AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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 [Hgb AS]) 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

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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 injuries, massive upper or lower GI hemorrhage, ruptured ectopic pregnancy, ruptured aneurysms, and DIC.
• Acute anemia due to hemoglobinopathies
  
  
  • 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 abnormalities
  
  
  • 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 coagulopathies
  
  
  • 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 acquired platelet disorders
  
  
  • 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.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Once anemia is suspected, additional laboratory studies can be used to determine acuity and etiology.
  
• Hemoglobin and hematocrit values are the initial laboratory studies. Pregnancy may lower hematocrit level because of an expanded plasma volume. An acutely bleeding patient may have a normal initial hematocrit level; therefore, in this clinical setting, serial hematocrit levels must be measured. The studies listed below may or may not be useful, depending on clinical presentation.
  
  • Peripheral indices
    
    • The most important index is the mean corpuscular volume (MCV). It allows for classifying anemia as microcytic, normocytic, or macrocytic.
      
    • Microcytic anemias (usually defined as MCV <80) include anemias of chronic disease, iron deficiency, lead poisoning, and the hemoglobinopathies (ie, sickle cell disease, sideroblastic anemia, thalassemias).
      
    • Macrocytic anemias (usually defined as MCV >100) include anemias related to alcoholism, folate and vitamin B-12 deficiencies (pernicious anemia), and some preleukemic conditions.
      
    • Normocytic anemias (MCV 80-100) include anemias of acute blood loss, hemolysis, uremia, and cancer. Early forms of microcytic anemia and multifactorial anemia may have normocytic MCVs.
      
  • Peripheral smear morphologies
    
    • Helmet cells and schistocytes are found in microangiopathic hemolysis (eg, TTP, ITP, HUS, DIC).
      
    • Sickle-shaped cells and Howell-Jolly bodies are found in sickle cell disease.
      
    • RBC fragments may be found in patients with traumatic valvular hemolysis.
      
    • Spherocytes are found not only in hereditary spherocytosis but also in autoimmune hemolytic anemias (eg, ITP).
      
    • Spur cells may be found in patients with underlying cirrhosis.
      
    • In megaloblastic anemia, the blood smear may show anisocytosis and poikilocytosis along with macroovalocytes (large oval hemoglobinized erythrocytes). Basophilic stippling and occasional nucleated RBCs may be present.
      
• Urinalysis and urine beta-hCG (if female)
  
  • Hemoglobinuria or urobilinogen could indicate hemolysis.
    
  • Obtain urinary beta-hCG in premenopausal women with anemia.
    
• Bilirubin level: The indirect or unconjugated form of bilirubin becomes elevated in patients with intravascular hemolysis.
  
• BUN/creatinine level: Due to digested blood, an elevated blood urea nitrogen level is common in patients with upper GI bleeding.
  
• Blood type and cross: Send a blood bank sample so type-specific or type and cross-matched blood can be readied.
  
• Reticulocyte count
  
  • This count may suggest inadequate bone marrow response to anemia, which can occur in patients with aplastic anemia or hematologic cancers, or it can be due to drugs or toxins.
    
  • For patients with hemolytic anemias, use a Finch reticulocyte count, which corrects for the anemia and the 2-day lifespan (versus 1-d lifespan, typically) of immature reticulocytes. The Finch count is the measured reticulocyte count multiplied by the measured hematocrit level, divided by 45, then divided by 2.
    
  • A simple corrected reticulocyte count is sufficient in patients with sickle cell disease. This is the measured reticulocyte count multiplied by the measured hematocrit level, divided by 45. Normal reticulocyte counts are 0.5-1%.
    
• Disseminated intravascular coagulation screen
  
  • This consists of prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, fibrin split products, and platelets.
    
  • Classic findings are elevated coagulation times, decreased platelets and fibrinogen, and the presence of fibrin split products.
    
  • DIC must be considered in patients with profound sepsis, obstetric complications, burns, or cancer. Also, DIC screen should be considered when hemorrhage is difficult to control.
    
