Posted in Med Surg

There are so many different types of anemia that it can sometimes feel overwhelming. That’s why I’m breaking down the key types in this article. Maximize your learning about anemias by reading this article and then listening to this information in episode 245 of the Straight A Nursing podcast. Tune in wherever you get your podcast fix, or straight from the website here.

Anemia overview

Anemia is defined as a “reduction in one or more of the major red blood cell (RBC) measurements”. This data is obtained through labs that provide a measure of the complete blood count, hemoglobin concentration, hematocrit and/or RBC count.

Recall that hemoglobin is the component of the red blood cell that carries oxygen. When hemoglobin levels are low, the patient has reduced oxygen carrying capacity which can lead to tissue hypoxia and the resulting symptoms such as shortness of breath. Note that a lower-than-normal hemoglobin level may be due to causes other than anemia, such as intense exercise, older age and pregnancy (due to increased plasma volume). 

Conversely, hemoglobin may be higher than normal due to a variety of reasons. These include:

  • Smoking – When an individual smokes, carbon monoxide is increased, which reduces oxygen delivery and stimulates the body to increase RBC production. 
  • Hemoconcentration – In cases of hypovolemia/dehydration, the concentration of hemoglobin will be higher. 
  • Polycythemia vera – A bone marrow disorder where the body produces too many blood cells. You can learn about it here.
  • Living at high altitude – This causes a “relative hypoxia” which leads to increased production of RBCs as a compensatory mechanism.

In order for the body to make healthy blood cells through erythropoiesis it must have sufficient amounts of iron and cobalt, key vitamins and hormones such as thyroxine. 

Classification of Anemia

Anemias can be classified in multiple ways including the mean corpuscular volume, the hemoglobin concentration and the severity of the anemia.

Mean Corpuscular Volume (MCV)

 One of the ways we classify anemia is by mean corpuscular volume, which is the size of the red blood cells. When the RBCs are of normal size, we call this “normocytic anemia.” This can be due to conditions such as blood loss, chronic kidney disease, cancer, aplastic anemia and sickle cell anemia. Essentially, the patient doesn’t have enough RBCs, and the ones they do have are normal in size and function.

When the RBCs are abnormally small, they don’t have enough hemoglobin. This is called “microcytic anemia.” Iron deficiency is the most common cause, but other causes include thalassemias, anemia of chronic disease, lead poisoning, Vitamin B6 deficiency and copper deficiency.

And when the RBCs are abnormally large, this is called “macrocytic anemia.” In macrocytic anemia the blood cells lack the nutrients they need to function normally. There are two types of macrocytic anemia. Megaloblastic macrocytic anemia occurs with Vit B6 and/or Vit B12 deficiency. Without these key nutrients, the bone marrow is unable to make healthy RBCs. Non-megaloblastic macrocytic anemia occurs in conditions where the body is unable to absorb nutrients, myelodysplastic syndrome, hypothyroidism, and alcohol use disorder. 

Concentration of hemoglobin

Another classification of anemias is by the concentration of hemoglobin in the cell. 

  • Normochromic – normal in concentration
  • Hypochromic – less in concentration
  • Hyperchromic – higher in concentration

You will often see anemia defined by the MCV and the concentration of hemoglobin. For example, anemia due to acute blood loss is “normochromic and normocytic.” Anemia due to iron deficiency is “hypochromic and microcytic” and anemia due to Vit B12 deficiency is “normochromic and macrocytic.”

Severity of Anemia

Yet another way to classify anemia is based on severity.

  • Moderate anemia is present when the hemoglobin is approximately 7 to 10 g/dL. Many patients in the clinical setting have moderate anemia with minimal or no signs and symptoms.
  • Severe anemia is present when the hemoglobin level is below 7 g/dL

Signs and Symptoms of Anemia

The general symptoms of anemia are going to be related to the lower oxygen carrying capacity of the blood and the body’s compensatory mechanisms. Note that symptoms aren’t typically evident until the anemia becomes moderate or severe. General signs and symptoms include:

  • Tachycardia, palpitations
  • Hypotension
  • Chest pain (angina)
  • Dyspnea on exertion, possibly tachypnea if severe
  • Pallor
  • Weakness, fatigue
  • Dizziness or syncope, headache

Types of Anemia

Now let’s look at the key types of anemia, their defining characteristics and treatments. 

Iron-Deficiency Anemia

Overview – Iron deficiency anemia occurs due to lower-than-normal iron levels. It is the most common type of anemia and is usually caused by blood loss. 

Signs/Symptoms – In addition to the general signs and symptoms of anemia, those with iron deficiency anemia may have koilonychia (spoon nails), restless legs, and atrophic glossitis which is a smooth, glossy tongue due to the absence of filiform papillae. This condition can cause pain, dry mouth, numbness and even loss of taste. Iron deficiency anemia often causes pica, which is the compulsion to eat non-food items (often ice, dirt, clay or starch).

