eMedicine Specialties > Emergency Medicine > Hematology & Oncology

Anemia, Acute

Author: Daniel Kahsai, MD, FACEP, Consulting Staff, Department of Emergency Medicine, Downey Regional Medical Center; Consulting Staff Per Diem, Department of Emergency Medicine, Kaiser Permanente-Bellflower
Coauthor(s): Craig N van Roekens, MD, MBA, MPH, FACEP, Director of Emergency Services, Vassar Brothers Medical Center
Contributor Information and Disclosures

Updated: Jun 1, 2009

Introduction

Background

Anemia is characterized by a reduction in the number of circulating red blood cells (RBCs), the amount of hemoglobin, or the volume of packed red blood cells (hematocrit). Anemia is classified as acute or chronic. Acute anemia denotes a precipitous drop in the RBC population due to hemolysis or acute hemorrhage. In the emergency department (ED), acute hemorrhage is by far the most common etiology. This article also discusses other causes of acute anemia.

Pathophysiology

The function of the RBC is to deliver oxygen from the lungs to the tissues and carbon dioxide from the tissues to the lungs. This is accomplished by using hemoglobin, a tetramer protein composed of heme and globin. Anemia impairs the ability of the RBCs to transport oxygen and carbon dioxide.

Physiologic response to anemia varies according to acuity and the type of insult. Gradual onset may allow for compensatory mechanisms to take place. With anemia due to acute blood loss, a reduction in oxygen-carrying capacity occurs along with a decrease in intravascular volume, with resultant hypoxia and hypovolemia. Hypovolemia leads to hypotension, which is detected by stretch receptors in the carotid bulb, aortic arch, heart, and lungs. These receptors transmit impulses along afferent fibers of the vagus and glossopharyngeal nerves to the medulla oblongata, cerebral cortex, and pituitary gland.

In the medulla, sympathetic outflow is enhanced while parasympathetic activity is diminished. Increased sympathetic outflow leads to norepinephrine release from sympathetic nerve endings and discharge of epinephrine and norepinephrine from the adrenal medulla. Sympathetic connection to the hypothalamic nuclei increases ADH secretion from the pituitary gland. ADH increases free water reabsorption in the distal collecting tubules. In response to decreased renal perfusion, juxtaglomerular cells in the afferent arterioles release renin in the renal circulation, leading to increased angiotensin I, which is converted by angiotensin-converting enzyme to angiotensin II.

Angiotensin II has a potent pressor effect on arteriolar smooth muscle. Angiotensin II also stimulates the zona glomerulosa of the adrenal cortex to produce aldosterone. Aldosterone increases sodium reabsorption from the proximal tubules of the kidney, thus increasing intravascular volume. The primary effect of the sympathetic nervous system is to maintain perfusion to the tissues by increasing systemic vascular resistance (SVR). The augmented venous tone increases the preload and, hence, the end-diastolic volume, which increases stroke volume. Therefore, stroke volume, heart rate, and SVR all are maximized by the sympathetic nervous system. Oxygen delivery is enhanced by the increased blood flow.

In states of hypovolemic hypoxia, the increased venous tone due to sympathetic discharge is thought to dominate the vasodilator effects of hypoxia. Counterregulatory hormones (eg, glucagon, epinephrine, cortisol) are thought to shift intracellular water to the intravascular space, perhaps because of the resultant hyperglycemia. This contribution to the intravascular volume has not been clearly elucidated.

Frequency

United States

The incidence of acute anemia due to blood loss is unknown. The incidence of sickle cell trait in African Americans is about 8%. Hemophilia A affects approximately 1 in 10,000 males.

International

Sickle cell disease is common in regions of Africa, India, Saudi Arabia, and the Mediterranean basin. The thalassemias are the most common genetic blood diseases and are found in Southeast Asia and in areas where sickle cell disease is common.

