Essay 296 - Sickle cell disease

A 23 year old woman with sickle cell disease has been referred for pre-conception counseling.

(a)   Discuss your assessment and counseling [14 marks].

Patient is best seen in a joint clinic with obstetric and haematologic input.I will ask her about her menstrual history,LMP and method of contraception.i will assess severity of disease by asking about cardiac symptoms and advise against pregnancy if history of pulmonary hypertension due to increased risk of maternal mortality.i will ask about renal complications and recurrent UTI and counsel that renal functions can deteriorate during pregnancy and frequency of UTI can increase during pregnancy.i will ask about the period since last sickle cell crisis occurred and advise to delay pregnancy and continue on contraception if recent crisis occurred.i will ask about hypertension and if present I will advise to stop ACEI and ARBS as soon as pregnant as well as receiving aspirin 75 mg/d from 12 weeks until delivery to reduce the risk of preeclampsia even if not hypertensive before pregnancy.i will ask history of VTE and if she is on long term anticoagulation I will advise stopping warfarin as soon as pregnant  (before 6 weeks gestation) and switching to LMWH and provide self injection instructions and probably a supply of LMWH if already stopped contraception,if not on anticoagulation I will counsl about the increased risk during pregnancy and need for assessment for  thromboprophylaxis during each ANC visit and receiving it if admitted and postpartum.i will ask if she is on a blood transfusion regimen and recommend continuing on the same regimen during pregnancy.i will ask about partner genetic status and if unknown or positive I will refer her to genetic counseling about chances of baby affection and reproductive options.i will ask about antibiotic prophylaxis and provide penicillin daily or erythromycin if allergic to penicillin.i will ask about vaccination history and provide necessary vaccines if not taken as flu,H. influenza,pneumococcal ,meningeococcal and HBV vaccine.i will prescribe folic acid 5 mg/d preconception and continue throughout pregnancy.i will advise to stop hydroxurea at least 3 months before pregnancy.examination will include BMI, blood pressure,pulse.pallor may indicate anaemia.cardiac and respiratory examination.fundus examination for retinopathy.investigations include base line FBC, kidney functions as u & e and creatinine clearance.liver functions.echocardiography for evidence of pulmonary hypertension.MSU for proteinurea,microscopy,culture and sensitivity.screening for iron overload.screening for atypical RBC antibodies.i will explain that there increased risk of miscarriage,preterm delivery and IUGR.i will explain that her ANC will be hospital based under MDT consisting of obstetrician,haematologists and anaesthetist and neonatologists.i will explain the need for closer monitoring and frequency of antenatal visits and tests and growth scans.

B) She subsequently becomes pregnant and presents in spontaneous labour at 35 weeks gestation. Discuss your management of her labour [6 marks]

Delivery should be in a consultant led unit under multidisciplinary team consisting of obstetrician,haematologists,anaesthetists and neonatologists.vaginal delivery is the rule,caesarean section for obstetric reasons.increased risk of sickle cell crisis precipitated by dehydration and cold and stress of labour and pain,the patient should be adequately hydrated and kept warm.pain relief include epidural analgesia and if not possible or not accepted other options include entonox or diamorphine but not pethidine.monitoring of blood pressure,pulse, oxygen saturation and urine output.continous electronic fetal monitoring due to increased risk of fetal distress.positioning in patients with avascular hip necrosis should have been discussed during ANC period.if hypertensive,antihypertensives should be prescribed and administered.no need to shorten second stage unless severe uncontrolled hypertension or in case of fetal distress.active management of third stage is recommended.blood should be grouped and saved and in prescence of atypical antibodies cross matched blood should be available.postpartum thromboprophylaxis for 6 days if vaginal delivery and 6 weeks if caesarean section.neonatal assessment of baby and manage as affected if father’s genetic status is unknown until baby is tested.

A.

I would ask about number of crises per year and date of last crisis to adopt an informed decision regarding conception. Prior blood transfusion should be enquired. I would ask about current medications like hyroxyuria and other drugs that must be stopped before conception. Also, I like to ask about vaccination she was given like rubella, hepatitis B, Influenza and pneumococcal vaccines.

BMI, BP, chest and heart should be examined. CBC for HB, Kidney function and liver functions should be done. In addition, serology for rubella, Hepatitis markers, and HIV to make sure that she was immunised and does not viral infection. Finally RBCs antibodies should be checked.

I will counsel her regarding the risk of pregnancy on her condition and effect of SCD on pregnancy that necessitate multidisciplinary care including haematologist, senior obstetrician, and perinatologist. Optimisation of disease is mandatory before conception. Advice to avoid dehydration, cold, and badly ventilated places. Folic acid 5mg should prescribed 3 months before pregnancy. Iron therapy not recommend as routine and if given should be after low serum ferritin proved. Aspirin 75 mg to be given ounce she get pregnant. Influenza and pneumococcal vaccine to be given if she is not immunised. Prophylactic oral penicillin to be given. She will also advised to review her doctor if she has any infection or feel unwell. LMWH thromboprophylaxis required if she bed ridden. More frequent antenatal visits as she is likely to more frequent crises and pre-eclampsia . fetal monitoring and serial growth scan required because of liability of fetal growth restriction.

B.

During labour continuous fetal monitoring is required. Proper hydration and worming should be considered. Intermittent pneumatic compression may be used. Proper analgesia should be given, considering meperedine is contraindicated, either morphine or epidural analgesia can be given. LMWH thromboprophylaxis for 6 weeks and early mobilisation are recommended. Vaginal delivery is preferable and Caesarean delivery for obstetric indications.

