Etiology

Anemia is present when the number of circulating RBCs is reduced, resulting in decreased oxygen-carrying capacity of the blood. Anemia is the most common hematologic condition of infancy and childhood. Most patients with anemia have an underlying disease, so anemia is a symptom rather than a disease. Causes of anemia include acute or chronic blood loss, decreased production of RBCs, splenic sequestration, and hemolysis (Box 15-2).

Pathophysiology

Anemia results from blood loss, decreased RBC production, or increased RBC destruction. The pathophysiology of each is different.

Blood Loss

When a patient experiences acute blood loss, the Hgb and Hct are not initially affected because both plasma and RBCs have been lost. If only crystalloid and colloids are used (without blood) for fluid resuscitation, then the Hct will fall because whole blood loss has been replaced with fluid that does not contain RBCs (Fig. 15-1). The patient may remain anemic until blood is administered.

Fig. 15-1 Effects of acute hemorrhage and crystalloid resuscitation on hematocrit. The patient’s hematocrit might not decrease initially following hemorrhage, because the loss of red blood cells is proportional to the loss of plasma. However, replacing the whole blood loss with crystalloids only will result in a decreased hematocrit.

Clinical Signs and Symptoms

The signs and symptoms of anemia will vary based on the acuity and severity of the anemia and the resultant effect on oxygen delivery. Mild anemia can manifest insidiously, and the patient may be asymptomatic because heart rate and cardiac output maintain oxygen delivery. In contrast, if anemia is acute or severe, overt clinical symptoms may be present. If anemia is chronic, the child retains fluid to maintain circulating blood volume and increases heart rate and cardiac output to maintain oxygen delivery. High-cardiac-output congestive heart failure may develop.

An increase in heart rate may be associated with a systolic flow murmur caused by high flow passing through normal valves. Patients often report fatigue, dizziness, lethargy, dyspnea on exertion, headache, and heart palpitations. Physical signs may include pallor and tachycardia.

Signs of congestive heart failure, including tachycardia with a gallop, pulmonary edema, poor peripheral perfusion and hepatosplenomegaly, usually develop once the Hct is less than 15% or the Hgb concentration is less than 5   g/dL.

Anemia from RBC hemolysis often causes jaundice. Splenomegaly will be noted if sequestration of RBCs develops.

Laboratory studies will demonstrate a fall in Hct; the average Hgb concentration varies based on age and gender, so values should be evaluated in light of these characteristics. Anemia can be classified on the basis of the mean corpuscular volume as microcytic if the RBCs are small, normocytic if they are normal, and macrocytic if the RBCs are large. Examination of a peripheral smear of blood enables assessment of RBC morphology (i.e., shape, size, and color). The reticulocyte count is helpful in diagnosing the cause of the anemia; it is decreased in disorders of RBC production and usually elevated in the presence of increased RBC destruction (e.g., a hemolytic process). Laboratory studies will differentiate whether the anemia is of one cell line (RBCs only) or all cell lines (RBCs, WBCs, and platelets).

Management

The management of a patient with anemia is influenced by the severity and cause of the anemia. If the child exhibits congestive heart failure or shock, initial therapy focuses on supporting oxygen delivery and cardiorespiratory function. Once the child’s condition is stable, the cause of the anemia must be identified to effectively restore the RBCs.

Management of anemia with severe cardiorespiratory distress (e.g., CHF) includes immediate oxygen administration, insertion of two large-bore venous catheters, or establishment of intraosseous access for blood product and fluid administration. Insertion of an arterial line is recommended to allow continuous blood pressure monitoring. Although phlebotomy should be limited in a child with severe anemia, obtain a CBC with a reticulocyte count, and blood for type and cross match. If shock is present, a venous pH will enable quantification of any acidosis. If possible, a purple-top EDTA (ethylenediamine tetraacetic acid) and a green-top (heparin) tube should be filled for later establishment of the cause of the anemia (e.g., these samples can be used for Hgb electrophoresis, osmotic fragility, or G-6 PD [Glucose-6-phosphate dehydrogenase] deficiency studies).

If chronic anemia is present, the child has retained fluid and albumin to maintain circulating blood volume and has increased cardiac output to maintain oxygen delivery. Transfusion therapy in this patient can produce hypervolemia and precipitate (or worsen) congestive heart failure. Administering PRBCs at the rate of approximately 3   mL/kg per hour should prevent hypervolemia and worsening of CHF. Often a diuretic is administered simultaneously.

If severe CHF or profound compensated anemia is present, a partial exchange transfusion will enable removal of some intravascular volume (which contains a low Hgb and Hct) and replacement with PRBCs (with an Hgb of approximately 18 to 20   g/dL and an Hct of approximately 65% to 70%). This will produce an improvement in oxygen-carrying capacity without expanding the intravascular volume (refer to Blood Component Therapy later in this chapter).

The symptomatic patient with hemolytic anemia caused by intrinsic RBC abnormalities will benefit from RBC transfusions. Because the transfused RBCs are unaffected, they will not be susceptible to hemolysis.

In contrast, immune-mediated hemolytic anemia might not be responsive to transfusions, because the offending antibodies might not distinguish between host and transfused RBCs. The presence of antibodies can preclude crossmatching of blood (in the blood bank) for these patients, using standard Coomb’s testing. Therefore virtually every unit of blood administered to the patient may be labeled as incompatible. In these patients, in vivo crossmatching is performed: blood is administered, and the patient is monitored closely for evidence of a severe transfusion reaction (see Blood and Blood Component Therapy). In some cases, steroid therapy (prednisone, 2 to 10   mg/kg per day) or splenectomy may be effective in reducing RBC antibody formation and RBC destruction.

Serial monitoring of blood counts is essential to evaluate response to therapy. Patients with some types of anemia, such as decreased production of RBCs, may benefit from the administration of hematopoietic growth factors. Administering growth factors may decrease the need for blood transfusions.

Etiology and Pathophysiology

Patients with thrombocytopenia have a decrease in circulating platelets. This condition can occur as a result of decreased production of platelets, increased destruction of platelets, or sequestration of platelets in the spleen or liver (Box 15-3). The cause of the thrombocytopenia affects the treatment.

Patients with decreased platelet production may have an underlying failure of hematopoiesis in their bone marrow. For example, in leukemia the bone marrow may be overwhelmed with blast cells, which overwhelm and replace the platelet-forming megakaryocytes, decreasing platelet production.

Thrombocytopenic patients with increased platelet destruction may have developed platelet antibodies. This process is immune mediated. The antibodies attach to the patient’s platelets, and the platelet-antibody complexes are rapidly removed from the circulation in the liver and spleen. Immune-mediated thrombocytopenia may be triggered by a viral illness, or it may be caused by drugs (e.g., heparin) or by a breakdown in the body’s ability to recognize its own antigens (e.g., systemic lupus erythematosus and other collagen vascular diseases).

Clinical Signs and Symptoms

There is no definitive test to determine the etiology of thrombocytopenia. Immune-mediated thrombocytopenia is a diagnosis of exception when other diseases or disorders have been ruled out. Diagnostic procedures include a CBC with evaluation of peripheral smear, coagulation studies, and a reticulated platelet value and platelet function testing. Normal platelet counts range from 150,000 to 400,000/mm³, and patients with severe thrombocytopenia may have a platelet count of less than 20,000/mm³. Spontaneous bleeding can occur when the platelet count is less than 20,000/mm³, and intracranial hemorrhage can occur when the platelet count is below 5000/mm³.

Reticulated platelets (RPs) are newly synthesized platelets with increased ribonucleic acid content. These new platelets can be identified and quantified, and the RP value can aid in determining the cause of the thrombocytopenia. A decrease in RP value in the patient with thrombocytopenia suggests bone marrow suppression (i.e., platelets are not being made despite a fall in platelet count), whereas a high RP value in a patient with thrombocytopenia suggests immune-mediated thrombocytopenia (i.e., platelets are being made but are not correcting the thrombocytopenia).²¹

The clinical presentation of thrombocytopenia will vary based on the platelet count and the patient’s activity level. The most common clinical signs of thrombocytopenia include: easy bruising, petechia, purpura, menorrhagia, and bleeding from mucous membranes such as the nose, mouth, and gastrointestinal tract. More worrisome signs and symptoms of internal bleeding include: hematuria, headache, dizziness, retinal hemorrhages, hematemesis, melena, precipitous decrease in Hgb and Hct levels, and symptoms of a cardiovascular collapse (e.g., tachycardia, hypotension, peripheral vasoconstriction).

