6.1 Sickle Cell Disease

Sickle cell disease (SCD) is not one diagnosis. It is a family of β-globin disorders in which hemoglobin S (HbS) polymerizes when deoxygenated, distorting red cells into the sickle shape that gives the disease its name. CPHON items test whether you can place a child on the genotype map, explain the linked loops of polymerization, vaso-occlusion, hemolysis, and endothelial inflammation, and run the prevention program that keeps children out of the emergency department. Acute vaso-occlusive crisis (VOC), acute chest syndrome (ACS), and splenic sequestration are named pediatric hematology emergencies later in this guide. This section is the disease framework: newborn identification, prophylaxis, hydroxyurea, transfusion strategy, stroke screening, and the few acute scripts—fever, parvovirus aplastic crisis, and priapism—you must not miss at a clinic visit.

Genotypes: HbSS, HbSC, and HbS–β-thalassemia

HbSS (homozygous sickle cell anemia) is the most common severe genotype. Both β-globin alleles carry the sickle mutation, so after fetal hemoglobin (HbF) declines in infancy there is essentially no hemoglobin A (HbA). Children develop chronic hemolytic anemia, dactylitis, functional asplenia, and a high rate of VOC, ACS, and ischemic stroke if they are not on a prevention plan.

HbSC disease is compound heterozygous for HbS and hemoglobin C. Steady-state hemoglobin is often higher and hemolysis milder than in HbSS, but vaso-occlusion still occurs. Families hear “milder” and delay fever care; that is a nursing failure. HbSC is also associated with avascular necrosis and proliferative retinopathy, so organ surveillance still belongs on the calendar.

HbS–β-thalassemia splits by residual β-globin production. HbS–β0-thalassemia makes no normal β-globin from the thalassemia allele and behaves like HbSS. HbS–β+-thalassemia retains some HbA and is often closer to HbSC in severity. A 9-year-old listed only as “sickle-beta thal” is incompletely labeled until you know β0 versus β+. Trait (HbAS) is not SCD; carriers are generally asymptomatic for vaso-occlusion and need counseling, not penicillin.

Newborn screening before the first symptom

Universal newborn screening detects HbS before dactylitis or pneumococcal sepsis. Methods vary by state (HPLC, isoelectric focusing, or related assays). The screen is not the final genotype. Confirmatory hemoglobin electrophoresis or HPLC, with parental studies or DNA when needed, distinguishes SS, SC, S–β-thalassemia, and trait. An FS pattern (fetal plus sickle, no A) in a neonate is presumed HbSS or S–β0 until confirmatory testing. Penicillin should not wait for a perfect genotype letter if SCD is likely.

Teach that the infant looks well because of residual HbF. The first teaching visit is fever response, spleen palpation for sequestration teaching, and prophylaxis—not waiting for a pain crisis to “prove” the diagnosis. A 6-week-old whose screen showed FS and whose confirmatory HPLC is still pending should already be on penicillin and have a written fever number.

Pathophysiology: three linked loops

Deoxygenation, acidosis, dehydration, cold, and stasis promote HbS polymerization. Rigid cells obstruct microvasculature (vaso-occlusion). Repeated membrane injury shortens red-cell survival (hemolysis). Free plasma hemoglobin scavenges nitric oxide; endothelium activates; leukocytes and platelets adhere; a chronic inflammatory vasculopathy develops. SCD is therefore ischemia plus hemolysis plus endothelial injury, not “just a low hemoglobin.”

The spleen infarcts in early childhood in HbSS, producing functional asplenia. Encapsulated organisms, especially Streptococcus pneumoniae, become life-threatening. That single anatomic fact drives penicillin, pneumococcal vaccination, and the rule that fever is an emergency.

Prevention backbone

Penicillin prophylaxis starts in infancy after SCD is identified or strongly suspected on the newborn screen and is typically continued at least through early childhood—commonly until about age 5 years in HbSS and similarly severe genotypes—per hematology protocol. Your job is adherence, liquid-to-tablet transitions, and not improvising a stop date because the child “looks well.”

Pneumococcal vaccination uses the pediatric conjugate series (PCV) plus polysaccharide vaccine (PPSV23) on the asplenia schedule, along with influenza and meningococcal vaccines as indicated. Vaccines do not replace penicillin; penicillin does not replace vaccines.

Hydroxyurea increases HbF, which interferes with HbS polymerization. It reduces VOC, ACS, and transfusion need and is offered broadly in children, including young children, on contemporary guidelines. Nursing monitoring is a CBC (often with reticulocyte count) because myelosuppression is dose-limiting. Hold or adjust per protocol for neutropenia, thrombocytopenia, or reticulocytopenia. Teach that hydroxyurea is not a daily pain pill; benefit requires consistent dosing and laboratory follow-up. A 4-year-old with HbSS whose parent stops hydroxyurea after one pain-free month needs restart counseling and a scheduled CBC, not scolding without a plan.

Transfusion and exchange. Simple transfusion treats symptomatic severe anemia—aplastic crisis, severe sequestration after initial volume resuscitation, or an abrupt drop from baseline. Exchange transfusion raises HbA and lowers the HbS fraction without overshooting viscosity; classic indications include overt ischemic stroke and severe ACS. Chronic transfusion programs prevent recurrent stroke and treat children with abnormal transcranial Doppler (TCD) velocities. Iron accumulation is the long-term cost: ferritin trends plus MRI T2* of liver and heart, then chelation (chelator toxicities are taught with thalassemia in the next section).

Stroke screening. In HbSS and similarly severe S–β0 disease, TCD from early childhood identifies elevated cerebral arterial velocities that predict ischemic stroke. An abnormal TCD leads to a chronic transfusion discussion, not a “see you next year.” This is primary prevention, distinct from the emergency chapter on acute stroke.

Clinic scripts that are not the full emergency chapters

VOC is ischemic pain. Use age-appropriate opioids (morphine, hydromorphone, fentanyl as indicated), hydration, and incentive spirometry to reduce ACS. Avoid meperidine; its metabolite normeperidine lowers the seizure threshold—a historically documented problem in SCD. NSAIDs may be adjuncts when kidneys and gastritis risk allow; they do not replace opioids for severe VOC. Detailed PCA titration and ACS respiratory support belong in later emergency sections.

Fever in SCD is an emergency because of functional asplenia. A 3-year-old with HbSS and 38.5°C does not wait for morning clinic. Blood culture, prompt parenteral antibiotics covering pneumococcus, and a CBC with reticulocyte count are the opening moves.

Aplastic crisis from parvovirus B19 arrests erythropoiesis. Short-lived SCD red cells make hemoglobin crash while reticulocytes disappear. Transfuse as needed; flag pregnant staff for exposure counseling. This is not sequestration: the spleen is not rapidly enlarging, and the reticulocyte count is low, not high.

Priapism is corporal vaso-occlusion. Time the event, give analgesia and hydration, involve hematology and urology, and teach boys and parents to report an erection lasting hours. Prolonged ischemia risks impotence.

ACS (new infiltrate plus respiratory symptoms or fever) and acute splenic sequestration (rapidly enlarging spleen, falling hemoglobin, high reticulocytes in a young child who still has a spleen) are signposted here so you recognize them as SCD complications. Their step-by-step emergency management is not duplicated in this chapter.

The CPHON product is a family that knows the genotype, gives penicillin, keeps vaccines current, understands hydroxyurea and CBC checks, treats fever as an emergency, and has a TCD and transfusion plan when the genotype demands it.