How to Manage Thromboembolism in the Setting of Pediatric Cancer

When treating thromboembolism in a patient with cancer, LMWH is the preferred choice. Warfarin, although it is less expensive and can be given orally, is difficult to regulate in the setting of multiple chemotherapy agents, frequent invasive procedures, and changing vitamin K stores because of antibiotics and illness.^1–3 A randomized clinical trial in adult cancer patients demonstrated that LMWH was more efficacious and as safe as warfarin in preventing recurrent thromboembolism.⁴ The 2008 ACCP guidelines recommend the use of LMWH in the treatment of cancer-related venous thromboembolism for a minimum of 3 months and until the precipitating factor (e.g., use of asparaginase) has resolved.²²² Other practical suggestions have been reported, but none are supported by any systematic observations.^2,5,6

Asparaginase-Related Thrombosis

Management of asparaginase-related thrombosis in ALL can be particularly challenging, and the Dana-Farber Cancer Institute has recently published its experience rechallenging pediatric and adult patients with asparaginase after a first thrombosis. In this retrospective review, survival was similar in patients with and without thrombosis, and the following guidelines were suggested:

Treatment of Immune-Mediated Thrombocytopenia After Solid Organ Transplantation in Children

There is no standard approach to the treatment of immune-mediated thrombocytopenia that occurs after solid organ transplantation. First, all other causes of thrombocytopenia should be ruled out before beginning therapy for what is often a presumptive diagnosis of immune-mediated thrombocytopenia. If the thrombocytopenia is mild to moderate (>20,000-30,000/µL) with no associated bleeding symptoms, we usually observe without intervention and monitor the platelet count on at least a weekly basis. If the platelet count is lower than 10,000 to 15,000/µL or if there is bleeding, immediate treatment is initiated with high-dose corticosteroids: 4 mg/kg/day of prednisone (or intravenous equivalent) divided in three or four doses and continued for 4 days. If there is a response (i.e., platelet count >20,000/µL), the corticosteroid is dropped to 2 mg/kg/day divided in two or three doses and then slowly tapered to zero over the subsequent 2 to 3 weeks. IVIG or anti-D in standard doses used for childhood ITP can be used if there is no response to high-dose corticosteroids.

For patients who have recurrent or chronic thrombocytopenia requiring multiple courses of treatment to maintain platelet counts greater than 10,000 to 15,000/µL, we have used vincristine (1.5 mg/M² [maximum dose, 2 mg] intravenously weekly for 6 weeks) with success. Rituximab (375 mg/M² IV weekly for 4 weeks) has infrequently been used in this situation. For patients taking tacrolimus with refractory thrombocytopenia, serious consideration should be given to switching to an alternative ISD because this may be necessary for resolution of the thrombocytopenia. Involvement of both the transplant team and the hematology team is necessary for ideal management of these complex patients.

Evaluation and Management of Children With Splenomegaly

When evaluating a child with chronic splenomegaly, the clinician must consider all of the possibilities noted in Table 68-4. Clues from the history and physical examination may suggest a specific etiology and direct a tailored approach to the diagnostic laboratory evaluation. If, on the other hand, there is no apparent cause of the enlarged spleen, a number of screening laboratory tests should be performed, including a complete blood count with differential, platelet count, and reticulocyte count; evaluation of the peripheral smear; determination of sedimentation rate; liver function tests; determination of antibody titers to EBV, CMV, and Toxoplasma spp.; antinuclear antibody assay; and ultrasound evaluation of the liver, spleen, and portal system (the last with Doppler flow technique). Further evaluation, including bone marrow examination, may be necessary if the screening tests do not reveal the cause of the splenic enlargement.

Management of splenomegaly usually is that of the underlying disease, when such treatment exists. Splenectomy may be indicated in selected conditions, but the potential benefits from splenectomy must be weighed against the risk of postsplenectomy sepsis, a rapidly progressive bacteremia, most commonly from S. pneumoniae, with a mortality rate of approximately 50%. The risk of postsplenectomy sepsis depends on the age of the patient and the nature of the underlying disorder. Patients younger than 3 years of age and those with a compromised immune or reticuloendothelial system are most susceptible. When elective splenectomy is indicated, it is advisable to (1) postpone surgery until the patient is at least 5 to 6 years of age; (2) administer pneumococcal, meningococcal, and H. influenzae vaccines (if the patient was not previously immunized) at least 1 to 2 weeks before splenectomy; (3) consider use of prophylactic penicillin for at least 4 years; and (4) manage significant febrile illnesses as possible postsplenectomy sepsis at all times. In addition to the risk of postsplenectomy sepsis, the rare complication of postsplenectomy portal or splenic vein thrombosis must also be considered.

For children younger than 5 years of age with severe symptoms from hemolytic anemia, hemoglobinopathy, or hypersplenism, partial splenectomy should be considered. In a number of studies, up to 90% of the spleen has been removed safely, with a high rate of success and preservation of splenic function.^7,8 Regrowth of the spleen to variable degrees has been noted, with occasional need for reoperation.

Table 68-4 Causes of Splenomegaly in Children

CMV, Cytomegalovirus; EBV, Epstein-Barr virus; TORCH, toxoplasmosis, other infections, rubella, cytomegalovirus infection, herpes simplex.