What does a positive hemoglobin S (HbS) screen indicate and how is it managed?

Positive Hemoglobin S Screen: Interpretation and Management

A positive hemoglobin S screen indicates the presence of hemoglobin S (HbS) in the blood, which requires confirmatory testing to distinguish between sickle cell disease (SCD), sickle cell trait (SCT), or other hemoglobin variants, followed by genotype-specific management protocols. 1, 2

Initial Interpretation and Confirmatory Testing

A positive HbS screen (such as solubility testing) is not diagnostic and requires immediate confirmatory testing because:

• Solubility tests cannot quantify HbS levels or distinguish between sickle cell trait (HbAS) and sickle cell disease (HbSS, HbSC, HbSβ-thalassemia) 3
• False positives can occur with rare hemoglobin variants that migrate similarly to HbS 4
• Confirmatory testing via hemoglobin electrophoresis or high-performance liquid chromatography (HPLC) is mandatory to establish the specific genotype 1, 3

Key Diagnostic Patterns by Genotype

The specific hemoglobin pattern determines disease severity and management 1:

Genotype	Newborn Screen	Adult Hemoglobin Pattern	Hemoglobin Level	Clinical Severity
HbSS	FS	S predominant	Decreased (7-11 g/dL)	Most severe
HbSC	FSC	SC	Decreased	Moderate
HbSβ⁰-thal	FS	S predominant	Decreased	Severe
HbSβ⁺-thal	FSA	SA	Decreased to normal	Mild to moderate
HbAS (trait)	FAS	AS	Normal	Benign

Management Based on Diagnosis

If Sickle Cell Disease (HbSS, HbSC, HbSβ-thalassemia) is Confirmed

Immediate actions required 1:

• Establish 24/7 access to knowledgeable emergency care for acute complications, as common symptoms can rapidly become life-threatening 1
• Initiate prophylactic penicillin starting by 2 months of age due to early splenic dysfunction and high risk of pneumococcal sepsis 1
• Complete pneumococcal vaccination series (PCV15 or PCV20) with catch-up dosing as needed, plus meningococcal vaccines per functional asplenia guidelines 1

Fever management protocol (critical for preventing mortality) 1:

• Any temperature ≥38°C (100.4°F) requires immediate evaluation within hours, not days
• Urgent laboratory testing: CBC with reticulocyte count and blood culture
• Immediate broad-spectrum parenteral antibiotic (ceftriaxone preferred for long half-life) before leaving the facility 1
• This protocol applies even if the child appears well, as sepsis can progress rapidly

Comprehensive care components 1:

• Baseline documentation: Establish baseline CBC, reticulocyte count, pulse oximetry, and blood pressure (noting SCD patients typically have lower BP than age-matched controls) 1
• Stroke prevention screening: Transcranial Doppler ultrasonography annually starting at age 2 years for HbSS and HbSβ⁰-thalassemia 1
• Annual screening starting at age 10: Dilated fundoscopic examination for retinopathy (especially important in HbSC, which has higher retinopathy rates) and urinary protein evaluation 1
• Parental education: Daily spleen palpation at home to detect acute splenic sequestration 1

Disease-modifying therapies 1, 5:

• Hydroxyurea therapy should be offered to reduce vaso-occlusive crises, acute chest syndrome, and mortality risk 5
• Chronic transfusion therapy for stroke prevention in high-risk patients or those with abnormal transcranial Doppler studies 6
• L-glutamine may reduce crisis frequency 1

If Sickle Cell Trait (HbAS) is Confirmed

Sickle cell trait is generally benign with minimal symptoms under normal conditions 2:

• Typical hemoglobin composition: 55-65% HbA and 30-40% HbS 2
• No routine medical interventions required for asymptomatic individuals 2

Counseling points 2:

• Avoid extreme conditions: Severe dehydration, high altitude, and intense physical exertion in hot environments can precipitate symptoms 2
• Genetic counseling is essential: If both parents carry the trait, there is a 25% chance of having a child with sickle cell disease 2
• Partner testing recommended for reproductive planning 1

Special Considerations for Blood Transfusion

When transfusion is indicated (acute chest syndrome, stroke, severe anemia, pre-operative preparation) 1, 6:

• Blood must be HbS-negative and matched for ABO, full Rh, and Kell antigens to reduce alloimmunization risk 1
• Target hemoglobin ~100 g/L to avoid hyperviscosity; do not increase Hb by more than 40 g/L in a single episode 1
• Pre-operative transfusion: Simple transfusion for low-medium risk surgery; exchange transfusion for high-risk surgery or significant comorbidities, targeting HbS <30% 1

Critical Pitfalls to Avoid

• Never dismiss fever in SCD patients as "just a virus"—treat as potential sepsis until proven otherwise 1
• Do not rely on solubility testing alone for diagnosis; always confirm with electrophoresis or HPLC 3, 7
• Do not undertransfuse based on "acceptable" low hemoglobin in SCD—transfuse when clinically indicated for oxygen delivery 6
• Recognize that HbSC disease can cause significant morbidity despite being "milder" than HbSS, particularly with higher retinopathy rates 1, 8
• Pain in SCD is real and requires aggressive treatment—delays and undertreatment are common and harmful 1