Preconception counselling and assessment should be performed by an experienced sickle cell specialist. History of frequency and nature of crises should be taken to assess control of disease. I will also ask if the patient is transfusion dependent as it can cause iron overload. Immunisation history of pneumococcus, meningococus and hemophillus influenzae b is important as she is more susceptible to such infections. Drug history of hydroxyurea, ACE inhibitors and iron chelators should be taken as they are teratogenic. Blood pressure and urinalysis done to assess for nephropathy. Abdomen should be palapated for organomegaly. BMI should be measured. Bloods should be sent for full blood count, vitamin b12, folate and ferritin to assess degree of anemia. Liver function test and renal function test should be done to assess for liver damage and renal damage. Red cell anti bodies should be taken due to increase risk of hemolytic anemia in the newborn. Eye examination shoulde be performed to assess for proliferative retinopathy. Echocardiography done to assess for pulmonary hypertension. If the patient is transfused multiple times and has a high serum ferritin level, a T2 weighted cardiac MRI should be performed to assess for iron overload. Aggressive iron chelation should be given if features of iron overload. Hemoglobinopathy status of the partner should be tested and referral to genetic counselling if positive. The patient should be advised on the role of dehydration, cold, hypoxia, stress and infection in causing acute sickle crise and how to avoid them. Nausea and vomiting increases risk of acute crises. Risks to the fetus include fetal growth restiction, miscarriage, stillbirth, preterm delivery and increased perinatal mortality. Risks to the mother include increased isk of acute sickle crises, pre-eclampsia, induction of labour and caeserean section. Risk of passing on the condition to the baby should be explained. Patient should be advised to delay conception if the condition is not well controlled or if there are complications. Effective contraception should be offered. Prophylatic penicillin should be given against encapsulated organisims. Patient should be offered immunisation against meningococcus, pneumococcus, h influenzae b and hepatitis b. Influenzae and swine flu vaccination if it is the right time of the year. 5mg of folate should be given preconceptually and throughout pregnancy. Stop hydroxyurea, ACE inhibitors and iron chelators 3 months before conception.

b) Patient should be managed by a multidisciplinary team consisting of senior obstetrician, senior midwife, hematologist, anaesthetist. She should deliver in a consultant led unit which has the facilties to bandle complications of sickle cell disease. She should be kept warm and well hydrated. Intravenous fluids should be given in accordance to a fluid balance chart. Special care for positioning a patient with hip replacement secondary to avascular necrosis of the hip. Maintain oxygen saturation at 94%. Cross match needed if there are atypical antibodies, if not group and save is sufficient. No need for routine antibiotics but hourly measurement of temperature need and low threshold for starting antibiotics if fever. Pethidine should be avoided in view of increase risk of siezures and regional anaesthesia should be used in caeserean section. Continuous electronic fetal monitoring in view of risk of fetal distress. Patient should be monitored for signs of acute sickle crisis and acute chest syndrome. Corticosteroids should be given at 35 weeks if fetus has fetal growth restriction. Vaginal delivery is not contraindicated. Caesarean section is only for obstetrics indication.

A)       My assessment will start by asking more about the current status of her disease. How frequent does she get blood transfusion? Her current immunization status will be obtained. Weather she has  any symptoms and signs of end organ damage like reduced exercise intolerance or right sided heart failure will be checked. BMI will be calculated. Blood pressure will be measured. Her current medication will be reviewed and guidance will be given to stop some of the medication like hdroxyurea for atleast 3 months prior to conception. Baseline full blod count will be taken to check her heamoglobin. Serum ferittin and folate levels will also be checked. Liver function test and renal function test will be carried out to check for any organ damage. Echocardiogram  to be carried out if not done in the last year.. Urine dipstick for protein will be checked as well. partner t be screened  for haemoglabinopathy, and if positive to refer clincal geneticist for counseling. Screen for HIV, Hepatitis B and rubella.  I will counsel the patient about the risk to her and her baby. She will be at increased risk of developing preeclemsia with its sequelae.  Nausea and vomiting in pregnancy can lead to dehydration which can precipitate sickeling crisis as well as thromboembolism. I will explain to her the need to maintain hydration and reduce stress. The fetus will be at increased risk of developing intrauterine growth restriction, premature delivery. There is also an increase risk of stillbirths and perinatal mortality. I will start her on folic acid 5mg 3 months before conception and to be continued throughout the pregnancy. I will start her on penicillin to cover encapsulated organisms as these patients  tend to have functional asplenia. Offer hepatitis b vaccination. Give her information leaflet.

B)       I will review her care plan of delivery. Her case should be managed in multisciplinary setting including senior obstetrician, senior midwife, senior anesthetist and haematologist. Try to keep her warm and avoid dehydration. Pethidine should be avoided as an analgesic as it increases the risk of seizures. Continuous electronic fetal heart monitoring is needed. Caserean section is indicated only for obstetric reasons. After delivery her hydration should still be maintained. LMWH started and continued for 7days if delivered vaginally and for 6 weeks after caesarean section. Advice on contraception is given. progesterone only contraceptions to be considered as a first line

]Patient with sickle cell disease (SCD) should be seen in Multidisciplinary unit involving obstetrician, hematologist, and geneticist.

Informed the risk of transmission to the fetus depend upon hamoglobinopathy in partner blood, hence need Hemoglobin electrophoresis. If normal, then the fetus  will be 100% sickle cell trait, if his sickle cell trait, then 50% chance of sickle cell disease, so offer prenatal diagnosis.

If SCD, then all fetuses with SCD.

History taken about her previous pregnancies, mode of delivery, and any complications.

Menstrual history taken, menarche, last menstrual period. History of Vasoocclusive crisis, and when was the last episode.

History of blood transfusion, exchange transfusion.

 Vaccination history taken, including Hepatitis B, rubella, pnemococcus, influenza, and meningococcus. Inquire about the compliance for pnemococcus  prophylaxis.

Drug history, history of allergy, smoking .

ON examination check BMI and blood pressure.

 Investigation include Anemia work up including FBC, Iron profile, Hb electrophoresis as a baseline for Fetal Hb, renal function test, Liver function MSU for culture and sensitivity.

 Do Blood group and antibody as a baseline.

B) During labor, she is at risk of vasoclusive crisis, therefore, need vigilant  care.

The fetus  at risk of IUGR  and preterm  therefore Pediatrician should be informed.

Delivery should be in the hospital where arrangement in place for an Emergency caesarean section blood transfusion service.

Exclude UTI, chorioamnitis  and abruption placenta as the cause of preterm labor.

Need continuous fetal monitoring by CTG.

She should be well hydrated with intravenous fluid to avoid dehydration, Early epidural and liberal use of sedation by morphine, avoid pathedine as it precipitates the crisis.