Intracranial bleeding is a serious potential complication of thrombocytopenia. Such bleeding may be particularly difficult to diagnose in infants and toddlers, because it can produce vague symptoms such as irritability, fussiness, and poor feeding. In patients with severe thrombocytopenia, nurses must quickly identify and investigate any change in level of consciousness or behavior, severe headache, vision changes, ataxia, slurred speech, complaints of weakness or numbness, and severe vomiting not associated with nausea; these may be signs of intracranial hemorrhage.

Management

The priority for management is to prevent, quickly detect, and treat bleeding episodes. Nurses should test urine, gastric drainage, and stool for the presence of blood, report any positive results, and watch for any signs of frank bleeding. Nurses should handle the patient gently, provide a soft mechanical diet, provide stool softeners, and avoid rectal medications. Intramuscular injections are to be avoided, and prolonged pressure must be applied to any injection or venipuncture sites. Aspirin and other drugs (e.g., some antiinflammatory agents) that inhibit platelet function are contraindicated.

If severe thrombocytopenia is present, nurses should perform neurologic examinations frequently and with any change in patient condition. Unilateral headache is often a sign of intracranial hemorrhage.

Prophylactic platelet transfusion is provided if the platelet count is less than 10,000/mm³, to reduce the risk of spontaneous intracranial hemorrhage. Although published data indicate no difference in outcomes for patients with leukemia when platelet transfusion thresholds were 10,000/mm³ or 20,000/mm³ in the absence of active bleeding, institutional practices vary widely based on local practice guidelines.²⁸ In general, lower thresholds are used for platelet transfusion for children with conditions such as fever, central nervous system tumors, bleeding, or coagulopathies or those requiring procedures.² Patients can safely have “major invasive procedures” such as bone marrow aspirate and biopsies with platelet counts of 50,000/mm³; the thresholds can vary slightly among institutions.^23,24,28

It is important to identify the underlying cause of thrombocytopenia to provide appropriate therapy. For patients with decreased platelet production or bone marrow failure, provide supportive care, including administration of platelet transfusions to maintain hemostasis and treatment of the underlying disorder or continuing support until the condition resolves.

Patients with immune-mediated thrombocytopenia typically do not benefit from platelet transfusions, because administered platelets will likely be destroyed by the same mechanism that produced the thrombocytopenia. However, when life-threatening bleeding is present, platelet transfusion is provided. HLA-matched platelet transfusions can increase platelet count more effectively, but will be more challenging to acquire.

Patients with immune-mediated platelet destruction can be treated with high-dose steroids (prednisone, 4 to 8   mg/kg per day), intravenous immune gamma globulin (0.5 to 1   g/kg of immunoglobulin G), or both. Children with exceptionally low platelet counts and acute bleeding require inpatient hospitalization with close observation. Bone marrow aspirate is recommended before initiating high-dose methylprednisolone (30 to 50   mg/kg per day) to treat severe bleeding. These children may also receive a 2- or 3-day course of intravenous immune gamma globulin.¹³ Frequent monitoring of laboratory tests may be necessary until the platelet count improves. Monitor the patient closely for signs of bleeding.

When thrombocytopenia is chronic, caretakers and patients (if age-appropriate) should be taught safety precautions, including restriction of high-risk activities and management of common bleeding episodes. Children with chronic thrombocytopenia should wear medical alert jewelry.

Etiology

Disseminated intravascular coagulation is characterized by the intravascular consumption of platelets and plasma clotting factors.¹³ DIC is not a primary disease but a complication of other disease processes.²⁷ DIC can complicate sepsis, hypoxemia, major trauma with severe tissue injury, malignancy, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome (HUS), extensive burns, and severe viral infections (Box 15-4).

Pathophysiology and Clinical Signs and Symptoms

DIC is characterized by an abnormal coagulation process—the entire clotting mechanism is triggered inappropriately. Unrestrained clotting causes systemic or local formation of fibrin clots. This development of fibrin clots leads to microthrombi and excessive bleeding secondary to the consumption of the platelets and clotting factors. The fibrin clot development triggers the clotting cascade process to break down the clots and fibrin that have been formed. Fibrinolysis results in the development of fibrin degradation products, which in turn will act as anticoagulants and promote more bleeding. Organ injury may be the end result of intravascular clots, which cause microvascular occlusions and anoxia.²⁰ In addition, when the RBCs flow through obstructed vessels the end result is additional hemolysis that can lead to hemolytic anemia (Fig. 15-2).

Fig. 15-2 Pathophysiology of disseminated intravascular coagulation.

DIC, Disseminated intravascular coagulation; FDP, fibrin degradation products.

(From Pagana K, Pagana T: Mosby’s manual of diagnostic and laboratory tests, St Louis, 2006, Mosby-Elsevier.)

The mechanisms producing DIC are not completely understood. Excess activation with subsequent depletion of essential coagulation factors produces unrestrained clotting and consumption of procoagulants, and bleeding results. The final common pathway includes production of thrombin, which converts the soluble clotting protein—fibrinogen—into insoluble fibrin, the major component of normal clots.

Microthrombi will be present, and fibrin deposition will occur in the microvasculature. In turn, disseminated deposits of fibrin trap and destroy platelets and RBCs and consume clotting factors, so that a consumptive coagulopathy (synonymous with DIC) results. This process, if unchecked, can result in continuous activation of clotting components and a collapse of normal hemostasis, with resultant widespread bleeding and clotting manifestations. The patient with DIC then demonstrates evidence of both excessive clotting (with a fall in fibrinogen, consumptive coagulopathy, and presence of fibrin monomer) and clot breakdown (with a resultant rise in levels of fibrin degradation products).

If low-fibrin degradation product DIC is present, a predominance of clot formation is present, and embolic vascular obstruction is likely to occur. Renal artery embolization will produce renal failure, and peripheral extremity embolization will result in ischemia and necrosis of digits or extremities.

The clinical signs and symptoms of DIC include: petechia, purpura, ecchymosis, hematomas, prolonged oozing, or bleeding from orifices or minor procedures such as venipuncture sites or incisions. Critically ill patients in the critical care unit may also experience life-threatening thrombotic complications of DIC, such as uncontrolled bleeding, pulmonary embolism, stroke, renal compromise, organ failure, ischemia, and possible gangrene of extremities. Closely monitor the child with DIC to detect changes in perfusion, level of consciousness, organ function, and urine output.

No single test can be used to diagnose DIC. Laboratory abnormalities consistent with the diagnosis of DIC include thrombocytopenia, prolonged PT or activated partial thromboplastin time (aPTT), decreased fibrinogen, elevated fibrin degradation products (fibrin split products), and anemia (Table 15-1). The presence of fibrin monomer indicates that fibrinogen is being broken down by thrombin and that clot is being formed. A rise in fibrin monomer is an early indication of DIC.

Table 15-1 Disseminated Intravascular Coagulation Blood Tests

Management

The primary goal of management of DIC is identification and treatment of the underlying cause. However, supportive therapy is often needed to reverse existing coagulation abnormalities and to treat shock. The healthcare team will use clinical and laboratory data to monitor the course of the disease and the patient’s response to therapy.

Perform frequent and ongoing assessment to detect and treat shock, bleeding, or any compromise in organ perfusion and function. Evaluate tissue perfusion and oxygenation and monitor for bleeding, petechiae, dyspnea, lethargy, pallor, tachycardia, hypotension, headache, dizziness, muscle weakness, and restlessness. When the patient is actively bleeding, the nurse must measure external blood loss, avoid disturbing clots, and control bleeding by applying pressure and ice. The nurse must also monitor for internal bleeding, by checking both the urine and stool for occult blood, and for signs of intraabdominal and intracranial bleeding.

Patients with DIC may require frequent administration of blood or blood components. The overall prognosis for DIC has improved significantly over the last two decades because of advances in critical care, such as prompt recognition of DIC, and improved supportive care such as treatment of shock and antifibrinolytic and blood transfusion therapy.

Heparin can be administered to patients with purpura fulminans (e.g., DIC with necrosis of digits and thromboembolic phenomena). In this case, the fibrin degradation products may be elevated moderately, suggesting that little clot breakdown is occurring, and clot formation predominates. Before heparin therapy is initiated under these conditions, plasma must be administered to restore levels of antithrombin III in order for heparin to provide anticoagulation.

