Pediatric Clinics of North America - CIPERJ

314 GOLDENBERG & BERNARD
feasible, with continued stability. The INR also should be evaluated at the
time of any bleeding manifestations or increased bruising. Warfarin must be
discontinued at least 5 days before invasive procedures, with an INR obtained
preprocedurally. Often, an anticoagulant transition (bridge) to
LMWH can be performed. The development of pediatric anticoagulation
monitoring and transition algorithms can assist in optimizing patient care.
Pediatric recommendations for the duration of antithrombotic therapy in
acute VTE [14] largely are derived from evidence in adult trials. For first-episode
VTE in children in the absence of potent chronic thrombophilia (eg,
APA syndrome, homozygous anticoagulant deficiency, and homozygous
factor V Leiden or prothrombin G20210A), the recommended duration of
anticoagulant therapy is 3 to 6 months in the presence of an underlying reversible
risk factor (eg, postoperative VTE), 6 to 12 months when idiopathic,
and 12 months to lifelong when a chronic risk factor persists (eg, systemic
lupus erythematosus [SLE]). Recurrent VTE is treated for 6 to 12 months
in the presence of an underlying reversible risk factor, 12 months to lifelong
when idiopathic, and lifelong when a chronic risk factor persists. In the setting
of APA syndrome or potent congenital thrombophilia, the treatment
duration for first-episode VTE often is indefinite. Some evidence suggests
that children who have SLE and persistence of the lupus anticoagulant
(LA) have a 16- to 25-fold greater risk for VTEs than children who have
SLE and no LA [20]. In children who have primary (ie, idiopathic) or secondary
(ie, associated with SLE or other underlying chronic inflammatory
condition) APA syndrome, however, it is possible that the autoimmune disease
will become quiescent in later years, such that the benefit of continued
therapeutic anticoagulation as secondary VTE prophylaxis may be re-evaluated.
Some experts recommend consideration of low-dose anticoagulation
as secondary VTE prophylaxis after a conventional 3- to 6-month course of
therapeutic anticoagulation for VTE in children who have SLE and who have
APA syndrome [21]. Such low-dose anticoagulation might, for example,
consist of enoxaparin 1.0–1.5 mg/kg subcutaneously once daily, enoxaparin
0.5 mg/kg subcutaneously twice daily, or daily warfarin with a goal INR of
approximately 1.5. Further study to optimize the intensity and duration of
therapy or secondary prophylaxis for VTE in children who have APA syndrome
urgently is needed, however, especially given the recent evidence in
adult VTE that secondary prophylaxis with low-dose warfarin not only
may offer little risk reduction beyond no anticoagulation but also is associated
with bleeding complications despite a reduced warfarin dose [22,23].
Thrombolytic approaches are gaining increasing attention and use during
acute VTE therapy in children, particularly in patients who have hemodynamically
significant PE or extensive limb-threatening VTE. Unlike conventional
anticoagulants, which attenuate hypercoagulability, thrombolytics
promote fibrinolysis directly. Tissue-type plasminogen activator is an intrinsic
activator of the fibrinolytic system and is administered as a recombinant
agent by various routes (eg, systemic bolus, systemic short-duration