 Administer Continuous oxygen inhalation to avoid hypoxia. Keep warm

The Investigation includes FBC, Blood group and cross match with extended antibody panel, cytomegalovirus negative kell negative.

Watch for the progress of labor on program, vital sign and pulseoximetry, aim vaginal delivery, caeserian for obstetric indication.

At delivery cord blood, send for Hb electrophoresis.

(A) A history is taken for duration of sickle cell disease, end-organ damage, type and frequency of sickle cell crisis experienced to assess her extent and severity of disease. I would like to know if she is transfusion dependent. A drug history is elicited for ACE-Inhibitors, ARB and hydroxyurea as these drugs are teratogenic. A vaccination hsitory is asked for Hepatitis B immunity, most recent meningococcal and Haemophilus B influenza vaccination to check if they are up to date. I would like to know her current contraceptive history and compliance for possible ongoing pregnancy. On examination, her weight and height is assessed to calculate BMI. An abdominal examination is conducted for organomegaly which may indicate iron overload. The range of movements of her hip joints are examined if she has a history of avascular necrosis of the femur head. A fundoscopy is done to assess for retionpathy. Investigations include FBC, ferritin, TIBC, B12 levels to check for iron overload, iron-deficiency anemia or B12 deficiency. Type and screen is sent to check for atypical red cell antibodies if she has previous transfusion. A liver function is done to exclude liver dysfunction and renal panel for baseline. I would perform a urinalysis for white cells and proteins. I will send a mid-stream urine for culture and sensitivity to exclude urinary tract infecttion. I will send her for a 2D echo to exclude pulmonary hypertension as this decides on the safety of embarking on pregnancy. I will request for an MRI to assess for end-organ damage from iron overload if she has had multiple transfusions prior.

She needs to be managed in a multidisciplinary setting with an experienced obstetrician, senior midwife and haematologist experienced in sickle cell disease. She may need to postpone pregnancy and continue contraception if her current disease is not under control or if she has pulmonary hypertension. Otherwise, hyperetensive drugs like ACE-I and ARBs need to be substituited and hydroxyurea to be stopped at least 3 months before conception. She will need to commence folic acid 5mgom till 12 weeks and commence aspirin from 12 weeks onwards as she is at risk of preeclampsia. She is advised to keep her vaccinations up to date including pneumococcal, meningococccal and haemophilus B influenza. She is to commence penicillin prophylaxis against encapsualted bacteria. She will need to be assessed by an anaesthetist in 3rd trimester for suitability for regional analgesia and advised on suitable analgesia. Delivery will be aimed at 38 weeks in a consultant led unit with neonatologist support.

She should be advised to avoid stress, dehydration and to keep warm in order to avoid precipitating a sickle cell crisis. She needs to report to hospital immediately if she feels unwell or has pain as she needs urgent treatment for sickle cell crisis. Signs and symptoms of impending eclampsia including headache, blurring of vision needs to be advised. Written information about her condition and its complications in pregnancy is provided and documented in the notes.

The genetic father needs to udnergo laboratory screening for sickle cell haemaglobinopathies as the fetus is at risk of sickle cell disease if he is a carrier.Genetic counselling is necessary. The fetus is at risk of fetal growth restriction and needs regular scans to assess growth and liquor volume 4 weekly from 24 weeks till delivery, First trimester screening for aneuploidies should be offered at 11-13 weeks and fetal anomaly screening at 18-20 weeks.

(B) I will arrange for anaesthetist assessment as intravenous access is potentially difficult. FBC is done to assess for anaemia and need for blood transfusion and group and save is done. I will keep her well-hydrated with an intravenous maintanence drip while monitoring fluid balance. I will keep her warm during labour to avoid precipitating a sickle cell crisis. I will avoid prolonged labour preferably not more than 12 hours to avoid precipitating Sickle cell crisis. As a result, amniotomy and syntocinon may be required. Caesarean section is for obstetric reasons only. I will  avoid the use of pethidine as it increases the risk of seizures. Regional anaesthesia is preferred for labour and delivery and to try to avoid general anaesthesia as far as possible. Continuous electronic fetal monitoring is necessary as the fetus is at risk of hypoxia and fetal distress. I will inform the neonatalogist for neonatal support in view of borderline preterm labour. She will require active third stage of labour to minimise her risk of post-partum haemorrhage.

A)     Assesment should be in the multi - disciplinary  setup, with  Sickle cell disease (SCD)specialist  ,haematologist and consultant obstetrician and specialist midwife. I would enquire regarding frequency of crisis episodes, frequency of requirement of blood transfusions, as this gives clues about disease control.

Previous  menstrual cycles, length and regularity ,and it important to assess current problems.

Past history of  Diabetes, Hypertension, thyroid dysfunction, cardiac problems,  respiratory symptoms , (as increased transfusions will lead to organ dysfunctions , secondary to iron overload,) current  use, of hydroxyurea, which reduces  sickling  crises,and  some anti hypertensives  in  particular  (ACE  inhibitors, ARB blockers ), need to be stopped atleast  3 months before  planning the pregnancy, enquiry regarding vaccinations (against meningococci, pnemococci, nesseria meningitides, H.influenzae) ,swine flu,and seasonal influenza vaccination is also important ,use of bone prosthesis ,due to femoral head necrosis is important and documented  appropriately. Present contraception use is enquired .

Examination will involve accurate blood pressure recording. BMI,  Cardiovascular system and respiratory system/ophthalmology referral to assess for proliferative retinopathy. Abdominal examination is done to note for  organomegaly.

Investigations to be assessed are: FBC, Ferritin, folate, vitamin b12 levels, blood grouping and type Rh, E,D, C, Anti kell, echocardiography, renal function test, serum electrolytes, and serum creatinine , liver function is assessed .chest x-ray, and screen for atypical antibodies, Rubella IgG, hepatitis B, Hepatitis C, Cytomegalovirus. Cardiac Echo is required to assess cardiac function, pulmonary hypertension, and cardiomegaly .

