Sickle Cell Disease in Pregnancy 2003

7/31/2019 Sickle Cell Disease in Pregnancy 2003

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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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http://bloodjournal.hematologylibrary.org/content/112/10/3927/F8.large.jpg


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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.



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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



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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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Sickle Cell Disease in Pregnancy 2003