Mortality/Morbidity

Mortality and morbidity are dependent on the etiology of the anemia and comorbid states. Significant causes of mortality and morbidity include the following:

• Bleeding from esophageal varices
• Approximately 30% of patients with cirrhosis die from variceal bleeding.
• Patients with Child class C have a 50% mortality rate.
• The rate of rebleeding in medically treated patients is in excess of 70%.
• Aortic rupture
• The prognosis for traumatic rupture is very poor, with approximately an 80% prehospital mortality rate. If untreated, the majority of patients die within 2 weeks.
• Nontraumatic aneurysmal rupture also has a poor prognosis and is essentially fatal if untreated.
• Immediate surgical repair still carries a high mortality rate, often greater than 80%.
• Other causes
• Ectopic pregnancy: The prognosis with prompt management is excellent, with a mortality rate of about 1-2%.
• Sickle cell anemia: Patients who are homozygous (hemoglobin SS [Hgb SS]) have the worst prognosis because they tend to have more frequent crises. Patients who are heterozygous (hemoglobin AS [HgbAS]) have sickle cell traits, and they have crises only under extreme conditions.
• Thalassemias: Patients who are homozygous for beta thalassemia (Cooley anemia) have a worse prognosis than those with any of the other thalassemias. Death among people with beta thalassemia usually occurs when they are younger than 30 years. Patients who are heterozygous for beta thalassemia have mild microcytic anemia that is not clinically significant.
• Hemophilia: About 15% of patients eventually develop inhibitors to factor VIII and may die of bleeding complications.
• Hemolytic-uremic syndrome (HUS): This carries a significant morbidity and mortality if untreated. As many as 40% of those affected die, and as many as 80% develop renal insufficiency.
• Idiopathic thrombocytopenic purpura (ITP): Patients usually respond to immunosuppression or splenectomy and have an excellent prognosis.
• Thrombotic thrombocytopenic purpura (TTP): Approximately 80-90% of patients who have TTP and undergo plasmapheresis recover completely.

Race

The role of race in mortality from acute anemia may be relevant in terms of access to early health care and the higher prevalence of violence in underserved areas. The genetically based anemias and hemophilias have a higher incidence in certain racial groups.

Sex

In the younger age groups, males have a higher incidence of acute anemia from traumatic causes. Lower GI bleeding tends to be more common in females, while upper GI bleeding predominates in males. Younger females have a higher incidence of anemia because of menstruation and pregnancy-related complications.

Age

• Acute anemia has a bimodal frequency distribution, affecting mostly young adults and those in their late fifties. Causes among young adults include trauma, menstrual and ectopic bleeding, and problems of acute hemolysis.
• In people aged 50-65 years, acute anemia is usually a result of acute blood loss in addition to a chronic anemic state. This is the case in uterine and GI bleeding. Individuals who take warfarin and nonsteroidal anti-inflammatory drugs (NSAIDs) are predisposed to bleeding. Finally, abdominal aortic aneurysmal rupture occurs in this age group.

Clinical

History

• Elicit a thorough and focused history while assessing ABCs and initiating resuscitation. In the critically ill patient, the emergency physician should attempt to obtain a focused history (per the mnemonic AMPLE: allergies; medications, including over-the-counter drugs such as NSAIDs; past medical and surgical history; last meal; and events preceding incident).
  • For noncommunicative patients, caretakers, paramedics, or primary physicians are a valuable source of information.
  • For injured patients, question paramedics about the circumstances of the accident, mechanism of the injury, initial vital signs, estimated blood loss in the field, prehospital treatment initiated, and response.
  • Patients with chronic illnesses are often knowledgeable about their condition and can provide information about prior complications and treatments. A call to their primary care physician may provide additional information and may help with disposition.
• Important specific queries should address GI and menstrual histories (where applicable).
  • Specific questions about menstrual timing, frequency, and duration of vaginal bleeding in premenopausal females are required. Denial of the possibility of pregnancy should not preclude a beta-human chorionic gonadotropin (beta-hCG) test in premenopausal females with acute anemia.
  • When concern for GI hemorrhage exists, obtain a full GI history including stool color, consistency, and frequency. Black, tarry, malodorous, and frequent stools characterize upper GI bleeding proximal to the ligament of Treitz. Maroon, lumpy, irregular stools characterize lower GI bleeding.
• Consider constitutional symptoms of chronic illnesses (eg, weight loss, night sweats, rashes, bowel changes).
• Consider family history of malignancy or hematologic problems.

