Learning Outcome

1. List the causes of pernicious anemia.
2. Describe the presentation of pernicious anemia.
3. Summarize the treatment of pernicious anemia.
4. Recall the nursing care plans for pernicious anemia.

Introduction

Pernicious anemia (PA) is a type of megaloblastic anemia. Megaloblastic anemia occurs due to vitamin B12 (cobalamin) deficiency. Vitamin B12 deficiency can occur via many mechanisms, but in PA, this occurs due to a lack of intrinsic factor (IF). Intrinsic factor is a glycoprotein that binds cobalamin and therefore enables its absorption at the terminal ileum. Pernicious anemia is an autoimmune disorder that occurs due to autoantibodies directed against IF or gastric parietal cells (that produce IF).[1] These antibodies lead to the destruction of gastric parietal cells or prevent the absorption of vitamin B12 by blocking IF binding sites for this vitamin. As a result, vitamin B12 cannot be absorbed from the alimentary canal, and vitamin B12-associated megaloblastic anemia occurs.

The clinical presentation of pernicious anemia is multifarious and insidious in onset. Symptoms may include fatigue, pallor, paresthesia, dyspepsia, depression, impaired memory, and even psychosis. Any number or combination of these symptoms may be present in patients with this disease, which causes a diagnostic dilemma. The diagnosis is also problematic secondary to imperfect diagnostic tools. The treatment of PA consists of life-long replacement of vitamin B12, usually via intramuscular injections. When the disease remains undiagnosed and untreated for an extended period, it may lead to neurological complications, gastric cancer, and even fatal anemia.

Nursing Diagnosis

• Fatigue
• Shortness of breath
• Lightheadedness
• Impaired sensation
• Impaired balance
• Dyspepsia

Causes

Autoimmune

Autoimmune gastritis is characterized by the destruction of gastric parietal cells and the resulting lack of intrinsic factor, which is secreted by these cells. The antibodies identified are: 

• Intrinsic factor antibodies (IFA)
• Parietal cell antibodies (PCA)

Parietal cell antibodies work against the parietal cell proton pump ATPase. The primary targets of parietal cell antibodies are the proton pump subunits: alpha and beta. They result in the destruction of the parietal cells of the gastric mucosa. Over time, atrophic gastritis with a complete lack of IF occurs, which impairs B12 absorption.[2] Intrinsic factor antibodies are of two types. Type 1 antibodies are directed against the cobalamin binding site on IF. Type 2 acts against the ileal mucosal receptor.[3] They also impair the absorption of B12 from the gut lumen resulting in PA. 

Pernicious anemia can be associated with autoimmune diseases, such as type 1 diabetes (3% to 4%), vitiligo (2% to 8%), and autoimmune thyroid disease (3% to 32%). This association has led to studies exploring HLA alleles that may be related to autoimmune gastritis. HLA-DRB1/03 and HLA-DRB1/04 alleles may predispose to autoimmune gastritis with subsequent PA.[4][1]

Genetics

Researchers have also identified congenital and juvenile forms of pernicious anemia, which are thought to follow an autosomal recessive inheritance pattern. These patients have ineffective IF secretion or abnormally formed IF secretion, which results in vitamin B12 deficiency due to malabsorption.[5]

Risk Factors

Older age is a major risk factor for PA. Some studies state that the prevalence of pernicious anemia is 0.1% in the general population which increases to 1.9% in patients aged older than 60 years.[6] All age groups are affected, yet it gets most frequently associated as a disease of adults greater than 60 years of age.[6] 

Assessment

The clinical presentation of pernicious anemia is often insidious, and symptoms may vary during its course. Patients often lack awareness of their symptoms, or they may have become used to them.

A clinician should perform a complete history, including a detailed past medical history and family history.

The clinician should conduct a complete physical exam with an emphasis on hematological, gastrointestinal, and neurological findings that are associated with this disease. Patients with PA can have symptoms due to anemia, atrophic gastritis, and/or nerve damage to the spinal cord.

