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.