haematology in pregnancy

Question 1

What is the inheritance for sickle cell

What is the gene mutation

Answer 1

Inherited autosomal recessive condition

point mutation where valine replaces glutamic acid at position 6 on the B globulin gene

Question 2

what is sickle cell like in neonates

Answer 2

Hbf protects from crises - as the Hb f reduces then the chronic haemolytic anaemia develops

Question 3

Clinical manifestation of sickle cell

Answer 3

Sickle cell - reduced life expectancy by 25 years
Sickle cell crises - precipitated by infection
vaso occlusive crises - increase viscosity causes infarction and end organ damage
sequestration
aplastic (often associated with parovirus infection)

Increase risk of infection by encapulated organisms as splenic function lost
Anaemia- haemolysis
Acute chest syndrome- fat emboli form bone infarction - fever, high P RR pain anaemia pulm infiltrates
Sudden death

carriers may not be anaemic but could have severe sickling in pregnancy or puerperium

Question 4

obstetric risks with sickle cell

Answer 4

perinatal mortality increases 4-6X
Increase risk miscarriage
IUGR
PET
Abruption
FD + LSCS 
Maternal: 2.5% mortality 

Carriers have increased risk of UTIs, renal papillary necrosis and PET

Question 5

Sickle cell antenatal management

Answer 5

First visit

All of the above if not performed pre pregnancy .. including genetic screening

MDT approach including obstetrician and haematologist experienced in SCD

Advice about avoiding precipitators to crises (cold, hypoxia, dehydration)

High dose folic acid throughout T1

Aspirin for PET prophylaxis from 12 weeks

Penicillin prophylaxis

SCD pts are hyposplenic and at risk of infections from encapsulated organisms eg Neisseria meningitides, streptococcus pneumonia, Haemophilis influenzae

Woman should have a viability scan at 7-9 weeks

Ongoing management

Routine nuchal scan

Detailed anatomy

Monitor anaemia – Hb each visit

Urine dip for protein and BP each visit for monitoring for PET

MSU for culture monthly

LMWH if admitted and throughout pregnancy on consideration of other risk factors

Monitor for complications eg sickle cell crisis, acute chest syndrome, and treat with analgesia and fluid

Growth scans 2-4 weekly from 24 weeks with umbilical artery doppler if FGR is diagnosed

Routine Blood transfusion is not recommended

If required for management of a sickle cell complication blood should have extended phenotype testing, Rh C,D,E and Kell – blood should be CMV negative

Anaesthetic review in pregnancy

Question 6

Sickle cell intrapartum management

Answer 6

Del 38-40 weeks  
Deliver in hospital 
LSCS for obstetric indications  
Recommend epidural  
Avoid pethidine – increases he risk of seizures  
Avoid sepsis and dehydration and hypothermia  
CEFM  
Cross match if  atypical antibodies

Question 7

how do you manage sickle cell crisis

Answer 7

Admission with input haematology and anaesthetics
Analgesia - IV opiates often required
Warm, hydrated, oxygenated, prophylactic

Question 8

what are thalassaemias

describe the pathophysiology

Answer 8

thalassaemias are inherited haemoglobinopathies
There is an imbalance of the normal globin genes causing and imbalance of the globin production.
A thalassaemia causes an excess of B and gamma globin
B thalassamia has an excess of A globin chains
Excess chains destroy the bone marrow and cause haemolysis in the circulation leading to anaemia and extra medullary haematopoesis

Question 9

what is the epidemiology of thalassaemias

Answer 9

A - southern chia, malaysia thailand (alpha thalassaemia 1 aa/– more severe + likely to result in neonatal hydrops)
mild forms in african orgin (altha thalassaemia 2 a-/a-)
B - African origin heterozygous 13% 4% asia, 2% US

Question 10

Prenatal sickle cell management

Answer 10

Immunise hep A, B, pneumococcal, meningococcal, H influenza - rubella
Hb
Cr, LFTs TFTs,
ECHO if had recurrent acute chest syndrome presentations as risk pulmonary hypertension
partner testing
Assess Hb S and Hb F
Stop hydroxyurea
Discussion of risks
folic acid 5mg 12/52 prepreg
Educate about signs of infection and risks

Question 11

What is the risks of iron overload

Answer 11

cirrhosis
cardiomyopathy
endocrine abnormality - hypothyroidism, diabetes, hypogonadotrophic hypogonadism

