Basics
Description
- Hemoglobin has four heme molecules composed of two alpha and two beta polypeptide chains (1).
- Sickle cell anemia (SCA) involves formation of abnormal hemoglobin S (Hb S) (1).
- Sickle cell disease (SCD) is associated with increased maternal and fetal morbidity/mortality related to maternal hemolytic anemia and vaso-oclusive multiorgan dysfunction. Risks include: (1)
- Spontaneous abortion and intrauterine fetal death (IUFD)
- Preterm labor and delivery
- Premature rupture of membranes
- Need for antepartum hospitalization
- Intrauterine growth restriction
- Low birth weight
- Maternal infection
- Maternal vaso-oclusive crisis (Acute chest syndrome is most severe.)
Epidemiology
- SCD is most common in people of African origin but may be seen in Greeks, Italians (Sicilian), Turks, Arabs, Southern Aranians, and Asian Indians in high frequency as well (1).
- Sickle cell trait is found in 1 in 12 African Americans (1).
- SCA is found in up to 1 in 600 African Americans (1).
- Some form of SCD is identified in 1 in every 300 African American newborns in the United States (1).
Etiology and Pathophysiology
- RBCs with Hb S are more prone to distortion (sickling) with decreased oxygenation.
- Abnormal RBCs aggregate within organs and small blood vessels.
- Abnormal RBCs result in increased viscosity, hemolysis, and shorter half-life.
Genetics
- A single nucleotide substitution of thymine for adenine in the Ä ▓-globin gene results in a substitution of valine for glutamic acid in the #6 position of the Ä ▓-globin polypeptide (1).
- Carrier has sickle cell trait with heterozygous Hb S, whereas homozygous Hb SS has SCA (1).
- SCA is inherited in an autosomal recessive form (1).
Risk Factors
Cold temperature, physical exertion, dehydration, and low oxygen tension (high altitude or scuba diving) may precipitate greater sickling (1). é á
Commonly Associated Conditions
- Growth and development (1)
- Retarded growth
- Skeletal changes
- Decreased life span
- Sickle cell crisis (1)
- Painful vaso-occlusive episodes of bones, abdomen, chest, and back
- Cardiovascular manifestation of hyperdynamic circulation
- Cardiomegaly
- Systolic murmurs
- Failure
- Pulmonary signs
- Infection: pneumococcus, mycoplasma, Haemophilus, Salmonella
- Vascular occlusion
- Abdominal involvement
- Painful vaso-occlusive episodes
- Hepatomegaly
- Hepatitis
- Cholecystitis
- Splenic infarction
- Bone and joint changes
- Bone marrow infarction
- Osteomyelitis: Salmonella
- Arthritis
- Genitourinary signs
- Hyposthenuria
- Hematuria
- Pyelonephritis
- Neurologic manifestations
- Vascular occlusion
- Convulsions
- Hemorrhage
- Visual disturbances
- Ocular manifestation
- Conjunctival vessel change
- Vitreous hemorrhage
- In pregnancy, also related to various forms of gestational hypertension and fetal growth restriction (2)
Diagnosis
History
- In those with SCA signs and symptoms related to hemolysis, vaso-occlusive disease, or increased susceptibility to infection
- Description of "typical crisis " Ł and need for blood transfusions
- SCA patients are usually functionally asplenic, but some have had splenectomy due to sequestration.
- Determine status of vaccinations.
- May also take family history to determine possibility of carrier state prior to testing
Physical Exam
- Routine prenatal exam should be performed (1)[A].
- Serial fetal ultrasound may be used to assess for growth restriction (1)[C].
- If sickle cell crisis is suspected, exam should be targeted to areas of suspected damage due to vaso-occlusion (1)[A].
- Fetal evaluation for well-being by antenatal testing should be done if maternal crisis suspected (1)[B].
Diagnostic Tests & Interpretation
- Hemoglobin electrophoresis to diagnose Hb S status of patients at recognized risk by ethnicity or family history (1)[A].
- Avoid use of solubility screens to evaluate for SCA or other hemoglobinopathies (1)[A].
- Serial complete blood counts to determine degree of anemia throughout pregnancy if SCA (1)[A]
- Urinalysis +/ ó ł ĺ urine culture should be performed due to increased risk of UTI and pyelonephritis (1)[A].
