Table of Contents

 

1. Abstract
2. Case Presentation
3. Introduction
4. Critical Appraisal Of The Literature
5. Etiology And Pathophysiology
6. Differential Diagnosis
   1. Decreased Red Blood Cell Production
      1. Microcytic Anemias
         • Iron-Deficiency Anemia
         • Thalassemia
         • Sideroblastic Anemia
         • Anemia Of Chronic Disease
      2. Macrocytic Anemia
      3. Normochromic And Normocytic Anemias
   2. Increased Red Blood Cell Destruction
      1. Extrinsic Alloantibodies
      2. Extrinsic Autoantibodies
      3. Extrinsic Mechanical Causes
      4. Abnormal Sequestration
7. Prehospital Care
8. Emergency Department Evaluation
9. Diagnostic Studies
10. Treatment
11. Special Circumstances
12. Controversies And Cutting Edge
13. Disposition
14. Summary
15. Risk Management Pitfalls For The Patient With Anemia
16. Time- And Cost-Effective Strategies
17. Case Conclusion
18. Clinical Pathway For The Evaluation Of Anemia
19. Tables
    1. Table 1. Normal Values
    2. Table 2. Common Causes Of Hemolysis
    3. Table 3. Red Blood Cell Indices
20. References

Abstract

Anemia is a common worldwide problem that is associated with nonspecific complaints. The initial focus for the emergency evaluation of anemia is to determine whether the problem is acute or chronic. Acute anemia is most commonly associated with blood loss, and the patient is usually symptomatic. Chronic anemia is usually well tolerated and is often discovered coincidentally. Once diagnosed, the etiology of anemia can often be determined by applying a systematic approach to its evaluation. The severity of the anemia impacts clinical outcomes, particularly in critically ill patients; however, the specific threshold to transfuse is uncertain. Evaluation of the current literature and clinical guidelines does not settle this controversy, but it does help clarify that a restrictive transfusion strategy (ie, for patients with a hemoglobin < 6-8 g/ dL) is associated with better outcomes than a more liberal transfusion strategy. Certain anemias may have well-defined treatment options (eg, sickle cell disease), but empiric use of nutritional supplements to treat anemia of uncertain etiology is discouraged.

Key words: anemia, transfusion, transfusion threshold, thalassemia

Case Presentation

A 54-year-old Hispanic male presents to the ED with the complaints of fatigue and weakness. The weakness is described as generalized, and the symptoms have been present and constant for the last 2 days. The patient denies hematemesis, hematochezia, dark-colored stools, hematuria, or other evidence of bleeding. He also denies chest or abdominal pain, dyspnea, diaphoresis, fever, or chills. The patient has not seen a doctor in the last 15 years and does not think he has any medical conditions. The only medication he has been taking is over-the-counter ibuprofen, which he has been taking daily since he injured his back at work 2 weeks ago. The patient works as a construction laborer and denies past surgeries or allergies. His vital signs are: blood pressure, 110/50 mm Hg; heart rate, 127 beats/min; respirations, 22 breaths/min; and SpO2, 97% on room air. The patient is afebrile. His skin is warm and dry but, despite being dark-skinned, he appears a little pale. On eye examination, the sclerae appear to have a yellow hue. Cardiovascular examination reveals bounding pulses, a hyperdynamic precordium, and a grade II over VI soft, systolic murmur. The remainder of the examination is unremarkable, including a rectal examination, which is negative for occult blood. An ECG shows a sinus tachycardia but is otherwise normal. A basic chemistry panel is within normal limits; however, the CBC reveals a hemoglobin of 5.4 g/dL, hematocrit of 16%, WBC of 8000, and platelet count of 154,000. Based on the presenting symptoms and signs, the patient is likely to need RBC transfusions. An IV catheter is placed, and a normal saline infusion is initiated. A 500-mL bolus of normal saline reduces the heart rate to 105 beats/min. As you write the order for the transfusion, your nurse asks, “What is the goal for the transfusion and what is the cause of the anemia?” You think, “Good questions!”

