Page 2496 - Hematology_ Basic Principles and Practice ( PDFDrive )

2228 Part XIII Consultative Hematology

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history of thromboembolism. Patients who develop DVT can be HEMATOLOGIC COMPLICATIONS OF SOLID
treated with the standard 3 months of anticoagulation. However, all
children with systemic inflammatory disorders such as SLE, rheuma- ORGAN TRANSPLANT IN CHILDREN
toid arthritis, and IBD are at risk for recurrent thrombi when their
inflammatory process is exacerbated. Therefore children with systemic The frequency and success of solid organ transplant in children have
inflammation and a history of thrombosis should receive prophylactic been increasing over the past decade. In 2004, there were 1816
anticoagulation until the inflammation is well controlled. 297,298 transplants in children, representing 7% of all recipients 308–310 This is
Antiphospholipid syndrome (APS) is defined as a thrombotic event an increase of 13% over the previous decade. Of the transplants done
and persistence of aPL positivity for at least 12 weeks after diagnosis of in 2004, the majority were renal transplants (n = 765), followed by
VTE and occurs both in children with SLE and in those who do not liver (n = 529) and then heart (n = 250–290). The success rate has
have underlying SLE, although they may develop the disease later. In been also improving impressively, with 5-year survival after kidney
a meta-analysis of 16 pediatric studies, there was a statistically signifi- transplant being 95% to 96%, liver transplant 79% to 83%, and
cant association between persistent aPL positivity and first thrombo- cardiac transplant 70% to 75%.
embolism, with an overall odds ratio of 5.9 (95% confidence interval, Hematologic complications after solid organ transplant are a
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3.6–9.7). The management of thromboembolism in primary and common problem. Although most of the evidence regarding the type,
secondary APS is different from most other pediatric thromboembo- frequency, and etiology of these complications has been studied in
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lisms. Patients with APS have a high risk of thrombus recurrence when adults, there are increasing reports in children. After renal trans-
off therapy, and most affected children are treated indefinitely. 289,297 plant, 60% of children are reported to be anemic. After liver trans-
However, the appropriate duration or intensity of prolonged therapy plant, 36% of children will have a hematologic problems, and of
is not known. For children with VTE in the setting of aPL, the ACCP these, 54% are anemic events, 19% anemia and neutropenia, 12%
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guidelines suggest management as per general recommendations in thrombocytopenia, 8% neutropenia, and 2% pancytopenia. After
pediatric VTE, given that there is no evidence to support or refute the heart, heart–lung, or double-lung transplant, 51% of patients have
role of extended anticoagulation in patients with APS. 271 been reported to have hematologic problems, including anemia
The international Ped-APS Registry was established in 2004, and (49%), neutropenia (14%), thrombocytopenia (14%), and anemia
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a published report of the first 121 patients has provided insight into plus neutropenia with or without thrombocytopenia (23%). The
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the clinical and immunologic manifestations of pediatric APS. As etiology of these hematologic problems is most commonly a result of
opposed to APS in adults, pediatric APS is only slightly more frequent infection followed by medication effect. Miscellaneous causes include
in girls (female-to-male ratio, 1.2 : 1), likely because women with blood loss, microangiopathic hemolytic anemia (MAHA), auto-
recurrent fetal losses are not included in this population. Similarly to immune cytopenias, posttransplant lymphoproliferative disease
adults, approximately half of patients present with primary APS. (PTLD), and multifactorial.
Thrombotic events are diverse and include DVT of the lower In the next section, discussion of the hematologic complications
extremities (40%), arterial ischemic stroke (26%), and cerebral sinus of solid organ transplant is divided into cell type and by organ type
vein thrombosis (7%). Multiple aPL positivity is frequent (81% with when feasible. The incidence, etiology, and natural history of the
anticardiolipin antibodies, 72% with lupus anticoagulants, and 67% problem are addressed. Much of the data is derived from adult
with anti–β 2 -glycoprotein I antibodies), but two-thirds of patients studies, but information from pediatric studies is emphasized.
tested negative for one or more of the aPL tests, emphasizing the
importance of testing for all subtypes in clinical practice. Nineteen
percent of pediatric patients with APS experienced a recurrent Red Blood Cells
thrombotic event, even higher than the proportion reported in adult
patients. 300,301 Catastrophic APS (life-threatening multiorgan throm- Anemia is a common problem after transplant, occurring in 66% of
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bosis) occurs rarely in pediatric patients (approximately 10% of all kidney transplant recipients at the time of transplant and in 60%
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cases occur in patients <18 years of age), but it has clinical and labora- to 84% after transplant. In liver transplant recipients, the incidence
tory features similar to those of adult catastrophic APS. 302 is 20% to 35%, 312,316,317 and in recipients of heart or heart–lung or
It is important to note that transient lupus anticoagulants, likely double-lung transplant, it is 30% to 70%. 313,318 There are distinct
the result of infections or immunizations, have been well described patterns of presentation of the problems associated with RBCs,
in healthy children. These incidentally found antibodies are not including early posttransplant anemia, HUS/MAHA, late anemia
associated with an increased risk of thrombosis or bleeding. from immunosuppressant drugs (ISDs), late anemia from other
causes, and pure red cell aplasia (PRCA).
Thromboprophylaxis During Childhood Illness
Early Posttransplant Anemia
The use of thromboprophylaxis to prevent hospital-acquired VTE
has become the standard of care in adult institutions. Even though Early posttransplant anemia is defined as anemia that occurs within
the risk of thrombosis in hospitalized children is much lower than in 6 months from the time of transplant. The etiologies include the
adults, there are patients in pediatric hospitals (particularly adoles- following:
cents and young adults) who should undergo systematic screening for
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thrombosis risk and application of prophylactic measures. Multi- 1. Postoperative hemorrhage
center prospective studies are required to determine the safety and 2. Hemolytic anemia secondary to passenger lymphocyte syndrome
efficacy of prophylaxis, as well as the age cutoff at which prophylaxis or HUS/MAHA
should begin to be considered, but these studies will be very difficult 3. Infection, including bacterial sepsis or viral infections such as
to complete because of the relative rarity of thrombosis in the pedi- CMV, EBV, or parvovirus
atric setting. In a single-center prospective safety evaluation of anti- 4. Medication, including immunosuppressive drugs and other drugs
coagulation prophylaxis in high-risk patients 14 years of age and 5. After renal transplant, iron deficiency or prior uremia or bone
older, there have been no major bleeding complications. 303 disease
The 2008 ACCP guidelines discuss the use of thromboprophylaxis
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in only a few specified settings. The guidelines recommend pro-
phylaxis for children receiving long-term home parenteral nutrition Passenger Lymphocyte Syndrome
and for patients with complex cardiac conditions and associated Passenger lymphocyte syndrome is a graft-versus-host reaction. 1,319–321
procedures. Routine prophylaxis is not recommended in children Antibodies made by donor B cells (“passengers”) transplanted with the
with central venous lines (including those with cancer). organ are made against host RBCs. This direct antiglobulin-positive