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    HGB

    HGB

    Haemoglobin: oxygen transport, reference ranges, causes and risks of anaemia and erythrocytosis.

    Haemoglobin (Hb, HGB) is the iron-containing protein inside red blood cells that carries oxygen from the lungs to every tissue and returns part of the carbon dioxide. Its concentration in blood is the main laboratory criterion for anaemia (too little) and one of the key criteria for erythrocytosis / polycythaemia (too much).

    Complete blood countOxygen transportAnaemiaPolycythaemia
    Men (adult)13.5–17.5 g/dL
    Women (adult)12.0–15.5 g/dL
    Anaemia (WHO)<13.0 men · <12.0 women
    Unit conversion1 g/dL = 10 g/L = 0.621 mmol/L

    What haemoglobin is

    Each red blood cell (erythrocyte) contains about 270 million haemoglobin molecules. Adult haemoglobin (HbA) is a tetramer of four globin chains — two α and two β — with a molecular mass of about 64.5 kDa. Every chain holds one haem group: a porphyrin ring with a single ferrous iron atom (Fe2+) that reversibly binds one molecule of oxygen. One haemoglobin molecule can therefore carry up to four O2 molecules.

    In healthy adults about 95–98 % of haemoglobin is HbA (α2β2), 2–3.5 % is HbA2 (α2δ2) and less than 1 % is foetal haemoglobin HbF (α2γ2). Inherited changes in globin genes cause the haemoglobinopathies — sickle-cell disease (HbS) and the thalassaemias — which are among the most common monogenic disorders in the world.

    Structure of haemoglobin: two alpha and two beta chains, each with a haem group binding oxygen α1β1β2α2 FeFeFeFe α-globin chain (141 amino acids) β-globin chain (146 amino acids) Haem group with Fe²⁺ 1 haem binds 1 O₂ 1 Hb molecule → up to 4 O₂ 1 g Hb binds ≈ 1.34 mL O₂ HbA = α₂β₂ (95–98 % in adults)
    Figure 1. Schematic structure of adult haemoglobin (HbA). Four globin chains each carry a haem group whose ferrous iron binds oxygen.

    How haemoglobin carries oxygen

    Oxygen binding is cooperative: when one haem binds O2, the tetramer changes shape and the remaining sites bind oxygen more easily. This gives the oxygen–haemoglobin dissociation curve its typical S-shape. In the lungs (PO2 ≈ 100 mmHg) haemoglobin is about 97–98 % saturated; in working tissues, where PO2 falls to 20–40 mmHg, it releases a large share of its oxygen. The PO2 at which haemoglobin is 50 % saturated (P50) is about 26–27 mmHg.

    Acidosis, higher CO2, fever and higher 2,3-bisphosphoglycerate shift the curve to the right (the Bohr effect), so oxygen is released more readily where it is needed. Alkalosis, hypothermia, carbon monoxide and foetal haemoglobin shift it to the left.

    The oxygen content of arterial blood depends mostly on haemoglobin:

    CaO₂ (mL O₂/dL) = 1.34 × Hb (g/dL) × SaO₂ + 0.003 × PaO₂ (mmHg)

    With Hb 15 g/dL and SaO2 98 %, arterial blood carries about 20 mL O2 per 100 mL. Halving haemoglobin halves this value, which is why anaemia reduces exercise capacity even when lung function and oxygen saturation are normal.

    Oxygen–haemoglobin dissociation curve with normal, right-shifted and left-shifted curves P₅₀ ≈ 27 mmHg 050100 04080 Partial pressure of oxygen, PO₂ (mmHg) Hb saturation, % Normal curve Right shift: ↑H⁺, ↑CO₂, ↑T° Left shift: CO, HbF, ↓T°
    Figure 2. The oxygen–haemoglobin dissociation curve. A right shift helps tissues receive oxygen; a left shift holds oxygen more tightly.