In the next room, there is a 68-year-old male who reports 1 week of increasing weakness, dyspnea on exertion, and mild chest pressure. He states the reason for coming in today is that his chest pressure was substantially worse and was associated with diaphoresis. The patient has a history of atrial fibrillation (rate controlled) and has been taking dabigatran for the past 2 years. The patient denies hematemesis but has a history of dark stools. However, he states that he was placed on iron supplementation by his primary care physician over a year ago. He denies back pain, abdominal pain, fevers, chills, or focal neurological complaints. The patient has no known drug allergy and denies past surgeries, but he does have a history of hypertension and chronic anemia in addition to atrial fibrillation. Based on his chief complaints, an ECG, CBC, BMP, PT/INR, portable chest radiograph, and 325 mg of aspirin are ordered. His vital signs are: temperature, 37°C; blood pressure, 105/65 mm Hg; heart rate, 105 beats/min; respirations, 26 breaths/min; and SpO2, 94% on room air. Overall, the patient’s examination is unremarkable except for an irregularly irregular heart rate accompanied by a soft blowing systolic murmur, pale conjunctiva, and a positive fecal occult blood test on digital rectal examination. The patient’s ECG is consistent with rate-controlled atrial fibrillation and shows ST-segment depression in the lateral leads. The CBC reveals a hemoglobin of 4.9 g/ dL and a hematocrit of 15.2%, with a normal WBC and platelet count, PT, INR, and aPTT. His basic chemistry panel reveals an elevated BUN of 64 mg/dL and a creatinine of 2.3 mg/dL. The troponin is within the normal range. A normal saline bolus of 500 cc is administered. As you call cardiology, you wonder: what is the optimal treatment for this patient’s presentation… cardiac catheterization or transfusion?

Just as you think you are getting control of the ED, a 6-month-old boy is brought in by his parents for congestion, increased work of breathing, and perioral cyanosis. The parents state that their child is taking longer to feed because he seems to be out of breath. This has been going on for several weeks, and they are unsure if their child has had a fever; they do not have a thermometer or a pediatrician. The patient was born at home with a midwife. The child’s vital signs are: blood pressure, 70/50 mm Hg; heart rate, 155 beats/min; respiratory rate, 53 breaths/min; SpO2, 92% on room air. He is afebrile. On your examination, the child is alert and responsive, but he is small for his age. He cries at appropriate aspects of the physical examination and is easily consoled by his mother. He is tachypneic with bilateral faint rales but does not demonstrate retractions or nasal flaring. The patient’s face is dysmorphic. His skin has a yellow hue with scleral icterus and perioral cyanosis and acrocyanosis. On abdominal examination, he has significant hepatosplenomegaly. The rest of his physical exam is unremarkable. A basic chemistry panel is otherwise normal; however, his CBC reveals a hemoglobin of 7.8 g/dL, with a normal WBC and platelet count. The mean corpuscular volume is 75.4 fL, mean corpuscular hemoglobin concentration is 29.1%, and red cell distribution width is 16.2%. A chest radiograph is suggestive of pulmonary congestion. Pediatrics isn’t your strength, and you wonder: why is this child anemic, and what are my next steps?

Introduction

Anemia is defined as an absolute decrease in the number of circulating red blood cells (RBCs). The diagnosis of anemia is based upon laboratory measurements of RBC indices that fall below accepted normal values. (See Table 1.) It is the most common hematologic disorder, and it is a global health problem. Worldwide, anemia affects 24.8% of the population and is more prevalent in children and pregnant women.¹ The prevalence of anemia varies depending on the RBC indices used to define it. In the Americas, anemia affects 29% of preschool children and 24% of pregnant women.1 Another age group associated with an increased incidence of anemia is the elderly (defined as age ≥ 65 years). From a 2010 prospective population-based study of 8744 elderly individuals, the prevalence of anemia was 11%.²

Data on the frequency of anemia in the emergency department (ED) are less robust. Anemia occurs in 9% to 14% of pediatric ED patients and 14% of obstetric ED patients.^3-5 Data defining the frequency of its occurrence in the general ED population is lacking. In emergency medicine, anemia is divided into 2 broad categories: acute, with potential lifethreatening complications; and chronic, with more stable clinical presentations. The focus of this issue of Emergency Medicine Practice is the ED evaluation of anemia and, more importantly, its management based on the best available evidence in the literature.