Counseling is done along with the team, of hematologist  , specialist midwife, obstetrician, the women must be aware that SCD is associated with both maternal and fetal complications. There is increase of perinatal  mortality, premature labour, fetal growth restriction, and acute painful crises during pregnancy.The importance of avoiding dehydration, cold, hypoxia, over exertion and stress, to reduce sickling is conveyed. She should know that pregnancy increases the sickling  by 30-35%,nausea and vomiting in pregnancy can result in crises,the risk of anemia,acute chest syndrome and increased infections ,there is increased risk of preeclampsia,fetal distress ,induction of labour is increased .She should be counselled about the risk of the baby being affected and therefore partner screening is important ,fetal  haemoglobinopathy does not occur, presence of atypical red cell antibodies may result in haemolytic disease in the newborn.There is increased chance of venous thromboembolism and she will require prophalaxis if she is admitted during pregnancy and for 7 days post delivery(if vaginal delivery),or 6 weeks after cesaerean section. She needs to know that awaiting the investigation results will serve to counsel l appropriately. She is advised that effective contraception is important until clinical condition is optamised. Folic acid 5mg (3 months preconception and continued throughout pregnancy),and   vaccination status should be up dated before pregnancy swine flu and influenza vaccine annualy, is provided .The drug hydroxyurea  should be stopped atleast  3 months before pregnancy. The importance of early booking, low dose ( 75mg) ecosprin from 12 weeks, frequent visits every 2 weeks, screening for preeclampsia ,it is important to advice infection prophalaxis with penicillin(or erythromycin if allergic to penicillin), daily for all hyposplenic  patients (u.k.guidelines)  ,aggressive chellation is recommended if there are increased ferritin levels.Chellating agents are stopped at least 3 months before embarking on pregnancy.

Patient information leaflet, information of support groups and further appointments are given at this gestation.

b)The plan of care during delivery and the mode and place of delivery  is documented antenatally, corticosteroids can be considered at this gestation, an  ultra sonogram to assess the presentation at this gestation will be required ,as breech presentation at this gestation will require an emergency cesarean section, the senior anesthetist, neonatologist, obstetrician and midwife in charge are informed, delivery should be at the tertiary centre with a special care baby unit, blood group and cross matching will be required in women with atypical antibodies, the women is given adequate hydration and pain relief is vital, pethedine is contraindicated  (increases risk of fitting)(other opiates can be given),regional anesthesia is not contraindicated, oxygen inhalation  and  continuous, discuss  suitable positions in women with hip replacements. Monitoring of the fetal heart continuously ( electronic monitoring )is essential, as fetal distress is increased in these women, prolonged labour should be avoided, routine antibiotic prophalaxis is not recommended ,however hourly observations of vitals should be documented,  timely intervention are necessary. Good hydration is required ,oral/ i.v. infusions may be necessary. Cardiotocography is advised  once she is in active labour, suitable position should be discussed if she has hip replacement, third stage is managed actively, ergometrine is withheld if she has preeclampsia. Keeping the women well hydrated and and warm, will reduce sickle crises. Acute crises is increased in labour,and managed promptly,increased risk of Cesarean section in women with end organ damage is anticipated and planned, otherwise cesarean section is only for obstetric indications.

a)I will ask her about  her general health and well being,asking her about the frequency and nature  of sickling  crises and the need for blood tranfusions, to know the current status of her disease. I will ask her about partners haemoglobinopathy status as this if present  increases risk of having a affected fetus.I will ask about her vaccination status regarding pneumococci,influenza,meningococci as she may be hyposplenic and at risk of infections.i will ask her drug history as medications like ACE inhibitors,angiotension receptor blockers,hydoxycarbamide  are not safe during pregnancy and need to be stopped before conception.

Her blood pressure and cardiovascular ,respiratory system needs to be examined  as these are mostly affected in sickle cell patients.

Investigations like retinal screening to rule out proliferative retinopathy needs to be done.B.P  to identify hypertension and urinalysis for  proteinuria should be checked.If history of multiple blood transfusions,s.ferritin to be checked and if it is high, cardiac MRI can be done to assess body iron loading.Red cell antibody screening to be done and if present indicates increased risk of haemolytic disease of newborn.Echocardiography to screen for pulmonary hypertension  which if present is associated with increased mortality and so pregnancy is contraindicated.Her renal function tests done to rule out nephropathy.Liver function tests  to be done to identify any deranged hepatic function.Immune status regarding Hepatitis B  needs to be checked.

I will counsel her regarding the need the need of her management  by a multidisciplinary team consisting of obstetrician,haematologist,anaesthetist and experienced midwife.S he will need to take 5 mg folic acid daily and throughout pregnancy.Screening for her partner regarding hemoglobinopathy status as if affected will need genetic counselling.I will tell her regarding methods and risk of prenatal diagnosis and about termination of pregnancy if fetus found affected.Her vaccination status needs to be updated before conception.She will need daily penicillin prophylaxis   daily.She may need to take 75mg daily from 12 weeks gestation to reduce risk of pre-eclampsia.I will counsel her regarding effects of pregnancy on HBSS and ways to prevent them.There is increased frequency of sickle cell crisis during pregnancy.Dehydration,cold,hypoxia and stress can precipitate this and so she should avoid these.There is increased frequency of painful crises and acute chest syndrome and she may need to be hospitalised.There is increased chance of infection especially UTI.

I will counsel her regarding effects of sickle cell disease on pregnancy.The fetal risks are increased miscarriage rate,fetal growth restriction,preterm birth,fetal distress and perinatal mortality.The risks for her are increased chance of pre-eclampsia,placental abruption,thromboembolism.C.S and increased mortality.She will need more number of antenatal visits ,serial growth scans as FGR is common.

b)She will need to give birth in hospital  involving the team of senior obstetrician,senior anaesthetist,heamologist ,senior midwife trained in high risk care and neonatologist.Va ginal delivery considered and C.S for obstretic indications. If it’s a growth restricted fetus,she may be considered for corticosteroids.Continous electronic fetal monitoring  is needed as there is increased rate of still birth,abruption and compromised placental reserve.she should be well hydrated and if she does not tolerate oral fluids,she may need IV fluids using a fluid balance chart.Labour should be carefully supervised as increased chance of sickle cell crisis and ACS in intrapartum period.Use of pulse oximeter  to detect hypoxia as increased demand of oxygen in intrapartum period.Hourly recording of pulse ,B.P,respiratory rate.A low threshold to commence broad spectrum antibiotic if pyrexic.Opiates can be used for pain relief with senior anaesthetic ivolvement.C.S if labour not progressing well and delivery not imminent.Thromboprophylaxis in form of LMWH during hospital stay and  for 7 days if vaginal birth and 6 weeks if C.S.

