Hematologic and Oncologic Emergencies

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Chapter 37 Hematologic and Oncologic Emergencies

Paul Ishimine, MD, Jenny Kim, MD

HEMATOLOGIC EMERGENCIES

1 How should one approach the evaluation of a child presenting with anemia to the emergency department (ED)?

Anemia is caused by problems of red cell destruction, red cell or hemoglobin production, or blood loss. After patient stabilization, the following features can help determine the underlying cause:

Historical features: Rapidity of onset, hemorrhage, diet, history of easy bruising or bleeding, family history of blood disorders

Physical examination findings: Jaundice, splenomegaly, enlarged lymph nodes, bruising/bleeding, occult blood on rectal examination

Laboratory studies: Complete blood count with manual differential, mean corpuscular volume (MCV), peripheral smear, reticulocyte count, Coombs test

Cohen AR: Pallor. In Fleisher GR, Ludwig S, Henretig FM (eds): Textbook of Pediatric Emergency Medicine, 5th ed. Philadelphia, Lippincott Williams & Wilkins, 2006, pp 535–543.

2 What is the underlying pathophysiology of sickle cell disease (SCD)?

SCD is due to an inherited hemoglobinopathy in which a single mutation causes an amino acid substitution in the β-globin chain. This results in abnormally shaped red blood cells (RBCs) that are prone to aggregation and vascular injury, resulting in vaso-occlusion and resultant complications, such as splenic infarction (resulting in increased susceptibility to infection), stroke, and pain from ischemia. There are many genotypes of sickle cell disease, including SCD-SS, -SC, -Sβ⁺ thalassemia, and -Sβ⁰ thalassemia. Patients with SCD-SS and SCD-Sβ⁰ thalassemia usually have a more severe clinical course.

3 What are the life-threatening complications of SCD?

Splenic sequestration crisis

Acute chest syndrome

Aplastic crisis

National Institutes of Health/National Heart, Lung, and Blood Institute Division of Blood Diseases and Resources: The Management of Sickle Cell Disease, 4th ed. Bethesda, MD, National Institutes of Health, 2002, NIH publication no. 02–2117, 2002, pp 1–188.

4 Why is a patient with SCD immunocompromised?

Splenic microinfarctions due to sickling of red cells cause altered splenic function. As a result, patients with SCD are prone to infection with encapsulated organisms, such as Streptococcus pneumoniae.

5 What causes painful crisis in patients with SCD?

Vaso-occlusive crises are due to localized sickling and vascular occlusion. This can occur in any organ, but most frequently affects bone and viscera. Most older children report long bone, back, and abdominal pain. Precipitating events may include infection, dehydration, fever, or exposure to cold.

6 How should painful crisis be treated?

Assess the severity of pain and associated organ systems. IV hydration, usually at 1.5 times the maintenance rate, and narcotic administration are frequently required. Administration of oxygen is often recommended. It is important to inquire about pain medications given at home, and if these were ineffective to administer an appropriate dose of a more potent analgesic medication. Morphine is often used at an IV dose of 0.1 or 0.2 mg/kg/dose every 1–4 hours.

7 What is dactylitis?

Dactylitis, or “hand-foot syndrome,” results from vaso-occlusion of the nutrient arteries that supply the metacarpal and metatarsal bones, causing bone marrow infarction in patients with SCD. This is a form of vaso-occlusive crisis most common in young infants (mostly under age 2 years) and results in pain and swelling of the hands and feet, irritability, and refusal to walk. It is usually bilateral, distinguishing it from cellulitis.

8 Define acute chest syndrome and its causes and treatment

Acute chest syndrome is a serious complication of SCD and can be life threatening. The syndrome is defined as a new pulmonary infiltrate and chest pain, hypoxia, fever, tachypnea, wheezing, or cough. Both infectious (e.g., chlamydia, mycoplasma, viruses, bacteria) and noninfectious (e.g., fat embolism, pulmonary infarction) causes have been described. Supportive care measures include analgesia, cautious hydration, oxygen, antibiotics, bronchodilators, and blood transfusions.

