Sickle Cell Anaemia – AR

Introduction

⚫ SCD comprises a group of conditions caused by the inheritance of the abnormal haemoglobin sickle gene (HbS).
The most severe form of SCD is homozygous SCD (HbSS) but SCD can also be due to compound heterozygous genotypes s of HbS and another haemoglobin variant (e.g., HbC, HbDPunjab, HbE or b thalassaemia).

⚫ In the UK it is estimated that there are 15 000 affected individuals, and approximately 300 infants born with the condition each year.

Genetics
⚫ It has an autosomal recessive inheritance pattern.

Pathophysiology

These cells are prone to increased breakdown, which causes haemolytic anaemia and the sickle shaped red cells do not flow through blood vessels easily, causing blockage (vaso-occlusion) in small vessels, leading to most of the clinical features, including acute painful crises.

Complications of SCD include

1. Acute pain Syndrome
2. Acute chest syndrome
3. Pulmonary hypertension (PH)
4. Stroke
5. Renal dysfunction
6. Retinal disease
7. Leg ulcers
8. Cholelithiasis
9. Avascular necrosis
   Pregnancy in women with SCD is associated with higher risk of morbidity and mortality
   Pregnancy adversely effects SCD (Increased acute pain, acute chest syndrome) as SCD adversely effects pregnancy [hypertension, venous thromboembolism (VTE) and urinary tract infections]
   Risks in pregnancy include
10. Increased maternal mortality
11. Increased acute pain Syndrome
12. Increased Acute chest syndrome
13. Hypertension + Preeclampsia
14. Venous Thromboembolism ( upto x5)
15. Urinary tract infection
16. Likely to require blood transfusion
17. Stillbirth
18. Preterm delivery

Preconception Management

1. Genetics and Genetic screening
2. Comprehensive Review of complications
3. Preconception Medication Review
   Genetics and Genetic screening
   Women with SCD who have a partner who is a carrier of a b globin variant (e.g., HbS, HbC, b thalassaemia) will have a risk of up to 50% in each pregnancy of having a child with a sickling disorder.
   
   As part of the annual review, all women with SCD should be encouraged to engage with partner testing prior to embarking on
   pregnancy
   
   High-risk couples should be counselled prior to pregnancy about their reproductive options:
   a. Non-intervention
   b. Prenatal diagnosis
   c. Pre-implantation genetic diagnosis (PGD)

Comprehensive Review of complications..

Preconception Medication Review

⚫ Folic acid 5mg daily
⚫ Vitamin D is recommended for all pregnant women in UK – 10 micrograms daily – This should be continued
Patients with SCD are hyposplenic and are at risk of infection, in particular from encapsulated bacteria such as
○ Neisseria meningitides
○ Streptococcus pneumonia
○ Haemophilus influenzae
○ Therefore need Penicillin Prophylaxis

Vaccination
○ Annual influenza vaccination
○ Pneumococcal vaccination if this has not been given within the previous five year

⚫ Pain management by PCM or Panadeine

Hydroxycarbamide

Many women will be taking hydroxycarbamide prior to pregnancy as this has been shown to decrease the incidence of acute painful crisis and acute chest syndrome in individuals with severe clinical manifestations of SCD and is the only currently licensed treatment for SCD in the UK.

○ Hydroxycarbamide is teratogenic in animals
○ Therefore stop preconceptionally

⚫ If patient having frequent and severe sickle pain episodes, treatment with regular red cell erythrocytapheresis should be discussed
⚫ Iron chelators are not recommended

Antenatal care

Antenatal haemoglobinopathy screening
The objective of the screening programme is to ensure that screening tests are offered by 8–10 weeks of pregnancy by primary care
or maternity services, so that early prenatal diagnosis can be offered

Prenatal diagnosis (by chorionic villus sampling or amniocentesis) should be offered as early as possible in pregnancy to ensure early
access to termination of an affected pregnancy if requested.

⚫ Prenatal diagnosis can be performed from 11 weeks of gestation and is associated with a low risk of miscarriage (~1%)
⚫ Cell free DNA is still not available

Maternal health

Scheduled ultrasound scanning

⚫ Women should be offered serial fetal biometry scans (growth scans) every four weeks from 24 weeks of gestation

Blood transfusion during pregnancy

Prophylactic transfusion is not routinely recommended for sickle pregnancy, but should be considered for women with:
○ Previous or current medical, obstetric or fetal problems, related to SCD
Women previously on hydroxycarbamide due to severe disease

Anaemia
○ Women previously on hydroxycarbamide due to severe disease
○ Multiple pregnancy
Women receiving long-term transfusions for stroke prevention or for the amelioration of severe sickle complications should continue with regular transfusions throughout pregnancy