• Other studies that may be helpful in evaluating anemia but may not be applicable to the acute ED setting include the following:
  
  • Iron studies: Serum iron test measures the amount of iron bound to transferrin. The reference range is 50-150 mcg/dL. Serum ferritin level effectively measures the total iron levels in the body. In adult males, the level is 50-150 mcg/L. In adult females, the level is 15-50 mcg/L. Transferrin iron-binding capacity (TIBC) is a measure of the total binding capacity of transferrin. Normal level is 300-360 mcg/dL. The percent saturation of transferrin is the serum iron/TIBC. The reference range is 30-50%. Patients with iron deficiency have levels below 20%, while patients with iron overload have levels higher than 50%.
    
  • Folate and vitamin B-12: Significant macrocytosis (MCV >100) suggests the presence of megaloblastic anemia. Most megaloblastic anemias are due to deficiency of cobalamin (vitamin B-12) or folic acid. Common causes include inadequate intake, inadequate production of intrinsic factor (ie, cobalamin deficiency), tropical sprue, parasites (eg, fish tapeworm), and drugs.
    
  • Lead levels: Anemia associated with lead poisoning is usually normocytic and normochromic. It may be accompanied by basophilic stippling. Symptomatic lead poisoning is seen in children when blood levels are in the 80 mcg/dL range. Children may present with abdominal pain, lethargy, anorexia, and pallor (from anemia). Ataxia, speech difficulties, seizures, and coma may occur in some patients.
    
  • Hemoglobin electrophoresis: Consider hemoglobin electrophoresis if sickling appears or if the patient is of Mediterranean or African descent.
    
  • Factor deficiency tests are required to diagnose hemophilia.
    
  • Bleeding time is a useful test measuring platelet function. Patients with bleeding time longer than 10 minutes have an increased risk of bleeding. This test should always be correlated with normally functioning platelet levels, but very low platelet counts can prolong the bleeding time.
    
  • Bone marrow aspiration should be considered when bone marrow reticulocyte response to the anemia is poor.
    
  • Coombs test: This important test can help diagnose autoimmune hemolysis. A direct Coombs test determines the ability of anti-IgG antisera to agglutinate the patient's RBCs. In the indirect Coombs test, the patient's serum is incubated with normal red cells, and IgG antibody is detected with anti-IgG.

Imaging Studies

• Chest radiography
  
  
  • Consider chest radiography in patients with significant anemia.
  • Those with chronic anemia frequently have radiographic cardiomyopathy. In patients with trauma hemothorax, pulmonary contusions or evidence of great vessel injury (aortic rupture) may be evident.
• Ultrasonography
  
  
  • Ultrasonography is a quick, noninvasive, and relatively simple bedside test useful for diagnosing intraperitoneal bleeding. When performed by experienced providers, the focused abdominal sonography for trauma (FAST) examination is very helpful in detecting blood in the Morison pouch, paracolic gutters, splenorenal area, and the pelvis. It is also useful for detecting pregnancy-related bleeding.
  • In pregnant females with suspected ectopic pregnancy, correlate sonograms with the serum beta-hCG. Remembering that most ectopic pregnancies occur 5-8 weeks after the last normal menses is important. Transvaginal ultrasonography is useful if the fetal age is greater than 5 weeks, as a gestation sac is not visible prior to this time. The serum beta-hCG corresponding to this period is 1200-2000 mIU/mL. Therefore, a patient with serum beta-hCG exceeding the 1200-2000 mIU/mL range who has an empty uterus as established by transvaginal ultrasonography has an ectopic pregnancy and needs emergent laparoscopy if clinically indicated. Conversely, if transabdominal ultrasonography is used, a gestational sac should be visible by 6 weeks and the serum beta-hCG should be greater than 6000-6500 mIU/mL. In this case, an empty uterus determined by transabdominal ultrasonography and a serum beta-hCG greater than 6000-6500 mIU/mL indicates an ectopic pregnancy.
• Mesenteric angiography is useful for diagnosing and treating hemorrhage from diverticula.
• Tagged RBC studies may be useful in cases of GI hemorrhage with an unidentified source.
• As clinically indicated, obtain skeletal films, including a pelvic view, in patients with multiple traumas to diagnose fractures and the associated sequestration of blood at the fracture site.
• Consider abdominal CT scan in all stable patients with significant abdominal trauma. CT scanning has a similar sensitivity to ultrasonography and diagnostic peritoneal lavage (DPL) for diagnosis of significant intraperitoneal bleeding, and CT scans identify etiology better. CT scanning is also superior to DPL and ultrasonography for diagnosing retroperitoneal, pelvic, and subcapsular injuries.