Vichinsky EP, Neumayr LD, Earles AN, et al: Causes and outcomes of the acute chest syndrome in sickle cell disease. N Engl J Med 342:1855–1865, 2000.

9 What is splenic sequestration crisis?

Splenic sequestration crisis is a life-threatening complication of SCD that occurs when a large portion of a patient’s blood volume becomes acutely trapped in the spleen. This leads to massive splenomegaly, acute anemia, and hypovolemic shock. Treatment is supportive and includes hospitalization, fluid resuscitation, and blood transfusion. Splenic sequestration is seen in young children, typically between 3 months and 5 years of age.

KEY POINTS: LIFE-THREATENING COMPLICATIONS OF SICKLE CELL DISEASE

3 Splenic sequestration crisis

4 Acute chest syndrome

5 Aplastic crisis

10 Which virus frequently leads to aplastic crisis in children with SCD?

Parvovirus B19. This causes brief suppression of erythropoiesis, which is not tolerated in patients with SCD who are already anemic, and patients may present with fatigue, shortness of breath, and severe anemia with reticulocytopenia. Treatment is supportive, and RBC transfusions are often necessary.

11 Are aplastic crises due to parvovirus B19 seen only in patients with SCD?

No. Parvovirus B19 can also cause aplastic crises in patients with other chronic hemolytic diseases, such as thalassemia or hereditary spherocytosis. These patients have shortened RBC survival and frequently cannot tolerate even a brief suppression of erythropoiesis.

12 How should patients with SCD and fever be treated in the ED?

Because these children are at high risk for serious bacterial infections, febrile children with SCD need rapid treatment with parenteral antibiotics after appropriate cultures are obtained. The greatest risk of serious bacterial infection is between the ages of 6 months and 3 years, when protective antibodies are not adequate and splenic function is greatly diminished. After administration of IV antibiotics, the conventional approach has been to admit these patients to the hospital. Currently, some hematologists advocate cautious outpatient management of selected well-appearing febrile patients.

13 What are considered to be low-risk criteria for outpatient management of febrile patients with SCD?

Well appearance

No focal findings

Temperature < 40°C

White blood cell count > 5000 but < 30,000 cells/mm³

No pulmonary infiltrates

Baseline hemoglobin, white blood cell, and platelet counts

Wilimas JA, Flynn PM, Harris S, et al: A randomized study of outpatient treatment with ceftriaxone for selected febrile children with sickle cell disease. N Engl J Med 329:472–476, 1993.

14 If a patient with SCD meets the above criteria, what is the recommended treatment plan?

These patients should receive an initial dose of parenteral ceftriaxone in the ED. Further treatment may consist of oral amoxicillin. Close follow-up must be arranged if febrile patients with SCD are discharged, including telephone follow-up or scheduling of a revisit within the next 24 hours.

Wilimas JA, Flynn PM, Harris S, et al: A randomized study of outpatient treatment with ceftriaxone for selected febrile children with sickle cell disease. N Engl J Med 329:472–476, 1993.

15 An ill-appearing 6-year-old girl presents with weakness for 2 days. On examination she has jaundice and pale conjunctivae but no bruising or petechiae. Her hemoglobin level is 4 g/dL, but her white blood cell and platelet counts are normal. Her reticulocyte count is 20%. She has unconjugated hyperbilirubinemia, and she has dark-brown urine (which is dipstick-positive for blood but has no RBCs on microscopic examination). This presentation suggests what broad category of anemia?

Hemolytic anemia. Hemolytic disease may be seen in children with red cell membrane defects, such as hereditary spherocytosis or liver disease. Enzyme defects, such as glucose-6-phosphate dehydrogenase deficiency, predispose the patient to hemolysis following an oxidant exposure. Autoimmune hemolysis occurs when antibodies directed against red cells cause hemolysis. This may be triggered by drugs, infections, autoimmune diseases, or maternal–fetal transfer, or it may be idiopathic. Nonimmune acquired hemolysis may be caused by drugs, infections, or chemicals that cause direct red cell injury. Patients with hemoglobinopathies, such as SCD and thalassemias, can have periods of increased hemolysis and worsening anemia. Finally, mechanical causes of red cell fragmentation, such as hemolytic uremic syndrome, may also cause hemolysis.

