Prehospital Management of the Anemia Patient
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Anemia is the most common blood disorder worldwide, affecting an estimated one-third of the population. The most common causes of anemia worldwide include iron and folate deficiencies, thalassemia and hemoglobinopathies (genetic disorders affecting hemoglobin). In the U.S., the most common causes are iron deficiency, thalassemia and anemia of chronic disease, such as liver and kidney disease.1 This article will explore the anatomy and physiology of the blood, pathophysiology of anemia, clinical manifestations of the disease and prehospital management of complications associated with the disease. In addition, we will explore one of the more common etiologies of anemia—sickle cell disease—that EMS encounters in the prehospital environment.
Anatomy and Physiology
Anemia exists when there is a decrease in the number of red blood cells (RBCs) or a decrease in the normal quantity of hemoglobin (Hb) in the blood. Any condition that reduces the oxygen-binding ability of Hb will also result in anemia. Anemia will lead to hypoxia secondary to the blood’s reduced ability to transport oxygen. To better understand the pathophysiology of anemia and the body’s response to the disease, it is necessary to understand the RBC and normal homeostatic mechanisms of the blood.
Blood is the fluid component of the cardiovascular system, which also consists of a pump (heart) and a container (blood vessels). Blood is actually considered a connective tissue with many functions, including stabilization of body temperature, clotting to prevent fluid loss at injury sites, defense against pathogens and toxins and maintenance of proper ion concentration (i.e., K+ and Ca++) and pH of the interstitial fluids. In addition, blood is responsible for transporting oxygen, nutrients and hormones to the peripheral tissues and carrying away the waste products of metabolism for excretion from the body.
Blood is made up of a fluid portion (plasma) and formed elements (cells, cell fragments and proteins) suspended in the plasma. The formed elements consist of red blood cells (RBCs), white blood cells (WBCs) and platelets. Platelets are an important part of the clotting process, and WBCs, or leukocytes, play a role in the body’s immune system. RBCs, or erythrocytes, are the most abundant cells in the blood and play an essential role in the transport of oxygen in the blood.
The plasma and formed elements together constitute whole blood, which can be separated, or fractionated, in a laboratory. A sample of whole blood normally consists of about 46%-63% plasma and 37%-54% formed elements. Platelets and WBCs each constitute about 0.1% of the total amount of formed elements, and RBCs account for about 99.9% of the total.2 Hematocrit is the percentage of total blood volume contributed by the formed elements. As 99.9% of the formed elements are RBCs, the hematocrit is commonly thought of as the percentage of RBCs in the blood. Normal hematocrit in an adult male is about 46%; the average hematocrit in adult females is about 42%. This difference is due to the fact that male sex hormones (androgens) stimulate production of RBCs, while female sex hormones (estrogens) do not.
An RBC has a shape commonly referred to as a biconcave disc, with a thin central region and a thicker outer rim. This distinct shape allows for three very important functions of the RBC: 1) It gives the RBC a large surface area to volume ratio, allowing for rapid exchange of oxygen between the RBC and the surrounding tissues; 2) it allows RBCs to stack up and travel efficiently through blood vessels only slightly more wide than the diameter of a RBC (about 8 μm); and 3) it enables the RBC to bend and flex, allowing it to travel through capillaries as narrow as 4 μm wide.
A RBC is essentially a “scaled down” version of a cell compared to others in the body, and is streamlined to perform its primary function extremely well: delivering oxygen to the peripheral tissues. During development, RBCs lose most of the organelles, such as a nucleus, ribosomes and mitochondria, that other cells in the body have. As a result, they do not have the ability to reproduce, repair themselves or synthesize proteins or enzymes. Since RBCs can neither reproduce nor repair, they have a relatively short lifespan compared with other cells?about 120 days. In addition, without mitochondria, they obtain their energy via anaerobic respiration utilizing glucose from the surrounding plasma. Since RBCs do not require oxygen, they do not in effect “steal” oxygen that they could otherwise be transporting to tissues that require it.
What RBCs lack in organelles, they make up for with the molecule hemoglobin. Hb accounts for about 95% of all the proteins inside the RBC; each RBC contains about 280 million Hb subunits. Hb is a quartenary structure in that it contains four protein subunits, or chains, each with a single iron-containing molecule of heme, meaning that each RBC can potentially carry more than 1 billion molecules of oxygen.2 Each heme unit is able to bind with a single oxygen molecule, forming oxyhemoglobin. A heme unit without an oxygen molecule attached is called deoxyhemoglobin.
