Kara Dent, West Midlands
Perinatal Institute - March 2001
Sickle cell disease (SCD) is the most
common haemoglobinopathy that we deal with in pregnancy.
It was first described in the literature in a paper
titled "Peculiar elongated and sickle shaped red
blood corpuscles in a case of severe anaemia" (1).
This is a lovely description of what happens to the
haemoglobin molecule when deoxygenated and is characteristic
of this autosomal recessive disorder.
There are different variations of this disease but
the 3 more severe types are:
- Homozygous Sickle Cell disease (HbSS)
- Sickle Cell/HbC (HbSC)
- Sickle-cell Thalassemia
The minor variant is Sickle cell trait (HbAS) that
affects around 1 in 12 adult African Americans (2).
Anaemia is seen with this disorder in pregnancy but
not the more severe complications of the above conditions.
What is more significant for this group is if both
parents carry the trait, putting the fetus at a 1 in
4 risk of developing SCD. This is relevant for prenatal
Haemoglobin S occurs when there is a substitution
of one amino acid by another: namely valine for glutamic
acid. Valine is neutrally charged whereas glutamic
acid has a negative charge. The latter allows hydrophobic
binding when haemoglobin (Hb) is deoxygenated, causing
the classic distortion of the molecule(3).
This is remedied when Hb is oxygenated initially but
not after recurrent episodes. Because of this, erythrocytes
in SCD have a grossly reduced life span of only 17
days to the expected 120 days in the unaffected population
This explains why we see a chronic anaemia in these
With around 5000 sickle cell sufferers in the UK,
it is estimated that there are about 150 births per
We are therefore talking about a restricted population
and relying on figures based on pretty small studies.
The Cochrane data, dealing with the question of whether
this population should be electively transfused, or
not, is based on only one study (5).
This study is judged to be of poor methodology with
only 72 women recruited and a data collection over
8 years. Other studies in the literature are retrospective
and equally sized. The quoted statistics are a perinatal
mortality rate of between 40 - 60 per 1000 deliveries
(4-6 times that of the normal population) with a maternal
mortality rate of around 2% (7).
The normal physiology of pregnancy means an increase
in oxygen consumption, blood viscosity and red cell
mass. These increases put an extra demand on a woman
suffering from sickle cell and increase the incidence
of complications seen.
|Clinical Features of Sickle Cell disease
Bone marrow fat embolism
Renal medullary infarction, hyposthenuria and papillary necrosis
Aseptic necrosis of bone
Painful crises are seen in around 35% of antenatal
These are vaso-occlusive attacks that result in pain
from bones, chest and abdomen and require prompt treatment
(namely: hydration, pain relief and analgesia.) They
are episodes that can be brought on by factors such
infection, acidosis, dehydration, hypertension, strenuous
activity, drug overdose, hypothermia, blood loss, trauma
and severe stress (8)
- all to be avoided!
Care of a woman with sickle cell disease in pregnancy
should be via a team approach involving a haematologist
and obstetrician working closely together. Seeing the
couple prenatally provides an opportunity to counsel
the couple about the risks for them associated with
pregnancy. If the sickle status of the partner is unknown,
he can be offered testing in order to predict the risk
of the baby. If he should then test positive, a prenatal
diagnosis is always an option - chorionic villous sampling
(CVS) provides an early diagnosis at 11 to 13 weeks.
Obviously it has its own risks.
Folic acid is advised throughout the pregnancy but,
because these women are at risk of iron overload, they
should not be routinely prescribed ferrous sulphate
They are reminded about diet and to be aware of the
risk of infection, with early referral if they are
in any doubt.
Because of the recognised association of sickle cell
disease with IUGR, pre-eclampsia and premature labour
early signs of these are screened for throughout the
The question mark raised at the forum is how often
should these women be screened? Do we need to send
an MSU at every visit? Should we be requesting 2
weekly growth scans? Starting at what gestation?
What about screening regularly for retinopathy and
evidence of anaemia? Where is the evidence?
Current suggestions for the initial investigations
- Full medical history, specifically regarding prior
- Haemoglobin electrophoresis and red cell indices
- Reticulocyte count
- Liver function tests
- Hepatitis screening
- Blood group and antibody screen
- Rubella antibodies
- Syphilis serology
The role of prophylactic blood transfusions is a controversial
area in the management of these women. There are studies
that show either a decrease in the incidence of painful
or no benefit at all (5,11,12).