A history from the woman including her previous obstetric history and outcome of any previous pregnancies. Current contraception, and advice regarding remaining on effective contraception until the sickle cell disease is optimised and stable. An idea of her current disease status including the frequency and nature of any sickle cell crisis. Her dependence on blood transfusions.

Her current medications will need to be reviewed in the context of possible teratogenicity. Hydroxycarbamide, Vitamin C, Iron chelators, ACE inhibitors, Angiotensin receptor blockers need to be stopped due to their teratogenicity.

As these patients are hyposplenic they are at an increased of infection and pregnancy increases their risk even more. It is important to assess her vaccination status and ensure she is immune to Heptitis B and C,  Rubella, Meningococcal C. She should have annual vaccination for Influenza. Her HIV status should be checked as this would lower her immune status. She should be started on antibiotic prophylaxis of penicillin due to her increased risk of infection.

I would examine her looking for signs of organomegaly.

She will need a number of investigations to assess her current disease status. I would do bloods of FBC, Vit B12, Folate and Ferritin assessing her anemia status. Her Folic acid dose should be increased to 5mg a day pre pregnancy and antenatally.

To assess her current renal function I would do U&E’s, BP and urinalysis looking for proteinuria. I would do LFT’s to assess her liver function. I would arrange for prenantal retinal screening. These patients who are having regular blood transfusions are at risk of iron loading, I would do a Cardiac MRI in order to assess. She will need to be screened for red cell antibodies as this may indicate an increased risk of haemolytic disease of the newborn.

In terms of councelling her. She will need to be informed that there is an approximate 35% of sickle cell crisis during pregnancy and in the puerperium. Her pregnancy will be classed as a high risk pregnancy and she will be under consultant led care in a specialist unit along with haemotologist input.

She needs to be aware of general measures to reduce the risk of sickle cell crisis. For example, avoiding dehydration, cold, hypoxia, overexertion, stress and infection. The early pregnancy symptoms of nausea and vomiting can lead to dehydration.

The maternal risks associated with sickle cell disease in pregnancy include increased maternal mortality from sickle cell crisis and she needs to be aware to access medical assessment without delay if she feels unwell. She is also at increased risk of infection, venous thromboembolism, antepartum haemorrhage, pre eclampsia and eclampsia and bone marrow embolism.

The fetal risks associated with sickle cell disease in pregnancy are miscarriage, stillbirth, premature labour, intrauterine growth restriction, and fetal distress in labour leading to an increased chance of emergency caesarean section.

She also needs to be councelled and assessed for the risk of passing the sickle cell disease onto her child. Her partner will need to assessed for his carrier status of sickle cell disease and other haemoglobinopathies and the couple will need to be referred for genetic councelling if he is a carrier of any of these.

B)

Firstly she needs to be in an obstetric led unit and ideally with haematology input readily available. The obstetric consultant, anaesthetic consultant, senior midwife, neonatologists and haematologist need to be informed of her arrival and that she is in labour.

IV access will need to be gained a cross match and FBC taken.

She is at an increased risk of sickle cell crisis due to the stresses of labour, it is therefore important to manage any potential exacerbating factors such as keeping her well hydrated with oral or IV fluids and keeping a fluid balance chart. She needs to be kept warm. Her BP needs to measured every 1hr as she is at risk of pre eclampsia. Her oxygen saturations need to monitored regularly to assess for signs of hypoxia.

It is important to manage her pain well and I would discuss with her the option of an epidural. Otherwise her pain can be managed with opiods with avoidance of pethidine due to the increased risk of seizures.

The fetus needs to be continuously monitored due to the increased risk of fetal distress.

Her labour progress needs to be monitored it is important to not allow a prolonged labour due to the increased risk of sickle cell crisis I would therefore have a low threshold for caesarean section if her labour was not progressing satisfactorily.

a)Assessment of the severity of sickle cell disease including detailed history of frequency of painful crisis; when her last crisis occurred and other organ involvement including retinopathy, nephropathy, previous chest symptoms- including PE, previous CVA, cardiac function if history of transfusion dependency or pulmonary hypertension, avascular necrosis of hips.  Review current medications and ensure that she is taking Penicillin V (protects against encapsulated organisms) and Folic acid 5mg (reduced risk of Neural tube defects). Advise to stop medications such as NSAID (may reduce chances of ovulation) and ACE inhibitors (teratogenicity).  Review immunisation history is up to date including pneumonoccocal vaccination, meningococcal vaccination, H influenza, Hep B, seasonal flu vaccination. Refer to genetic counselling after obtaining sickle cell status of partner this will provide information about risk to a child and sensitively identify patients’ thoughts and wishes for pregnancy if has an affected child this will help guide if pre-natal testing will be required or if referral for pre-implantation genetic testing is required.  Review current conceptive methods and compliance.  Review current social circumstances including housing ensure warm & dry as if not this can precipitate painful crisis. Advise to stop smoking and refer to smoking cessation. Patient will be managed in MDT setting including Medical medicine Obstetrician who has expertise in managing Sickle cell disease and Haematologist.  Refer for assessment of Retinopathy prior to pregnancy. Perform baseline U & E, Cr clearance, 24 hour urinary protein, FBC including haematinics.