Question 12

Causes of anaemia in pregnancy

Answer 12

1. Iron deficiency anaemia
   Microcytic (pregnancy increases iron requirement 2-3X)
2. Folate deficiency
   (increased req 10-20X) megaloblastic
3. Haemolytic anaemias
4. B12 deficiency - inflammatory bowel / pernicious anaemia (test high LHD, pancytopenia, low holotranscobalamin, low B12)
5. Anaemia prepreg - short pregnancy interval, menorrhiagic, poor diet malaria

Question 13

Causes of megaloblastic anaemia

Answer 13

B12 or folate deficiency
Azathioprine
alcohol

Question 14

Indications for 5mg folic acid

Answer 14

Woman with spinabifida
previous sibling spina bifida
haemoglobinopathy 
Obese BMI over 30
Diabetes
AED
known folate deficiency
known malabsorption syndrome

Question 15

what is a thalassaemia major, trait and HbH disease

Answer 15

Major –/–
4 gene deletion -make Hb Barts and Hb portland - not compatible with life (affinity for oxygen too high and doesnt release into the tissue, precipitates and haemolysed in the spleen)

a thal trait a-/a- carriers

HbH a-/– Variable, haemolytic anaemia, some transfusion dependent, jaundice, hepatospenomegly, growth restriction
worsened by infection parovirus 19 pregnancy fever

Question 16

B thalassaemia 
What is 
major 
minor  
\+ clinical consequence

Answer 16

in B thalassaemia the alleles have either been deleted (-) or are mutations (o)
Major - B(o or -) / B (o or -)
anaemia, splenomegly, infections, multiple bony deformity, transfusion dependent, iron overload,

minor B/ B(o or -)
mild disease / carrier

Presents in 4-6 months as Hb F has no B chains in it (A and Gamma)

Question 17

what are the types of haemophilia
What factor is involved
treatment options if the woman is symptomatic

Answer 17

Rare X linked disorders - mainly affect men, carriers can have sx

A - Factor VIII def 1:10 000
Some respond to desmopressin, or factor VIII

B - Factor IX def 1: 50 000 - more severe
TXA or factor IX

C- factor XI def
measure levels in pregnancy and just before del

Question 18

What is von willebrand disease
how common
what is the test
What to avoid

Answer 18

1% of the population
inherited deficiency in VWB factor. This protein stabilized factor VIII and helps with platelet aggregation on disrupted endothelium
APTT prolonged
A functional measure of vWF is the ristocetin cofactor

Question 19

What is the affect of VWBD on pregnancy

Answer 19

No increase in APH or miscarriage
Early pregnancy bleeding (miscarriage or ectopic) can be increased
pregnancy causes an increase in FVIII and VWB - normal levels
Drop rapidly PP - can have secondary PPH

Question 20

VWB management in pregnancy

Answer 20

Need to ascertain prepreg / early preg what type of VWB - if it responds to desmopressin
Avoid NSAIDS and Aspirin
Possible to give concentrates of factor VIII and VWB

Question 21

Pre pregnancy consult for Sickle cell disease

Answer 21

Prepregnancy

Education for the woman on pregnancy risks – it should be discussed at each consultation from adolescence

Contraception advice so pregnancy can be planned

Genetic screening for the partner

If the partner has a trait or affected by a haemoglobinopathy then the couple should receive appropraite counselling

Discussions around preimplantation genetic diagnosis, prenatal diagnosis and TOP

High dose folic acid pre conception and throughout pregnancy

SCD are on folic acid 1mg daily usually

Stop any teratogenic treatments – may need to wean them down

Hydroxycarbamide (hydroxyurea) should be stopped 3 months pre conception

ACEi stopped (often on as renal protective)

Screen for rubella, Hep B, HIV, Varicella,

Recommend vaccinations if not up to date and immune

H Influenza type b

Conjugated meningococcal C

Pneumococcal every 5 years

Hep B if not immune

Influenzas (should get annually)

Screen for chronic disease complications

ECHO for pulmonary hypertension (associated with an increase in mortality)

BP + Urinalysis – PET + renal disease

Retinal screening for proloferative retinopathy

Iron overload from multiple transfusions – aggressive chelation is recommended

Screen for red cell antibodies