Hemoglobin blood test: what low and high hemoglobin mean

Smoking

Carbon monoxide in smoke binds hemoglobin far more tightly than oxygen, so a proportion of it is useless for oxygen transport. The kidneys sense low oxygen delivery and release erythropoietin, and the marrow makes more cells. Heavy smokers often run 1 to 2 g/dL above non-smokers; it normalizes within months of stopping.

Dehydration or hemoconcentration at the time of the draw

Not drinking before an early-morning draw, vomiting or diarrhea, heavy sweating, or a recent hard workout all reduce plasma volume and concentrate the blood. Diuretics do the same. A well-hydrated repeat usually brings the value back into range; this is the commonest explanation for an isolated, mildly high reading.

Living at altitude

Lower oxygen pressure at altitude drives erythropoietin production. Residents of Denver (1,600 m) average about 0.5 to 1 g/dL higher than at sea level, and residents above 3,000 m considerably more. Labs in high-altitude cities adjust their ranges accordingly.

Low oxygen from lung or heart disease

COPD, pulmonary fibrosis, severe asthma and congenital heart disease with right-to-left shunting all lower blood oxygen chronically, and the kidneys respond with erythropoietin. Oxygen saturation below about 92 percent on a fingertip monitor points here.

Obstructive sleep apnea and obesity hypoventilation

Repeated drops in oxygen during sleep stimulate erythropoietin. Loud snoring, witnessed pauses in breathing, morning headaches and daytime sleepiness in someone with a mildly high hemoglobin should prompt a sleep study; CPAP treatment lowers the count over months.

Testosterone and anabolic steroids

Testosterone directly stimulates red cell production and suppresses hepcidin. Erythrocytosis is the most common side effect of testosterone therapy, affecting up to 20 percent of men on injectable forms. Guidelines recommend dose reduction or pausing treatment when the hematocrit exceeds 54 percent.

Polycythemia vera

A clonal bone marrow disorder, usually driven by a JAK2 mutation, in which the marrow makes too many red cells (and often platelets and white cells) regardless of erythropoietin, which is suppressed. It typically affects people over 60, may cause itching after warm showers, facial redness, headaches and an enlarged spleen, and raises clot risk; it is treated with venesection and sometimes medication.

Erythropoietin-producing tumors and kidney conditions

Kidney cysts, kidney cancer, liver tumors, uterine fibroids and some brain tumors occasionally secrete erythropoietin. A high hemoglobin with a high (rather than low) erythropoietin level and no lung or sleep cause prompts imaging of the kidneys and liver.

Erythropoietin or androgen misuse

Erythropoietin injections or anabolic steroids used for athletic performance raise hemoglobin and hematocrit substantially and markedly increase clot risk, particularly when combined with dehydration during endurance events.

Stress or apparent erythrocytosis (Gaisbock syndrome)

A chronically reduced plasma volume, typically in middle-aged men who are overweight, hypertensive, smoke and drink, gives a persistently high hemoglobin with a normal red cell mass. Treating the risk factors is the approach.

Iron deficiency

The leading cause of anemia worldwide and in the US. Without iron the marrow cannot build hemoglobin. In menstruating women heavy periods are the usual reason; in men and post-menopausal women, slow bleeding from the gut (ulcers, polyps, bowel cancer, aspirin or NSAID use) must be excluded. Poor absorption from celiac disease, bariatric surgery or long-term acid suppression and the demands of pregnancy are the other main drivers.

Anemia of chronic disease or inflammation

Rheumatoid arthritis, inflammatory bowel disease, chronic infection, cancer, heart failure and obesity all raise hepcidin, which blocks iron release and blunts the marrow's response to erythropoietin. The anemia is usually mild (hemoglobin 9 to 11 g/dL), normocytic, with a normal or high ferritin.

Chronic kidney disease

The kidneys make erythropoietin, the hormone that tells the marrow to produce red cells. As kidney function falls below an eGFR of about 45, erythropoietin production drops and anemia develops. It is treated with iron first, then erythropoietin-stimulating agents or newer oral drugs.

Acute or recent blood loss

Surgery, trauma, a bleeding ulcer or heavy menstrual bleeding lower hemoglobin directly. Immediately after a bleed the hemoglobin may read normal because cells and plasma are lost together; it falls over the next 24 to 72 hours as plasma volume is restored.

Vitamin B12 or folate deficiency

Both are needed for DNA synthesis in developing red cells; deficiency produces large, fragile cells and a slowly developing anemia. Pernicious anemia, metformin, acid suppressants, vegan diets, alcohol and malabsorption are the common causes. B12 deficiency also damages nerves, which is why it must not be missed.

Pregnancy (dilutional)

Plasma volume rises by about 50 percent in pregnancy while red cell mass rises by only about 25 percent, so hemoglobin falls, reaching its lowest in the late second trimester. A hemoglobin of 10.5 to 11 g/dL at that stage is normal; below that, iron deficiency is usually present as well.

Medications

Chemotherapy, azathioprine, methotrexate, zidovudine, linezolid and chloramphenicol suppress the marrow directly. Aspirin, NSAIDs and anticoagulants cause blood loss. Metformin and proton pump inhibitors reduce B12 and iron absorption over years. ACE inhibitors lower hemoglobin slightly by reducing erythropoietin. Some antibiotics, dapsone and ribavirin cause hemolysis.

Thalassemia and sickle cell disease

Inherited hemoglobin disorders. Thalassemia trait causes a mild, lifelong, small-cell anemia that needs no treatment; thalassemia major and sickle cell disease cause significant anemia from early childhood. Hemoglobin electrophoresis makes the diagnosis.

Hemolysis

Red cells being destroyed faster than they are made, by antibodies (autoimmune hemolytic anemia), mechanical damage (heart valves, microangiopathy), inherited membrane or enzyme defects (spherocytosis, G6PD deficiency) or drugs. Reticulocytes, bilirubin and LDH are high and haptoglobin low.

Bone marrow disorders and hypothyroidism

Myelodysplastic syndromes, aplastic anemia, leukemia, myeloma and marrow infiltration reduce red cell production and usually affect platelets and white cells as well. An underactive thyroid causes a mild anemia that resolves with thyroid replacement.