b) Delivery should be on labour ward with involvement of obstetricians, haematologist and senior Anaesthetist.  Ensure that she is well hydrated in labour with i.v. Hartman’s. Minimise risk of infection by infection control measures, avoid in-dwelling catheter and treat infections promptly if suspected.  Regular assessment of O2 saturations maintaining saturations above 92% and use O2 supplements if requires.  Avoid pethidine as associated with seizures in sickle cell patients. Offer epidural early in labour depending on patient’s wishes.  Inform SCBU of admission and availability of SCBU beds.  Positions in labour may be restricted if previously affected by avasucular necrosis of hip.  FBC and X match if atypical antibodies (due to previous history of blood transfusions). Paediatrician present at delivery due to gestational age of 35 weeks. Active management of the 3^rdstage in labour to mininse risk of PPH.  VTE assessment consider TEDs in labour and post partum LMWH.  Manage in HDU post partum as high risk of crisis. 

a, History should be taken about the severity of the disease, frequency of sickling crisis and frequency of blood transfusions. Partners sickling status should be enquired.  Obstertric history ,any complications in  previous prenancies and any children affected with SCD should be asked. Current contraceptive history should be elicited. Drug history of taking any chelating agents like hydroxy urea and antihypertensive drugs like ACE inhibitors should be asked as these should be stopped before pregnancy as associated with teratogenicity. Immunisation history should be asked.

BP should be cheched . Abdomen should be examined for hepatosplenomegaly

Fbc , serum ferritin, LFT and RFT should be done to detect anaemia, nephropathy and liver dysfunction.

Immunisation status for rubella, HIV, Hep B ,should be checked.Red cell antibodies should be checked.

Echocardiography shpuld be done to exclude pulmonary hypertension. T2 cardiac MRI scanning to detect iron overload .If iron overload is detected adequate chelation should be done before pregnancy. Retinal screening should be done if any visual symptoms

Partner testing should be done if not done before  

 Counselling should be done by MDT involing obsterician and midwife with experience in managing high risk pregnancies and haematologist with special interest in SCD in pregnancy.

She should be told about the effect of SCD on preg and the effects of pregnancy on scd.

Precipitating factors like dehydration, stress, hypoxia infection and how to avoid them in pregnancy.

Vomiting in pregnancy cause dehydration and preipitae crisis should seek medical help if unwell.

Counselled about early booking , need of frequent visits,increased monitoring.

advice to take vaccinations if not taken . Pencillin prophylaxis shoulb be continued. Folic acid 5 mg should be started and continue througout pregnancy.Adequate contraception should be taken till disease optimised

B, Management in labour should be by MDT involving senior obstetrician,anaesthetist, paediatrician, senior midwife and haematologist., Blood should be crossmatched early if red cell antibodies identified early otherwise group and save enough. Hydration  should be maintained by adequate oral fluids ,if not tolerated by IV fluids. Hypoxia should be avoided . O2 therapy may be required if so2 below 94%. Continuous electronic  fetal monitoring should be done as there is risk of fetal distress. Adequate analgesia should be provided for pain relief. Pethidine should be avoided as it precipitates seizures. Vaginal delivery should be the aim. 

A. Assessment would include a thorough history, examination and investigations within a multidisciplinery team involving a haematologist, specialist nurse and obstetrician with a special interest in sickle cell disease.

History would include number and nature of recent sickle cell crisis for example acute chest syndrome, admissions to intensive care units, and reliance on blood transfusion or exchange transfusion to assess disease severity with aim to stabilising the condition pre-pregnancy.  Establish co-morbidites such as hypertension, hip replacement and full drug history.  ACE inhibitors and angiotensin receptor blockers are terratogenic and should be changed to labetalol or a calcium channel blocker pre pregnancy.   Hydrocarbimide should be stopped three months prior to conception.  Establish current contraception use and advise that pre-conception optimisation of blood pressure and general health is important to try to minimilise risks associated with pregnancy.  I would discuss the nature of the disease being genetic and advise partner testing, if partner is a carrier there are options of pregenetic diagnosis or prenatal testing.

Examination should include retinal assessment to look for proliferative retinopathy which may worsen with pregnancy.  Blood pressure should be taken to establish if pre-exisiting hypertension and allow for stablisation pre-pregnancy.  

Investigations would include urinalysis and 24 hour protein collection done to establish pre-existing proteinura or infection.  An MSU should be sent and any UTI treated.  A FBC to assess for anaemia, iron studies to assess for iron deficency and urea and creatinine and electrolyes taken to assess current renal function.  Severe renal impairment is associated with a poorer pregnancy outcome.  An echocardiogram should be done to look for pulmonary hypertension which if present and severe would mean that pregnancy would be advised against due to high risk to the mother of heart failure.  A cardiac MRI should be considered to assess for iron overload and aggressive chelation considered pre-pregnancy if iron overload present. Screening for HIV, CMV, Hep B and C and rubella advised and appropriate vaccinations for hepatitis B, pneumococcus, influenza and rubella given if required.

I would counsel the woman that sickle cell disease in pregnancy is associated with risks for the woman and the baby.  Maternal risks include increased number of painful crisis including acute chest syndrome, increased number of infections in particular urinary tract infection, worsening of hypertension and development of pre-eclampsia and this all may result in increased hospital admission.  There is an increased rate of induction of labour and caesarean section.  Fetal risks include intrauterine growth restriction due to placental insufficiency, fetal distress and premature delivery.

The woman should be advised to take prophylactic antibiotics as hyposplenia predisposes to infections and advise folic acid 5mg once daily to decrease risk of neural tube defects.  We would advise to book early once the pregnancy test is positive and present early if has nausea and vomiting for IV fluid rehydration to prevent painful crisis.  We would stress importance of hydration, mobilisation and keeping warm to avoid crisis and the need for VTE prophylaxis with LMWH for admission.  We would advise 75mg aspirin to be started at 12 weeks to reduce risk of developing PET.

b.  The lady should be monitored in a high risk labour ward and be reviewed by the obstetric and anaethetic team on arrival.  Vaginal delivery is not contraindicated in sickle cell disease and caesarean section is for obstetric indications.  During labour it is important to keep the woman well hydrated with IV fluids and keep warm to prevent painful crisis.  Pethidine is to be avoided due to the risk of seizures, though other opiates or epidural anaesthesia is fine.  Continuous CTG is recommended due to high risk of fetal distress due to underlying placenta pathology.  An extended crossmatch should be performed as patient may have unusual antibodies.  VTE prophylaxis should be started with TED stockings applied, post delivery LMWH is indicated. Her oxygen saturations should be monitored throughout along with regular vital signs and oxygen given if saturation less than 96%.

a)Preconceptional assessment and counselling of a woman with sickle cell disease should be done in a specialist centre. Ask history about the frequency of sickling episodes and blood transfusions. Taking any medications like hydroxycarbamide - should be stopped 3-6 months before planning conception as these are teratogenic. History of vaccination for H. influenza and pneumococcus and penicillin prophylaxis.ask partners status with respect to sickle cell disease

Examine for pallor, BP, BMI . Per abdominal examination for splenomegaly

Investigations for FBC to check for degree of anaemia. S. ferritin to assess for iron deficiency. Hb electrophoresis if not already done to check for other coexisting haemoglobinopathies. Urea, electrolytes and creatinine to check for renal function. Liver function test. Urine test to look for evidence of infection and proteinuria. Partners FBC and smear if sickle cell disease status unknown.

