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PubMed This is a summary of 10 peer-reviewed journal articles Updated
Hematology · Sickle cell-hereditary persistence of fetal hemoglobin syndrome

S-HPFH vs. Sickle Cell Trait: What Is the Difference?

At a Glance

S-HPFH and sickle cell trait are genetically distinct conditions. Sickle cell trait is a carrier state with normal adult hemoglobin. S-HPFH is a mild form of sickle cell disease with zero normal adult hemoglobin but high levels of protective fetal hemoglobin, causing very few or mild symptoms.

No, S-HPFH (Sickle cell-hereditary persistence of fetal hemoglobin syndrome) is not just a complicated name for sickle cell trait. They are two genetically different, lifelong conditions inherited from your parents. While both conditions often cause very few symptoms, they involve inheriting different combinations of genes and look distinctly different on a blood test [1][2].

The Genetic Difference

Your hemoglobin is the protein in your red blood cells that carries oxygen. The genes you inherit from your parents determine the types of hemoglobin you make.

  • Sickle Cell Trait (HbAS): A person with sickle cell trait inherits one normal adult hemoglobin gene (A) and one sickle hemoglobin gene (S) [2]. Because they have the normal “A” gene, their body makes plenty of normal hemoglobin, which prevents the sickle hemoglobin from causing problems under most circumstances [2][3].
  • S-HPFH: A person with S-HPFH inherits one sickle hemoglobin gene (S) and one gene for Hereditary Persistence of Fetal Hemoglobin (HPFH) [1][4]. The HPFH gene causes the body to keep making high levels of fetal hemoglobin (HbF) into adulthood [5]. Fetal hemoglobin is excellent at carrying oxygen and powerfully blocks sickle hemoglobin from sickling [1].

The Laboratory Test Difference

Because the genetics are different, the results of a hemoglobin blood test (like hemoglobin electrophoresis) will look completely different:

  • In Sickle Cell Trait, the blood test will show the presence of normal Hemoglobin A (typically making up more than half the hemoglobin) along with Hemoglobin S [2][6].
  • In S-HPFH, there is no gene for normal adult hemoglobin. Therefore, the blood test will show zero Hemoglobin A. Instead, it will show high levels of Hemoglobin S and very high levels of Hemoglobin F (fetal hemoglobin, usually between 15% to 30% or more) [1][4][7].

Clinical Differences

  • Sickle Cell Trait is a carrier state, not a disease [2]. People with the trait generally have a normal life expectancy and no daily symptoms, though they can rarely experience complications under extreme physical stress or dehydration [2][6].
  • S-HPFH is considered a very mild form of sickle cell disease [1][4][8]. Hearing the word “disease” can be scary if you thought you had a trait, but rest assured that people with S-HPFH generally have a normal life expectancy and excellent long-term health [1][8]. The high levels of fetal hemoglobin protect the body so well that many people with S-HPFH have no symptoms and may only be diagnosed by chance [9][10]. However, because it is a compound syndrome (having two different abnormal hemoglobin genes), they can occasionally experience mild sickle cell-related symptoms, such as joint or bone pain [1][9]. This pain is generally mild enough to be managed at home with rest, hydration, and over-the-counter pain relievers, and can sometimes be triggered by extreme temperatures, stress, or dehydration [1].

Family Planning

Understanding whether you have a trait or a mild compound syndrome ensures you have accurate information for family planning, often with the help of a genetic counselor. Because a person with S-HPFH has no normal “A” gene, they will pass either the “S” gene or the “HPFH” gene to their future children [1]. This makes it important for partners to be tested to understand the chance of having a child with a more severe form of sickle cell disease.

Summary Comparison

Feature Sickle Cell Trait (HbAS) S-HPFH
Genetics One “A” gene, one “S” gene One “S” gene, one “HPFH” gene
Lab Results Hemoglobin A is present (often >50%) Zero Hemoglobin A, high Hemoglobin F
Status Carrier state Very mild compound syndrome
Symptoms Generally asymptomatic Generally asymptomatic, occasionally mild pain

Common questions in this guide

Is S-HPFH the same thing as sickle cell trait?
No. Sickle cell trait is a carrier state where you inherit one normal hemoglobin gene and one sickle gene. S-HPFH is a mild form of sickle cell disease where you inherit a sickle gene and a gene that causes you to keep making high levels of fetal hemoglobin.
Will my lab results look different if I have S-HPFH instead of sickle cell trait?
Yes. A person with sickle cell trait will have normal adult hemoglobin (Hemoglobin A) on their blood test. A person with S-HPFH will have zero Hemoglobin A, but will show high levels of fetal hemoglobin (Hemoglobin F) instead.
Can S-HPFH cause sickle cell symptoms like pain?
Most people with S-HPFH have a normal life expectancy and no daily symptoms because the fetal hemoglobin protects them. However, some people may occasionally experience mild joint or bone pain triggered by extreme temperatures, stress, or dehydration.
How does having S-HPFH affect family planning?
Because people with S-HPFH do not have a normal hemoglobin A gene, they will pass either the sickle gene or the high fetal hemoglobin gene to their children. It is important for your partner to get tested and to consult a genetic counselor to understand the risks for your future children.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Does my lab report show any Hemoglobin A?
  2. 2.What are the exact percentages of the different types of hemoglobin in my blood?
  3. 3.Do I need to take any special precautions during extreme exercise, dehydration, or altitude changes based on my diagnosis?
  4. 4.Can you refer me to a genetic counselor to discuss how my specific hemoglobin profile affects family planning?
  5. 5.Are there any routine screenings I should be having to monitor my long-term health with this condition?