Other Tests

• ECG is recommended for patients older than 40 years, for those with chest pain, for all patients with profound anemia, and for those with other underlying disease or increased risk factors for cardiac ischemia.
• A nasogastric tube is the initial test of choice in the ED to diagnose an ongoing upper GI hemorrhage. Bile must be aspirated to rule out bleeding proximal to the ligament of Treitz.
• Esophagogastroduodenoscopy (EGD) is the study of choice for the specific diagnosis of an acute upper gastrointestinal (UGI) bleed.
• Sigmoidoscopy or colonoscopy may be useful in diagnosing and treating lower GI bleeds, but it is rarely useful in the acute setting. Tagged RBC studies or angiography may be more useful for the localization of massive ongoing lower GI bleeding.
• Arterial blood gas (ABG) measurement is an excellent, simple, bedside study that can give a wealth of information about a patient's oxygenation and acid-base status as well as the hemoglobin level.

Procedures

• Perform DPL to diagnose intra-abdominal hemorrhage in unstable trauma patients.
• Culdocentesis
  
  
  • Perform this test for pregnant patients with acute anemia, hemodynamic instability, and no available pelvic ultrasonography.
  • Bleeding from an ectopic pregnancy appears as nonclotting blood.
  • False-positive results may occur with a ruptured hemorrhagic cyst. A dry tap does not rule out ruptured ectopic pregnancy.
• Perform thoracostomy tube drainage in patients with trauma who have a hemothorax.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Prehospital Care

• Initial care of patients includes supplemental oxygen, intravenous fluid resuscitation, applying direct pressure to any external hemorrhage, fracture splinting, and rapid transport.
• Recent prehospital studies suggest that trauma patients should receive minimal fluid resuscitation. This remains unproven and controversial.
• The military antishock treatment (MAST) suit is occasionally used in the prehospital setting for trauma patients with pelvis and lower extremity injuries. It is contraindicated in patients with pulmonary edema or a ruptured diaphragm. It is also contraindicated in pregnant patients.

Emergency Department Care

Evaluate ABCs and immediately treat any life-threatening conditions. Crystalloid is the initial fluid of choice.

• Acute anemia due to blood loss
  
  
  • Monitor with pulse oximetry, cardiac monitor, and a sphygmomanometer.
  • Provide supplemental oxygen via nasal cannula or face mask.
  • Establish 2 large-bore intravenous lines and rapidly infuse 1-2 L of crystalloids while monitoring the patient carefully for signs and symptoms of iatrogenic congestive heart failure.
  • Consider type O or type-specific blood transfusions for patients who remain hypotensive after 2 L of crystalloid infusion for young healthy patients with a hematocrit level below 20 or for elderly patients with a hematocrit level below 30.
  • Vasopressors are relatively contraindicated in the treatment of hypovolemic shock.
  • Obtain fresh frozen plasma (FFP), coagulation factors, and platelets, if indicated.
  • Patients with hemophilia should have samples of the deficient factors sent for measurement.
  • Pregnant patients who are bleeding should be given Rh-immunoglobulin (RhoGAM) if they are Rh negative.
  • Once the patient is stabilized, begin specific measures to treat the underlying cause of bleeding.
• Acute anemia due to hemoglobinopathies
  
  
  • The decision to transfuse depends on the rate of fall of the hemoglobin and the patient's clinical condition.
  • In sickle cell anemia, correction of simple anemia alone by transfusion is adequate.
  • For severe anemia (levels <5 g/dL), full-volume transfusion may lead to volume overload. These patients should be transfused cautiously, often with concurrent use of diuretics.
  • If the clinical picture is urgent, exchange transfusion, especially in vasoocclusive crisis, is the treatment of choice. This rapidly reduces the number of sickle cells while lowering blood viscosity.
  • In patients with aplastic crisis, a decrease in reticulocyte count indicates the need for transfusion.
• Acute anemia due to acquired platelet disorders
  