Patients verbal counselling should be supported by written information in the form of leaflets. If partner is a carrier or disease status for sickle cell ds, refer for genetic counselling. Inform about the availability of prenatal diagnosis and risk associated with it. Patients with sickle cell disease are at increased risk of pregnancy complications including miscarriage, prematurity, IUGR, abruptio,still birth and increased perinatal morbidity and mortality. Increased risk of pre-eclampsia. Frequency of sickling episodes may increase during pregnancy precipitated by dehydration, infection,over-exertion. increased chances of infections like UTI and pyelonephritis.

Advice to take vaccine for pneumococcus, meningococcus and influenza, if not taken already. Check immunity and advice for hepatitis B and rubella vaccine accordingly. Advice folic acid supplementation 400mcg daily. Iron supplementation only if iron deficiency documented. Continue penicillin prophylaxis. Postpone pregnancy till disease status is stabilised.

b) Her labour should be managed in a multidisciplinary centre with a senior obstetrician, senior midwife, haematologist and neonatologist. Per abdominal examination to assess for severity, frequency and duration of contractions. Pelvic examination to assess for cerical dilatation, effacement and station of presenting part. Prophylactic corticosteroids as patient is is preterm labour. Prophylactic antibiotics. Keep the patient well hydrated and mobile. Oxygen by face mask. Avoid prolonged labour, dehydration, hypoxia and acidosis. Continous electronic fetal monitoring. Epidural analgesia for adequate pain relief. Assess for need for thromboprophylaxis. Plan for vaginal delievry, CS only for obstetric indications. Avoid general anaesthesia. Active management of third stage of labour.

A)History of frequency and nature of crises is taken.This would reflect the severity of disease.Blood transfusion history is taken .If she is transfusion dependant.,there is high risk of iron overload

.HIstory of hypertension,and symptoms of  dyspnea are enquired,as she is at risk of renal disease and pulmonary hypertension.Presense of severe renal disease or pulmonary hypertension cause adverse pregnancy outcome and maternal morbidity and mortality.She should be advised to avoid pregnancy until she is optimally treated

Drug history is taken.If she is taking hydroxurea for irn chelation,that should be stopped at least 3months before conception.Anti hypertensivses ,ACE inhibitors and ARBs should be stoppped before conception as these are teratogenic.She should be switched to other safer antihypertensives

Immunization history is taken .She is at high risk of infection due to hyposplenism and she should  be immunized against Hepa B,Meningocoocal  C,and Influenza type b as a single dose,if she has not recieved.Pneumococcal vaccine once in 5 yrs and yearly vaccine for swine flue and influenza.Penicillin prophylaxis given daily.

On examination BMI and BP noted .Abdomen examined for any organomagaly.

Investigations include,FBC for Hb level, Serum ferritin is done and if high levels are found Cardiac MRI is done so that aggressive chelation is done before pregnancy.

..Hemoglobinopathhy status of partner.If he is found to be a carrier,she should be referred  to geneticist .

Liver function tests and Renal functions to identify nephropathy and deranged liver functions.

Urine tested for presense of  proteinuria and 24 hr urinaryprotein is estimated.

2D echo  for pulmonary hypertension  and retinal assessment is done, if this has not been done in  previous year. .

Woman should be couselled by Sicle cell specialist and given adequate information  regarding the effect of her disease on pregnancy and effect of pregnancy on disease.

Results of investigations are reviewed and she is advised to use contraception until she is optimally treated.

Whenn she becomes pregnant, she should avoid cold excercise ,stress  and hypoxia which would trigger crises.Vomiting and nausea of pregnancy may cause dehydration and precipitate a crises.She should report to hospital early if she feels unwell.She is at increased risk of infections specially  UTIs and chest infections.

She should start taking folic acid 5mg and continue through out pregnancy.If partner is found to be a carrier ,there is high risk fetus being affected.She should be given option of prenatal diagnosis by CVS or smniocentesis.Fetus is also at risk of growth retardation ,which may necessitate induction of labor or

 CS.

Sorry, part B is here.

B)During labor ,she should be managed by multidiciplinary team of  senior obstetrician,senior midwife,hematologist and  neonatolgist.Since she is 35wks,SCBU should be informed . If facilities are not available in utero or ex-utero transfer to a unit with neonatal facilities should be arranged depending upon her condition.Inj Betamethasone  should be given for lung maturation.

IV line is secured and she should be kept well hydrated and oxygenated.

Blood should be crossmatched if atypical anti bodies are present.

If she has hip repalacement she should be placed in a comfortable postion.Adequate analgesia is ensured .Epidural is advisable.BP, pulse and oxygen saturation is monitored continuously.Oxygen therapy is given if level falls below 94%.Progress of labor is monitored closely as protracted labor may precipitate crisis.

Active management of third stage should be done as she is at risk of PPH.

Management of patient with sickle cell disease should be by multidiscplinary  team including obstetrician  , haematologist and specialist midwife  .                                                                                                                       

History                                                                                                                                                                            

I will ask her about her last menstrual  period and current use of contraception's.  History and frequency of sickle cell crises  . IF she had  any blood transfusion because it can increase red cell antibody .  Review her treatment if she is on angiotensin –converting enzyme and angiotensin receptor blocker she should stop before pregnancy , if she is on hydroxurea she should stop 3 month before pregnancy. Current use of prophylactic antibiotics .    Whether she had vaccination against  Neisseria  meningitis,  HaemophILus  influenza  annually  and streptococcus pneumonia last 5 years and also hepatitis B vaccination. IF her  partner has haemoglobinpathy because risk of having affected baby so offering genetics counseling.