17 Why is excessive cow’s milk consumption associated with iron-deficiency anemia in young children?

Overconsumption of cow’s milk decreases the toddler’s appetite for other foods, and cow’s milk does not contain adequate iron for nutrition. There may also be a concomitant cow’s milk enteropathy, causing microscopic intestinal blood loss.

18 Describe appetite abnormalities associated with iron-deficiency anemia

Pica refers to an appetite for unusual substances not regarded as food, such as clay, paper, or dirt.

Pagophagia, or pica for ice, is thought to be a specific finding in iron-deficiency anemia. Patients are treated with iron.

Osman YM, Wali YA, Osman OM: Craving for ice and iron-deficiency anemia: A case series from Oman. Pediatr Hematol Oncol 22:12, 2005.

19 What is transient erythroblastopenia (TEC) of childhood? How does it present?

TEC is an idiopathic disorder of acquired RBC aplasia characterized by a gradual onset of pallor. The median age at the time of diagnosis is 23 months, and there is often a history of a preceding viral illness. Except for pallor, the patient’s physical examination is otherwise normal, with the absence of bruising, fever, lymphadenopathy, and hepatosplenomegaly. The CBC in a patient with TEC shows an isolated normochromic normocytic anemia with reticulocytopenia. TEC can be confused with leukemia, and bone marrow biopsy may be needed to exclude this diagnosis in a patient suspected of having TEC.

20 What are the causes of methemoglobinemia?

Methemoglobinemia may occur after exposure to oxidizing drugs (e.g., benzocaine, sulfonamide antibiotics), well water that contains nitrites, mothballs, and aniline dyes. Acute gastroenteritis can lead to methemoglobinemia in infants. The heme iron is converted from a ferrous to a ferric state, resulting in hemoglobin with impaired oxygen binding and manifests as cyanosis. Congenital methemoglobinemia is a rare cause of cyanosis in the newborn.

21 How do patients with idiopathic (or immune) thrombocytopenic purpura (ITP) typically present?

ITP most commonly presents in children ages 1–4 years with the acute onset of bruising and petechiae. There is often a history of a preceding viral illness. Children with ITP generally do not appear ill, and frank bleeding is surprisingly less common than would be expected in patients with thrombocytopenia.

22 What is the most serious complication of ITP?

The most serious concern in young children with ITP is intracranial hemorrhage. The risk of intracranial hemorrhage is highest in the first week after diagnosis and when the platelet count is less than 20,000 cells/mm³. Intracranial hemorrhage is seen more frequently in patients who present with mucosal bleeding.

23 How is ITP treated?

The treatment of ITP is controversial. Options include close observation only, IV γ-globulin (which is thought to block the uptake of antibody-coated platelets by the spleen), antibodies directed against the D-antigen of RBCs (only effective in Rh-positive patients), steroids, or splenectomy. Some physicians feel that not all patients with ITP need treatment, given the generally benign course and significant costs and side effects of treatment.

Tarantion MD, Buchanan GR: The pros and cons of drug therapy for immune thrombocytopenic purpura in children. Hematol Oncol Clin North Am 18:1301–1314, 2004.

24 Name the three most common bleeding disorders and the deficient factors associated with each

The most common inherited bleeding disorders are:

Hemophilia A (factor VIII deficiency)

Hemophilia B (factor IX deficiency)

Von Willebrand disease (von Willebrand factor)

25 What are the typical findings of an acute hemolytic transfusion reaction?

Fever and chills

Chest tightness

Abdominal or flank pain

26 How is a suspected hemolytic transfusion reaction initially treated?

Stop the transfusion immediately.

Give saline at twice the maintenance rate.

Confirm that the blood was intended for this patient.

Examine the urine for hemoglobin.

Send a tube of blood from the unit of transfused blood to the blood bank for confirmation of initial compatibility.

Cohen A, Manno C: Hematologic emergencies. In Fleisher G, Ludwig S, Henretig FM (eds): The Textbook of Pediatric Emergency Medicine, 5th ed. Philadelphia, Lippincott Williams & Wilkins, 2006, p 948.

