Anemia – Diagnosis, Symptoms, and Treatment

What is Anemia?

Anemia is a medical condition characterized by low red blood cell count or mass (hemoglobin).  This can be caused by blood loss, decreased red blood cell production, or increased red cell destruction.  Some common forms of anemia include iron deficiency, vitamin B12 deficiency, thyroid disease, and liver disease.  Patients with specific blood or bone marrow cancers may also develop anemia.  Individuals with anemia often develop symptoms when their hemoglobin is very low or a rapid hemoglobin drop.

Symptoms typically include fatigue, low energy, exertional shortness of breath, and pale skin.  Severe anemia due to bleeding may lead to death, particularly in elderly individuals with chronic heart or lung disease.

What Causes Anemia?

It can be caused by a variety of conditions.  Doctors most often categorize the cause based on the size of the red blood cells on laboratory tests.  They look at a parameter called the MCV (mean corpuscular volume) – this is the average volume of red blood cells in your serum.  Individuals can have red blood cells with low, normal, or high MCV.

Low MCV (microcytic anemia) is typically caused by one of the following conditions:

• • Iron deficiency
  • Anemia of chronic disease
  • Thalassemia

• Lead poisoning

• Sideroblastic anemia – alcohol or lead intoxication

Normal MCV (normocytic anemia) is usually caused by one of the following:

• • Chronic kidney disease
  • Blood loss
  • Anemia of chronic disease
  • Hemolytic anemia

• Aplastic anemia

High MCV (macrocytic anemia) is frequently due to one of the following:

• • Folate deficiency
  • Vitamin B12 deficiency
  • Hypothyroidism
  • Alcoholism
  • Liver disease

• Multipla myeloma

• Myelodysplastic syndrome

• Medication side effects (i.e., phenytoin and methotrexate)

Anemia is caused by either blood loss, increased red cell destruction, or decreased red blood cell synthesis.

Blood loss most commonly results from:

• Gastrointestinal bleeding – stomach ulcers, varices, diverticulosis, hemorrhoids, colon cancer
• Menstrual periods in women
• Surgery
• Spontaneous bleeding in patients on oral anticoagulation
• Traumatic bleeding – motor vehicle accidents

Iron deficiency in an individual > age 50 is colon cancer until proven otherwise.

Increased red blood cell destruction may occur due to the following conditions:

• Microangiopathic hemolytic anemia – red cells get destroyed by artificial heart valves.
• Autoimmune hemolytic anemia – the body inappropriately attacks its own red cells

Decreased red blood cell synthesis can be caused by the following:

• Inadequate nutrients – folate, iron, or vitamin B12 deficiency
• Bone marrow & blood cell cancers – multiple myeloma, leukemia, myelodysplastic syndrome
• Decreased erythropoietin production – chronic kidney disease

How Common is Anemia?

It is exceedingly common in the United States and responsible for frequent primary care visits.  Common causes include iron deficiency, vitamin B12 deficiency, chronic kidney disease, gastrointestinal bleeding, and surgical blood loss.  Cases with unclear etiology or associated with other blood cell line abnormalities typically require referral to a hematology-oncology specialist.

In 2008, about 98 million people over age 80 were diagnosed - the world population was approximately 6.7 billion.  Approximately 3%-50% of elderly men and 3-40% of elderly women have anemia.  Hospitalized older adults have the highest prevalence.  Nursing home residents are also at increased risk.

Signs and Symptoms

The most common symptoms of anemia include:

• • Fatigue
  • Low energy
  • Exertional shortness of breath

• Pallor (Whiteness of the skin or mucus membranes)

Symptoms typically occur in patients with significantly reduced hemoglobin or in those who have a rapid reduction in hemoglobin levels.  Severe cases can lead to increased heart rate and confusion.  Patients with chronic lung or heart disease may develop worsening of their conditions and chest pain.

Patients may have symptoms related to the cause of their blood loss, for example:

• Gastrointestinal cancer - abdominal pain, hematemesis, hematochezia, and weight loss
• Menorrhagia – increased vaginal bleeding
• Leukemia - fever, night sweats, and weight loss
• Multiple myeloma – bone pain
• B12 deficiency – dementia, sensory loss, and impaired balance
• Trauma – pain, swelling, bruising, and hematoma formation

Signs of anemia may include increased heart rate and pale conjunctiva, mucous membranes, and skin.  Individuals taking oral anticoagulants or who have sustained trauma may have extensive ecchymosis or hematomas on physical examination.  Patients with underlying cancer may be cachectic.  Vitamin B12 deficiency is associated with a positive Romberg sign, during which the doctor asks you to maintain your balance standing with your eyes closed.

Diagnosis

Anemia is suggested based on symptoms and physical examination but is typically confirmed with a CBC (complete blood cell count).  Your doctor will also usually order a CMP (comprehensive metabolic panel), thyroid function (TSH, free T4), vitamin B12, iron studies (ferritin, iron saturation, total iron-binding capacity), and coagulation studies (PT/INR, PTT).

Other tests may include a urinalysis, heme occult stool study, reticulocyte count, haptoglobin level, SPEP and UPEP (serum and urine protein electrophoresis), and peripheral blood smear.

If you are over age 50 and have evidence of iron deficiency anemia, your doctor will likely refer you to a gastroenterologist to undergo upper endoscopy and colonoscopy.  These tests are done to rule out gastrointestinal cancer.

If you are having chest pain or difficulty breathing, your doctor may obtain a chest x-ray, EKG (electrocardiogram), and ultrasound of the heart (echocardiogram).

Anemia Treatment and Medication

The treatment of anemia is based on its severity.  Severe anemia due to blood loss often requires blood transfusion with packed red blood cells.  Less urgent forms of anemia may be treated with a variety of therapies depending on their cause.

For instance, iron deficiency anemia is typically treated with oral iron sulfate supplements such as Slow-Fe.  Patients that cannot tolerate oral formulation may receive intravenous iron therapy – DexFerrum or InFeD (iron dextran).  Individuals with vitamin B12 deficiency are typically supplemented with oral or intramuscular vitamin B12.  Patients with hypothyroidism usually require treatment with Synthroid (levothyroxine).  Patients with chronic kidney disease frequently require the use of Epogen (epoetin alfa).  Gastrointestinal ulcers typically warrant therapy with proton pump inhibitor therapy such as Prilosec (omeprazole) or Prevacid (lansoprazole).

References:

1. Beutler E, Waalen J. The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration? Blood 2006; 107:1747. - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895695/
2. Shander A. Anemia in the critically ill. Crit Care Clin 2004; 20:159. - https://www.ncbi.nlm.nih.gov/pubmed/15135458
3. Price EA, Mehra R, Holmes TH, Schrier SL. Anemia in older persons: etiology and evaluation. Blood Cells Mol Dis 2011; 46:159. - https://www.ncbi.nlm.nih.gov/pubmed/21208814