Physical

• Initial evaluation
  • Monitor initial vital signs and address any abnormality. Periodic measurement of vital signs and examinations of appropriate organ systems are helpful in assessing ongoing hemorrhage.
  • In patients with multiple traumas, presume that every body cavity contains blood until investigation suggests otherwise. The chest, abdomen, pelvis, and extremities must undergo thorough physical examination with imaging, as clinically indicated.
• Cutaneous findings
  • In early hemorrhagic shock, capillary refill time may increase and the skin may feel cool to touch. With progressive shock, the skin is cold to touch, and it appears pale and mottled.
  • Flank ecchymosis (Grey-Turner sign) suggests retroperitoneal hemorrhage, while umbilical ecchymosis (Cullen sign) suggests intraperitoneal or retroperitoneal bleeding. Both are rare findings in acute states.
  • Patients with jaundice may have liver disease, hemoglobinopathies, or other forms of hemolysis. Purpura and petechiae suggest platelet disorders, and hemarthrosis may be due to hemophilia. Diffuse bleeding from intravenous sites and mucous membranes may be due to disseminated intravascular coagulation (DIC). In patients with alcoholic liver disease, spider angiomata, caput medusae, umbilical hernias, and hemorrhoids may be appreciated.
• Neurologic findings
  • Agitation may present secondary to acute blood loss.
  • When blood loss exceeds 40% of total volume, the patient may lose consciousness.
• Cardiovascular and respiratory findings
  • With chronic anemia, a hyperdynamic heart, with a prominent point of maximal impulse (PMI), a systolic flow murmur and, occasionally, an S₃, may be heard.
  • Advanced trauma life support classifies shock into 4 levels.
    • In class I (<15% blood loss), mild tachycardia may be present, but blood pressure is normal.
    • In class II (15-30% blood loss), tachycardia, tachypnea, and a decreased pulse pressure are seen.
    • Class III (30-40% blood loss) always leads to a measurable decrease in blood pressure as well as a significant tachycardia and a narrow pulse pressure.
    • Class IV (40% and greater blood loss) leads to patient demise unless prompt resuscitative measures are taken. Marked tachycardia and significantly decreased blood pressure are common findings.
    • Blood loss greater than 50% leads to loss of pulse and blood pressure.
  • Tachypnea may occur with blood loss greater than 15% of total volume (class II).
  • Patients with exacerbations of chronic anemia occasionally may present with signs and symptoms of congestive heart failure.
• Genitourinary findings: Urinary output is decreased in class III shock and is negligible in class IV shock.
• Other findings
  • Organomegaly is a common finding in patients with chronic blood disorders.
  • A palpable spleen and an enlarged hepatic inferior border (more than 3 cm below the right midclavicular costal margin) may suggest chronic anemia.

Causes

The common pathway in life-threatening acute anemia is a sudden reduction in the oxygen-carrying capacity of the blood. Depending on the etiology, this may occur with or without reduction in the intravascular volume. It is generally accepted that an acute drop in hemoglobin to a level of 7-8 g/dL is symptomatic, while levels of 4-5 g/dL may be tolerated in chronic anemia, as the body is able to gradually replace the loss of intravascular volume.

• Acute anemia due to blood loss
  • Blood loss is the most common cause of acute anemia seen in the ED.
  • Iron deficiency anemia is due to chronic slow bleeding and nutritional deficits.
  • Some life-threatening causes include traumatic injury, massive upper or lower GI hemorrhage, ruptured ectopic pregnancy, ruptured aneurysm, and DIC.
• Acute anemia due to hemoglobinopathy
  • Sickle cell anemia is caused by a point mutation on the DNA of the beta-globin chain. Valine is substituted for glutamine in the sixth position of the amino acid sequence. In response to oxidative stress, hemoglobin S polymerizes, leading to sickling and hemolysis.