    Reference ranges

    Haemoglobin is measured as part of the complete blood count, usually photometrically after converting all forms of haemoglobin to a stable coloured compound. Reference intervals depend on age, sex, pregnancy, altitude and the laboratory, so always compare the result with the range printed on the report. Typical values are shown below.

    GroupTypical reference rangeAnaemia threshold (WHO)
    Adult men13.5–17.5 g/dL (135–175 g/L)<13.0 g/dL
    Adult non-pregnant women12.0–15.5 g/dL (120–155 g/L)<12.0 g/dL
    Pregnant women≥11.0 g/dL (2nd trimester ≥10.5)<11.0 g/dL (<10.5 in 2nd trimester)
    Children 6–23 months≈10.5–13.5 g/dL<10.5 g/dL
    Children 2–4 years≈11.0–14.0 g/dL<11.0 g/dL
    Children 5–11 years≈11.5–15.5 g/dL<11.5 g/dL
    Newborns (first days)14–22 g/dLage-specific
    Thresholds follow the WHO guideline on haemoglobin cutoffs (2024) for people living at sea level who do not smoke. Laboratory ranges may differ slightly.
    Haemoglobin scale from 4 to 22 g/dL with zones for severe, moderate and mild anaemia, normal range and high values in adult men and women MenWomen severemoderatemildnormalhigh severemoderatenormalhigh 48111317.522 48111215.522 Haemoglobin, g/dL (non-pregnant adults at sea level)
    Figure 3. Interpretation zones. Anaemia severity follows WHO (mild 11.0 to the sex-specific threshold, moderate 8.0–10.9, severe <8.0 g/dL). "High" starts above the upper reference limit; values above 16.5 g/dL in men or 16.0 g/dL in women need evaluation for polycythaemia.

    Low haemoglobin — anaemia

    Anaemia affected roughly one-third of the world's population in 2010 and is a major cause of years lived with disability, especially in women of reproductive age and young children. It is a sign, not a diagnosis: the cause must always be found. A practical first step is to look at the red-cell size (MCV) together with the reticulocyte count.

    Type (by MCV)Main causesUseful next tests
    Microcytic
    MCV <80 fL
    Iron deficiency (blood loss, poor intake, malabsorption, pregnancy), thalassaemia trait, anaemia of chronic inflammation, sideroblastic anaemiaFerritin, transferrin saturation, CRP, haemoglobin electrophoresis
    Normocytic
    MCV 80–100 fL
    Acute blood loss, chronic kidney disease (low erythropoietin), chronic inflammation, haemolysis, bone-marrow failure or infiltration, early iron deficiencyReticulocytes, creatinine/eGFR, LDH, bilirubin, haptoglobin, blood smear
    Macrocytic
    MCV >100 fL
    Vitamin B12 or folate deficiency, alcohol, liver disease, hypothyroidism, drugs (methotrexate, hydroxyurea), myelodysplastic syndromesB12, folate, TSH, liver tests, reticulocytes

    Typical symptoms of anaemia

    • Tiredness, weakness, reduced exercise tolerance
    • Shortness of breath and palpitations on exertion
    • Pale skin, lips and conjunctivae
    • Headache, dizziness, poor concentration
    • Cold hands and feet
    • Iron deficiency: brittle or spoon-shaped nails, hair loss, restless legs, craving for ice or non-food items (pica)
    • B12 deficiency: numbness, tingling, balance problems, sore tongue

    Why it matters

    • The heart compensates by beating faster and pumping more blood; in older people this can provoke angina or heart failure
    • In pregnancy, anaemia is associated with preterm birth, low birth weight and maternal complications
    • In children, iron deficiency can impair growth and cognitive development
    • In chronic heart and kidney disease, anaemia is linked to more hospital admissions and higher mortality
    • Unexplained iron deficiency in adults may be the first sign of gastrointestinal bleeding, including colorectal cancer

    High haemoglobin — erythrocytosis

    A haemoglobin above the reference range means either less plasma (relative erythrocytosis) or a true increase in red-cell mass (absolute erythrocytosis). Absolute erythrocytosis is secondary when it is driven by erythropoietin, or primary when the bone marrow produces red cells on its own, as in polycythaemia vera.

