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Sickle Cell Disease in
PregnancyAli Al-Ibrahim
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Mrs. TH, 33 years old lady G3, P2+0.
Presented at 16 weeks of gestation.
Sickle Cell Disease
1-2 major painful crises per year.
On/Off Hydroxyurea Frequent Blood Transfusion.
Never admitted to ICU, no Acute ChestSyndrome
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This pregnancy is unplanned
Not on Hydroxyurea when she conceived
Husband not a carrier of Sickle Cell or otherhemoglobinopathies
Not on Folic Acid.
First pregnancy: 31 weeks IUGR, failedinduction, C-Section
Second pregnancy: IUFD while admitted at 39weeks.
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Examination showed:
Well built
Jaundice
Normal Vital Signs
No Spleenomegaly detected
Ejection Systolic Murmur
Clear Chest
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How do I monitor disease activity?
How do I prevent crises?
How do I manage crises?
How do I counsel the patient?
What investigations do I order? What to do for the pregnancy?
When to deliver the baby?
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One of the most common single gene
disorders in the world. Certain areas in sub-Saharan Africa 40-60%
of population heterozygote 1-4% of babiesborn have disease.
HbS is resistant to P. Falciparum
Sickle Cell Disease
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Is it an autosomal recessive disease?
Co-Dominance
Phenotypically complex
Association with other hemoglobinopathies
Hb SS, Hb SC, Hb SD-Punjab, Hb SO-Arab, Hb S-Thal, Hb SA
Inheritance
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Sickle Cell Disease is an extremely variable
disease. HbSS: Disease severity is variable, HbF key
factor. (Benin type HbSS, Indian Type HbSS)
The presence of another type of hemoglobin
modulates the severity (Sickle-Thal, HbSC,HbSD)
HbSA: Heterozygous individuals
Phenotypes
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HbS polymerises on deoxygenation rigidity
of erythrocyte, distorts its shape & causesstructural damage in red cell membrane.
Altered rheologic properties of cell impairsblood flow through microvasculature
haemolysis &vaso-occlusive episodes. A Normal RBCs life span is: 120 day. A typical
sickle RBCs lifespan is: 10-20 days.
Pathophysiology
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Acute Painful Episodes
Recurrent episodes of severe pain in SCD
Caused by microvascular entrapment of RBC& WBC obstruction in blood flow & organischaemia
Microvascular events episodes of explosive
pain & inflammation. May be accompanied by fever & leukocytosis+/- bone marrow necrosis with pulmonaryemboli.
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The anemia of SCA is usually a chronic
Reasonably well-compensated hemolyticanemia with an appropriate reticulocytosis.
SCD variants are less anemic with anappropriate compensated reticulocytosis
Hemolysis is the primary mechanism
Anemia
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Factors other than chronic hemolysis can
contribute to the anemia. These include: Inappropriately low serum erythropoietin
concentrations, worse in overt renal disease
Folate and/or iron deficiency resulting from
increased utilization of folate
Anemia
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Splenic sequestration crisis
Aplastic crisis
Hyperhemolytic crisis
Acute severe anemia
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ACUTE COMPLICATIONS (Triad of Acute ChestSyndrome) Infection Embolic phenomena due to bone marrow infarction and fat
emboli Infarction caused by in-situ thrombosis
A working definition of ACS is the presence of thefollowing signs and symptoms in a patient with sickle celldisease: Presence of a new pulmonary infiltrate, not due to
atelectasis, involving at least one complete lung segment Chest pain
Temperature >38.5CTachypnea, wheezing, or cough
Pulmonary Complications
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Sickle cell chronic lung disease Essentially
progressive lung fibrosis
Alterations in baseline pulmonary function:Total lung capacity and vital capacity may be
reduced. Arterial oxygen saturation (SaO2) is reduced, with
steady-state baseline values below 96 percent inan appreciable percent of patients.
Even when corrected for anemia, the diffusingcapacity for carbon monoxide (DLCO) is abnormallylow, particularly in patients with a history of theacute chest syndrome.
Pulmonary Complications
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The alveolar-arterial difference is widened both
at rest and with exercise, which most likelyresults from ventilation and perfusionabnormalities.
Mild to moderate airflow obstruction may bepresent, particularly among patients withrecurrent episodes of acute chest syndrome
Pulmonary Hypertension
Pulmonary Complications
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24% of individuals with sickle cell anemia
experienced a clinical overt stroke by age 45 Risk for neurocognitive decline and
intracranial hemorrhage
Chronic transfusion therapy is the mainstay
therapy for patients with overt centralnervous system injury
Neurologic complications
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The patient is susceptible to overwhelming
infection by encapsulated organisms,especially Streptococcus pneumoniae andHaemophilus influenzae.