Etiology

Hyperleukocytosis is defined as a peripheral WBC count greater than 100,000/mm³. This common oncologic emergency is often a presenting symptom of patients with leukemia, specifically acute myelogenous leukemia and acute lymphoblastic leukemia.

Pathophysiology

As the patient’s WBC count increases, so do the complications that may be present. Hyperleukocytosis results in increased blood viscosity, which can in turn obstruct blood vessels, leading to thrombi development in the microcirculation. Patients with acute nonlymphoblastic leukemia (ANLL) may develop sequestration of blast cells in the lungs, producing intrapulmonary shunting. Patients with ANLL are most likely to develop cerebral thromboembolic events, because the myeloblasts readily adhere to one another. All patients with hyperleukocytosis may develop metabolic abnormalities from cell lysis (see Acute Tumor Lysis Syndrome), including hyperkalemia, hyperuricemia, hyperphosphatemia, and hypocalcemia.

Clinical Signs and Symptoms

Patients with hyperleukocytosis often have clinical complications from clumping of the leukemia cells in the lungs and brain,²⁷ with resultant pulmonary sequestration or cerebral thromboembolic events. Signs and symptoms of pulmonary sequestration include hypoxia, restlessness, agitation, shortness of breath, tachypnea, cyanosis, decreased lung sounds, and increased work of breathing. Respiratory distress will persist despite oxygen administration.

The clumping of the WBCs in the central nervous system and cerebral thromboembolic events (infarct or hemorrhage) can cause blurred vision, headache, decreased level of consciousness, confusion, disorientation, inability to follow commands, and pupil dilation. Stroke or intracranial hemorrhage can produce increased intracranial pressure with decrease in level of consciousness and pupil dilation. Signs of impending cerebral herniation include bradycardia, systolic hypertension and abnormal breathing pattern (possible apnea).

If there is reason to suspect intracranial bleeding or infarct, a neurosurgeon should be consulted. Diagnostic testing can include computed tomography (CT) or magnetic resonance imaging (MRI) if the patient’s clinical condition is stable.

Management

Perform frequent pulmonary and neurologic assessment to detect early respiratory or neurologic compromise. Evaluate oxygenation and respiratory effort, and evaluate the patient’s ability to follow commands, pupil size, and response to light. Next, immediately investigate any change in level of consciousness or headache (see Increased Intracranial Pressure in Chapter 11). In addition, monitor systemic perfusion and fluid and electrolyte balance.

The initial intervention for patients with an increased WBC count is hyperhydration (approximately 3000   mL/m² per day). In general, avoid (or use with caution) fluids containing potassium, because the rapid WBC turnover increases the risk of hyperkalemia.

Uric acid-lowering agents such as oral allopurinol (rasburicase [Elitek]) are given. These drugs assist in reducing the uric acid level and usually prevent the development of hyperuricemic nephropathy (renal failure). For the majority of newly diagnosed oncology patients, oral allopurinol is sufficient as a uric acid lowering agent; the intravenous form is reserved for patients with large tumor burdens and/or for children who are unable to take oral medications.

Closely monitor the patient’s fluid intake and output, CBC, electrolytes, and daily weight. Test the urine for the presence of blood. Urine output should average 1-2   mL/kg per hour.

In addition to hyperhydration, other methods to reduce hyperleukocytosis can include leukapheresis, exchange transfusions, and chemotherapy administration. Improved supportive care in the critical care environment has greatly reduced the permanent complications of hyperleukocytosis and has improved the quality of life of oncology patients experiencing this medical emergency.

Etiology

Acute tumor lysis syndrome (ATLS) is a metabolic condition that can occur as a result of rapidly proliferating malignancies, such as Burkitt’s lymphoma, or following induction chemotherapy for malignancies that have a large tumor burden, leukemia with high WBC count, and tumors that respond rapidly to chemotherapy. ATLS can occur immediately after therapy, but most often will be observed 2 to 3 days after initiating treatment. The syndrome typically lasts approximately 7 days.⁴

One of the key factors in development of ATLS, regardless of the underlying malignancy, is the presence or development of hyperuricemia. As a result, oncology patients at risk for ATLS include those with impaired renal status such as those with dehydration, hyperuricemia, or underlying renal abnormalities.

Pathophysiology

ATLS occurs when there is a rapid breakdown of cells with a release of intracellular contents into the circulation. These metabolites can overwhelm the ability of the kidneys to excrete them, so they accumulate in the blood. Electrolyte abnormalities include hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. Hyperuricemia can result in the formation of uric acid crystals in the kidneys and urinary tract, producing renal obstruction and failure.

Destroyed cells release a large amount of potassium, producing hyperkalemia that can rapidly worsen with the development of renal failure (Fig. 15-3). Hyperkalemia is one of the most dangerous electrolyte imbalances, and fatal arrhythmias may occur with potassium levels greater than 7.0   mEq/L. Hyperphosphatemia can cause the formation of calcium phosphate crystals. Similar to uric acid crystals, calcium phosphate crystals can also obstruct the renal tubules compromising renal function. The precipitation of calcium phosphate crystals also may cause a secondary hypocalcemia.

Fig. 15-3 Acute tumor lysis syndrome.

Clinical Signs and Symptoms

Identifying patients at risk for tumor lysis syndrome can assist in prompt recognition and treatment. Hallmark metabolic abnormalities are hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. Patients may also develop an elevated blood urea nitrogen (BUN) and creatinine, elevated lactic dehydrogenase (LDH) and elevated WBC. Because the LDH is a marker of cell turnover, a high initial value is suggestive of rapid cell turnover, such as with Burkitt’s lymphoma or leukemia; ongoing monitoring of LDH is not typically needed.

Clinical symptoms include abdominal or flank pain, nausea, vomiting, decreased urine output, edema, muscle cramps, twitching, numbness, tingling, lethargy, and fluid overload. Symptoms can include those of complications of renal failure and signs of hypervolemia, hyperkalemia, and hypocalcemia, such as CHF, cardiac arrhythmias, seizures, and cardiac arrest.

Management

The best treatment for ATLS is identifying patients at risk and instituting therapy to avoid the complications of rapid cell breakdown. Once ATLS is present, nurses should closely monitor the patient’s heart rate and rhythm, systemic perfusion, fluid intake and output, CBC, electrolytes, and daily weight.

Uric acid crystal formation can be reduced with intravenous hyperhydration (approximately 3000   mL/m² per day). Avoid, or use cautiously, intravenous fluids that contain potassium, because the patient is already at risk for hyperkalemia.

A uric acid-lowering agent such as oral allopurinol (rasburicase) is administered. Allopurinol assists in reducing the uric acid level and usually prevents the development of hyperuricemic nephropathy (renal failure). Currently, the intravenous form of allopurinol is extremely costly; in light of the effectiveness of oral allopurinol (rasburicase) the intravenous form is reserved for children who are unable to take oral medications.

Closely monitor renal function; place a urinary catheter to enable continuous evaluation of urine output. In general, fluids are administered to maintain urine output of at least 2   mL/kg per hour. Test the urine for the presence of blood.

For asymptomatic hyperkalemia, treatment includes diuretics such as furosemide (Lasix) or mannitol or the administration of sodium polystyrene sulfonate (Kayexalate) orally or rectally. The rectal route (i.e., enema) will reduce the serum potassium faster than oral administration, but the oral route will result in a greater reduction over several hours.¹² Symptomatic hyperkalemia requires more aggressive interventions such as calcium, sodium bicarbonate, and insulin and glucose infusion, which shift potassium back into cells. Other interventions for symptomatic hyperkalemia can include peritoneal dialysis, hemodialysis, and continuous venovenous hemofiltration. For additional information about hyperkalemia, see Chapter 12; for additional information about renal failure, see Chapter 13.

Hyperphosphatemia does not produce symptoms, but it will produce hypocalcemia and related symptoms. The phosphate combines with calcium and forms a precipitate in tissues. The serum ionized calcium is considered a more sensitive and reliable indicator of effective calcium concentration than the total calcium concentration.²⁰ Signs of hypocalcemia include: a positive Chvostek’s sign (spasm of facial muscle following a tap over facial nerve, seen in tetany), a positive Trousseau sign (carpal-pedal spasms resulting from compression of an extremity artery, indicative of latent tetany), and prolongation of the Q-T interval on the electrocardiogram. Correction of the hypocalcemia is usually contraindicated unless the patient is symptomatic with the neuromuscular irritability (e.g., seizures, positive Chvostek or Trousseau signs).