    MechanismExamples
    Relative (low plasma volume)Dehydration, vomiting and diarrhoea, diuretics, burns, "stress" erythrocytosis
    Secondary — chronic hypoxiaSmoking (carbon monoxide), living at high altitude, COPD, obstructive sleep apnoea, cyanotic congenital heart disease, high-affinity haemoglobin variants
    Secondary — excess erythropoietin or androgensKidney cysts or tumours, liver cancer, after kidney transplantation, testosterone or anabolic steroid use, erythropoietin doping; SGLT2 inhibitors cause a modest rise
    PrimaryPolycythaemia vera — a myeloproliferative neoplasm; a JAK2 mutation is found in about 95–98 % of patients

    High haemoglobin makes blood more viscous. This raises the risk of arterial and venous thrombosis — stroke, myocardial infarction, deep-vein thrombosis and pulmonary embolism. Possible symptoms are headache, dizziness, blurred vision, a red face (plethora), itching after a warm bath, burning pain in the fingers and toes (erythromelalgia) and, in polycythaemia vera, an enlarged spleen.

    What affects the result

    • Altitude: haemoglobin rises with elevation; WHO advises adjusting the cutoffs above 1000 m.
    • Smoking: carbon monoxide binds haemoglobin and raises its level; the WHO cutoffs are corrected upwards for smokers.
    • Hydration and posture: dehydration raises the value; lying down for a long time or receiving intravenous fluids lowers it. Values taken while standing can be several percent higher than lying down.
    • Pregnancy: plasma volume grows faster than red-cell mass, so haemoglobin falls physiologically, mainly in the second trimester.
    • Sampling: a tourniquet applied for a long time or a capillary (finger-prick) sample can shift the result.
    • Endurance training: athletes often have slightly lower haemoglobin because of plasma expansion ("sports anaemia"), without real iron deficiency.

    When to see a doctor

    Seek urgent medical care if

    haemoglobin is below 7–8 g/dL, falls rapidly, or is accompanied by chest pain, fainting, severe breathlessness, black or bloody stools, vomiting blood or heavy bleeding. Also seek urgent care if a high haemoglobin comes with sudden weakness of an arm or leg, speech problems, chest pain or a painful swollen leg.

    Arrange a planned visit if

    haemoglobin is repeatedly below or above the reference range, even without symptoms. The doctor will usually repeat the full blood count and add ferritin, vitamin B12, folate, kidney function and other tests depending on the findings. Do not start iron supplements without testing: they can mask bleeding and are harmful in iron overload.

    References

    1. World Health Organization. Guideline on haemoglobin cutoffs to define anaemia in individuals and populations. Geneva: WHO; 2024. ISBN 978-92-4-008854-2. who.int/publications/i/item/9789240088542
    2. Camaschella C. Iron-deficiency anemia. N Engl J Med. 2015;372(19):1832–1843. doi:10.1056/NEJMra1401038
    3. Beutler E, Waalen J. The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration? Blood. 2006;107(5):1747–1750. doi:10.1182/blood-2005-07-3046
    4. Kassebaum NJ, Jasrasaria R, Naghavi M, et al. A systematic analysis of global anemia burden from 1990 to 2010. Blood. 2014;123(5):615–624. doi:10.1182/blood-2013-06-508325
    5. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–2405. doi:10.1182/blood-2016-03-643544
    6. McMullin MF, Harrison CN, Ali S, et al. A guideline for the diagnosis and management of polycythaemia vera. A British Society for Haematology Guideline. Br J Haematol. 2019;184(2):176–191. doi:10.1111/bjh.15648

    This article is for general information and does not replace a consultation with a doctor. Reference ranges vary between laboratories; interpret your result together with a healthcare professional who knows your history.

    Published on 2 June 2019