Antithrombotic Therapy In Neonates And Children

Publication Date: February 1, 2012
Last Updated: March 14, 2022

Recommendations

Antithrombotic Therapy in Pediatric Patients

We suggest that where possible, pediatric hematologists with experience in TE manage pediatric patients with TE. (2, C)
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When this is not possible, we suggest a combination of a neonatologist/pediatrician and adult hematologist supported by consultation with an experienced pediatric hematologist. (2, C)
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Heparin in Neonates and Children

We suggest that therapeutic UFH in children is titrated to achieve a target range of anti-Xa activity of 0.35 to 0.7 units/mL or an aPTT range that correlates to this anti-Xa range or to a protamine titration range of 0.2 to 0.4 units/mL. (2, C)
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We suggest that when initiating UFH therapy, UFH boluses be no greater than 75 to 100 units/kg and that boluses be withheld or reduced if there are significant bleeding risks. (2, C)
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We suggest avoiding long-term use of therapeutic UFH in children. (2, C)
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LMWH in Neonates and Children

We suggest, for neonates and children receiving either once- or twice-daily therapeutic LMWH, that the drug be monitored to a target anti-Xa activity range of 0.5 to 1.0 units/mL in a sample taken 4 to 6 h after subcutaneous injection or 0.5 to 0.8 units/mL in a sample taken 2 to 6 h after subcutaneous injection. (2, C)
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VKAs in Neonates and Children

We suggest, for children receiving VKAs, that the drug be monitored to a target INR of 2.5 (range, 2.0-3.0), except in the setting of prosthetic cardiac valves where we suggest adherence to the adult recommendations outlined in Whitlock et al. Chest 2012;141(2)(suppl): e576S-e600S. (2, C)
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We suggest that INR monitoring with point-of-care monitors be made available where resources make this possible. (2, C)
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Aspirin

We suggest that when aspirin is used for antiplatelet therapy in children, it is used in doses of 1 to 5 mg/kg per day. (2, C)
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Recommendations for Antithrombotic Therapy in Specific Clinical Situations

VTE in Neonates

We suggest that CVADs or UVCs associated with confi rmed thrombosis be removed after 3 to 5 days of therapeutic anticoagulation rather than left in situ. (2, C)
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We suggest either initial anticoagulation or supportive care with radiologic monitoring for extension of thrombosis rather than no follow-up. (2, C)
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However, in previously untreated patients, we recommend the start of anticoagulation if extension occurs. (2, C)
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We suggest that anticoagulation should be with either¨

(1) LMWH or
(2) UFH followed by LMWH.

We suggest a total duration of anticoagulation of between 6 weeks and 3 months rather than shorter or longer durations. (2, C)
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If either a CVAD or a UVC is still in place on completion of therapeutic anticoagulation, we suggest a prophylactic dose of anticoagulation until such time as the CVAD or UVC is removed. (2, C)
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We suggest against thrombolytic therapy for neonatal VTE unless major vessel occlusion is causing critical compromise of organs or limbs. (2, C)
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We suggest if thrombolysis is required, tPA is used rather than other lytic agents, (2, C)
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and we suggest plasminogen (FFP) administration prior to commencing therapy. (2, C)
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Renal Vein Thrombosis in Neonates

For unilateral RVT in the absence of renal impairment or extension into the IVC, we suggest either:
  • (1) supportive care with radiologic monitoring for extension of thrombosis (if extension occurs, we suggest anticoagulation) or
  • (2) anticoagulation with UFH/LMWH or LMWH in therapeutic doses rather than no therapy. If anticoagulation is used, we suggest a total duration of between 6 weeks and 3 months rather than shorter or longer durations of therapy.
(2, C)
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For unilateral RVT that extends into the IVC, we suggest anticoagulation with UFH/LMWH or LMWH for a total duration of between 6 weeks and 3 months. (2, C)
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For bilateral RVT with evidence of renal impairment, we suggest anticoagulation with UFH/LMWH or initial thrombolytic therapy with tPA followed by anticoagulation with UFH/LMWH. (2, C)
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CVAD Prophylaxis in Neonates

For neonates with CVADs,
  • we recommend to maintain CVAD patency with UFH continuous infusion at 0.5 units/kg per h over no prophylaxis or
(1, A)
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  • or intermittent local thrombolysis.
(2, C)
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For neonates with blocked CVADs, we suggest local thrombolysis after appropriate clinical assessment. (2, C)
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Thromboprophylaxis for Blalock-Taussig Shunts and Modifi ed Blalock-Taussig Shunts

For neonates and children having MBTS, we suggest intraoperative UFH therapy. (2, C)
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For neonates and children after MBTS surgery, we suggest either aspirin or no antithrombotic therapy as compared with prolonged LMWH or VKAs. (2, C)
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Therapy for Femoral Artery Thrombosis in Neonates and Children

