Cardiac Interventions in Children with HIT

Recommendations concerning anticoagulation in children with HIT undergoing cardiac surgery have been published in recent reviews (Alsoufi et al., 2004; Greinacher and Klenner, 2005; Boshkov et al., 2006). In patients with a history of HIT who need repeat cardiac surgery, the intraoperative use of UFH is recommended for anticoagulation during CPB, if a sensitive assay excludes the presence of HIT antibodies (Warkentin and Greinacher, 2004). This is because rapid recurrence of HIT antibodies (before postoperative day 5) will not occur. Further, whereas UFH is the standard anticoagulant for CPB, and its effects can be readily antagonized (protamine), there is minimal experience with newer anticoagulants for CPB (particularly in children) and no antidotes exist. However, for pre- and postoperative anticoagulation, a non-heparin anticoagulant should be given.

For patients with acute HIT or patients with persistently circulating platelet-activating antibodies, this approach cannot be used. Therefore these patients require alternative anticoagulation during cardiac surgery. The most practical approach (when feasible) is to postpone surgery until the antibodies disappear or reach very low levels (usually, within 4-10 wk). After their disappearance, heparin can be used (discussed above). If surgery cannot be delayed, an alternative non-heparin regimen can be used (see Chapter 19). In children, Boshkov et al. (2002) started argatroban infusion with a 250 mg/kg bolus followed by continuous infusion of 10 mg/kg/min in a 6-mo old child with HIT for anticoagulation during CPB.

For patients with subacute or previous HIT who require cardiac catheteriza-tion, the use of an alternative anticoagulant such as bivalirudin, argatroban, lepirudin, or danaparoid is recommended over the use of heparin (as heparin use might boost antibody levels, complicating use of heparin for subsequent surgery). Porcelli and coworkers (2003) gave 150 mg/kg of argatroban i.v. over 10 min at the start of cardiac catheterization in a 6-yr-old boy with HIT and congenital heart disease. No continuous infusion of argatroban was given due to relatively brief procedure. In a 14-mo-old boy with tetralogy of Fallot and HIT after cardiac surgery, danaparoid was used for cardiac catheterization (Girisch et al., 2001), with a loading dose (30 U/kg) followed by an i.v. infusion (2 U/kg/h).

Boning et al. (2005) reported four children with anti-PF4/heparin antibodies without clinically manifest HIT requiring cardiac surgery with CPB. In these four patients, surgery was performed using lepirudin. Three of the four children had an uneventful procedure and postoperative course. In one patient, after total cavopulmonary connection, reoperation was necessary on postoperative day 7 because of partial thrombosis of the lateral tunnel.

VII. PREVENTION OF HIT IN CHILDREN

Since the pivotal trial in adult orthopedic patients (Warkentin et al., 1995), it is known that LMWH induces HIT less frequently than does UFH. In children, HIT appears to occur most often among the very young following cardiac surgery, and among adolescents given UFH to treat spontaneous thrombosis. Data from Pouplard and colleagues (1999) suggest that HIT might also occur less with LMWH than with UFH thromboprophylaxis after cardiac surgery. This approach should be investigated in children.

Similarly, in the second group of at-risk pediatric patients (adolescents with thrombosis), it is possible that the frequency of HIT would be reduced if LMWH is given instead of UFH. Pharmacokinetic studies of LMWH in infants and children have been conducted for several LMWH preparations. The safety and efficacy of prophylactic and therapeutic doses of LMWH in children have been evaluated in clinical trials for a variety of conditions. LMWH is safe and effective for anticoagulation of infants and children of varying age (Albisetti and Andrew, 2002; Monagle et al., 2004; Sutor et al., 2004; Merkel et al., 2006; Massicotte et al., 2003a,b,c).

VIII. SUMMARY

HIT appears to be rare in children. The incidence depends somewhat on patient age and indication for heparin. Two major pediatric at-risk groups are apparent: newborns/infants after cardiac surgery (incidence ~1%), and adolescents treated with UFH for spontaneous thrombosis. HIT can be life-threatening in children (~12% mortality). Venous thrombosis is the most frequent HIT-associated complication. For laboratory confirmation of HIT, antigen assays are most appropriate (small blood volumes required). Although there are conflicting data on the optimal laboratory cutoff for antigen assays, a randomized, double-blind clinical trial suggests that the cutoff level established in adults is also appropriate for children. There are no prospective studies of alternative anticoagulants in children with HIT. Most available data are for lepirudin, danaparoid, and argatroban. Greater use of LMWH in children may lead to a reduced risk of HIT, as is seen in adults.

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