CBC Biomarkers: Hemoglobin

Optimal Takeaways

Hemoglobin is a globular protein found in red blood cells. It is the constituent responsible for carrying the vast amount of oxygen in the blood. Each hemoglobin molecule contains four atoms of iron, the element responsible for binding oxygen. A reduction in hemoglobin is a sign of anemia, blood loss, or nutrient deficiencies and must be investigated further to determine its cause. Elevated hemoglobin may be associated with dehydration, chronic disease, or testosterone therapy.

Standard Range:

Male 13.2 - 17.1 g/dL (132 - 171 g/L)

Female 11.7 - 15.5 g/dL (117 - 155 g/L)

Optimal Dx’s Optimal Range:

Male 14 - 15 g/dL (140 - 150 g/L)

Female 13.5 - 14.5 g/dL (135 - 145 g/L)

Low hemoglobin is associated with anemia, bleeding, hemolysis, hemoglobinopathies (e.g., sickle cell disease, thalassemia), neoplasia, lymphoma, lupus, sarcoidosis, kidney disease, splenomegaly, deficiency of iron, folate, B12 (Pagana 2022), B2, or B6 (Northrop-Clewes 2013), fluid overload, hemodilution of pregnancy, and inflammatory conditions and cancer (which suppress RBC production) (Fulks 2015, WHO 2011). Medications that may decrease hemoglobin include antibiotics, aspirin, indomethacin, rifampin, sulfonamides, and antineoplastic drugs (Pagana 2022).

High hemoglobin is associated with dehydration, hemoconcentration, congenital heart disease, congestive heart failure, COPD, severe burns, polycythemia vera, heavy smoking, and living at higher altitudes. Medications that may increase hemoglobin include gentamicin and methyldopa (Pagana 2022).

Increased hemoglobin levels may also be associated with aerobic fitness, androgens (Fulks 2015), testosterone therapy (Fernández-Balsells 2010), increased blood viscosity, and increased mortality (Kabat 2016, Lee 2018).

Overview

Hemoglobin is the iron-containing, oxygen-carrying protein in red blood cells that determines the efficiency of oxygen delivery to tissues. Hemoglobin is responsible for carrying 98% of oxygen in circulation. Alterations or depletion of hemoglobin can severely impair oxygen delivery to cells and tissues (Rhodes 2021).

The concentration of hemoglobin in the blood reflects the number of circulating RBCs, and levels will decrease as RBCs decrease. Hemoglobin concentration is considered when diagnosing anemia, along with other RBC indices, including total RBCs, hematocrit, mean corpuscular volume, mean corpuscular hematocrit, serum iron, serum ferritin, transferrin, and total iron binding capacity.

Hemoglobin below 13 g/dL in men and 12 g/dL in women meets the World Health Organization's definition of anemia (WHO 2011). However, anemia is not a disease itself but is instead a symptom of an underlying pathology that must be investigated.

In a comprehensive literature review of risk prediction, hemoglobin of 13 g/dL or lower in women aged 50 and older was associated with increased mortality. However, for women of menstruating age or those who are pregnant, lower hemoglobin may not necessarily be associated with an increased risk of mortality (Kabat 2016).

Hemoglobin below 13.5 g/dL prior to elective spinal surgery in elderly males was associated with significantly greater postoperative delirium, non-wound infection, hematoma, and length of hospital stay. The mean hemoglobin in the normal cohort was 14.9 mg/dL (Elsamadicy 2018).

In a prospective cohort study of 510,620 Korean adults, hemoglobin of 13-13.9 g/dL in men and 11-11.9 g/dL in women was associated with a new diagnosis (and double the risk) of end-stage renal disease (Yi 2019).

Low hemoglobin is also a risk for contrast-induced acute kidney injury (CI-AKI), a condition associated with increased mortality. A retrospective study found that those with a baseline hemoglobin of 13 g/dL or less had a significantly greater risk of developing CI-AKI, which became progressively more prevalent as hemoglobin dropped below 11.1 g/dL (Sreenivasan 2018).

Both high and low levels of hemoglobin are associated with increased overall mortality and mortality from coronary heart disease and cancer. Research suggests that a hemoglobin of 15 g/dL in men or 13.3-13.7 g/dL in post-menopausal women may represent the lowest risk value for hemoglobin. In the large prospective Malmo Cohort Study, mortality risk rose sharply when hemoglobin dropped below 14.5 g/dL in men or 12 g/dL in women or increased above 16.5 g/dL in men or 14.5 g/dL in women (Kabat 2016).

In a retrospective study of 9542 hospitalized COVID-19 patients, those with a hemoglobin of 16 g/dL or above had significantly higher mortality than those with a level of 12-14 g/dL. Researchers suggest that exceedingly high levels of hemoglobin increase the risk of systemic thrombosis (Kuno 2021).

References

Elsamadicy, Aladine A et al. “Preoperative Hemoglobin Level is Associated with Increased Health Care Use After Elective Spinal Fusion (≥3 Levels) in Elderly Male Patients with Spine Deformity.” World neurosurgery vol. 112 (2018): e348-e354. doi:10.1016/j.wneu.2018.01.046

Fernández-Balsells, M Mercè et al. “Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis.” The Journal of clinical endocrinology and metabolism vol. 95,6 (2010): 2560-75. doi:10.1210/jc.2009-2575

Fulks, Michael et al. “Hemoglobin Screening Independently Predicts All-Cause Mortality.” Journal of insurance medicine (New York, N.Y.) vol. 45,2 (2015): 75-80. doi:10.17849/insm-45-02-075-080.1   

Kabat, Geoffrey C et al. “Association of Hemoglobin Concentration With Total and Cause-Specific Mortality in a Cohort of Postmenopausal Women.” American journal of epidemiology vol. 183,10 (2016): 911-9. doi:10.1093/aje/kwv332

Kuno, Toshiki et al. “U shape association of hemoglobin level with in-hospital mortality for COVID-19 patients.” Journal of thrombosis and thrombolysis, 1–5. 2 Jul. 2021, doi:10.1007/s11239-021-02516-

Lee, Gyeongsil et al. “Association of Hemoglobin Concentration and Its Change With Cardiovascular and All-Cause Mortality.” Journal of the American Heart Association vol. 7,3 e007723. 29 Jan. 2018, doi:10.1161/JAHA.117.007723

Patel, Kushang V. 2008. “Epidemiology of Anemia in Older Adults.” Seminars in Hematology 45 (4): 210–17.

Rhodes, Carl E., et al. “Physiology, Oxygen Transport.” StatPearls, StatPearls Publishing, 19 November 2021.

Sreenivasan, Jayakumar et al. “Anemia (Hemoglobin ≤ 13 g/dL) as a Risk Factor for Contrast-Induced Acute Kidney Injury Following Coronary Angiography.” The American journal of cardiology vol. 122,6 (2018): 961-965. doi:10.1016/j.amjcard.2018.06.012

Yi, Sang-Wook et al. “Low-normal hemoglobin levels and anemia are associated with increased risk of end-stage renal disease in general populations: A prospective cohort study.” PloS one vol. 14,4 e0215920. 25 Apr. 2019, doi:10.1371/journal.pone.0215920

WHO. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Vitamin and Mineral Nutrition Information System. Geneva, World Health Organization, 2011 (WHO/NMH/NHD/MNM/11.1)