Sickle Cell Disease & Pregnancy
/What is sickle cell disease?
Sickle hemoglobin (HbS) results from a point mutation in the beta hemoglobin gene.
Sickle hemoglobin disease results from inheritance of at least one sickle mutation, and co-inheritance of another beta-hemoglobin modifying gene.
Classically, this is homozygosity for HbS genes (HbSS); however, sickle disease also manifests with co-inheritance of hemoglobin C (HbSC); beta-thalassemia; and others.
The disease causes significant pain crises and multi-system disease, thought to arise primarily from hemolytic anemia as well as vaso-occlusion.
Importantly from an infection perspective, splenic infarction is common early in life and thus results in a hyposplenic, immunocompromised state.
Manifestations of disease can be seen in:
Infection, particularly a susceptibility to pneumonia and a related but indistinguishable complication known as acute chest syndrome
Anemia
Pain from vaso-occlusive crisis
Stroke and myocardial infarction
Renal disease
Retinopathy (particularly with HbSC disease)
Pregnancy complications, including growth restriction, preeclampsia, stillbirth, and maternal mortality.
Who should be screened, and how?
Screening for sickle trait and sickle cell disease is now part of universal newborn screening in all 50 US states.
Screening in adults is done via hemoglobin electrophoresis.
Screening should be offered if:
A partner is known to have sickle cell disease, and the other partner does not know their carrier status, or;
A patient does not know their carrier status and wishes to know.
IMPORTANT: race/ethnicity-based screening is ineffective and problematic in identifying at-risk individuals, and thus anyone who desires testing should be offered it!
ACOG PB 78 on hemoglobinopathies in pregnancy, updated in 2007, notes that “ethnicity is not always a good predictor of risk,” though focuses to a large degree on observed ethnic group differences.
Similarly, ACOG CO 691 endorses hemoglobinopathy screening via CBC for all women, and electrophoresis for women “suspected of hemoglobinopathy based on at risk ethnicity”
Other ACOG guidance now endorses offering hemoglobinopathy screening universally, including the ACOG FAQ document for patients on carrier screening.
However, there are risks to screening that your patients should be made aware of, particularly with respect to genetic discrimination.
Health insurance markets and employer-based plans are prohibited from this through the Genetic Information Non-Discrimination Act (GINA).
These protections do not extend into:
life, disability, or long-term care insurance markets,
employers with fewer than 15 employees
US military and the TRICARE health system
the Indian Health Service
the Veterans Health Administration
Federal employees Health Benefits Program.
A quick plug here for licensed genetic counselors – they are awesome and know lots of things, as well as when your patients may benefit from different types of screening! If you have access, we totally recommend listening in on a counseling session with them!
What should be done to optimize pregnancy in the preconception period for those with sickle cell disease?
Most pregnancies can be managed successfully and result in live birth, with proper surveillance and preparation.
Partner screening is recommended if status is not known, as we previously mentioned, as the likelihood of the fetus having a hemoglobinopathy can be 0% (if partner is not a carrier) or 50% (if the partner is a carrier).
This can also help to inform approach to prenatal genetic testing and subsequent decisions for the pregnancy, if desired.
Baseline preeclampsia screening
Hypertension may be present due to renal disease in pregnant patients, and sickle nephropathy can result in significant proteinuria.
Baseline 24 hour urine protein, in addition to LFTs, BUN, and creatinine, are useful.
Ophthalmologic screening for retinal disease, which has a tendency to worsen in pregnancy
Hemoglobin and iron studies
Frequently, due to hemolysis, those with sickle disease are severely iron-overloaded and should potentially delay pregnancy until they receive chelation therapy (which cannot be given in pregnancy).
Prenatal vitamins with iron should be avoided in this particular group.
Baseline urine culture as asymptomatic bacteriuria and UTIs are more common in sickle disease, and are often more difficult to treat due to renal disease.
Pulmonary function tests can be considered, as those with particularly severe sickle cell disease are at higher risk of pulmonary embolus and reactive airway disease, in addition to having a baseline to reference for acute concern for acute chest syndrome.
Echocardiography may also be useful in severe cases to assess for underlying pulmonary hypertension.
Type and screen is often one of the most important tests:
Often due to a history of transfusion, multiple antibodies may be present on screening, which can be significant for alloimmunization of the fetus and hemolytic disease of the fetus/newborn (HDFN).