Dysfunctional IgG and IgM antibody
responses Defects in alternative pathway fixation of
complement, and opsono-phagocyticdysfunction may also play a role in the
predisposition to invasive infection
Infection
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Bone infarction and necrosis
Osteonecrosis
Pulmonary fat embolism is a complication ofbone marrow infarction
Orbital compression syndrome
Osteomyelitis
Bone Complications
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Common, often unrecognized
No specific cardiomyopathy in Sickle CellDisease
Chronic Anemia leads to increased cardiacoutput and enlarged chambers
Myocardial infarction without coronarydisease
Cardiac complications
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Acute hepatic ischemia
Benign cholestasis Hepatic sequestration crisis
Transfusional iron overload
Acute and chronic cholelithiasis secondary topigmented gallstones
Acute and chronic liver disease secondary tohepatitis C virus infection (HCV) complicatingblood transfusion
Drug toxicity (eg, deferasirox, hydroxyurea)
Hepatobiliary complications
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Enuresis secondary to hyposthenuria
Painless hematuria due to papillary infarcts Proteinuria and hypertension Renal infarction, papillary necrosis, and renal colic Nephrogenic diabetes insipidus that can lead to
polyuria
Focal segmental glomerulosclerosis that can leadto end-stage renal disease Renal medullary carcinoma is a malignancy found
almost exclusively in black patients with HbSCdisease or sickle cell trait.
Renal complications
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Retinopathy: proliferative retinopathy, retinal
artery occlusion, and retinal detachment andhemorrhage
Priapism
Leg ulcers
Meningitis specifically in Children
Growth failure and delayed puberty
Psychosocial issues
Other complications
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Pre-conceptional Counseling is of paramount
importance. Combined clinic ideal
Partner testing/PND discussion
Pattern and frequency of crises
Previous CVA, infarction, VTE Analgesic dependency
Transfusion history
Echocardiography
Pregnancy and Sickle CellDisease
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Immunization status
Antibiotics prophylaxis Renal and hepatic status
Cardiopulmonary status
Eye status
High dose folic acid Past Obstetric history
Individualized care plan
More Counseling
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The safety of Hydroxyura in pregnancy is
unclear. Very large doses in animals are teratogenic,
but no teratogenicity ever reported inhumans
Follow up of children inadvertently exposed toHU shows no major anomalies orcomplications
Avoid pregnancy while on HU
If pregnant while on HU, Stop and termination
If the patient is onHydroxyurea
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If infertile, it would be ideal
If the patient can not have a termination ofpregnancy
Not suitable for majority of couples
Stressful, time-consuming, requiring high
level of commitment Only 15-20% of PGD cycles result in babies
Reduces risk rather than eliminates - roughly5% failure rate, due to limitation of single-cellanalysis
Suitability of PGD
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What happens after the diagnosis?
Dependent on the population and healthpractices
National Programs proved VERY successful
Problems with CVS/Amnio
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Non-invasive FetalDiagnosis
Isolation of fetal DNA from maternal blood small amounts of free fetal DNA present in
maternal plasma
technically easy to concentrate and analyse byPCR
limited application - dominant diseases,screening for paternal contributions to compoundheterozygous states
currently being developed at Kings College
Hospital for HbSC and HbSS
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Maternal Complications
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The maternal mortality rate was 72deaths per 100,000 in SCD comparedwith 12.7 deaths per 100,000
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Fetal complications are usually related to
compromised placental blood flow andinclude the following:
Spontaneous abortion
Intrauterine growth restriction
Increased rate of fetal death in utero
Low birthweight
Preterm delivery
Fetal Complications
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To give appropriate care to ensure healthy
mother and babyAvoidance and early treatment of crises
Low threshold for admission if unwell
Screening of partner and offer prenatal
diagnosis where indicated
Multidisciplinary Care
Goals of Antenatal Care
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Dating scan to reduce postmaturity
Uterine artery doppler (Placental Ultrasound) Growth Scan and BPP
Delivery between 38-40 weeks if notindicated earlier for obstetric reasons
Prevent dehydration
High incidence of alloimmunization
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Maternal crises are usually treated as in nonpregnantwomen, with some exceptions:
Medications such as nonsteroidal anti-inflammatory drugsand hydroxyurea can be teratogenic and arecontraindicated during pregnancy.
Iron chelation therapy should be stopped once pregnancy isrecognized.
Urinary tract and pulmonary infections should be diagnosedpromptly and treated with appropriate antibiotics.
Close monitoring of blood pressure and hemoglobinthroughout the pregnancy is necessary.
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Sickle Cell Disease patients require folate
supplementation No Iron supplementation without Iron studies
(Ferritin, Transferrin and TIBC)
Iron and Folate
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Pregnancy in sickle cell disease in the UK:
results of a multicentre survey of the effect ofprophylactic blood transfusion on maternaland fetal outcome. Howard RJ, Tuck SM,Pearson TC. Br J Obstet Gynaecol.1995;102(12):947
A randomized, controlled trial in 72 patientsfound no significant difference in perinataloutcome between the offspring of motherswith SCD treated with prophylactictransfusions and those who were not
Prophylactic Transfusion
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Prophylactic transfusion significantly reduced
the incidence of painful crises. Thisadvantage must be weighed against theassociated increases in cost, number ofhospitalizations, and risk of alloimmunization.
Prophylactic Transfusion
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Hydrate, hydrate, hydrate, hydrate, hydrate
Proper analgesia Low threshold for admission
Low threshold to start antibiotics
Painful crises in pregnancy are seldom solitary,monitor for hemolysis and acute chest syndrome
When in doubt, give blood MgSO4
Dont miss HELLP Syndrome
When painful crises strike
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