Additional management of ATLS includes: strict monitoring of intake and output, checking weight at least daily (twice per day is preferable), assessing for edema and ascites, assessing fluid volume status, and monitoring laboratory values. Serial electrolytes may be ordered every 6 to 8 hours. Close attention to electrolyte abnormalities is important to prevent further complications and to quickly detect and treat imbalances.

Etiology

Severe hypercalcemia is defined as a total calcium greater than 15   mg/dL. Total calcium concentration above this level may be life threatening.¹⁴ Hypercalcemia is associated with malignancies such as acute lymphoblastic leukemia, lymphomas, some soft tissue sarcomas, renal cell carcinoma, and lung and breast cancer. It is less common in pediatric than in adult oncology patients.

Pathophysiology

Mild hypercalcemia (total calcium less than 15   mg/dL) is generally not life threatening; however, significant elevations in calcium levels (greater than 15   mg/dL) can produce cardiovascular and renal complications. Hypercalcemia develops when a parathormone-like substance is released from malignant cells. This substance stimulates bone reabsorption and the release of calcium. Hypercalcemia can also result from malignancies causing bone destruction and from decreased renal calcium excretion.^16,20,26

Hypercalcemia can produce complications similar to hyperparathyroidism, including development of renal stones, osteoporosis, and neuromuscular pain and tingling. Severe hypercalcemia can produce a polyuria-polydipsia syndrome with dehydration. If the polyuria produces dehydration, renal excretion of calcium is reduced; this can exacerbate the hypercalcemia.

Clinical Signs and Symptoms

Most children with hypercalcemia are asymptomatic. As calcium levels increase, clinical signs include polyuria, increased thirst (polydipsia), dehydration, anorexia, nausea, vomiting, constipation, depressed reflexes, decreased muscle strength, and bone pain and fractures. Hypercalcemia can cause electrocardiogram changes, including shortened Q-T interval and depressed T waves, that when severe can cause cardiac arrest. Hypercalcemia and hyperparathyroidism produce similar signs and symptoms; astute clinical assessment is needed to distinguish them.

Management

The healthcare team should identify patients at risk for hypercalcemia and monitor serum and ionized calcium levels throughout therapy to evaluate response to treatment. Treatment of mild hypercalcemia (calcium less than 15   mg/dL) is directed at the primary disease process and is largely supportive. Administer intravenous normal saline in quantities sufficient to promote diuresis.

For symptomatic patients with calcium greater than 15   mg/dL, the priority of care is support of intravascular volume with administration of intravenous normal saline. Carefully monitor intake and output, obtain urine for analysis (specific gravity is usually low, indicating the kidneys’ inability to concentrate urine), and administer loop diuretics (such as furosemide) to promote calcium excretion.

With life-threatening hypercalcemia, more aggressive therapy is needed to reduce the serum calcium. Biphosphonate inhibits bone reabsorption, calcitonin inhibits calcium reabsorption from bone, mithracin reduces osteoclast activity, and gallium nitrate interferes with osteoclast function (Table 15-2).¹⁴ These drugs typically reduce the serum calcium concentration over several days.

Table 15-2 Medications for Severe Hypercalcemia

* Pamidronate dose from Kerdudo C and others: Hypercalcemia and childhood cancer: a 7-year experience. J Pediatr Hematol Oncol 27:23-27, 2005. Remaining doses from National Cancer Institute: Hypercalcemia (PDQ). Available at: http://www.cancer.gov/cancerinfo/pdq/supportivecare/hypercalcemia. Accessed January 4, 2012.

When treating hypercalcemia, closely monitor the child’s urine output, renal function, serum calcium, and phosphate and magnesium levels. Delayed hypokalemia, hypophosphatemia and hypomagnesemia may develop. Renal replacement therapies may be needed if hypercalcemia is complicated by renal failure.

Etiology and Pathophysiology

Neutropenia is defined as an absolute neutrophil count of less than 1000/mm³ in infants younger than 1 year and 1500/mm³ in children older than 1 year.¹³ The ANC is the total number of WBCs multiplied by the percentage of neutrophils (segmented neutrophils or segs plus bands). (For calculation, see Box 15-1.) The National Cancer Institute neutropenia grading system developed a classification scale for neutropenia (Box 15-5). The risk of serious bacterial infection increases dramatically when the ANC is less than 500/mm³.

In addition to the classification of severity, neutropenia can be further classified as acquired or congenital; acquired neutropenia is more common than the congenital form. Acute acquired neutropenia can be caused by an acute transient neutropenia or infections. Viral infections that may cause acquired neutropenia include respiratory syncytial virus, hepatitis A and B, Epstein-Barr virus, measles, rubella, and varicella. Bacterial infections that can cause acquired neutropenia include typhoid, paratyphoid, tuberculosis, and rickettsia infection.¹³ Acquired chronic neutropenia can be caused by bone marrow aplasia, bone marrow infiltration, or treatment such as chemotherapy, radiation therapy, or immunosuppressive medications. Bone marrow infiltration leading to neutropenia can result from diseases such as neuroblastoma, lymphoma, or rhabdomyosarcoma.

Congenital neutropenia, or primary neutropenia, is usually profound and is caused by a genetic abnormality. Examples include severe combined immunodeficiency syndrome, Wiskott-Aldrich syndrome, and Kostmann’s syndrome. Often these congenital neutropenia disorders are associated with the future development of more serious illnesses, such as myelodysplastic syndromes or acute myelogenous leukemia.

Neutrophils provide the major defense against bacterial invasion, so neutropenia is associated with increased risk of infection. Patients with neutropenia can develop infection or sepsis from organisms in the body. These opportunistic infections may include Staphylococcus epidermidis, S. aureus, Klebsiella species, Escherichia coli, and Pseudomonas species.

Clinical Signs and Symptoms

The child with neutropenia requires a detailed history and physical examination. Carefully assess for signs or symptoms of infection, especially infection of the mouth, skin, ears, and perianal area. Neutropenia produces no symptoms. Because neutrophils play a major role in the inflammatory response, signs of inflammation (e.g., redness, edema, drainage) may be absent from sites of infection. Fever may be the only clinical sign of an infection. Assess for the presence of lymphadenopathy, organomegaly, pallor, bruising, petechia, and other abnormalities. Ask patients about any localized pain or discomfort. Infants and small children may exhibit nonspecific clinical signs and symptoms of infection or sepsis, such as irritability, fussiness, and poor feeding, and can develop a change in level of consciousness.

If fever is present in a child with neutropenia, obtain blood and urine cultures. Additional evaluation as indicated by physical assessment findings often includes a chest radiograph, and cultures of stool, throat culture, cerebral spinal fluid (CSF), and any wounds. Be vigilant while evaluating for potential infections, because this patient population is at high risk for developing life-threatening infections.

If the child has other clinical findings such as pancytopenia (all cell lines depressed) with no known cause, then a bone marrow aspirate may be indicated. The bone marrow aspirate often determines the cause of the neutropenia.

Management

The most important aspect of care for patients with neutropenia is to protect them from potential infections. Every member of the healthcare team should practice strict hand hygiene using both soap and water and alcohol based gels for all contacts with patients with neutropenia. Patients with neutropenia should have limited invasive procedures if possible. In addition, nurses should avoid obtaining rectal temperatures or giving medications via the rectal route.

Treatment of neutropenia is primarily supportive with a focus on evaluating risk for infection and on detecting and treating infection. Patients may be treated with colony-stimulating factors such as granulocyte colony-stimulating factor (GCSF; Neupogen [Amgen]) that stimulate the bone marrow to produce more neutrophils.¹³

Fever, defined as an oral temperature greater than 38° C, in the patient with neutropenia should be treated as a potential medical emergency because the patient may develop septic shock.⁹ After cultures are obtained, administer broad-spectrum antibiotics while waiting for culture results; administer antibiotics within 1   hour of the child’s first medical contact. Dosing is often adjusted based on reported culture and sensitivity results. Monitor the child’s vital signs and appearance to detect clinical signs of sepsis or septic shock, such as hyperthermia, hypothermia, tachycardia, hypotension, and changes in perfusion. Note that children with gram-negative bacteremia may deteriorate after antibiotic administration, because lysis of the gram-negative bacteria results in endotoxemia that can perpetuate the septic cascade.