Causes/Patho – Iron deficiency anemia occurs when there is not enough iron in the body. This can be due to a variety of reasons: 

  • Blood loss through conditions such as GI bleeds and heavy menstruation. Note that blood loss is the most common cause of iron deficiency anemia. 
  • Poor absorption of iron which can occur in celiac disease, Crohn’s disease, ulcerative colitis and h. Pylori infection. It can also occur after surgery of the GI tract such as weight loss surgery. In rare cases, it is due to genetic conditions.
  • Medications may cause poor iron absorption. Common culprits are medications that decrease stomach acid such as proton pump inhibitors (ex: pantoprazole), antacids, and histamine receptor blockers (ex: famotidine).
  • A lack of iron intake may cause iron deficiency anemia. This is usually in children between 9 months and 1 year of age. It is also more common in vegetarians.
  • Treatment with erythropoietin can use up the body’s stores of iron as it is stimulated to produce more red blood cells. 
  • Hemodialysis can also cause iron deficiency anemia. One study showed that patients receiving hemodialysis may lose up to 2 g of iron per year. 
  • Pregnancy can also cause iron stores to be low. During pregnancy, the body produces more red blood cells to support the developing fetus, which uses up the mother’s iron stores. For this reason, women are encouraged to take prenatal vitamins that contain iron. If not treated, there’s a higher risk for preterm labor and for the infant to have low birth weight, developmental delays and, not surprisingly, anemia.

Treatment – Treatment of iron deficiency anemia will depend on the cause. This type of anemia is most often due to blood loss so a key treatment is to identify the source of the bleeding and address it. In severe cases of blood loss, transfusions may be necessary. 

Low iron intake or malabsorption can also lead to anemia so the individual may be prescribed an iron supplement. To increase absorption, supplements should be taken with Vitamin C (such as orange juice) and should not be taken at the same time as antacids. Teach your patient about the side effects of iron supplementation which include GI upset, constipation, and a metallic taste in the mouth. Advise them to take liquid formulations with a straw to prevent tooth discoloration.

You can also teach your patient about increasing dietary iron by consuming more beans, lean red meat, eggs, fortified bread and cereal, leafy green vegetables and salmon. Cooking in a cast iron skillet can increase iron levels as well.

Severe cases may require IV iron supplementation which can be administered in an outpatient infusion clinic.

Vitamin-Deficiency Anemia

Overview – Vitamin-deficiency anemia occurs when the body doesn’t have enough Vit B12 and/or folate to make healthy red blood cells. Pernicious anemia is a type of B12-related anemia. 

Signs/Symptoms – In addition to the general signs and symptoms of anemia, your patient with vitamin-deficiency anemia may have difficulty walking, diarrhea, weight loss, changes in taste and smell and atrophic glossitis. Additionally, if left untreated, the patient can have neurological symptoms that aren’t necessarily related to the anemia but are related to the vitamin deficiency. These include memory loss, confusion, uncontrolled muscle movements or twitching, numbness/tingling, vision problems and changes in mood.

Causes/Patho – The cause of vitamin-deficiency anemia is a low level of Vit B12 and/or folate. This can be due to: 

  • Poor dietary intake of Vit B12. Since the body does not produce B12, it must be obtained through the diet. Strict vegetarian or vegan individuals are at highest risk for B12 deficiency.
  • High alcohol intake can affect the body’s ability to absorb nutrients, including B12 and folate.
  • Medications can cause vitamin deficiencies, including antibiotics, antacids, metformin (antidiabetic) and phenytoin (antiseizure).
  • Tapeworm infections can lead to lower vitamin levels.
  • Some conditions increase the risk for vitamin-deficiency anemia. These include Type 1 DM, thyroid disease, ulcerative colitis, Crohn’s disease, h. Pylori infection, chronic pancreatitis and vitiligo. Vitamin-deficiency anemia can be related to a genetic disorder as well.
  • Pernicious anemia is a specific type of vitamin deficiency anemia where B12 cannot be absorbed in the GI tract due to a lack of intrinsic factor (a protein produced by parietal cells in the stomach). This is an autoimmune condition where antibodies attack the cells making up the stomach’s mucosal lining.

Treatment – Treatment for vitamin-deficiency anemia will be focused on treating the underlying cause. 

Dietary supplements of B12 and folate may be prescribed. The individual will also be advised to increase dietary intake of these key vitamins. Good sources of B12 include eggs, fish, cheese, milk, lean red meats, chicken, yogurt and fortified cereals. Dietary sources of folate are dark leafy greens, beans, fresh fruits, whole grains, seafood, eggs, and fortified foods such as cereal.

Pernicious anemia is treated with IM B12 injections or possibly high-doses of PO B12 supplements with hopes that some of it will be absorbed. 

Severe cases of anemia may require blood transfusion.

Aplastic Anemia

Overview – Aplastic anemia is a serious condition that occurs when there is a failure of the bone marrow to produce adequate blood cells. Though it can be an inherited disorder, it typically develops in children and young adults. It is thought by many to be an autoimmune disorder. A bone marrow biopsy is necessary to diagnose aplastic anemia.