RBC production (erythropoiesis) occurs in the red bone marrow found in the vertebrae, proximal femur and humerus, pelvis, scapula, sternum and ribs. For erythropoiesis to occur normally, adequate supplies of nutrients like amino acids and vitamins (B-12, folate, iron) must be supplied to the red bone marrow. Erythropoiesis is controlled by the hormone erythropoietin (EPO), which is produced primarily in the kidneys and to a much lesser extent the liver. When released into the bloodstream it travels to the red bone marrow and stimulates the synthesis and maturation of RBCs. EPO release is stimulated by tissue hypoxia, and blood levels are elevated in many types of anemia.
The typical RBC has a life span of about 120 days, after which it is removed from circulation by phagocytotic cells which engulf and destroy damaged or old cells. Under normal conditions the rate of RBC production equals the rate of RBC destruction.
Specific etiologies of anemia are often broadly classified into the categories of increased RBC destruction, impaired RBC production, fluid overload and excessive blood loss (see Table 1).
Increased RBC Destruction
Anemias that occur secondary to increased RBC destruction are generally classified as hemolytic anemias and result from both intrinsic and extrinsic etiologies. All except one (paroxysmal nocturnal hemoglobinuria) of the intrinsic etiologies are hereditary genetic disorders that result in defects to the RBC membrane. Sickle cell anemia, which is perhaps the most common and well-known of these etiologies, is discussed in detail later in this article. Extrinsic etiologies of RBC destruction include antibody-mediated causes and trauma to red blood cells. Autoimmune hemolytic anemias occur when an autoimmune response by the body’s native antibodies (primarily IgG and IgM) target and destroy RBCs. In Rh disease, maternal antibodies cross the placenta and destroy fetal RBCs, resulting in hemolytic disease in the newborn. Trauma and destruction of RBCs can occur with extensive burns or any injury that results in disseminated intravascular coagulation (DIC), infections such as malaria, and poisonous venoms like those from a cobra or brown recluse spider.
Impaired RBC Production
Impaired RBC production can occur secondary to problems with RBC synthesis or maturation. Pure red cell aplasia is a type of anemia that results from decreased production of RBCs, but not white blood cells (WBCs), by bone marrow. Causes include autoimmune disease, viral infections, drug reactions, congenital defects or idiopathic etiologies. In aplastic anemia, both RBCs and WBCs are affected. RBC maturation can be affected by deficiencies of nutrients such as vitamin B12 (pernicious anemia), folate or iron. Renal failure can cause anemia due to decreased EPO production. Thalassemia is an autosomal recessive blood disease that results in the formation of abnormal hemoglobin molecules and decreased oxygen-carrying capacity of the affected RBCs.
Anemia during pregnancy occurs when the normal increase of a pregnant female’s blood volume has a dilutional effect on the RBCs. Iron deficiency during pregnancy is not uncommon, further contributing to anemia. In non-pregnant individuals, increased sodium or fluid intake can also result in increased fluid volume and a dilutional effect, as will any mechanism that results in an intravascular shift of fluid from the interstitial or intracellular spaces.
Blood loss resulting in anemia can be classified as acute or chronic. Acute etiologies include trauma or surgery that results in the loss of large volumes of blood. Anemia of prematurity occurs in premature newborns that tend to have insufficient RBC production and are subjected to frequent blood draws from laboratory tests. The frequent small-volume blood draws can be sufficient to remove a substantial portion of the newborn’s total blood volume. Chronic blood loss from gastrointestinal hemorrhage or excessive menstrual bleeding can also result in anemia.
Physiologic Response to Anemia
The body will respond to anemia in several ways to compensate for the reduction in oxygen-carrying capacity of the blood. The specific compensatory mechanism depends on the acuity of onset, etiology of the insult and underlying health of the patient. For example, to compensate for the hypoxia and hypotension that occur in acute anemia secondary to blood loss, the body will mount a sympathetic response that results in increased heart rate (HR) cardiac output (CO) and systemic vascular resistance (SVR), which preserves perfusion of the vital organs. If the sympathetic stimulation is unsuccessful at correcting tissue hypoxia, peripheral vasodilation will occur and hypotension (and decompensated shock) will result.
Within the kidney, juxtaglomerular cells and peritubular capillary cells release renin and EPO, respectively, in response to decreased renal perfusion or sympathetic stimulation. Release of EPO stimulates the red bone marrow to produce red blood cells. After entering the bloodstream, renin starts an enzymatic cascade known as the renin-angiotensin system. Renin first converts angiotensinogen, a plasma protein synthesized by the liver, to angiotensin I. In the lungs, angiotensin I is converted to angiotensin II, which causes vasoconstriction to arterial smooth muscle, resulting in increased SVR and blood pressure In addition, angiotensin II stimulates the release of antidiuretic hormone (ADH) by the pituitary gland and aldosterone by the adrenal cortex. ADH increases water reabsorption in the distal collecting tubules of the kidneys, reducing water loss in urine and restoring intravascular volume. Aldosterone also results in reabsorption of water in the kidney via reabsorption of sodium, further increasing intravascular volume. The end result of all of these systems acting together is an increase in HR, CO and SVR, which increases blood pressure and perfusion of peripheral tissues. In addition, intravascular fluid volume is replaced and RBCs are produced to increase the oxygen-carrying capacity of the blood. Oxygen delivery is enhanced with the improved perfusion, resulting in correction of the underlying hypoxia.