• Symptoms due to anemia: Pallor, fatigue, shortness of breath, dizziness, tachycardia, lightheadedness
• Symptoms due to atrophic gastritis: Abdominal bloating, dyspepsia, loss of appetite, weight loss, and diarrhea 
• Symptoms due to spinal cord nerve damage: Paresthesia, weakness, ataxia, spasticity

Evaluation

A stepwise diagnostic approach is required for patients suspected to have PA. 

• The first step is to test for anemia.
  • Complete blood count (CBC) will demonstrate a low hemoglobin level (less than 13 g/dL for men and less than 12 g/dL for women) and an elevated mean corpuscular volume (MCV) of greater than or equal to 100 fL.
  • The peripheral blood smear will demonstrate large ovalocytes instead of normal red blood cells.
  • PA also affects the development of white blood cells, which can be seen on the peripheral smear as the presence of hyper-segmented neutrophils.
• The next step is to establish the presence of vitamin B12 deficiency.
  • Serum B12 levels under 200 pg/mL are considered deficient.
  • If this level is borderline low or normal, and suspicion for PA is high, other laboratory tests can be used to establish B12 deficiency. These include homocysteine level and methylmalonic acid level.
• The final step is to confirm the presence of autoimmunity.
  • Serum antibody testing for IFA and PCA will be required after B12 deficiency is established.
  • Patients will also undergo upper gastrointestinal endoscopy with gastric biopsy to test for the presence of atrophic gastritis.[1]

Medical Management

Patients generally receive lifelong intramuscular (IM) injections of vitamin B12 (typically at a dose of 1000 mcg per month). Initially, the injections are given daily or every other day for a week. The injections are then reduced in frequency to every week for 1 to 2 months. Life-long maintenance therapy with once-monthly injections is provided thereafter. Some patients may be able to take high-dose oral therapy for maintenance. A 1000 to 2000 mcg/day has been demonstrated to be effective, although recommendations are to always use the parenteral route in severe neurological manifestations. Some patients may opt for self-administration of IM injections during the maintenance phase. 

Nursing Management

• Check vitals
• Neurological assessments
• Administer vitamin B12 injection
• Educate the patient about the disorder and encourage medical compliance to prevent complications
• Encourage a healthy diet
• Assess gait, balance, and paresthesias
• Assist with mobility and advise fall precautions
• Educate the patient on symptoms of dyspepsia to ensure complications of atrophic gastritis and possible gastric malignancy are caught early

When To Seek Help

• Shortness of breath
• Rales
• Severe confusion
• Severe neurological deficits

Outcome Identification

With treatment, the anemia will resolve, and the prognosis will be excellent. Some neurologic symptoms, especially if present for a long time prior to diagnosis, may not resolve completely. Delayed treatment can lead to permanent neurological deficits. Most patients will experience at least some improvement in neurologic symptoms when treatment is initiated. If left untreated, severe anemia can lead to heart failure.

The risk of gastric cancer persists throughout the patient's life, even if treatment is initiated.

Medical noncompliance can lead to a recurrence of all symptoms. 

Coordination of Care

Pernicious anemia is often an insidious and under-diagnosed autoimmune disorder, which can lead to fatal complications. The most appropriate way to supervise this disorder is through interprofessional team coordination with clinicians, nurses, and pharmacists working together to ensure the patient is treated promptly. The healthcare team should strive to increase awareness of the disease and educate patients on potential complications. The nurse can intervene in a primary screening during triage by asking for signs and symptoms suggestive of neurologic or gastric complications. The most at-risk population includes people over 60 years of age. Once treated, the patients should be supervised routinely by a well-integrated interprofessional team of providers and nurses to help improve clinical outcomes for these patients.[Level 5]

Health Teaching and Health Promotion

Patients require teaching regarding the importance of life-long therapy to prevent clinical complications. They also require teaching regarding the risk of gastric cancer, despite treatment, and red flag symptoms that should prompt evaluation. These include:

• New or worsening dyspepsia
• Bloody or melanotic stools
• Unexplained weight loss
• Loss of appetite

If self-administration of B12 injections is planned, they will require teaching regarding the administration of IM injections.

Discharge Planning

• Maintain regular clinical follow up with medical providers
• Education regarding symptoms of anemia
• Education regarding red flag symptoms suggestive of gastric complications
• Encourage and emphasize compliance with life-long therapy