Treatment of septic shock requires immediate antibiotics, aggressive fluid resuscitation, and hemodynamic support with vasoactive agents. Survival from septic shock has increased dramatically in recent years following appreciation of the need for repeated fluid bolus therapy (often totaling 80   mL/kg or more in the first hour of therapy and 240   mL/kg or more in the first 8   h of therapy) and early vasoactive support. For further information, see Chapter 6, and Fig. 6-8.

Nurses should teach patients with neutropenia the importance of strict handwashing, avoiding crowds and contacts who are ill, meticulous skin and oral care, and a low-microbial diet. Adolescent females with neutropenia should not use tampons, to reduce the risk of toxic shock syndrome. Patients should be aware of signs and symptoms that should be reported to a healthcare provider immediately including fever, pain, inflammation, and changes in level of consciousness.

Etiology and Pathophysiology

Spinal cord compression is a neurologic emergency that requires immediate treatment to prevent permanent disability. It is usually attributed to tumor growth near the spinal cord or increased pressure in the spinal column. Tumors most likely to cause spinal cord compression include brain and central nervous system tumors, sarcomas (rhabdomyosarcoma, Ewing’s sarcoma, and primitive neuroectodermal tumors), neuroblastomas, and lymphomas.

Clinical Signs and Symptoms

Many patients with spinal cord compression complain of back pain. Other clinical symptoms will be related to the level and degree of cord compression. Motor deficits may include weakness, unsteady gait, paralysis, hyporeflexia, muscle atrophy, and paralysis. Sensory deficits can include the inability to sense pain or changes in temperature, bowel or bladder dysfunction, and paresthesias. A thorough neurologic evaluation with special attention to reflexes and strength will help identify these deficits.

A preliminary spine radiograph is the often the first and most convenient diagnostic test, but it is not definitive. To image the soft tissues involved, a CT scan is definitive, and an MRI study can further delineate the size and location of the tumor. If the patient with suspected spinal cord compression has possible increased intracranial pressure, such as caused by brain tumors with spinal (drop) metastases, then a CT scan should be obtained to rule out increased intracranial pressure before a lumbar puncture is performed to evaluate the cerebral spinal fluid. CSF protein will be elevated in patients with complete spinal cord obstruction.²²

Management

Children with the diagnosis of cancer and complaints of back pain should be evaluated for a spinal cord compression. Prompt referral to a neurologist and neurosurgeon is needed to provide immediate treatment and prevent permanent neurologic dysfunction. Some patients will require surgical intervention, such as tumor debulking or laminectomy. Medical treatment includes high-dose corticosteroids (dexamethasone 1 to 2   mg/kg), chemotherapy, or emergency radiation (if the tumor is radiosensitive) therapy directed to the tumor site.

Some patients may be candidates for newer treatments such as spinal stereotactic radiosurgery (i.e., stereotactic radiotherapy or CyberKnife [Accuray Incorporated]). These therapies deliver higher radiation directly to the tumor and attempt to preserve surrounding tissue.

Several factors influence the outcome of a spinal cord compression treatment plan. Patients with minimal neurologic involvement have more favorable outcomes than do patients with complete paralysis or other severe neurologic deficits. The importance of prompt assessment and treatment cannot be overstated.

Nursing responsibilities include supportive care measures. The child requires pain management, frequent neurologic assessment, position changes with skin care assessment, and maintenance of bowel and bladder function. Provide explanations to the child and family throughout the child’s care.

Etiology

A mediastinal mass is a tumor that may be growing rapidly and thus causing respiratory compromise and airway obstruction. Some mediastinal masses also produce superior vena cava (SVC) obstruction. Childhood cancers most often causing mediastinal mass are non-Hodgkin’s lymphoma, Burkitt’s lymphoma, T cell lymphoblastic lymphoma or leukemia, neuroblastoma, and sarcomas.²² The most common cause of mediastinal mass in pediatric oncology is non-Hodgkin’s lymphoma.

Pathophysiology

Tumors of the mediastinum can affect the airway structures of the trachea and main bronchus. These tumors often grow rapidly, producing airway compression that progresses rapidly. In addition to respiratory compromise, the mediastinal mass may produce compression or obstruction of the superior vena cava, causing SVC syndrome. SVC compression results in a decreased venous return from the head, neck, and upper chest area to the heart. In some cases, this obstruction may be life-threatening. Often collateral flow through the intercostal veins will aid venous return.

Clinical Signs and Symptoms

Patients with mediastinal airway or vascular compression can be asymptomatic until the compression is critical or the patient receives sedation or anesthesia. Changes in airway tone, chest wall compliance, and respiratory effort that may result from sedation or anesthesia can contribute to collapse or compression of airways and nearby vascular structures, with consequent cardiorespiratory collapse.

Once the patient with mediastinal mass develops symptoms of airway compression, these symptoms typically progress rapidly. The initial clinical symptoms can include mild respiratory distress such as cough, hoarseness, orthopnea, and chest pain. These symptoms can quickly progress to moderate or severe respiratory distress, and the patient may experience wheezing, stridor, dyspnea, increased respiratory effort, and changes in level of consciousness. If the mass produces SVC obstruction, the patient may also develop edema of the face, neck, and upper extremities, cyanosis, or a plethora of upper body and distended neck veins.

A chest radiograph will usually reveal a large mass in the anterior mediastinum and possible tracheal deviation. Be extremely careful during positioning of the child for diagnostic procedures, because the supine position will often exacerbate tumor compression of the airways and increase respiratory distress. A CT or MRI scan may be useful in determining the extent of tracheal compression, but the patient’s condition may be too unstable to tolerate the transport to the radiology department or the time or positioning required for the studies (see Fig. 10-24).

Management

Patients with a mediastinal mass require immediate treatment and may deteriorate rapidly as treatment is provided. The goal of treatment is to prevent further respiratory deterioration; the basic principle of management is to keep the patient breathing spontaneously if possible. Emergent tracheal intubation may be required, but will not maintain the airway if the mass compresses the trachea distal to the end of the tube. If such distal compression is present, the airway can be maintained by rigid bronchoscopy. For severe distal airway compression, rapid initiation of extracorporeal membrane oxygenation (ECMO) support may be required (see Chapter 7).

Perform thorough and ongoing assessment of cardiorespiratory function, and support adequate airway, oxygenation, and ventilation. Positioning the child on the side or even the prone position may minimize airway compression. Intubation must be performed by skilled providers and the nurse should be prepared for the need for emergent bronchoscopy or ECMO. Healthcare providers should use extreme caution when administering sedation to the nonintubated patient with a mediastinal mass, because a decrease in the child’s respiratory effort and change in muscle tone can result in cardiorespiratory collapse.

A malignant mass is treated with emergent radiation therapy, chemotherapy, steroids, or surgical resection. Tissue diagnosis is desirable to guide treatment, but in emergent situations chemotherapy can be initiated based on a presumed diagnosis. A tissue biopsy can be performed when the patient’s clinical condition permits.

Most mediastinal tumors are radiosensitive, so radiation therapy can effectively shrink large mediastinal tumors. However, radiation therapy is usually not a desirable option for pediatric patients with critical airway compromise. If radiation is administered, the patient may initially experience some airway edema, so that symptoms may become worse before they improve. The majority of these masses are associated with the diagnosis of T cell leukemia or a type of lymphoma. Surgery is occasionally needed in select cases.

Etiology and Pathophysiology

Typhlitis is an invasion of bacteria in the intestines, most commonly the cecum, leading to necrotizing colitis. The consequences of the bacterial invasion can range from a mild inflammation to a severe full thickness infarction, which may progress to an acute bowel perforation. The primary organisms responsible for typhlitis are anaerobes and gram-negative bacilli. Also, Clostridium difficile is becoming more prevalent as an etiology of typhlitis. The patient population most at risk is the oncology patient with prolonged neutropenia. In fact, it is the most likely cause of abdominal pain in an oncology patient with prolonged neutropenia. High-risk patients include leukemia patients (e.g., those with acute myelogenous leukemia) on induction therapy or leukemia patients with a high WBC count and patients with infections or mucositis.

Clinical Signs and Symptoms

The patients most at risk should be identified and assessed thoroughly for possible typhlitis. The presenting symptoms are abdominal pain to the right lower quadrant, fever, distended abdomen, diminished or absent bowel sounds versus high pitched bowel sounds, nausea, vomiting, and diarrhea. Patients with neutropenic enterocolitis, typhlitis, or appendicitis may have similar presenting signs and symptoms. To accurately diagnose typhlitis, an ultrasound examination of the abdomen and a CT scan may be necessary. The area of the bowel most often affected is the cecum of the large intestine.