Signs/Symptoms – In addition to the general signs and symptoms of anemia, there are quite a few that are very specific to aplastic anemia. These include long-lasting infections, bruising and bleeding easily, petechiae, mucosal hemorrhage and very heavy menstrual bleeding (menorrhagia). Additionally, the defining characteristic of this type of anemia is a loss of hematopoietic stem cells. These are the cells in the bone marrow that develop into different types of blood cells. Your patient with aplastic anemia will have pancytopenia, meaning all blood cell lines will be low (RBCs, WBCs and platelets).

Causes/Patho – Aplastic anemia is due to a failure of the bone marrow. In many cases it is idiopathic, meaning there is no identifiable cause. However, it is often thought to be due to autoimmune damage of the hematopoietic stem cells. The destruction of the hematopoietic stem cells can also be due to things like radiation therapy, viral infections (HIV and hepatitis), and exposure to toxic chemicals such as pesticides, benzene and industrial chemicals. In rare cases, aplastic anemia can be inherited.

Certain medications can also cause aplastic anemia: 

  • Chemotherapy
  • Seizure medications (phenytoin, valproic acid, carbamazepine and felbamate)
  • Nifedipine – a calcium channel blocker used in the management of hypertension and angina pectoris
  • Sulfonamides such as Bactrim – a common medication used to treat infections such as UTI and bronchitis
  • Chloramphenicol – an antibiotic used to treat serious infections including meningitis and cholera
  • Azathioprine – an immunosuppressant used to prevent renal transplant rejection as well as severe rheumatoid arthritis

Treatments – The treatment for aplastic anemia is to address the underlying cause whenever possible. Patients will likely need blood transfusions and may receive injections of erythropoietin to stimulate the bone marrow to produce RBCs. Severe cases may require bone marrow transplant.

Hemolytic Anemia

Overview – In hemolytic anemia, the red blood cells are destroyed faster than the body can replace them. Hemolytic anemias are classified as intracorpuscular or extracorpuscular

  • Intracorpuscular – Defects of the red blood cell (ex: sickle cell anemia and thalassemia)
  • Extracorpuscular  – RBCs are damaged due to external factors (ex: red blood cell transfusion, malaria and the presence of microthrombi).

Signs/Symptoms – In addition to the general characteristics of anemia, signs and symptoms of hemolytic anemia include an enlarged spleen and/or an enlarged liver. Patients with very severe or untreated disease may develop heart failure, arrhythmias or an enlarged heart. 

Hemolytic anemia can come on quickly, which causes a rapid decrease in hemoglobin with an increased reticulocyte count (reticulocytes are immature red blood cells.)  The patient may also have dark urine or blood-tinged urine due to hemolysis and circulating free hemoglobin. Additionally the circulating free hemoglobin from destroyed cells can cause acute renal failure, jaundice, thrombus and disseminated intravascular coagulation. Note that mild cases may have no symptoms. 

Sickle cell anemia specifically can cause an  incredibly painful event called vaso-occlusive crisis, making pain a distinguishing symptom of this condition.

Causes/Patho – Hemolytic anemia occurs when RBCs are broken down in the spleen or bloodstream faster than they can be replaced by the body. Hemolysis stimulates the body to produce erythropoietin which, in turn, leads to the production of new RBCs. These new RBCs (reticulocytes) are immature and don’t function optimally.  

While some types of hemolytic anemia are inherited, such as sickle cell anemia and thalassemia, it can also be acquired. Some acquired causes include: 

  • Viral and bacterial infections (ex: hepatitis, cytomegalovirus, Epstein-Barr, malaria)
  • Mechanical heart valves can damage RBCs leading to hemolysis
  • Autoimmune conditions including rheumatoid arthritis and systemic lupus erythematosus
  • Bone marrow disorders and blood cancers
  • Blood transfusion reaction
  • Medications – the most common are cephalosporins (a class of antibiotic). Other culprit medications include NSAIDs, levodopa, quinidine and levofloxacin. 
  • Some tumors 
  • Venomous snake bites

As for the inherited conditions, thalassemia is a group of inherited disorders that affect the production of hemoglobin. Sickle cell anemia is another form of inherited hemolytic anemia. In sickle cell anemia, the RBCs are rigid and malformed so they don’t flow easily through microvasculature. These cells become lodged in the vessels in a very painful condition known as a vaso-occlusive crisis.

Treatment – As with the other anemias, treatment will focus on the underlying cause. Blood transfusions may be necessary and some patients will require surgical removal of the spleen, which puts them at high risk for infection. 

Specific treatments for thalassemia include blood transfusions, chelation therapy and bone marrow transplant. Chelation therapy may be needed to remove excess iron which can build up with frequent blood transfusions.

Specific treatments for sickle cell anemia include blood transfusions, pain medication during crisis, and medications that are aimed at decreasing hemolysis and the frequency of vaso-occlusive crisis. These include:

  • Hydroyxyurea (Hydrea) 
  • Voxelotor (Oxbryta) 
  • L-glutamine (Endari) 
  • Crizanlizumab (Adakveo) 

I hope this quick overview of the different types of anemia helps you understand this complex condition better so you can feel confident in school and at the bedside! Looking for more hematology topics? Explore them here!

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