  
  • Patients with thrombocytopenia who have clinical evidence of bleeding should receive a platelet transfusion.
  • Patients with platelet counts lower than 10,000/µL are at risk for spontaneous cerebral hemorrhage and require a prophylactic transfusion.
  • The preferred treatment for TTP and HUS is large-volume plasmapheresis with FFP replacement. Many patients require daily plasmapheresis. Increasing platelet count, decreasing lactate dehydrogenase (LDH), and decreasing red blood cell fragments indicate a positive response to treatment. Most patients also receive high-dose glucocorticoids as well as antiplatelet agents (aspirin). Patients who do not respond to plasmapheresis can be treated with splenectomy or immunosuppression.
  • ITP is rarely treated with transfusion because the transfused platelets are destroyed rapidly. In stable patients, the initial treatment is supportive care. Patients with active bleeding are treated with high-dose immunoglobulin and steroids. Platelet transfusion is also indicated if active bleeding is present. Patients with chronic ITP who are not responsive to steroids may be candidates for immunosuppressive therapy, intravenous IgG, danazol, or splenectomy.
• Acute anemia due to congenital bleeding disorders
  
  
  • Treat von Willebrand disease with cryoprecipitate. Each unit of cryoprecipitate will raise the VWF by 3%.
  • Treat hemophilia A with factor VIII concentrate.
  • Treat hemophilia B with factor IX concentrate. Dosage is based on the site of the bleeding.
• Acute anemia due to disseminated intravascular coagulation
  
  
  • The role of heparin in treating DIC remains controversial. If heparin is used, it should be in conjunction with platelet transfusion.
  • Maintain platelet count above 50,000/µL. Use FFP and cryoprecipitate to correct coagulation factor and fibrinogen deficiency.
• Blood products
  
  
  • Whole blood contains RBCs, platelets, and coagulation factors; however, it is rarely used as a treatment option.
  • Packed red blood cells (PRBCs) are the remaining components of whole blood after the plasma and platelets are removed. One unit of PRBCs is the product of 1 unit of whole blood and has a volume of 250-300 mL. Each unit of PRBCs is expected to raise the hematocrit level by 3 points.
  • Each unit of platelets contains 50 mL of plasma and has normal amounts of fibrinogen and coagulation factors. Some decrease in factors V and VII is noted compared with whole blood. Each unit of platelets raises the platelet count by approximately 10,000/µL. The usual adult dose is 1 U/10 kg.
  • FFP is the medium that suspends RBCs and platelets and contains all the coagulation factors. The coagulation factors are diluted. Patients with factor V and XI deficiency and those with coagulopathies due to liver disease are the best candidates, as most of the other coagulation factors are now available in concentrated forms.
  • Cryoprecipitate is derived from the precipitate collected from thawed FFP. It contains fibrinogen, factor VIII, VWF, and factor XIII. It is ideal for treatment of mild hemophilia A and conditions that lead to afibrinogenemia.
• All blood products have the potential to transmit bacterial and viral diseases.
  
  
  • The rate of hepatitis B infection is estimated to be 1 infection per 200,000 units.
  • Prevalence of hepatitis C infection ranges from 1 infection per 2000 to 1 infection per 6000 units. This is a recent revision from the 1992 Centers for Disease Control and Prevention (CDC) estimate of 3.2 infections per 100,000 transfusions.
  • Other complications of transfusion therapy include volume overload, hypothermia, allergic reactions, anaphylaxis, DIC, hypocalcemia, and graft-versus-host disease.
  • In individuals who do not consent to blood transfusion (eg, Jehovah's Witnesses), crystalloid solutions in the acute phase and erythropoietin and iron supplements in the subacute phase may be beneficial. Currently, exciting research is under way to evaluate the effectiveness of inorganic compounds such as dodecafluoropentane emulsion (DDFPe) as a blood substitute. DDFPe is an inorganic fluorocarbon compound that expands at body temperature and has a strong affinity for oxygen. PolyHeme is an oxygen-carrying blood substitute made from human blood. While PolyHeme may not be appropriate for patients who are Jehovah's Witnesses, it is an excellent option for those willing to receive human-blood–derived products. PolyHeme does not require crossmatching, has a shelf life of more than 12 months, and has virtually no risk of transmitting infections.

Consultations

• For admitted patients, surgical evaluation or hematologic consult may be indicated.
• If a patient is expected to be discharged, notify the primary care physician to ensure adequate follow-up care.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Therapeutic approaches to treat anemia include blood and blood products, immunotherapies, hormonal/nutritional therapies, and adjunctive therapies.