Management

Patients with typhlitis are severely neutropenic, so they are best managed medically. Treatment includes administration of broad-spectrum antibiotics, bowel rest, hydration, nutritional support, pain management, and administration of blood products as needed. Infectious disease specialists are often consulted to assist in antibiotic selection. A surgical evaluation may be necessary if the patient has symptoms of an acute abdomen, including active bleeding despite correction of thrombocytopenia and coagulopathies, free air in abdomen, or overwhelming sepsis.

Additional nursing interventions include administration of intravenous antibiotics, pain management, careful gastrointestinal assessment, and monitoring for signs of an acute abdomen, including auscultation of bowel sounds and measurement of abdominal girth. All healthcare providers should adhere to neutropenic precautions.

Etiology and Indications

Treatment for some hematologic, oncologic, and genetic diseases includes hematopoietic stem cell transplant (HSCT), also referred to as bone marrow transplantation. The goal of this therapy is to cure the patient’s illness.

Preparation and Procedure

The preparative regimen consists of near-lethal doses of chemotherapy, radiation, or both. This regimen is designed to ablate the defective bone marrow and create space for new healthy cells to populate. In addition, it is an immunosuppressant to reduce the risk of graft rejection and to decrease the risk of graft-versus-host disease.¹⁷ The combination of the patient’s illness and conditioning regimen can produce severe complications that require critical care. These patients often experience severe myelosuppression and multisystem failure.

There are three types of HSCT: autologous, allogeneic, and umbilical cord blood. Autologous transplantation uses the patient’s own stem cells. These donor stem cells can be harvested through peripheral access or directly from the bone marrow. Patients with solid tumors such as neuroblastoma and brain tumors may be candidates for autologous transplants.

Allogeneic transplantation requires matching of a compatible donor with the recipient’s human leukocyte antigens (HLAs). In the optimal allogeneic transplant, six of six HLAs match between the donor and the recipient. The preferred donor is a sibling of the patient; this is termed a matched related donor. The best allogeneic transplant is a syngeneic transplant; in this transplant, the donor and recipient are identical twins. In most cases, the allogeneic donor may be a matched unrelated donor who has been identified from the registry of bone marrow donors. Use of an unrelated donor often results in more complications than use of sibling-matched donors.

The third type of HSCT is an umbilical cord blood stem cell transplant obtained from a cord blood bank. A cord blood HSCT is also an allogeneic transplant. These stems cells are obtained in the delivery room after childbirth. Stem cells have only recently become available as a viable type of bone marrow transplantation.³

Management

The phases of the bone marrow transplant process are classified as early, immediate, and late. Complications can occur during any phase of the transplant process; see Table 15-3 for complications of the bone transplant process. These patients require numerous admissions to the critical care setting for management of their disease.

Table 15-3 Complications of Hematopoietic Stem Cell Transplant

GVHD, Graft-versus-host disease.

Obtaining a Type and Crossmatch

Before a transfusion is needed, send a patient blood sample for type and crossmatch. The typing identifies the patient’s general blood type (A, B, O, or AB) and whether the patient’s blood type is Rh-negative or Rh-positive (Table 15-5). When blood is sent for typing and crossmatch, the patient’s blood is crossmatched with donor blood to determine compatibility. To reduce error, hospitals require labeling of the patient blood specimen that is sent for typing at the bedside, and placement of a blood bracelet containing the crossmatch number at the time the blood sample is obtained (Box 15-6). In addition, most facilities require a double check with the patient identification and two signatures to prevent fatal errors associated with incorrect blood typing.

In general, to reduce Rh-sensitization in females, Rh-negative blood and blood products are ideally used for female patients of child-bearing age who are Rh-negative. Rh-positive blood and blood products are used for male patients and for female patients who are beyond child-bearing age. This attention to Rh sensitization can reduce the risk of Rh incompatibility during pregnancy.²⁴ Patients who receive multiple transfusions can develop antibodies, and additional blood samples may be required to complete the necessary crossmatching.

Febrile Nonhemolytic Reaction

Fever is one of the most common adverse reactions observed during transfusion, although its frequency has been reduced with the use of leukocyte-depleted blood products. In some cases, pre-medication with acetaminophen can prevent this type of adverse reaction.

A febrile reaction usually occurs upon initiation or shortly after initiation of a transfusion. Signs and symptoms that can occur during a febrile nonhemolytic transfusion reaction include fever, chills, nausea, vomiting, abdominal cramps, and skin flushing. The reaction can progress to include more serious complications such as hemolysis or anaphylaxis with respiratory failure, hypotension, shock.

Monitor the patient’s temperature to identify febrile reactions early and enable prevention or treatment of complications. If the patient develops a febrile reaction, the nurse must immediately stop the transfusion, restart intravenous fluids per physician order or protocol, notify a physician or on-call provider, and closely monitor vital signs and cardiorespiratory function.

Febrile reactions can be caused by bacterial contamination of a unit of blood, because blood products provide an excellent medium for bacterial growth. Bacterial contamination is more common with platelets than other blood products because platelets are stored at room temperature, which allows more bacterial growth than refrigeration.²⁴ Contamination of products can occur at any phase of the transfusion process, from collection to administration. Guidelines from the American Association of Blood Banks¹ require strict adherence to the completion of all transfusions within 4   hours or less to reduce the risk of contamination and cell lysis. In addition, blood collection centers should function within strict guidelines for screening of potential donors and for collection and storage of blood products.

Hemolytic Reaction

The most serious blood transfusion reaction is an acute hemolytic reaction from ABO blood type incompatibility or mismatch. This acute reaction is a medical emergency produced by rapid destruction of the donor red blood cells by the host antibodies. Signs and symptoms include fever, chills, anxiety, lower back pain, pink or red urine, jaundice, disseminated intravascular coagulation, hypotension, renal failure, and death.

If you suspect a hemolytic reaction, stop the transfusion immediately and administer intravenous fluids per physician or provider orders or per protocol; support airway, breathing, and circulation as needed; evaluate patient vital signs; notify a physician; recheck the patient’s identification and compatibility label; and notify the blood bank. Return the unit of blood to the blood bank for re-crossmatching, and obtain blood samples and the first posttransfusion urine sample for urinalysis.

Most hemolytic reactions are from red blood cells. A hemolytic reaction can develop if sufficient incompatible plasma is given during a platelet transfusion.

Allergic Reaction

Another common reaction to transfusion is an allergic reaction triggered by allergens found in the plasma of donor blood. Most of these reactions occur during transfusions in patients who have had a previous exposure to a particular allergen in a blood product. The previous exposure to the allergen stimulated development of antibodies, and the next exposure results in an allergic reaction. The reaction can occur during the next infusion after exposure or during subsequent transfusions.

Symptoms can develop within seconds to hours of the transfusion and include rash, hives, pruritus, swelling of the lips, wheezing, and anxiety. If the patient experiences an allergic reaction, stop the transfusion immediately and restart intravenous fluids per physician order or protocol; assess and support airway, breathing, and circulation; evaluate vital signs; and notify a physician. If the allergic reaction is mild, the transfusion can be restarted after administering an antihistamine such as diphenhydramine (Benadryl). Monitor the patient closely when the transfusion is restarted. In moderate to severe allergic reactions, the patient may require the administration of steroids such as hydrocortisone and possibly epinephrine. The nurse must follow the procedure for transfusion reaction, including documentation and return of the blood product to the blood bank. Future blood transfusions may require prophylaxis with diphenhydramine and hydrocortisone.

Anaphylaxis

In rare cases, an allergic transfusion reaction can progress to life-threatening anaphylaxis, a medical emergency. Patients with immunoglobulin A deficiency may be more susceptible to these reactions. A classic anaphylactic reaction has a sudden onset after administration of only a few milliliters of the blood product. The patient develops bronchospasm, shortness of breath, respiratory distress, and hypotension. The designated staff member at the bedside during the first 15 minutes of the transfusion should be prepared to rapidly identify and respond to these severe adverse reactions. In severe anaphylaxis, stop the transfusion and administer intravenous fluids per physician order or protocol); support airway, oxygenation, ventilation, and circulation as needed; evaluate vital signs; notify a physician; and activate the emergency response system, as appropriate. For further information, see Anaphylaxis earlier in this chapter and in Chapters 6 and 16.