ONCOLOGIC EMERGENICIES

27 What are the most common childhood malignancies?

Leukemia is the most common childhood malignancy, and acute lymphoblastic leukemia (ALL) is the most common type of childhood leukemia.

The most common solid organ tumors are brain tumors, and most of these tumors are infratentorial. Medulloblastomas and cerebellar astrocytomas are the most common central nervous system tumors in children.

National Cancer Institute. Available at www.cancer.gov/.

28 Why are children with malignancies at risk for sepsis?

Several factors contribute to the risk of severe infections and sepsis in pediatric oncology patients:

Most importantly, there can be replacement of the bone marrow by malignant cells and direct suppression of granulocyte production by chemotherapeutic agents, resulting in neutropenia.

Other mechanisms of defense against infection, including mechanical barriers (e.g., intact mucous membranes and skin), cell-mediated and humoral immunity, and splenic function, are frequently impaired in patients with cancer.

Indwelling central venous catheters, ventriculoperitoneal shunts, and other implanted devices may become sites of infection.

29 How should febrile children with cancer be managed?

Febrile children with cancer must be approached carefully. The most important component in the evaluation of a febrile oncologic patient is the patient’s overall appearance. Any ill-appearing child needs broad-spectrum antibiotic coverage and admission to the hospital. If a febrile child is neutropenic (absolute neutrophil count < 500 cells/mm³) or if his or her absolute neutrophil count is < 1000 cells/mm³ and expected to drop further, broad-spectrum antibiotic therapy should be administered after blood and other appropriate cultures are obtained. These patients are also admitted to the hospital. Well-appearing febrile patients who are not neutropenic may be treated more selectively. The treatment and disposition of all febrile children with cancer should be discussed with the child’s oncologist.

Rheingold SR, Lange BJ: Oncologic emergencies. In Pizzo PA, Poplack DG (eds): Pediatric Oncology, 4th ed. Philadelphia, JB Lippincott, 2002, pp 1177–1203.

30 An ill-appearing 6-year-old boy with acute myelogenous leukemia presents with fever and right-lower-quadrant abdominal pain. In addition to the usual causes of fever and right-lower-quadrant pain, what other entity needs to be considered in a neutropenic patient?

Typhlitis, a necrotizing colitis and inflammation of the cecum, can be seen in neutropenic patients. The etiology is multifactorial and includes infection and mucosal injury from chemotherapy or radiation therapy. Typhlitis usually presents with fever, abdominal pain, and bloody diarrhea. The diagnosis is best made by computed tomography, and treatment includes gut rest, antibiotic therapy and, rarely, surgery. The mortality rate with typhlitis is very high.

31 A teenager with a diffuse headache is found to have a white blood cell count of 200,000 cells/mm³. What treatment should be initiated in the ED while awaiting confirmatory studies?

This child has hyperleukocytosis, which is very suggestive of leukemia. This degree of white blood cell elevation leads to increased blood viscosity, which, in turn, predisposes a patient to thrombosis, leading to neurologic, pulmonary, and hemorrhagic symptoms. These patients are also at high risk for tumor lysis syndrome. Treatment includes hydration and alkalinization; more refractory cases are treated with leukapheresis. Platelet transfusions should be given if the platelet count is < 20,000 cells/mm³ to reduce the risk of central nervous system hemorrhage. RBC transfusions should be given judiciously because they can increase blood viscosity.

33 What are some of the risks associated with an anterior mediastinal mass?

Anterior mediastinal masses are associated with superior mediastinal syndrome in 12% of patients at the time of presentation. This is defined as compression of the superior vena cava (SVC syndrome) and trachea.

34 What are the presenting symptoms of anterior mediastinal mass?

These symptoms may include stridor, cough, dyspnea, hemoptysis, and orthopnea.

35 How should a patient with an anterior mediastinal mass be studied?

The initial diagnostic test should be a chest radiograph, with posteroanterior and lateral views. Perform chest computed tomography to investigate tracheal involvement. Finally, echocardiography and pulmonary function tests will further delineate circulatory and respiratory functional impairment.