- Serial ultrasonography for fetal growth (1)[B]
- Antenatal testing at the discretion of the physicians (1)[B]
Treatment
General Measures
- Symptomatic treatment focused on pain control, identification and treatment of infection, and restoration of tissue oxygenation (1)[A]
- Hydration, oxygen therapy to maintain O2 sat >95% by pulse oximetry, pain management with opiates, and blood transfusion if needed (1)[A]
- Antibiotics for UTI and pulmonary infections
- Transfusion therapy if necessary; optimal hematocrit value to guide need for transfusion, and use of prophylactic transfusions still remains controversial and management should be individualized (1)[A].
- Anemia is common: Do not prescribe iron supplementation without confirmed iron deficiency by serum iron studies.
- Increased hemolysis and unnecessary iron supplementation may result in iron overload.
Pregnancy Considerations
- Women with SCD should seek preconception care (3)[B].
- Prenatal folic acid supplementation with 4 mg/day needed to support rapid turnover of RBCs (1)[A]
- Ensure complications of pregnancy are ruled out prior to assuming sickle cells crisis (1)[A].
- Offer testing for father of the baby to determine inheritance risk to the fetus and referral for genetic counseling if the father is an identified carrier (1)[A].
- Patients with homozygous sickle cell and related sickle hemoglobin variants are at high obstetric risk and require management by obstetricians/perinatologists familiar with this disease working collaboratively with hematologists (1)[C].
- Management in labor
- Routine cesarean delivery not indicated for SCA alone and should only be performed for obstetric indications (1)[A].
- Epidural analgesia is reasonable with avoidance of hypotension and hypoxemia (1)[B].
- Prenatal care and delivery should be at a center with resources to support SCA and pregnancy-related complications (3,4)[A].
Medication
First Line
Hydroxyurea é á
- May increase hemoglobin F production and lead to fewer painful crisis episodes in patients with severe SCA
- Limited data in pregnancy but known teratogenic in animals. Currently not recommended in pregnancy (1)[A].
Issues for Referral
Should consider referral to obstetrician or maternal " ôfetal medicine specialist due to risk of complications during pregnancy (1)[A] é á
Ongoing Care
Follow-up Recommendations
- Following resolution of pregnancy, important to discuss contraception and option of sterilization due to the chronic complications associated with SCD and pregnancy
- Progesterone-only methods have been suggested to prevent painful sickle cell crises.
Patient Monitoring
- Regular screening for asymptomatic bacteriuria
- May become anemic: confirm iron deficiency prior to supplementation (1)[A]
- Serial ultrasounds to monitor normal fetal growth (1)[B]
- Prenatal vitamins with addition of folic acid (1)[A]
Patient Education
Patients should be encouraged to avoid precipitating factors of painful crisis including (1)[A]: é á
- Cold environment
- Heavy physical activity
- Dehydration
- Stress
References
1.American College of Obstetricians and é áGynecologists. ACOG practice bulletin no. 78: hemoglobinopathies in pregnancy. Obstet Gynecol. 2007;109(1):229 " ô237. é á
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2.Alayed, é áN, Kezouh é áA, Oddy é áL, et al. Sickle cell disease and pregnancy outcomes: population-based study on 8.8 million births. J Perinat Med. 2014;42(4):487 " ô492. é á
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3.Barfield é áWD, Barradas é áDT, Manning é áSE, et al. Sickle cell disease and pregnancy outcomes: women of African descent. Am J Prev Med. 2014;38(4)(Suppl):S542 " ôS549. é á
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4.Sun é áPM, Wilburn é áW, Raynor é áBD, et al. Sickle cell disease in pregnancy: twenty years of experience at Grady Memorial Hospital, Atlanta, Georgia. Am J Obstet Gynecol. 2001;184(6):1127 " ô1130. é á
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Codes
ICD09
- 648.20 Anemia of mother, unspecified as to episode of care or not applicable
- 282.60 Sickle-cell disease, unspecified
- 282.5 Sickle-cell trait
ICD10
- O99.019 Anemia complicating pregnancy, unspecified trimester
- D57.1 Sickle-cell disease without crisis
- D57.3 Sickle-cell trait
SNOMED
- 27342004 Anemia of pregnancy (disorder)
- 127040003 Hereditary hemoglobinopathy disorder homozygous for hemoglobin S (disorder)
- 16402000 Sickle cell trait (disorder)