As mentioned before, there is only one RCT quoted in
Cochrane on this. Whatever the effect on maternal morbidity,
there is no evidence to show any advantage for perinatal
The potential benefits for the pregnancy have to be
offset against the disadvantages of transfusions.
Disadvantages of prophylactic blood transfusions (7):
- Increased cost
- Immediate and delayed transfusion reaction
- Can precipitate crisis (if sudden increase
- Infection Risk (Hep B, C or HIV)
- Red cell antibody formation
- Iron overload
NB.The problem with delayed haemolytic transfusion
reactions is that these antibodies can be serologically
undetectable and cause terrible problems for future
cross matching (13).
A caesarean section is only indicated for obstetric
reasons. This is because it provides a higher risk
for thromboembolism in an already at-risk population
Good pain relief in labour and adequate hydration are
very important to reduce stress and sickling. Oxygen
via a nasal prong or mask is advised to improve cardiac
As these infants are considered higher risk, especially
if small for gestational age (SGA), continual monitoring
is also suggested, as well as taking steps not to prolong
the labour. For some units, assisted deliveries with
an epidural are part of their standard protocol for
these women (3).
- Early ambulation
- Anti-embolic stockings
- Appropriate hydration
- Aggressive treatment of suspected infection
- Breastfeeding with good hydration
- Neonatal testing (electrophoresis)
- Family planning advice
Review of the literature on sickle cell disease in
pregnancy shows a lack of evidence on which to base
management. One of the main reasons for this is that
the population being looked at is so small and large
RCTs are therefore not possible. We know that those
of African, Mediterranean and East Indian ancestry
are at risk but should also be aware that with travel
and inter-racial marriages, more may be at risk. Here
in the West Midlands, it has been suggested that all
women should be screened routinely in early pregnancy
for sickle cell disease or trait.
What is important is to have clear protocols and management policies during
pregnancy in place, dealing with the question of elective transfusions and
delivery plans. An anaesthetist's collaboration at delivery can be invaluable
and the antenatal care should be combined between the obstetric and haematological
team. In this way, the patients' best interests should be served.
1. Herrick JB. Peculiar elongated and sickle-shaped
red blood corpuscles in a case of severe anaemia. Arch
intern Med. 1910;6:517,
2. Stein J. A screening protocol for a prenatal population at risk for inherited
haemoglobin disorders: results of its application to a group of Southeast Asians
and blacks. Am J Obstet Gynecol. 1984;150:333, Abstract
3. Rust OA. Pregnancy complicated by Sickle hemoglobinopathy. Clinical Obstetrics
and Gynecology 1995;38(3):472-84, Abstract
4. Darbyshire P. Sickle cell diseases in the United Kingdom. The Practioner
5. Koshy M. Prophylactic red cell transfusion in pregnant patients with sickle
cell disease. A randomised co-operative study. N Engl J Med 1988;319:1447-52, Abstract
6. Howard RJ. Pregnancy in sickle cell disease in the UK: results of a multicentre
survey of the effect of prophylactic blood transfusions on maternal and fetal
outcome. Br J Obstet Gynaecol 1995;102:947-51, Abstract
7. Howard RJ. Management of sickling conditions in pregnancy. British Journal
of Hospital Medicine 1996;56(1):7-10, Abstract
8. Martin J. Sickle cell crisis. In: Clark SL, Cotton DB, Hankins GDV, Phelan
JP, eds. Critical care Obstetrics. 2nd ed. Cambridge, Massachusetts: Blackwell
Scientific Publications, 1991:212
9. Koshy M. Sickle cell disease and pregnancy. Blood Reviews 1995;9:157-64, Abstract
10. Morrison JC. Prophylactic transfusions in pregnant patients with sickle
cell disease. N Engl J Med 1989;320:1286-7, Abstract
11. Tuck S. Prophylactic blood transfusion in maternal sickle cell syndromes.
Br J Obstet Gynaecol 1987;94:121-5, Abstract
12. Tuck S. Pregnancy in sickle cell disease in the UK. Br J Obstet Gynecol
13. Lauren A. Transfusion issues in a gravida with sickle cell disease. Obstetrics & Gynaecology.
14. ACOG technical bulletin. Haemoglobinopathies in pregnancy. International
Journal of Gynecololgy & Obstetrics 1996;53:184-94