The goal of therapy in acute anemia is to restore the hemodynamics of the vascular systems and to replace lost RBCs. To achieve this, the practitioner may use mineral and vitamin supplements, blood transfusions, vasopressors, histamine (H2) antagonists, and glucocorticosteroids.

Drug Category: Blood and blood products

Correction of acute anemia often requires blood and/or blood products. With significant ongoing hemorrhage or hemolysis, transfusion of blood alone is insufficient. Nonetheless, providing timely transfusion to restore hemoglobin to safe levels can prevent major complications of acute anemia.

Drug Category: Vasopressors

These drugs decrease portal circulation pressure by diminishing blood flow due to vasoconstriction. Major indication is variceal bleeding.

Drug Category: Histamine (H2) antagonists

These agents produce blockade of H2 receptors.

Drug Category: Glucocorticoids

These agents are used to treat idiopathic and acquired autoimmune hemolytic anemias.

Drug Category: Vitamin

Vitamin K deficiency causes elevation of prothrombin time and is commonly seen in patients with liver disease.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Inpatient Care

• Ongoing inpatient diagnostics should be based on all possible etiologies of the anemia, but a repeat hematocrit is mandatory.
• Consider steroids, immunoglobulins, plasmapheresis, immunosuppressive agents, and splenectomy for patients with hemolysis refractory to transfusions.

Further Outpatient Care

• The emergency physician should provide anticipatory guidance and detailed discharge instructions, including advice about what symptoms necessitate a return to the ED. The emergency physician should also arrange follow-up with the patient's primary physician and/or hematologist so that repeat laboratory studies and reexamination can occur in a timely fashion.
• Discharge instructions should recommend avoiding trauma, physical activity, alcohol, NSAIDs, and other antiplatelet agents, as pertinent.
• Discharge may be considered in the stable patient without further evidence of hemolysis or bleeding. Check and verify that vital signs are within the reference range. The patient should be competent to make decisions and should have access to a telephone and/or transportation.

In/Out Patient Meds

• Vasopressin (antidiuretic hormone [ADH]/somatostatin)
• Propranolol and isosorbide dinitrate are used in combination to decrease incidence of bleeding in some groups of patients with esophageal varices. This combination is not useful with acute bleeding.
• Vitamin K may be used to correct prolongation of prothrombin and factors VII, IX, and X in patients with mild-to-moderate liver dysfunction who are not bleeding. The preferred route of administration is subcutaneous. Intravenous administration of vitamin K should be avoided, as rapid infusions can cause dyspnea, chest pain, and even death.
• Gastric acid inhibitors (eg, H2-receptor antagonists) are of limited benefit for actively bleeding patients. They are effective in promoting the healing of gastric and duodenal ulcers and in preventing their recurrence. Some controversial evidence exists about the utility of proton pump inhibitors in preventing recurrent acute bleeding from ulcers.
• Prednisone

Transfer

• Transfer may be considered for patients who are hemodynamically and neurologically stable or when a higher level of care is required. Benefits of transfer must outweigh the risks of transfer.
• Patients with ongoing hemorrhage or ongoing hemolysis are unstable and should not be transferred unless the initial facility cannot adequately care for the patient. If unstable patients must be transferred, obtain specialty consultation and initiate all available recommended initial therapy.

Patient Education

• For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center; Skin, Hair, and Nails Center; and Pregnancy and Reproduction Center. Also, see eMedicine's patient education articles Anemia, Bruises, and Ectopic Pregnancy.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Given heightened public awareness of transmissible diseases through blood and blood products, discussion and documentation of the risks, benefits, and alternative treatments is medicolegally prudent. When this is not possible because of altered level of consciousness, critical illness, or unavailable family, documenting reasons consent could not be obtained is appropriate.
• In the case of minors or those with religious or cultural beliefs prohibiting transfusion, involve hospital ethics and/or legal counsel when possible. Always attempt to clearly explain the risks, benefits, and alternatives to the patient and his or her family. Document these conversations in the medical record.
• Involve consultants early and document the consultant's name, specialty, time, and discussion topics. Involve hematology for significant cases of thrombocytopenia and hemolysis; similarly, surgical consultation is appropriate in significant trauma cases.
• Although controversial, transfusion of platelets may be considered in cases of ITP or TTP, even when transfusion is unlikely to be clinically useful. These situations arise with platelet counts below 10,000/µL and with life-threatening hemorrhages. Obtain emergent hematologic consultation for plasmapheresis, steroids, immunoglobulins, and/or FFP.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Sickle cells.
	View Full Size Image
Media type:  Photo