Circulatory Overload

An uncommon transfusion reaction is circulatory overload, also known as transfusion-associated circulatory overload. This complication is caused by rapid administration of a blood transfusion with resulting hypervolemia. At-risk patients include very young patients, patients with impaired cardiac and renal function, and patients with chronic anemia. Clinical signs and symptoms include respiratory distress with pulmonary edema (including dyspnea, rales or crackles, and hypoxemia), distended neck veins, hypertension or hypotension, tachycardia or bradycardia, clammy skin, and peripheral cyanosis. If these symptoms develop, immediately stop the transfusion; support airway, oxygenation, and ventilation and circulation as needed; monitor vital signs; elevate the head of the bed, with the feet in dependent position; and notify a physician (activate the emergency response system if needed). Diuretics may be ordered. Closely monitor cardiorespiratory function and evaluate intake and output.

Transfusion-Related Acute Lung Injury

Transfusion-related acute lung injury (TRALI) is a serious blood transfusion reaction characterized by acute onset of pulmonary edema, a similar clinical picture to acute respiratory distress syndrome. TRALI and clerical error causing mismatched blood transfusion reaction are the most common causes of transfusion-related deaths.⁵ TRALI occurs when there is an atypical antigen-antibody reaction caused by human leukocyte antibodies in the donated blood. These donor antibodies are transfused to the patient during the transfusion; they attach to the patient’s WBCs and form microaggregates. When the microaggregates circulate to the lungs, they trigger an inflammatory response that causes increased vascular permeability, pulmonary edema, and life-threatening respiratory failure.¹⁰

Patients experiencing TRALI can develop sudden signs of respiratory distress such as shortness of breath, hypoxia, hypotension, fever, and abnormal breath sounds. This reaction typically occurs within 1 to 2 hours after the transfusion has started, and full blown acute respiratory distress syndrome can develop within 6   hours.¹⁰ For mild cases of TRALI, the patient may respond to oxygen administration (perhaps with bilevel positive airway pressure) and diuretics. In severe cases, patients will also require intubation and mechanical ventilation with positive end-expiratory pressure. If TRALI is suspected, this transfusion reaction is reportable to the FDA.

Erythrocytapheresis (Red Blood Cell Exchange)

The patient’s RBCs are removed from the patient’s blood and replaced by donor RBCs that are infused into the patient with the patient’s plasma, WBCs, and platelets. This treatment can be used for sickle cell anemia with acute crises, such as acute chest syndrome, cerebral vascular accident, or severe priapism. Other diseases that can benefit from an RBC exchange include erythrocytosis polycythemia vera and severe malaria.¹⁹

Plasmapheresis

Plasma may contain components such as circulating immune complexes, antibodies, inflammatory mediators, lipoproteins, protein-bound toxins, and platelet aggregating factors that can contribute to inflammation and disease. With plasmapheresis, plasma alone is extracted from the patient’s blood and replaced by donor plasma or a plasma substitute that is infused with the patient’s own blood components. Plasmapheresis may be helpful for patients with HUS, autoimmune hemolytic anemia, thrombotic thrombocytopenic purpura, meningococcemia, toxic ingestion, Guillain-Barré syndrome, and systemic lupus erythematosus.

Leukapheresis (Stem Cell Collection or Leukodepletion)

Leukapheresis for a stem cell collection harvests hematopoietic progenitor cells (identified by markers on the white cell called a CD34 antigen) for autologous or allogenic hematopoietic stem cell transplant. Several sessions may be required to collect an appropriate amount of CD34 targeted cells. Hematopoietic growth factors can be administered before the leukapheresis to improve the yield of stem cells. After collection, these cells are cryopreserved for future use; they will be reinfused at a later date, after the preparative regimen has ablated the patient’s bone marrow.

Leukapheresis can also be used to remove excess WBCs in the circulation when patients have high WBC counts (e.g., newly diagnosed patients with T cell lymphomas and patients with acute or chronic leukemias) at risk for acute complications. The patient’s clinical condition, WBC counts, and renal status will determine the need for this type of pheresis, although leukapheresis is commonly used for patients with WBC counts of 100,000/mm³ and greater.

WBC transfusions may be administered to severely neutropenic oncology patients who are septic and unresponsive to traditional therapy. This type of treatment modality is controversial and often a method of last resort.

Adverse Effects of Apheresis

During the apheresis process, there is potential for adverse effects. Table 15-6 summarizes potential complications of apheresis.

Table 15-6 Complications of Apheresis

Etiology

Sickle cell anemia is one of the most common genetic hematologic conditions in children. The disease is transmitted by an autosomal recessive pattern of inheritance; both parents are carriers of the sickle cell gene (For more information, see Evolve Fig. 15-4 in the Chapter 15 Supplement on the Evolve Website).^13,27

Patients with sickle cell disease are homozygous for the sickle cell gene; this means that both genes are abnormal.²⁷ Patients with sickle cell trait are heterozygous for the sickle cell gene; these patients are generally asymptomatic because they possess one sickle and one normal gene.

Pathophysiology

In sickle cell disease, the patient has inherited two copies of the gene for an abnormal Hgb protein, called Hgb S. Hgb S has a single amino acid substitution of valine for glutamine that makes the protein polymerize upon desaturation (i.e., loss of oxygen). The RBC is more susceptible to deformity, causing it to assume the characteristic sickle shape when the Hgb loses oxygen. The higher the percentage of Hgb S in the circulating blood, the more likely the RBCs are to “sickle” during periods of decreased oxygenation.

Sickled RBCs have reduced flexibility and tend to be “sticky” so that they will adhere more readily to the blood vessel walls and to each other, causing occlusion of small vessels and tissue ischemia. Sickled RBCs are more fragile (i.e., they readily hemolyze) so turnover of RBCs is more rapid, causing chronic anemia.¹⁹ These changes in RBC morphology compromise microvascular blood flow and tissue oxygenation that can lead to ischemia and infarcts, in a cycle of hypoxia and RBC sickling called a vasoocclusive crisis.

Sickle cell vasoocclusive crises can involve the central nervous system, bone, lungs or other visceral organs. Sickled cells have the tendency to clump and can cause splenic sequestration (RBC trapping within the spleen that causes sudden anemia, hypotension, and shock), functional asplenia (loss of splenic function from chronic occlusion of splenic vessels), cerebral vascular accident, acute chest syndrome, avascular necrosis of the femoral head, leg ulcers, priapism, hand-foot syndrome (dactylitis), and chronic organ damage.

Complications of hemolysis include anemia, cholelithiasis (gallstones), jaundice, and retarded growth and sexual maturation. The complications that may require critical care are the occurrence of acute chest syndrome, cerebral vascular accident, and priapism (painful and continuous erection of the penis).

The definitive diagnostic test for sickle cell disease or trait is Hgb electrophoresis.¹⁹ This test measures the various types and percentages of Hgb present.

Clinical Signs and Symptoms

The signs and symptoms associated with sickle cell anemia largely result from microvascular occlusions created by the sickled red blood cells; these may be diffuse and may result in organ or tissue ischemia or infarct. Children with sickle cell anemia may also have clinical manifestations of anemia, including weakness, pallor, and fatigue. Patients with sickle cell disease have decreased Hgb and Hct and an elevated reticulocyte count.

Vasoocclusive crises requiring critical care include the complications noted above, acute chest syndrome, cerebral vascular accident and priapism. These conditions are medical emergencies and treatment must be provided immediately to prevent permanent disability or death. Pain associated with vasoocclusive crises may be severe.

Management

Excellent outpatient care of patients with sickle cell anemia may reduce the frequency of many of the complications of the disease. This care includes promoting adequate hydration and avoiding conditions that can contribute to Hgb desaturation (e.g., change in altitude, strenuous exercise) or decreased blood flow (e.g., shock, infection).

At times of crisis, provide immediate hydration with intravenous crystalloids (normal saline or oral re-hydration if tolerated); typically fluids are administered at a rate of 1.5 times maintenance requirements. Adequate hydration promotes hemodilution, increasing blood flow and decreasing risk of microvascular occlusion and tissue ischemia. If the child with splenic sequestration exhibits hypovolemic shock, provide PRBC transfusion to restore intravascular volume and RBC mass. Ultimately, splenectomy may be required.