Critical Appraisal Of The Literature

A literature search of PubMed was performed using the search terms anemia, transfusion, transfusion threshold, and emergency department. Studies within the last 12 years were analyzed and included reviews, case reports, case series, and prospective randomized trials. More than 300 articles were reviewed, and 57 were selected for inclusion in this issue. In addition, data from the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews were used. The literature, much of it observational in form, shows that hemoglobin levels < 6 g/dL, especially in acute anemia, are associated with worse outcomes compared to individuals with hemoglobin levels above this value. On the other hand, the literature has also shown that the use of RBC transfusions is associated with poor outcomes. Randomized controlled studies show that using a restrictive transfusion strategy (defined as a transfusion hemoglobin threshold of < 6-8 g/ dL) is associated with better outcomes than using a liberal strategy (defined as a transfusion hemoglobin threshold of < 9-10 g/dL). However, the hemoglobin level that should be the endpoint of transfusion therapy still has not been defined in the literature.

Risk Management Pitfalls For The Patient With Anemia

1. “He didn’t say he was on warfarin, so why would I check an INR?” Many elderly patients are poor historians secondary to dementia or polypharmacy. In an elderly patient being evaluated for anemia, the INR should be considered, as elderly patients are more likely to omit mentioning prescribed medications than their younger counterparts and are more likely to develop coagulopathies from other causes.
2. “Patients always exaggerate how much bleeding there is. Most is self-limited anyway.” Bleeding (eg, from the gastrointestinal tract and upper airway) can produce a significant amount of hemorrhage that may require admission to the hospital for observation.
3. “The patient with a gastrointestinal bleed was old, but he didn’t have any chest pain, so why would I get an ECG?” Many older patients have major cardiovascular risk factors. With enough bleeding, there may be ECG changes to suggest cardiac ischemia secondary to supply/demand mismatch.
4. “The hemoglobin was 9 g/dL, so I didn’t think she needed a transfusion; I just gave her 1.5 L of normal saline for resuscitation.” By initiating too much crystalloid, there is the possibility of dilution of RBCs, causing decreased oxygen-carrying capacity and further injury (such as cardiac ischemia).
5. “The patient came in with a history of moderate gastrointestinal bleeding and a blood pressure of 90/60 mm Hg. I gave him 2 L of crystalloid. The blood pressure improved, but the bleeding restarted.” While not true for every patient, it may be more advantageous to allow a patient to be mildly hypotensive as long as they do not show signs of tissue hypoperfusion. Increasing the blood pressure may disrupt primary hemostasis as hydrostatic forces within the blood vessels increase.
6. “The vital signs are normal, so he can’t be bleeding much.” Many patients are on beta blockers or other atrioventricular nodal blocking agents that may falsely normalize the vital signs in the face of significant hemodynamic compromise.
7. “I gave the patient 4 units of packed RBCs, but she continued to bleed and deteriorate.” When patients bleed, they lose more than just RBCs. Coagulation factors and platelets are also lost as hemorrhage continues, and dilutional coagulopathies can occur. Resuscitation with fresh frozen plasma (and possibly platelets) may be required, depending on the degree of bleeding and amount of RBCs that are transfused.
8. “Since the patient’s hemoglobin was 11 g/dL with a low MCV of 78 fL, I figured the anemia was due to iron deficiency and I discharged him on iron supplements.” Although iron deficiency is the most common cause of a microcytic anemia, other causes of a low MCV need to be considered. As it turned out, this patient had thalassemia minor, which is usually asymptomatic and does not require treatment.
9. “The hemoglobin was 9.8 g/dL; since it was < 10 g/dL, I transfused the patient.” No isolated threshold hemoglobin value has been shown to correlate with outcome of RBC transfusion. The use of blood transfusions should be based on whether the patient has clinical symptoms or signs suggesting a clinically significant anemia and not on as specific number.
10. “The parents said there was blood in their baby's diaper, so I felt I needed to work up a potential coagulopathy and anemia.” In infants with a history of rectal bleeding, the first step is to confirm that what the parents saw was really blood. Even if blood is not confirmed on the rectal examination, a laboratory screening for anemia and coagulopathy should be pursued.

Tables

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study will be included in bold type following the reference, where available.

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