For anemia with an etiology other than hypovolemia secondary to blood loss, the normal compensatory mechanisms may be interrupted by the underlying etiology, the patient's health, or even by medications. For example, a patient with pure red cell aplasia or aplastic anemia will not be able to effectively produce RBCs to increase oxygen-carrying capacity. A patient with anemia secondary to kidney failure may not be able to effectively synthesize and secrete renin or EPO. Medications like beta blockers and angiotensin-converting enzyme (ACE) inhibitors may interfere with an increase in HR or peripheral vasoconstriction, respectively.
History and Clinical Features of Anemia
When considering the signs and symptoms characteristic of anemia, it is useful to stratify patients into one of two groups: those with chronic or non-emergent anemia and those with more acute emergent anemia.
Patients with non-emergent anemia may present with vague, non-specific complaints that make diagnosing anemia difficult on clinical grounds alone. When the progression of anemia is very slow, the patient may be able to adapt via the normal compensatory mechanisms until hemoglobin concentration is very low. Symptoms can include fatigue, weakness, dizziness, lethargy, cold intolerance, decreased exercise tolerance, dyspnea with exertion, headache and chest pain. A patient with a history of angina may report chest pain that is more severe in the presence of anemia. If questioned, the patient may describe a history of poor nutrition or vegetarianism, both of which can result in vitamin deficiency. Question the patient about any possible chronic bleeding from gastrointestinal (GI) sources, frequent epistaxis, abnormal menses, pregnancies or abortions. Inquire about any episodes of hemoptysis, epistaxis, hematuria or abnormal bruising. Clinical exam findings include pallor to the skin, nailbeds or conjunctiva. Jaundice can occur secondary to hemolytic causes of anemia as the waste products of RBC metabolism, such as bilirubin, accumulate. In addition to jaundice, an enlarged spleen (splenomegaly) may be palpable in cases of hemolytic anemia as the spleen becomes engorged with RBCs and debris. As a result of the sympathetic response to developing anemia, tachycardia, a bounding pulse and widened pulse pressure may be present.
The most common cause of acute or emergent anemia is blood loss.3 In cases of acute, emergent anemia, all of the signs and symptoms listed above may be present. In cases of trauma or extensive hemorrhage secondary to medical procedures, the source of blood loss may be obvious. In the absence of obvious sources of hemorrhage, question the patient about any history of GI bleeding evidenced by hematemesis, hematochezia or melena. Be sure to ask females about heavy menses or intercycle vaginal bleeding. Severe weakness, lethargy and dizziness may progress to near-syncope, syncope, altered mental status and loss of consciousness. In addition, dyspnea and chest pain may be present while at rest. Patients may experience exacerbations of their underlying illnesses such as cardiovascular and respiratory disease, which can also reduce their ability to compensate for acute blood loss. Tachycardia, hypotension and an increased respiratory rate will be present to a degree, dependent on the severity of blood loss and the patient’s ability to compensate. Oxygen saturation may be normal in anemic patients who are without respiratory pathology, as it is only a reflection of the percentage of hemoglobin saturated, not the amount of hemoglobin present.
Prehospital management of the anemic patient varies, depending on the clinical manifestations and complaints present. The patient should be placed in a position of comfort and be kept warm. For patients with signs or symptoms that suggest possible life-threatening conditions (hypotension, pallor, cyanosis, chest pain, dyspnea, etc), administer oxygen, initiate IV access and monitor cardiac status during transport. If the patient complains of chest pain or discomfort, perform a 12-L ECG and administer an aspirin. Oxygen should be provided via an appropriate delivery device based on the FiO2 desired. Specifics regarding IV access should be determined based on the patient’s hemodynamic status and the etiology of the anemia. For example, hypovolemic anemia secondary to a GI hemorrhage would necessitate large-bore IV access to allow for rapid fluid volume administration in the prehospital environment and possible administration of blood or blood products in the emergency department.