For neonates and children with acute femoral artery thrombosis,
  • we recommend therapeutic doses of IV UFH as initial therapy compared with aspirin or no therapy or
(1, B)
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  • or LMWH.
(2, C)
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We suggest subsequent conversion to LMWH, or else continuation of UFH, to complete 5 to 7 days of therapeutic anticoagulation as compared with a shorter or longer duration. (2, C)
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For neonates and children with limb-threatening or organ-threatening (via proximal extension) femoral artery thrombosis who fail to respond to initial UFH therapy and who have no known contraindications, we recommend thrombolysis. (1, C)
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For neonates and children with femoral artery thrombosis, we recommend surgical intervention compared with UFH therapy alone when there is a contraindication to thrombolytic therapy and organ or limb death is imminent. (1, C)
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Prophylaxis for Peripheral Arterial Catheters in Neonates and Children

For neonates and children with peripheral arterial catheters in situ, we recommend UFH continuous infusion at 0.5 units/mL at 1 mL/h compared with normal saline. (1, A)
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Therapy for Peripheral Artery Thrombosis Secondary to Peripheral Artery Catheters in Neonates and Children

For neonates and children with a peripheral arterial catheter-related TE, we suggest immediate removal of the catheter. (2, B)
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For neonates and children with a symptomatic peripheral arterial catheter-related TE, we suggest UFH anticoagulation with or without thrombolysis or surgical thrombectomy and microvascular repair with subsequent heparin therapy. (2, C)
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Prophylaxis of Umbilical Arterial Catheters in Neonates

For neonates with UACs, we suggest UAC placement in a high rather than low position. (2, B)
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For neonates with UACs, we suggest prophylaxis with a low-dose UFH infusion via the UAC (heparin concentration of 0.25-1 unit/mL, total heparin dose of 25-200 units/kg per day) to maintain patency. (2, A)
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Prophylaxis for Cardiac Catheterization in Neonates and Children

For neonates and children requiring CC via an artery
  • we recommend administration of IV UFH as thromboprophylaxis over no prophylaxis or
(1, A)
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  • or aspirin.
(1, B)
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For neonates and children requiring CC via an artery, we recommend the use of UFH doses of 100 units/kg as a bolus compared with a 50-unit/kg bolus. (1, B)
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In prolonged procedures, we suggest further doses of UFH rather than no further therapy. (2, B)
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Cerebral Sinovenous Thrombosis in Neonates

For neonates with CSVT without significant ICH, we suggest anticoagulation, initially with UFH or LMWH and subsequently with LMWH, for a total therapy duration between 6 weeks and 3 months rather than shorter or longer treatment duration. (2, C)
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For neonates with CSVT with signifi cant hemorrhage, we suggest either:

(1) anticoagulation or
(2) supportive care with radiologic monitoring of the thrombosis at 5 to 7 days and anticoagulation

if thrombus extension is noted as compared with no therapy. (2, C)
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Arterial Ischemic Stroke in Neonates

For neonates with a first AIS in the absence of a documented ongoing cardioembolic source, we suggest supportive care over anticoagulation or aspirin therapy. (2, C)
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For neonates with a first AIS and a documented cardioembolic source, we suggest anticoagulation with UFH or LMWH. (2, C)
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For neonates with recurrent AIS, we suggest anticoagulant or aspirin therapy. (2, C)
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Neonates With Purpura Fulminans

For neonates with clinical presentations of homozygous protein C deficiency, we recommend administration of either 10 to 20 mL/kg of FFP every 12 h or protein C concentrate, when available, at 20 to 60 units/kg until the clinical lesions resolve. (1, A)
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For neonates
with homozygous protein C deficiency, after initial stabilization,
  • we recommend long-term treatment with VKA,
(1, C)
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  • LMWH,
(1, C)
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  • protein C replacement,
(1, B)
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  • or liver transplantation
(, )
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compared with no therapy.