Questions For You

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Related questions

Can Children with S-HPFH Play Competitive Sports?Can You Pass Severe Sickle Cell Disease if You Have S-HPFH?Does S-HPFH Cause Sickle Cell Pain Crises?Do Fetal Hemoglobin Levels Decrease in S-HPFH?Do I Need Hydroxyurea for S-HPFH?How Long is S-HPFH Testing After an FS Screen?Is High Altitude and Flying Safe with S-HPFH?Is Pregnancy Safe with S-HPFH? Risks & PrecautionsWhat is the Life Expectancy for Someone with S-HPFH?Why Do S-HPFH Patients Need Routine Spleen Monitoring?

References

References (10)
  1. 1

    Sickle cell disease severity: an introduction.

    Pace BS, Goodman SR

    Experimental biology and medicine (Maywood, N.J.) 2016; (241(7)):677-8 doi:10.1177/1535370216641880.

    PMID: 27190296
  2. 2

    Sickle Cell Trait, Rhabdomyolysis, and Mortality among U.S. Army Soldiers.

    Nelson DA, Deuster PA, Carter R, et al.

    The New England journal of medicine 2016; (375(5)):435-42 doi:10.1056/NEJMoa1516257.

    PMID: 27518662
  3. 3

    The current state of sickle cell trait: implications for reproductive and genetic counseling.

    Pecker LH, Naik RP

    Blood 2018; (132(22)):2331-2338 doi:10.1182/blood-2018-06-848705.

    PMID: 30487130
  4. 4

    The Natural History of Hb S/Hereditary Persistence of Fetal Hemoglobin in 13 Children from the State of Minas Gerais, Brazil.

    Belisário AR, Sales RR, Silva CM, et al.

    Hemoglobin 2016; (40(3)):215-9 doi:10.3109/03630269.2016.1149076.

    PMID: 27117574
  5. 5

    Optimization of CRISPR/Cas9 Delivery to Human Hematopoietic Stem and Progenitor Cells for Therapeutic Genomic Rearrangements.

    Lattanzi A, Meneghini V, Pavani G, et al.

    Molecular therapy : the journal of the American Society of Gene Therapy 2019; (27(1)):137-150 doi:10.1016/j.ymthe.2018.10.008.

    PMID: 30424953
  6. 6

    Pregnancy in sickle cell trait: what we do and don't know.

    Wilson S, Ellsworth P, Key NS

    British journal of haematology 2020; (190(3)):328-335 doi:10.1111/bjh.16518.

    PMID: 32064587
  7. 7

    Blessing in disguise; a case of Hereditary Persistence of Fetal Hemoglobin.

    Shaukat I, Pudal A, Yassin S, et al.

    Journal of community hospital internal medicine perspectives 2018; (8(6)):380-381 doi:10.1080/20009666.2018.1536241.

    PMID: 30559951
  8. 8

    Clinical variability and molecular characterization of Hbs/Gγ (Aγδβ)0-thal and Hbs/HPFH in Indian sickle cell disease patients: AIIMS experience.

    Pandey H, Singh K, Ranjan R, et al.

    Hematology (Amsterdam, Netherlands) 2019; (24(1)):349-352 doi:10.1080/16078454.2019.1579985.

    PMID: 30777489
  9. 9

    Microcytosis Merits Evaluation: A Case Report of Hemoglobin S With Hereditary Persistence of Fetal Hemoglobin (HbS-HPFH Syndrome).

    Daniel CE, Bejjani A

    Cureus 2025; (17(2)):e78827 doi:10.7759/cureus.78827.

    PMID: 40084327
  10. 10

    A Rare Case of Multiple Bone Infarctions and Abnormal Pulmonary Function Tests in a Patient With Compound Heterozygous Hemoglobin S and Type 2 Hereditary Persistence of Fetal Hemoglobin.

    Alnaqbi KA

    Cureus 2024; (16(8)):e66395 doi:10.7759/cureus.66395.

    PMID: 39113817

This page explains the differences between S-HPFH and sickle cell trait for educational purposes. Always consult your hematologist or genetic counselor for accurate interpretation of your specific hemoglobin lab results.

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