Professional Documents
Culture Documents
Disease
in pregnancy
BY
DR. JAMES E. OMIETIMI
Department Of Obstetrics & Gynaecology
University Of Port Harcourt Teaching
Hospital
Port Harcourt
Introduction
Normal haemoglobin
Type of normal haemoglobin molecule in normal
human adult
Abnormal haemoglobin
Mutations of structural gene
Genetically determined defects in the production
rate of one or more of the globin chain
Effect of HbSS on pregnancy
Effect of pregnancy on HbSS
Management of pregnancy in HbSS
Introduction:
Sickle cell syndromes are the most
widespread of all genetic disorders. The
disease manifest as chronic haemolytic
anaemia, painful vaso-occlusive crises of
varying severity and organ damage due to
repeated episodes of micro-infarction.
TYPES OF THALASSAEMIA
alpha Thalassaemia (minor and
major)
beta Thalassaemia (minor and major)
ALPHA THALASSAEMIA
– results from defect in the Haemoglobin H disease –
synthesis of the alpha globin results from deletions of 3 of
chain. the 4 alpha globin chain
Alpha Thalassaemia major – genes. This is compatible with
results from complete deletions of extrauterine life. The
all 4 alpha globin chain genes. abnormal red cells at birth
There is complete absence of
alpha globin chain synthesis. The contain a mixture of Hb Bart,
fetus is affected because HbF is HbH and HbA. The neonate
not produced. The absence of appears well at birth, but after
alpha globin chain results in early infancy, hemolytic
production of haemoglobin Bart (4 anaemia develops. Most of
gamma globin chains) and the 20-40% Hb Bart at birh is
haemoglobin H (4 beta globin replaced later by HbH. In
chains) as abnormal tetramers. adults, HbH constitute 5-30%
Haemoglobin Bart has an of their haemoglobin. The
appreciably increased affinity to
oxygen, the fetus usually dies in- disease is characterized by
utero or immediately after anaemia of varying severity
delivery – demonstrates typical and the anaemia worsens
clinical features of non-immune during pregnancy in such
hydrops fetalis (fetal ascites women.
following intrauterine cardiac
failure, large placenta), Hb Bart is
a common cause of stillbirth in
Southeast Asia.
Alpha Thalassaemia minor
– results from deletions of 2 of Silent carrier state – results
the 4 alpha globin chain from single gene deletion
genes. of the 4 alpha globin chain
It is characterized by minimal genes. No clinical
to moderate hypochromic abnormality is evident in
microcytic anaemia. these individuals.
There is no associated clinical
abnormality, hence it often
Incidence – alpha
goes unrecognised. thalassaemia minor, Hb
Hb Bart is present at birth, Bart and HbH disease are
but it is not replaced by HbH common in Asia.
in later life. Alpha thalassaemia minor
The red blood cells are occurs in 2% of African,
hypochromic and microcytic. HbH is extremely rare,
The haemoglobin while Hb Bart is un-
concentration varies between reported.
normal to slightly depressed.
Women with alpha
Thalassaemia minor appear to
tolerate pregnancy quite well.
BETA THALASSAEMIA
– results from defect If they are entered into an
in the synthesis of adequate transfusion
beta globin chain. programme, they develop
normally until the 1st
Beta thalassaemia decade of life, when the
major (Cooley’s effect of iron overload
anaemia) – excess of becomes apparent, but
alpha globin chain prognosis is improved with
iron-chelation therapy.
precipitates resulting
in red cell membrane
Females who survive
beyond childhood usually
damage. are sterile. Life expectancy
The neonate is normal even with transfusion
at birth, but as HbF therapy is short.
Pregnancy is rare, but
level falls, the infant successful outcomes have
becomes severely been reported.
anaemic and fails to
thrive.
Beta thalassaemia minor
– percentage of HbA2 in There is usually
the adult is higher than pregnancy-induced
3.5%, while that of HbF erythropoiesis with
is > 2%. resultant normal blood
volume expansion and
The red cells are a slightly subnormal
hypochromic and red cell mass
microcytic, but anaemia expansion. Women
is mild. with beta
The haemoglobin thalassaemia minor do
concentration is not require any
typically 8-10g/dl in late specific therapy
second trimester, rising during pregnancy –
to 9-11g/dl near term maternal and fetal
compared to outcome usually is
haemoglobin satisfactory. Daily
concentration of 10- prophylactic iron and
12g/dl in the non-
Some abnormal haemoglobin variants
produce clinical manifestations only in the
homozygous state (e.g. HbSS) or when
combined with a second haemoglobin
variant (e.g. HbSC).
The major complication of sickle cell
disease is anaemia and intravascular
thrombosis. In the oxygenated state, the
solubility of HbS is nearly equal to that of
HbA. However, in the deoxygenated state;
A significant increase in blood
viscosity is produced by a level of
sickling greater than 15%. If the total
HbS can be reduced to less than 20%
of total haemoglobin (i.e. 80% HbA),
blood viscosity will not increase
except in states of severe
deoxygenation, and this provides the
basis for prophylactic blood
transfusion therapy.
In sickle cell disease, where 75-100%
of the total haemoglobin in the rell
cell is HbS, crises may occur when
oxygen tension is only slightly
The kidneys with its hypertonic milieu in the
medulla present an opportunity for sickling even
at a relatively high oxygen tension – the
microinfarctions result in peritubular
haemorrhage, interstitial scarring and an
increased susceptibility to pyelonephritis (UTI).
HbSS are prone to respiratory infection –
pneumonia, skeletal complications resulting from
erythroid hyperplasia (very marked) may produce
osteoporosis and pathological fractures, bone
infarction (aseptic necrosis of femur head), this
could lead to fat and marrow embolism.
Crises may result following infections,
dehydration, extreme of heat or cold, or stress.
The treatment of a painful crisis should include
careful search for and treatment of the
precipitating cause as well as general supportive
measures such bed rest, analgesia, warmth,
rehydration and oxygen therapy.
Haemolytic crises is diagnosed following sudden
drop in blood count and rise in reticulocyte count
HbC does not in itself sickle.
HbC and HbD moves with HbS on electrophoresis
in alkaline buffers but which do not themselves
sickle.
Sickle cell disease is a sickling disorder in which
the sickle gene is present with another abnormal
gene affecting either the production or structure
of haemoglobin (i.e. HbSC, HbSThal)
Sickle cell anaemia is HbSS
Sickle cell trait is HbAS - prone to UTI in
pregnancy, do not normally suffer from sickling
crises and the presence of the S haemoglobin
confers partial protection from Plasmodium
falciparum malaria.
Patient with HbSC and HbSThal may not be aware
of their haemoglobinopathy status, because they
usually have very few crises. However, those with
HbSS usually know their status because of
repeated crises.
EFFECT OF HbSS ON PREGNANCY