If the patient is positive for an offending antibody, this will allow for partner testing to occur to determine if a fetus may be at risk for HDFN.
Medication Management:
Hydroxyurea: is generally a mainstay of sickle cell disease management in the nonpregnant patient which works by increasing Hemoglobin F production. Gamma globulin is not affected by sickling, so decreased overall concentration of HbS
Regrettably in the peri-conception period, there is not much data regarding its use – but guidelines recommend discontinuing in the three months prior to conception, though the limited data that exists suggest there is no increase in major anomalies.
Folic acid: due to increased red cell turnover, generally there is consensus that folate supplementation should be higher in those with sickle cell disease; 4mg daily is recommended (versus the 0.4mg – 0.8mg/day recommended universally).
Iron chelators: should be discontinued for conception, as they are associated with some risk of anomalies.
Antihypertensive medications: often patients with SCD may be taking ACE-Is or ARBs, as they are renal protective. However, these are teratogenic and should be replaced with agents that are safe in pregnancy.
Pain medication: opioids are standard of care for management of severe pain in sickle cell disease. Patients who are on standing doses of opioids should be counseled with regards to risk of neonatal abstinence syndrome but should not routinely discontinue their pain medications.
Acetaminophen, non-medicinal strategies for pain control are also appropriate.
Short courses of NSAIDs may be appropriate in some circumstances, but generally are avoided in pregnancy.
Aspirin in low dose should be considered in pregnancies of patients affected by sickle cell disease to help reduce preeclampsia risk.
Anticoagulation: patients with sickle cell disease are not typically on anticoagulants just for sickle disease; though with a history of DVT/PE, they might be, and in those cases you should treat them like other patients with that history.
Absent a high-risk DVT/PE history, pharmacologic thromboprophylaxis should just be considered with any hospitalization given the high risk of clotting.
Immunizations: should be up to date, and also remember due to functional hyposplenism, additional vaccines should be considered: meningococcal, pneumonia, and H. influenzae type b are all recommended for patients with sickle cell disease.
Breastfeeding: should still be encouraged! Resumption of hydroxyurea use may be delayed with breastfeeding, as its not well studied in terms of its effects on infants.
Pain crises in pregnancy – how to manage them?
Avoid triggers for pain crises as best as possible – dehydration, hypoxia, acidosis, infection, and cold temperatures are all common triggers.
Termination of pregnancy and delivery/postpartum are two common times for pain crisis development – so appropriate hydration and monitoring are key at those time points!
With crisis, one key management point is reversal/correction of the trigger – and in or out of pregnancy, hydration is often key to that.
Oxygen therapy is often also needed due to inadequate oxygen delivery during vaso-occlusive crisis.
In crisis, pain control should be aggressive!
Opioids are the therapy of choice, if acetaminophen is not satisfactory.
The patient’s experience, and their hematologist’s knowledge of the patient, are often of significant benefit in these situations!
Keep your diagnostician hat on!
Pain crises can often be part of, or proceed significant events for patients with sickle cell disease – including DVT/PE, acute chest syndrome, or stroke.
Each complication of sickle cell disease could be a podcast of management on its own – so a multidisciplinary approach is often required to ensure good patient outcomes.
If patient or family is telling you the pain is different – listen! This can be a clue that something else is going on than usual pain crisis.
Use your hematology colleagues to guide, but often management will consist of at least CBC, chemistry panel with LFTs, and a chest xray.
Acute Chest in Pregnancy - ACS is the leading cause of death in SS disease
Often preceded by a vaso-occlusive pain episode, present with chest, arm, and leg pain consistent with a pain crisis, and follow a much more severe clinical course, often requiring mechanical ventilation, and sometimes resulting in death
Dx = radiographic evidence of consolidation + one of the following:
Temperature >38.5C
>2% decrease in O2 sat
Tachypnea
Intercostal retractions, nasal flaring, or use of accessory muscles
Chest pain
Cough
Wheezing
Rales
Treatment: a lot of this overlaps with pain crisis:
Treat pain
Fluids - prevent hypovolemia
O2
Blood transfusion - discuss with heme about simple vs exchange transfusion
Bronchodilators
Antibiotics - usually empiric to cover things like C. trachomatis, strep, and H.flu. Usually a third gen cephalosporin with a macrolide (ie. CTX + azithromycin)
Escalation of care - may need to go to the ICU!