KEY POINTS: METABOLIC DISTURBANCES SEEN IN ONCOLOGY PATIENTS

1 Hyperkalemia: Seen with tumor lysis syndrome

2 Hyperphosphatemia: Seen with tumor lysis syndrome

3 Hyperuricemia: Seen with tumor lysis syndrome

4 Hypercalcemia: Seen in patients being treated with cis-retinoic acid or those with significant bony metastases

5 Hypernatremia: Seen in patients with diabetes insipidus, which can occur frequently in patients with central nervous system tumors or Langerhans cell histiocytosis

6 Hyperglycemia: Seen in patients on steroids or asparaginase

36 What are the pitfalls of managing the ABCs of a patient with an anterior mediastinal mass?

Endotracheal intubation may be difficult because of tracheal or bronchial compression. Cardiac output may be compromised by positive-pressure ventilation. Be particularly wary of the patient who has worsening respiratory difficulty when placed in the recumbent position, and avoid sedating patients and lying patients flat because doing so may result in cardiorespiratory arrest.

37 A 4-year-old girl with lymphoma presents with shortness of breath. What are some possible causes of her symptoms?

See Table 37-1.

Table 37-1 Causes of Shortness of Breath in Patients with Cancer

Superior vena cava (SVC) syndrome: Compression or thrombosis of the SVC can cause dyspnea, and may result in facial plethora, jugular venous distention, and headache

Superior mediastinal syndrome: Compression of the trachea by tumor; often used interchangeably with SVC syndrome

Pleural effusions

Pericardial effusion

Cardiomyopathy: Commonly associated with anthracycline chemotherapeutics

Dysrhythmias: Electrolyte disturbances

Pneumonia

Pulmonary embolism

Anemia

39 An 8-year-old girl who has been reporting back pain intermittently for several months presents to the ED with a sudden inability to move her right leg. What does this presentation suggest, and what is the treatment?

Spinal cord compression can present with back pain (typically worse when lying down), leg paresis or paralysis, and bowel and/or bladder incontinence or retention. Examination may reveal back tenderness, leg weakness, decreased rectal tone, and hyperreflexia or hyporeflexia. Plain radiography may reveal vertebral abnormalities, but the diagnostic study of choice is magnetic resonance imaging. Treatment should be initiated immediately to minimize permanent neurologic sequelae and may include a combination of chemotherapy, radiation therapy, and surgical decompression.

40 What is tumor lysis syndrome (TLS)?

TLS is a metabolic syndrome of hyperkalemia, hyperphosphatemia, and hyperuricemia resulting from release of intracellular contents from dying cells. This is seen most commonly in cancers with large tumor burdens and rapid cellular turnover, such as lymphomas and leukemias. Although TLS usually occurs soon after initiation of chemotherapy, patients can present at the time of initial diagnosis with TLS, especially in patients who present with Burkitt’s lymphoma. TLS can cause numerous complications, such as dysrhythmias and renal failure.

41 How is TLS treated?

Treatment of TLS consists of hydration and alkalinization of the urine. The recommendation is to start 5% dextrose in one-quarter normal saline with 50–100 mEq/L sodium bicarbonate at 2–4 times maintenance rates. Potassium should not be added to the IV fluids. Allopurinol or rasburicase is administered to reduce uric acid, and aluminum hydroxide or calcium carbonate is started for hyperphosphatemia. Hyperkalemia can be treated with a potassium-binding resin, calcium gluconate, sodium bicarbonate, or insulin with glucose, depending on the patient’s clinical status. Hemodialysis may be used for uncontrolled TLS and renal failure.

42 A 5-year-old girl with all presents with fever and hypotension. Antibiotics and IV fluid resuscitation are started immediately, but she has persistent hypotension. In addition to fluids and pressors, what other therapies should be considered?

Consider adrenal suppression in patients with persistent hypotension who recently (in the past year) have been treated with steroids. These patients may need stress-dose hydrocortisone. If worsening hypotension is associated with flushing of the central line or infusion of IV antibiotics through the central line, be suspicious of central line infection.

ACKNOWLEDGMENT

The authors would like to thank Janet Friday, MD, for writing this chapter for the first edition of this book.

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