• In mild sickle syndromes, the hemoglobin level is 9-11 g/dL. In more severe variants, the hemoglobin level is typically 6-8 g/dL. Patients with sickle cell anemia may have life-threatening complications during acute splenic sequestration and aplastic crisis. Although most adults have undergone autosplenectomy from repeated bouts of microocclusion in the spleen, young children can present with hemoglobin levels of 2 g/dL from sequestration of RBCs. If the patient survives the initial event, a recurrence rate of 40-50% can be expected. An aplastic crisis is due to cessation of erythropoiesis, which is caused by the human parvovirus B19.

• • Thalassemias are characterized by decreased production of globin (alpha and beta) chains. Patients with thalassemia major (homozygous for beta thalassemia) develop severe anemia that requires transfusion in the first year of life. Other forms of thalassemia may cause acute anemia during periods of oxidative stress.
• Acute anemia due to RBC enzyme abnormality
  • Glucose-6-phosphate dehydrogenase (G-6-PD) and pyruvate kinase (PK) deficiency are the 2 most common enzyme defects that cause hemolytic anemia. G-6-PD deficiency affects the pentose phosphate pathway, and PK deficiency affects the glycolytic pathway.
  • The 2 variants of G-6-PD deficiencies are African and Mediterranean. The Mediterranean variant has decreased enzyme activity in nearly all circulating RBCs. When cells are exposed to oxidant stress, a life-threatening hemolytic crisis ensues. In the African variant, only a limited portion of the RBC population is vulnerable at a given time; therefore, life-threatening complications are rare.
• Acute anemia due to congenital coagulopathy
  • Von Willebrand disease is the most common congenital bleeding disorder. The disease is characterized by a deficient or defective von Willebrand factor (VWF), which is essential for platelet adhesion. Transmission is by an autosomal dominant pattern.
  • Hemophilia A (classic hemophilia) is caused by factor VIII deficiency. Severe bleeding is common. Transmission is autosomal recessive.
  • Hemophilia B (Christmas disease) is due to a factor IX deficiency. Only males are affected.
• Acute anemia due to autoimmune hemolytic anemia
  • This group of acquired hemolytic anemias may be life threatening. The disorder is seen in association with autoimmune diseases (eg, lupus, certain types of lymphomas and leukemias), or it may be drug induced. In about 50% of cases, no identifiable etiology is found.
  • Hemolysis is caused when immunoglobulin G (IgG) autoantibody binds to RBCs, which then lose part of the plasma membrane because of the interaction of the autoantibodies with macrophages. With loss of their plasma membrane, affected RBCs become spherocytes.
• Acute anemias due to an acquired platelet disorder
  • Thrombotic thrombocytopenic purpura (TTP) is rare. Arteriolar lesions with localized platelet thrombi and fibrin deposits lead to thrombocytopenia and hemolytic anemia. The tissue hypoxia from occlusion of the vessels in the affected organ causes the symptoms of TTP. However, the cause of the occlusion remains unknown. Microangiopathic hemolytic anemia, thrombocytopenia, normal coagulation test, and renal and neurologic abnormalities should lead the physician to the diagnosis.
  • Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease often precipitated by viral infections. IgG autoantibodies bind to platelets, which then undergo destruction in the spleen. The platelet count may fall as low as 10,000/µL, leading to bleeding.
• Acute anemia due to the hemolytic-uremic syndrome
  • This type of anemia is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. It is similar to TTP, but arteriolar lesions are limited to the kidney. In children, the disease is sometimes seen after diarrheal illness caused by Escherichia coli, Shigella and Salmonella species, or viral gastroenteritis. In adults, it may be precipitated by estrogen use or pregnancy.
  • Uremia may also lead to bleeding due to abnormal platelet function.
• Acute anemia due to disseminated intravascular coagulation
  • DIC can be caused by systemic infection, massive transfusions, severe head injury, trauma, burn, septic abortion, retained products of conception, or cancer.
  • DIC initially causes thrombosis due to excess release of thrombin, followed by bleeding due to consumption of coagulation factors.

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