylaxis is required if a RhD-negative woman receives RhD-positive FFP or
cryoprecipitate.
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Fresh frozen plasma
— Do not offer fresh frozen plasma transfusions to
correct abnormal coagulation in patients who:
—are not bleeding (unless they are having invasive
procedures or surgery with a risk of clinically
significant bleeding)
—need reversal of a vitamin K antagonist.
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Cryoprecipitate
— Consider cryoprecipitate transfusions for patients without major
haemorrhage who have:
— clinically significant bleeding and
— a fibrinogen level below 1.5 g/litre.
— Do not offer cryoprecipitate transfusions to correct the fibrinogen level
in patients who:
— are not bleeding and
— are not having invasive procedures or surgery with a risk of clinically significant bleeding.
— Consider prophylactic cryoprecipitate transfusions for patients with a
fibrinogen level below 1.0 g/litre who are having invasive procedures or
surgery with a risk of clinically significant bleeding.
— Doses
— Use an adult dose of 2 pools when giving cryoprecipitate transfusions (for children, use
5–10 ml/kg up to a maximum of 2 pools).
— Reassess the patient's clinical condition, repeat the brinogen level measurement and give
further doses if needed.
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When should platelets be used?
— For a bleeding patient or having invasive procedures or surgery
— Aim to maintain the platelet count above 50 x 109/l in the acutelyA platelet
transfusion trigger of 75 x 109/l is recommended to provide a margin of
safety in active bleeding.
— The platelets should ideally be group compatible. RhD-negative women
should also receive RhD-negative platelets.
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not bleeding or having invasive procedures or
surgery
— Thresholds and targets
— Patients who are
— Offer prophylactic platelet transfusions to patients with a platelet count
below 10×109 per litre
— Do not routinely transfuse more than a single dose of platelets.
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Requirements for group and screen
samples and cross-matching
— All women should have their blood group and antibody
status checked at booking and at 28 weeks of gestation.
— In a woman at high risk of emergency transfusion, e.g.
placenta praevia, and with no clinically significant
alloantibodies, group and screen samples should be sent
once a week to exclude or identify any new antibody
formation and to keep blood available if necessary.
— Close liaison with the hospital transfusion laboratory is
essential.
— Group and screen samples used for provision of blood in
pregnancy should be less than 3 days old.
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Blood product specification in pregnancy
and the puerperium
— ABO-, rhesus D- (RhD-) and K- (Kell-) compatible red cell units should be
transfused.
— Cytomegalovirus- (CMV-) seronegative red cell and platelet components
— The FFP and cryoprecipitate should ideally be of the same group as the
recipient. If unavailable, FFP of a differentABO group is acceptable, provided
that it does not have a high titre anti-A or anti-B activity.
— The platelets should ideally also be group compatible.Anti-Rh D
immunoglobulin (at a dose of 250 iu) will be needed if the platelets are Rh D
positive and the recipient Rh D negative.
— If clinically significant red cell antibodies are present:
— blood negative for the relevant antigen should be cross-matched before
transfusion
— close liaison with the transfusion laboratory is essential to avoid delay in
transfusion in life-threatening haemorrhage.
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Some targets and actions during transfusion
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Complications of Blood Transfusion
— Acute hemolytic from the
mistransfusion of ABO-incompatible
red cells.
— Febrile —presence of cytokines
produced by passenger leukocytes.
— Anaphylactic reactions
— Bacterial contamination
— Immune reactions
— Physical complications
— Circulatory overload
— Air embolism
— Pulmonary embolism
— Thrombophlebitis
— ARDS
— Metabolic complications
— Hyperkalaemia
— Citrate toxicity & hypocalcaemia
— Haemorrhagic reactions (DIC)
— After massive transfusion of stored blood
— Transmission of disease
— Hepatitis, CMV. EBV
— AIDS
— Syphilis
— Malaria
— Trypanosomiasis
— Iron overload (Haemosiderosis)
— After repeated transfusion in patients with
haematological diseases
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Infection risks from blood transfusions
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Intraoperative cell salvage (IOCS)?
— It is recommended for patients where the anticipated blood loss is
great enough to induce anaemia or expected to exceed 20% of
estimated blood volume.
— It should only be performed by multidisciplinary teams who have
the experience
— Where IOCS is used during caesarean section in nonsensitised
RhD-negative women and where cord blood group is confirmed as
RhD positive (or unknown):
— A minimum dose of 1500 iu anti-D immunoglobulin should be administered
following the reinfusion of salvaged red cells.
— A maternal blood sample should be taken for estimation of fetomaternal
haemorrhage 30–40 minutes after reinfusion in case more anti-D is
indicated.
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