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www.chestpubs.org CHEST / 141 / 2 / FEBRUARY, 2012 SUPPLEMENT e 771S

There are two RCTs reporting thromboprophy-laxis of CVADs to prevent CVAD-related DVT.113 The PROTEKT Study randomized 186 childrenaged 3 months with varying underlying conditionsto reviparin (n5 92) (anti-Xa levels, 0.1-0.3 units/mL) vs standard care (n5 94) (up to 3 units/kg per hUFH). 113 The incidence of asymptomatic CVAD-related thrombosis was 14.1% (11/78) in the reviparin

group vs 12.5% (10/80) in the standard care group(OR, 1.15; 95% CI, 0.42-3.23).113 The study wasclosed early because of slow patient recruitment.Schroeder et al47 reported a single-center RCT com-paring 10 units/kg per h continuous UFH infusionto placebo in 90 children aged , 1 year with CVADspostcardiac surgery. There was no difference in CVAD-related thrombosis in the treatment or placebo groups(15% vs 16%; difference of 1%; 95% CI,2 14%-16%).The study was closed after an interim analysis showedfutility.

The incidence of CVAD-related thrombosis varies with the underlying patient population, and this hasled to some more-specic disease-related studiesto examine the role of primary prophylaxis. CVAD-related thrombosis is reported to be common inchildren with cancer.484,485 There are two RCTs thatstudied thromboprophylaxis in children with cancer.The Prophylactic Antithrombin Replacement in Kids with Acute Lymphoblastic Leukemia Treated withAsparaginase (PARKAA) trial studied the use of anti-thrombin concentrate vs no therapy in 85 patients with pediatric acute lymphoblastic leukemia (ALL)treated with asparaginase.486 Seven of 25 (28%) patientstreated with antithrombin compared with 22 of 60(37%) not treated had thrombosis (difference, 2 9%;95% CI, 2 30%-13%), but the study was not poweredto show efcacy. Ruud et al529 studied the use of war-farin compared with no therapy in the prevention ofCVAD-related thrombosis in children with cancer.The study enrolled 73 children, and 15 of 31 (48%)on warfarin and 17 of 42 (40%) on no therapy devel-oped a VTE (difference, 12%; 95% CI,2 15%-31%).The study was terminated without full recruitmentafter an interim study showed futility.

Cohort studies and case series have also addressedthis issue. Elhasid et al107 found LMWH (mean dose,0.84 mg/kg once daily) to be apparently safe whencompared with historical controls in preventing throm-bosis in 41 patients with ALL. Nowak-Gttl et al530 gave LMWH (dose, 1 mg/kg once daily) as primarythromboprophylaxis to children and adolescents withEwing sarcoma (n5 36) and osteogenic sarcoma(n 5 39). None of the patients developed TE compli-cations during the postoperative period. Meister et al531 reported that enoxaparin (1 mg/kg per day) in addi-tion to antithrombin supplementation reduced therate of thrombosis in children with ALL and CVADs

CVAD heparin, or saline infusions. Taurolidine-citratelocks have been compared with heparin locks andshown to reduce rates of bloodstream infection.521 Restoration of CVAD patency has usually involvedintermittent bolus dosing of a variety of agents, withfailure to restore patency being dened as the CVADremoval and replacement rate. Primary prophylaxisto avoid large-vessel thrombosis around the CVAD

usually involves systemic anticoagulation and needsto be considered separately.Studies that have addressed the issue of CVAD

patency include a trial that evaluated the use of saline vs combination saline and 1 unit/mL UFH in a single-center, blinded randomized clinical trial.522 The studyfailed to demonstrate or exclude a benecial or detri-mental effect on CVAD patency between the twogroups (RR, 7.63; 95% CI, 0.4-144.9).

An unblinded, randomized crossover study in which14 children received UFH 50 units/kg ush vs stan-dard care every 12 h failed to demonstrate or excludea benecial or detrimental effect on CVAD paten-cy.523 A literature review by Kannan524 provided noevidence to support heparin over normal saline as anintermittent ush.

In contrast, a meta-analysis of studies in adults with CVADs reported benet of heparin compared with saline in terms of thrombosis, bacterial coloniza-tion, and possible bacteremia.447 More than 40% ofchildren with cancer had CVAD occlusions despite weekly heparin locks.525 In the hemodialysis setting,alteplase 1 mg/mL was shown to be more effectivethan heparin 5,000 units/mL in reducing intraluminalclot between hemodialysis sessions.526 A multicenterstudy of 577 pediatric cancer patients with CVADsreported that urokinase administration every 2 weeksreduced both CVAD occlusion rates and catheter-related infections compared with heparin adminis-tration.527 Most other studies that have reportedthe use of local thrombolytic agents reported ther-apy for CVAD blockage and, hence, restoration ofpatency.241,243,246,528

Recommendation

2.30. For CVADs, we suggest ushing with nor-mal saline or heparin or intermittent recom-binant urokinase (rUK) to maintain patencyas compared with no therapy (Grade 2C). Forblocked CVADs, we suggest tPA or rUK to restorepatency (Grade 2C). If after at least 30 minfollowing local thrombolytic instillation CVADpatency is not restored, we suggest a seconddose be administered. If the CVAD remainsblocked following two doses of local thrombo-lytic agent, we suggest radiologic imaging torule out a CVAD-related thrombosis (Grade 2C).

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