A Closer Look at Sickle Cell Anemia
Sickle cell disease (SCD), or sickle cell anemia, is closely related to thalassemia, in that they are both genetic disorders that interfere with the normal function of hemoglobin. With thalassemia, the genetic defect results in decreased production of hemoglobin. In sickle cell anemia (and other hemoglobinopathies) the genetic defect results in production of normal amounts of hemoglobin with altered amino acid sequences that result in deranged function and altered physical properties. SCD and its variants are characterized by the presence of a mutated form of hemoglobin, hemoglobin S (HbS), which causes RBCs to assume a sickle, or crescent shape when the cells are exposed to low oxygen levels.4 Since it is an autosomal recessive disorder, an affected individual would have to inherit two sickle cell genes—one from each parent—to have sickle cell anemia. Individuals who inherit a sickle cell gene from one parent and a normal gene from another have what is called sickle cell trait and will experience few if any complications throughout their lives.5
The sickle-cell trait is most common in people of sub-Saharan African descent and less frequent in those of Eastern Mediterranean and Middle Eastern descent.6 It is thought to have been evolutionarily selected in these populations, as it appears to offer some resistance to malaria; those with sickle cell trait tend to have milder infections compared to those without the gene. SCD is the most common inherited blood disorder in the U.S. More than two million people have the trait, and more than 72,000 have SCD. About 1 in 500 African Americans has SCD.7
The sickle-shaped cells deliver less oxygen to the peripheral tissues, and, because of their abnormal shape, can become lodged in the peripheral capillaries. In such cases, perfusion is altered and ischemia or infarct of the affected tissues can occur. The physiological changes in RBCs result in three cardinal manifestations of SCD: hemolytic anemia, vaso-occlusive crisis and multiple organ damage from microinfarcts, including the heart, bones of the skeleton, spleen and central nervous system.6
EMS providers often come in contact with SCD patients during a vaso-occlusive crisis, which can be triggered by any stressor that leads to local tissue hypoxia. Stressors include cold weather, infection, dehydration, pregnancy, alcohol intoxication, or even emotional anxiety. Once cells sickle, the resultant increase in blood viscosity, sludging of blood and microvascular obstruction all contribute to an increase in local hypoxia, which leads to a cycle of worsening sickling. Tissue hypoxia leads to ischemia and, if uncorrected, tissue and organ infarction. The associated pain is often described as deep and aching, and commonly occurs in the extremities, chest, abdomen and back.
Management of the patient with vaso-occlusive crisis includes placing the patient in a position of comfort, administration of oxygen to correct hypoxia and the cycle of sickling, and administration of IV fluids to correct dehydration and intravascular sludging. Analgesia is a major benefit to the patient with vaso-occlusive crisis and an essential therapy that should be considered early, as with any patient experiencing pain. Contact your medical control for recommendations regarding specific analgesics.
1. Hemphil RR. Anemia. In: Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7ed. McGraw-Hill, 2011.
2. Martini FH. Fundamentals of Anatomy and Physiology, 7th edition. San Francisco, CA: Pearson/Benjamin Cummings, 2006.
3. Janz TG, Hamilton GC. Chapter 119: Anemia, polycythemia, and white blood cell disorders. In: Marx: Rosen’s Emergency Medicine, 7th ed, Chapter 119. Philadelphia, PA: Mosby, 2009.
4. Benz EJ. Hemoglobinopathies. In: Harrison’s Principles of Internal Medicine, 16th ed.
5. National Heart, Lung and Blood Institute. Sickle cell anemia, key points. www.nhlbi.nih.gov/health/dci/Diseases/Sca/SCA_Summary.html.
6. Arnold JL, Besa EC. Sickle cell anemia. http://emedicine.medscape.com/article/205926-overview#a0104.
7. National Institutes of Health. Introduction to Genes and Disease: Anemia, Sickle Cell. National Center for Biotechnology Information. www.ncbi.nlm.nih.gov/books/NBK22238/.
Scott R. Snyder, BS, NREMT-P, is the EMS education manager for the San Francisco Paramedic Association in San Francisco, CA, where he is responsible for the original and continuing education of EMTs and paramedics. Scott has worked on numerous publications as an editor, contributing author and author, and enjoys presenting on both clinical and EMS educator topics. Contact him at email@example.com.
Sean M. Kivlehan, MD, MPH, NREMT-P, is an emergency medicine resident at the University of California San Francisco and a former New York City paramedic for 10 years. Contact him at firstname.lastname@example.org.
Kevin T. Collopy, BA, FP-C, CCEMT-P, NREMT-P, WEMT, is an educator, e-learning content developer and author of numerous articles and textbook chapters. He is also a flight paramedic for Ministry Spirit Medical Transportation in central Wisconsin and a lead instructor for Wilderness Medical Associates. Contact him at email@example.com.