⚫ Transfusion may be required in women with worsening anaemia
⚫ Transfusion should be considered for those with acute SCD complications (e.g., acute chest syndrome, stroke)
If transfusion is needed, pregnant women with SCD should be given ABO-compatible, extended Rh- and Kell-matched, CMV-negative units

Management of Acute pain Syndrome during Pregnancy

⚫ Acute pain was the most common complication, affecting 57% of pregnant women with SCD
There are a number of possible reasons for the increased incidence of crisis including
○ increased physical and psychological stress
○ dehydration, particularly in early pregnancy when nausea and vomiting are common
○ worsening anaemia, which is common in pregnancy, related to increased iron requirements and red cell turnover;
○ the pro-coagulant state in pregnancy predisposing to vaso-occlusive disease
○ the increased risk of infection, for example, urinary infection or influenza, which can precipitate a sickle crisis

⚫ Mild pain may be managed in the community with rest, oral fluids and paracetamol or weak opioids
NSAIDs should be used with caution in the first trimester and avoided after 31 weeks of gestation due to the risk of premature closure of the patent ductus

⚫ If a woman needs strong opiate therapy, she will need to be admitted to the hospital
The management of acute crisis advocate that analgesia be given within 30 min of arrival in hospital after a rapid initial assessment and the pain should be controlled within 60 min of starting analgesia

⚫ Pethidine should be avoided because of the risk of toxicity and pethidine-associated seizures in patients with SCD
⚫ A full set of observations, using a modified obstetric early warning chart should be done when admitted
Oxygen saturations should be monitored and if oxygen saturation falls below the woman’s baseline or below 95% urgent medical review should be requested, due to the risk of acute chest syndrome and pulmonary embolism (PE)

⚫ Women with SCD should be prescribed prophylactic low-molecular-weight heparin during any antenatal hospital admission

Management of Acute Chest Syndrome

⚫ Affecting up to 10% of pregnant women with SCD
⚫ Characterised by fever and/or respiratory symptoms and a new pulmonary infiltrate on chest X-ray
⚫ The main differential diagnosis is PE which should be considered in patients with a normal chest examination and chest X-ray

Basic management will include
○ prompt pain relief
○ incentive spirometry
○ treatment of bacterial or viral infection
○ Blood transfusion should be considered early in the hypoxic patient

Other acute complications
Acute stroke should be considered in women presenting with acute neurological impairment and requires urgent consideration of exchange transfusion.

⚫ Acute erythrovirus (Parvovirus B19) infection should be considered in women presenting with acute anaemia

VTE and Thromboprophylaxis

All women with SCD should have risk assessments performed in early pregnancy, if admitted to hospital, in the intrapartum and early postpartum period

Women with SCD should be considered for prophylactic low-weight heparin (LMWH) from 28 weeks of pregnancy until six weeks
postpartum and if women have additional risk factors, prophylaxis should start from the beginning of pregnancy
⚫
Women admitted to hospital with a vaso-occlusive crisis or for other reasons should be offered LMWH throughout their admission unless there are contraindications

Intrapartum care
Timing of birth

The complications of SCD -The risks of abruption, unexplained stillbirth, pre-eclampsia, peripartum cardiomyopathy and acute sickle
cell crisis are increased and unpredictable

Due to the increased risk of placental insufficiency and pre-eclampsia, delivery between 38 and 40 weeks is often indicated to prevent late-pregnancy complications and associated adverse perinatal outcomes.

⚫MOD

Women with SCD can be offered vaginal delivery and vaginal birth after previous caesarean (VBAC) if there are no other contraindications
⚫
In women who have hip replacements (because of avascular necrosis) suitable positions for delivery should be discussed prior to delivery

Optimal Intrapartum Care
⚫ Blood should be cross-matched for delivery if there are atypical antibodies present (since this may delay the availability of blood)
⚫ Women should be kept warm and given adequate fluid during labour, using a fluid balance chart to avoid fluid overload
Continuous intrapartum electronic fetal heart rate monitoring is recommended owing to the increased risk of fetal distress, which may necessitate operative delivery

⚫ Opiates may be used for analgesia, except for pethidine
⚫ Regional analgesia is recommended for caesarean section

Postpartum Care

Risk of sickle cell crisis remains increased with 21–25% of women having a crisis post delivery and crisis being more common following
general anaesthesia

⚫ Women should receive thromboprophylaxis with LMWH for six weeks after delivery
Contraceptive
The choice of contraception should be individualised but methods that eliminate user failure, such as LNG IUS and intramuscular
DMPA are preferred

⚫ There is some evidence for reduction in sickle pain associated with progesterone-only preparations
⚫ CHCs are an option for women with SCD but cardio vascular risk factors should be minimised to mitigate potential risk

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