Media file 2:  Aplastic anemia.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

• Alayash AI, D'Agnillo F, Buehler PW. First-generation blood substitutes: what have we learned? Biochemical and physiological perspectives. Expert Opin Biol Ther. May 2007;7(5):665-75. [Medline].
• Blanchette V, Carcao M. Intravenous immunoglobulin G and anti-D as therapeutic interventions in immune thrombocytopenic purpura. Transfus Sci. Sep 1998;19(3):279-88. [Medline].
• Cone JB, Wallace BH, Caldwell FT, Smith SD, Searcey R. Beneficial effects of a hypertonic solution for resuscitation in the presence of acute hemorrhage. Am J Surg. Dec 1987;154(6):585-8. [Medline].
• Fortune JB, Feustel PJ, Saifi J, Stratton HH, Newell JC, Shah DM. Influence of hematocrit on cardiopulmonary function after acute hemorrhage. J Trauma. Mar 1987;27(3):243-9. [Medline].
• Gould SA, Rosen AL, Sehgal LR, et al. Fluosol-DA as a red-cell substitute in acute anemia. N Engl J Med. Jun 26 1986;314(26):1653-6. [Medline].
• Gregg SG, Mazzeo RS, Budinger TF, Brooks GA. Acute anemia increases lactate production and decreases clearance during exercise. J Appl Physiol. Aug 1989;67(2):756-64. [Medline].
• Isselbacher KJ, Adams RD, Braunwald E, eds. Harrison's Principles of Internal Medicine. 9^th ed. New York, New York: McGraw-Hill; 1980:262-278.
• Jahr JS, Varma N. PolyHeme. Northfield Laboratories. IDrugs. May 2004;7(5):478-82. [Medline].
• Jan KM, Chien S. Effect of hematocrit variations on coronary hemodynamics and oxygen utilization. Am J Physiol. Jul 1977;233(1):H106-13. [Medline].
• Koren A, Segal-Kupershmit D, Zalman L, et al. Effect of hydroxyurea in sickle cell anemia: a clinical trial in children and teenagers with severe sickle cell anemia and sickle cell beta-thalassemia. Pediatr Hematol Oncol. May-Jun 1999;16(3):221-32. [Medline].
• Koskolou MD, Roach RC, Calbet JA, Rådegran G, Saltin B. Cardiovascular responses to dynamic exercise with acute anemia in humans. Am J Physiol. Oct 1997;273(4 Pt 2):H1787-93. [Medline]. [Full Text].
• Laks J, Pilon RN, Klovekorn WP, Anderson W, MacCallum JR, O'Connor NE. Acute hemodilution: its effect of hemodynamics and oxygen transport in anesthetized man. Ann Surg. Jul 1974;180(1):103-9. [Medline].
• Lundgren CE, Bergoe GW, Tyssebotn I. The theory and application of intravascular microbubbles as an ultra-effective means of transporting oxygen and other gases. Undersea Hyperb Med. 2004;31(1):105-6. [Medline].
• Mintz P, ed. Transfusion medicine. Hematology Oncology Clinics. 1994;8(6):1045-1104.
• Sassetti B, Vizcarguenaga MI, Zanaro NL, et al. Hemolytic uremic syndrome in children: platelet aggregation and membrane glycoproteins. J Pediatr Hematol Oncol. Mar-Apr 1999;21(2):123-8. [Medline].
• Tintinalli J, Ruiz E, Krome RL. Emergency Medicine: A Comprehensive Study Guide. 4^th ed. New York, New York: McGraw-Hill; 1996:1-7,447-53.
• Valenzuela JE, Schubert T, Fogel MR, et al. A multicenter, randomized, double-blind trial of somatostatin in the management of acute hemorrhage from esophageal varices. Hepatology. Dec 1989;10(6):958-61. [Medline].
• Veng-Pedersen P, Chapel S, Schmidt RL, Al-Huniti NH, Cook RT, Widness JA, et al. An integrated pharmacodynamic analysis of erythropoietin, reticulocyte, and hemoglobin responses in acute anemia. Pharm Res. Nov 2002;19(11):1630-5. [Medline].

Article Last Updated: Jul 26, 2007