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A Review of Anemias for the Physician Assistant Exam

The Physician Assistant Exam (PANCE) will expect you to be familiar with different types of anemia, like macrocytic anemia, normocytic anemia and aplastic anemia. Make sure you know the basics.

Vitamin deficiencies: Macrocytic anemias

Macrocytic anemias are associated with a large MCV, usually > 100 fL. The two most common causes are vitamin B12 and folate (folic acid) deficiencies.

In addition to being macrocytic anemias, vitamin B12 and folic acid deficiencies are both megaloblastic anemias. Therefore, you see hypersegmented neutrophils on a peripheral blood smear.

Vitamin B12 deficiency

B12 deficiency can affect the blood, nerve function, and yes, even bowel function. This cause of anemia is easy to test for and easier to treat.

Following are some points on the causes of anemia due to B12 deficiency:

  • B12 is found in meat, and the Western animal-based diet is built around meat, so unless someone’s a vegan, being B12 deficient due to diet is very hard.

  • Common causes of B12 deficiency include malabsorption syndromes (such as celiac sprue or tropical sprue), any prior intestinal surgeries (including gastric bypass and other stomach surgeries), inflammatory bowel disease (IBD), Diphyllobothrium latum infection, pancreatic insufficiency, and pernicious anemia. Pernicious anemia is caused by a lack of intrinsic factor, usually due to an autoimmune condition in which the body forms antibodies against the gastric parietal cells and can destroy them.

  • Any type of bacterial overgrowth syndrome in the bowel can cause malabsorption of key nutrients, including B12. You can see this with any process that can affect bowel integrity (for example, diverticulosis or colonic stricture) or bowel motility.

Here are some high-yield points concerning the symptoms, testing, and treatment of B12 deficiency:

  • Signs of B12 deficiency include weakness, diarrhea or constipation, weight loss, and feeling just awful. The deficiency can also affect the nervous system and cause numbness and tingling of the hands and feet because of its effect on the peripheral nerves.

    It can cause subacute combined degeneration, which concerns a diminishing of the positional and vibratory senses. SACD is caused by a degeneration of the lateral and posterior columns of the spinal cord. B12 deficiency can also be a cause of dementia.

  • You can diagnose B12 deficiency with a simple blood test, namely a B12 level. A normal level is > 300 pg/mL.

  • You may have a suspicion that someone with low-level normal levels of B12 has B12 deficiency. In that situation, you’d order a methylmalonic acid level and homocysteine level. In B12 deficiency, both of these would be elevated, whereas only homocysteine would be elevated in folic acid deficiency.

  • To assess for pernicious anemia as a cause of B12 deficiency, you’d order antiparietal cell antibodies and anti-intrinsic factor antibodies lab tests. Treatment with steroids may help, although this practice isn’t common.

  • No one does a Schilling test anymore. These tests are cumbersome and a pain to do.

  • Treatment for B12 deficiency is B12 supplementation. Intramuscular injections of B12 can be given, usually once a week. These injections can transition to once a month or oral supplementation. B12 can be given sublingually (under the tongue) as well.

Folic acid deficiency

You commonly see folic acid deficiency along with B12 deficiency. Common causes of folic acid deficiency include the malabsorption syndromes, including celiac disease (celiac sprue) and tropical sprue.

Here are the high-yield tips concerning folic acid deficiency:

  • A simple blood test can help you assess for folic acid deficiency.

  • Pregnant women need to take prenatal vitamins fortified with folic acid to prevent birth defects, including spina bifida.

  • Folic acid deficiency can be caused by malabsorption, excessive alcohol intake, and certain medications, such as methotrexate used for the treatment of rheumatoid arthritis or phenytoin sodium (Dilantin) and other seizure medications. Another common medication that causes folic acid deficiency is zidovudine (AZT), which is used in the treatment of HIV.

  • The treatment is folic acid supplementation. Supplements are usually given orally in doses of 400 mcg to 1,000 mcg (1 mg) daily. Because folic acid can be found in leafy greens, eating veggies is also important.

In addition to B12 and folic acid deficiencies, other causes of macrocytic anemias include alcoholism, hypothyroidism, chronic liver disease, and hemolysis.

Normocytic anemias

How about anemias with a normal MCV (76–100 fL)? In these anemias, the hemoglobin is low. They include the following:

  • Anemia secondary to kidney disease

  • Anemia of chronic disease

  • Myelophthisic anemia

Be aware of this short list in case you’re asked on the test.

Aplastic anemia

Aplastic anemia is a disorder in which the bone marrow no longer produces red blood cells. The person is also pancytopenic because the bone marrow doesn’t make platelets or white blood cells, either. In a person with aplastic anemia, the CBC shows pancytopenia and a low reticulocyte count. On presentation, the person is usually normocytic but occasionally has a large MCV.

Known causes of aplastic anemia include viruses (including hepatitis, Epstein-Barr, HIV, and parvovirus B19), medications (including antibiotics, chloramphenicol, NSAIDs, anti-seizure medications, and chemotherapy), toxin exposure (including heavy metals such as mercury), and autoimmune diseases. There can also be congenital causes of this condition. However, in many cases, the etiology of aplastic anemia isn’t clear.

One particular medical condition that’s closely associated with aplastic anemia is paroxysmal nocturnal hemoglobinuria, or PNH. It’s characterized by a hemolytic anemia and venous thrombosis. The bone marrow isn’t doing its job, and you see low white cell and low platelet counts on a CBC. People diagnosed with paroxysmal nocturnal hemoglobinuria are at risk of developing aplastic anemia later in life. People with aplastic anemia are often screened for PNH.

The treatments for aplastic anemia can include a stem cell transplant and/or immunosuppressive therapy through drugs such as cyclosporine (Neoral). Immunosuppressive medication is used especially if the cause of the aplastic anemia is likely autoimmune in nature. Often the person requires blood and platelet transfusions.

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