Examination and investigations                                                                                                                            

. Check her blood pressure . urine dipstix for  . urine albumin. She should has assessment for chronic disease complications  .Screen for pulmonary hypertension  with echocardiography . retinal assessment for proliferative retinopathy. Screening for iron over load  and  red cell antibody .full blood count to exclude anemia . renal and liver function test. Urine protein /creatinine  protein  ratio .Midstream urine .

Counseling.                                                                                                                                                            

Explain risk of sickle cell disease in the pregnancy  for her and her baby . It increase risk of pre eclampsia  , pregnancy induced hypertension . acute crisis, acute chest syndrome , stroke ,anemia ,hospital  admission ,infections.It increase risk of miscarriage , intrauterine growth restriction ,preterm labour and perinatal mortality .  advice her for low thershold  to ask  for medical advice  , informations  should include the effect  of dehydration  , stress , exposure  to cold or hypoxia on increase risk of crisis . Effect of nausea  and vomiting  which cause dehydration and precipitation of the crisis . worsening of anemia and increase  of infections . Possibility of having baby with sickle cell disease and offer partner screen for haemogloinpathy  and update assessment of chronic  disease .complications. folic acid 5mg prepregnancy  till 12w  . Low dose aspirin from 12w  pregnancy till delivery  as a prophylaxis's against  pre eclampsia .Provided her with written    informations .                                                                                                                                                             

B.                                                                                                                                                                                   

She came at 35w in labour delivery should be in hospital where there is bed in scabu for management  of preterm labour , Aim of delivery is vaginal except if there is indications for cesarean section  . blood cross matching if there is atypical  antibodies otherwise group and save . Establishment of iv line in the early labour .Avoid dehydration, stress  it increase crises O2 if spo2 less than 95% . Analgesia better regional  avoid pethidine it increase risk of seizures. Continuous ctg monitoring . antibiotics if she has temperature of 37.5 c. during labour .Hourly check pulse blood pressure temperature . Avoid prolonged labour  .Suitable position  in women with avasclure bone necrosis  with hip replacment                                                             

This woman should be seen jointly with a haemotologist.

To assess her, I would firstly take a history to establish the severity of her disease. I would ask about complications like the number of acute crises she has had, blood transfusion dependence and other complications like renal disease, previous thrombosis, heart disease, leg ulcers, retinal disease or stroke. I would want to know her previous obstetric history.

I would then examine her blood pressure and look for any signs of organomegaly on abdominal and chest examination. I would perform FBC, B12, Folate and Ferritin to assess anaemia, UEs to assess renal function and LFTs .I would test for red cell antibodies, especially if she had received multiple transfusions in the past. I would test her urine for proteinuria.  I would consider retinal screening and echocardiogram  if not performed within 12 months. If she has had multiple blood transfusions and is at risk of iron overload I would consider MRI of her heart. If I did not know her genotype for sickle cell disease I would send blood for karyotyping to establish whether she is HbSS or heterozygous for example HbSC. I would also want to know her partners status and offer testing to assess his genotype. This would enable us to make an informed decision regarding invasive testing in pregnancy, the role of IVF or preimplantation genetic testing.

I would check her immunisation history; she should receive annual influenza and H1N1 vaccinations and 5 yearly meningococcal, haemophillus and pneumoccal vaccinations. I would check her Rubella and Hep B status and if not immune offer vaccination. Her HIV and Syphillis status should also be tested as routine.

After assessing her I would counsel her about the effects pregnancy can have on SCD. If she is not sure what SCD is I would explain it is a problem with the structure of haemaglobin and is genetic. It is passed on in a autosomal recessive pattern and would explain what this means. In pregnancy,there is an increase in acute crises both acute pain crises and acute pulmonary syndrome. There is also an increase risk of thrombosis. I would advise about how to try and lower this risk by avoiding exertion, hypoxia and stressful situations  and to keep well hydrated. She should seek help early if she becomes unwell and I would provide her with information telling her where and how to attend for help. I would then explain the effect SCD has on pregnancy; there is an increase risk of miscarriage, peritnatal mortality, preterm delivery (both spontaneous and iatrogenic), IUGR, blood pressure problems and need for caesarean section. I would recommend she has MDT input from obstetrician and haematology throughout her pregnancy  and would be seen regularly in a consultant lead ANC (every 4 weeks) with serial growth scans (4 weekly from 24 weeks) and regular assessment of proteinuria and monthly urine cultures. I would advise hospital delivery and would aim to induce labour at 38 weeks.

I would then counsel her about the risks of passing on the condition to her baby which would depend on the status of her partner.

Finally, I would recommend she takes 5 mg Folic Acid and I would commence her on prophylactic Penicillin. I would consider Vitamin D supplements  depending on her ethnicity or other risk factors and I would recommend Aspirin from 12 weeks until delivery. I would provide her with written information about SCD.

If her disease was severe and she would benefit from further investigations or optimisation of treatment, I would recommend she used effective contraception until this was achieved .

B)

She should be managed on labour ward. The consultant, anaesthatist and neonatal team  and hematologist should be made aware that she is in labour. Close monitoring of her fluid balance should be recorded and she should be kept well hydrated and warm. Her labour should be managed in the routine way with regards to progress and assessment and CS should be performed for obstetric reasons. She should have continuous electronic monitoring. Pethidine is contraindicated as it is associated with an increase risk of seizures but regional anaesthetic is acceptable. Epidural may help to minimize her stress response and risk of acute crisis. She should be crossmatched if atypical antibodies are present, otherwise group and save is sufficient.If she has had complications of avascular necrosis of the femoral head with total hip replacement consideration as to the best position in labour is required. She should wear TEDs in labour and will require post natal LMWH, There are no contraindications to instrumental deliveries. The baby should be tested soon after delivery for SCD.