RBC exchange is used for severe crises, to reduce the concentration of Hgb S. Generally the goal is to reduce the concentration of Hgb S to less than 30%, although this goal is tailored to the patient and the patient’s clinical condition. Pain control is essential, ideally with a combination of both pharmacologic and nonpharmacologic therapies (see Chapter 5); intravenous narcotic administration may be needed. It is helpful to determine the pain control measures that have worked previously.

Assess and support respiratory status and oxygenation. Monitor for signs and symptoms of respiratory distress, auscultate lung sounds (decreased and abnormal breath sounds may indicate complications such as effusion, pulmonary infarct, pneumonia, or edema), evaluate respiratory rate and effort, perform continuous monitoring of oxyhemoglobin saturation, and monitor color and perfusion. Administer oxygen as needed to maintain oxyhemoglobin saturation above 92% to 93%. Inform the medical team immediately of any abnormal findings. Pneumonia and pulmonary infarcts occur more often in this patient population.

Hypertransfusion can be provided for patients who have experienced severe complications, such as a stroke and acute chest syndrome, to prevent further episodes. The patient receives monthly scheduled PRBC transfusions to keep the Hgb S level below 30% (may be tailored to the patient). Hematopoietic stem cell transplant may be performed to cure the sickle cell anemia (see Hematopoietic Stem Cell Transplantation earlier in chapter).

Hemophilia

Pathophysiology

This group of bleeding disorders is characterized by a deficiency of either factor VIII or IX that results in the inability to form a clot at a site of injury. Hemophilia A, also known as classic hemophilia, is characterized by a deficiency of factor VIII. Hemophilia B, also known as Christmas disease, is a deficiency of factor IX.²⁵ Children with hemophilia have prolonged bleeding.

Hemophilia is classified as mild, moderate, or severe; the severity of the bleeding disorder is directly related to the degree of factor deficiency (Table 15-7). The child with a significant factor deficiency will experience more bleeding episodes than the child with mild deficiency. Bleeding is not faster in these patients; bleeding is prolonged and causes the clinical manifestations and risks of complications such as intracranial bleeding, hemorrhage, and hemarthrosis.

Table 15-7 Relationship of Factor Levels to Severity of Clinical Manifestations of Hemophilia A and B

From Lanzkowsky P: Manual of pediatric hematology and oncology, ed 4. Philadelphia, 2005, Elsevier, p. 311.

Clinical Signs and Symptoms

The most obvious sign of a bleeding disorder is persistent oozing, associated with small lacerations or minor procedures. Infant males may be diagnosed after prolonged bleeding after circumcision; the older child may exhibit bleeding after a dental procedure or tooth loss (Table 15-8). Other potential clinical signs and symptoms of factor deficiency include pain, swelling, bleeding into a joint after injury, bleeding from the mouth or nose, and menorrhagia. Life-threatening bleeding events for hemophiliacs include head injury, neck and throat bleeding, an acute abdomen, and bleeding into the iliopsoas muscle near the femoral artery.

Patients with bleeding disorders who develop any head, neck, or torso injury must be evaluated immediately, because bleeding in these areas can be life threatening. When treating life-threatening bleeding, the first and most important step is to stop the bleeding; the diagnostic analysis is completed after replacement factors are initiated.²⁵

Common laboratory tests include aPTT and PT; both will be elevated (prolonged). The most important test is the direct assay of plasma factor activity level for hemophilia A and B.⁸

Management

For any patient with active bleeding, the first priority is to control or stop the bleeding. After bleeding is controlled, patients with hemophilia should receive replacement factor products. The appropriate type and dose of factor products is determined by the location or body part affected and the type of hemophilia present. For example, a patient with factor VIII deficiency with minor trauma can be managed with replacement factor VIII products to raise the factor activity levels to 20% to 40%; this level should provide adequate hemostasis in most circumstances. To control life-threatening (e.g., head injury) bleeding in the same patient requires administration of replacement factors to raise the factor activity levels to 100%. The aPTT should normalize after factor VIII transfusion.

Some patients with hemophilia may benefit from factor prophylaxis to prevent complications and bleeding episodes. Patient treatment plans are individualized, but typically call for infusions three times per week for patients with hemophilia A and infusions twice per week for patients with hemophilia B.²⁵

Rarely, patients with hemophilia can develop inhibitors to coagulation proteins after receiving numerous (more than 20 to 30) doses of replacement factor products.⁸ You should suspect development of inhibitors in patients who have continued prolongation of the aPTT despite receiving 100% of corrective dose of factor products. If the patient develops inhibitors, changes in or additions to the treatment regimen may be necessary to provide adequate replacement factors.

Nursing priorities for the child with hemophilia include control of bleeding, timely administration of factor products, monitoring of laboratory values, and supportive measures including treatment of pain. Patient and family teaching should focus on safety, injury prevention, and avoiding high-risk activities. Patients should also be instructed to wear medical alert jewelry, avoid nonsteroidal antiinflammatory drugs, and intramuscular injections. Finally, for women of child-bearing age with a family history of hemophilia, genetic counseling is recommended.

Procedure

The patient is positioned in the side with the head flexed (chin to chest) and the knees drawn; this position opens the intravertebral spaces. Alternatively, patients can be positioned sitting upright, with the buttocks placed on the edge of the procedure table with the head flexed (chin to chest). Nurses will need to assist the child in maintaining proper position (Fig. 15-4).

Fig. 15-4 Lumbar puncture. (A) The infant or child is usually restrained firmly in the lateral decubitus position, with the spine maximally flexed. The iliac crest is palpated to identify the level of the interspaces between the third and fourth or fourth and fifth lumbar vertebrae. (B) Using sterile technique, and following application of local anesthetic, insert the needle with bevel up, stabilizing the needle with the fingers of both hands. (C) The child may also be restrained in a sitting position for the lumbar puncture. The iliac crest is still palpable. (D) The needle should be advanced slowly into the intervertebral space.

(From Fleisher G, Ludwig S: Textbook of pediatric emergency medicine, ed 2. Baltimore, 1988, Williams and Wilkins.)

Often, pediatric patients will be sedated for this procedure (see Chapter 5). If the patient is not sedated, a topical anesthetic is applied to the puncture site and additional local anesthetic may be used.

This procedure is always performed under sterile conditions. The nurse assists the practitioner with obtaining appropriate supplies and in positioning the patient.

Following sterile preparation and administration of local anesthetic, an appropriately sized spinal needle with stylet is inserted through the skin and into the intervertebral space at the midline, between the third and fourth or the fourth and fifth lumbar vertebrae. The spinal needle is then inserted through the dura and into the subarachnoid space. The stylet is removed and, if indicated, the opening CSF pressure is measured with a manometer. A pressure measurement of 20   cm of water or greater is considered abnormal and is suggestive of increased intracranial pressure.²⁰ The appropriate collection tubes are placed under the needle to collect the cerebral spinal fluid. Providers should describe the color and clarity (or opacity) of the fluid in the chart. For cancer patients who require intrathecal therapy, the appropriate volume of CSF is removed and the chemotherapy is administered.

When the procedure is complete, the spinal needle is removed and an adhesive dressing (typically an adhesive bandage strip) is applied to site. The postprocedure care includes observing the site for any CSF leak and instructing the patient to lie flat for a minimum of 30 minutes to prevent headache. If intrathecal medication is administered, the patient should remain flat to promote even distribution of chemotherapy throughout the CSF.

The CSF specimen is sent to the laboratory to determine WBC count, protein and glucose values (see Table 11-11) and, if appropriate, for cytologic examination for cancer cells and cultures for possible infections. CSF is examined for color and presence of blood. Normal CSF is clear and colorless.

Procedure

Both of these procedures are performed under sterile conditions, and both use large bore needles that contain stylets. After the site is prepared and appropriate local or systemic analgesia is provided, the needle is inserted through the soft tissue of the skin, into the outer layer of the pelvic bone, and into the marrow cavity. The most common site used is the posterior superior iliac crest. Alternative collection sites include the anterior iliac crest, proximal tibia, and sternum. Once the needle is inside the marrow, the stylet is removed and a syringe is attached to obtain specimens. A portion of these specimens is often placed on slides for microscopic examination.²⁰ When the procedure is complete, the bone marrow needle is removed and a dressing is applied. If the patient has a low platelet count, less than 50,000/mm³, then a pressure dressing is recommended.

If an inadequate specimen is obtained with a bone marrow aspirate (often referred to as a dry tap), then a bone marrow biopsy is required for diagnostic purposes. The specimen may indicate little cellular activity or that the bone marrow is packed with abnormal cells, such as in leukemia.