DVT and PE in Children

In children with first VTE (CVAD and non-CVAD related), we recommend acute anticoagulant therapy with either UFH or LMWH. (1, B)
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We recommend initial treatment with UFH or LMWH for at least 5 days. (1, B)
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For ongoing therapy, we suggest LMWH or UFH. For patients in whom clinicians will subsequently prescribe VKAs, we recommend beginning oral therapy as early as day 1 and discontinuing UFH/LMWH on day 6 or later than day 6 if the INR has not exceeded 2.0 compared with no therapy. (1, B)
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We suggest that children with idiopathic VTE receive anticoagulant therapy for 6 to 12 months compared with no therapy. (2, C)
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In children with secondary VTE (ie, VTE that has occurred in association with a clinical risk factor) in whom the risk factor has resolved, we suggest anticoagulant therapy be administered for 3 months. (2, C)
as compared with no further therapy.
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In children who have ongoing, but potentially reversible risk factors, such as active nephrotic syndrome or ongoing asparaginase therapy, we suggest continuing anticoagulant therapy beyond 3 months in either therapeutic or prophylactic doses until the risk factor has resolved. (2, C)
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In children with recurrent idiopathic VTE, we recommend indefi nite treatment with VKAs. (1, A)
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In children with recurrent secondary VTEs with an existing reversible risk factor for thrombosis, we suggest anticoagulation until resolution of the precipitating factor but for a minimum of 3 months as compared with no further therapy. (2, C)
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In children with a CVAD in place who have a VTE, if a CVAD is no longer required, or is nonfunctioning, we recommend it be removed. (1, B)
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We suggest at least 3 to 5 days of anticoagulation therapy prior to its removal rather than no anticoagulation prior to removal. (2, C)
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If CVAD access is required, and the CVAD is still functioning, we suggest that the CVAD remain in situ and the patient be given anticoagulants. (2, C)
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For children with a first CVAD-related VTE, we suggest initial management as for secondary VTE as previously described. (, )
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In children with CVAD in place who have a VTE and in whom the CVAD remains necessary, we suggest after the initial 3 months of therapy, that prophylactic doses of VKAs (INR range, 1.5-1.9) or LMWH (anti-Xa level range, 0.1- 0.3 units/mL) be given until the CVAD is removed. (2, C)
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If recurrent thrombosis occurs while the patient is receiving prophylactic therapy, we suggest continuing therapeutic doses until the CVAD is removed and for a minimum of 3 months following the VTE. (2, C)
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Thrombolysis in Pediatric Patients With DVT

In children with VTE, we suggest that thrombolysis therapy be used only for life- or limb-threatening thrombosis. (2, C)
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If thrombolysis is used in the presence of physiologically low levels or pathologic deficiencies of plasminogen, we suggest supplementation with plasminogen. (2, C)
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In children with VTE in whom thrombolysis is used, we suggest systemic thrombolysis or catheter-directed thrombolysis depending on institutional experience and, in the latter case, technical feasibility. (, )
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Thrombectomy and IVC Filter Use in Pediatric Patients With DVT

In children with life-threatening VTE, we suggest thrombectomy. (2, C)
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In children who have had a thrombectomy, we suggest anticoagulant therapy as per recommendations under "DVT and PE in Children." (2, C)
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In children >10 kg body weight with lower-extremity VTE and a contraindication to anticoagulation, we suggest placement of a retrievable IVC filter. (2, C)
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In children who receive a filter, we suggest that the filter be removed as soon as possible if thrombosis is not present in the basket of the filter and when contraindication to anticoagulation is resolved. (2, C)
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In children who receive an IVC fi lter, we recommend appropriate anticoagulation for VTE (see "DVT and PE in Children") as soon as the contraindication to anticoagulation is resolved. (1, C)
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DVT in Children With Cancer

In children with cancer, we suggest that management of VTE follow the general recommendations for management of VTE in children. We suggest the use of LMWH in the treatment of VTE for a minimum of 3 months until the precipitating factor has resolved (eg, use of asparaginase). (2, C)
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Children With Antiphospholipid Antibodies and DVT

For children with VTE in the setting of APLAs, we suggest management as per general recommendations for VTE management in children. (, )
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Children With DVT and Positive Inherited Thrombophilia Testing

For children with VTE independent of the presence or absence of inherited thrombophilic risk factors, we suggest that the duration and intensity of anticoagulant therapy as per "DVT and PE in Children."
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Children With VTE and Structurally Abnormally Venous Systems

For children with frst VTE secondary to structural venous abnormalities, we suggest anticoagulation as per other “spontaneous” VTE ("DVT and PE in Children") and consideration of subsequent percutaneous or surgical interventions depending on patient factors and institutional experience. For children with recurrent VTE secondary to structural venous abnormalities, we suggest indefinite anticoagulation unless successful percutaneous or surgical interventions can be performed. (2, C)
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Children With Right Atrial Thrombosis

For children with right atrial thrombosis related to CVAD, we suggest removal of the CVAD with or without anticoagulation depending on the individual risk factors compared with leaving the CVAD in situ. (2, C)
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For children with large ( >2 cm), mobile, right atrial thrombosis, we suggest anticoagulation with appropriately timed CVAD removal and consideration of surgical intervention or thrombolysis based on individualized risk-benefit assessment compared with no anticoagulation therapy. (2, C)
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Children With CVADs

For CVADs, we suggest flushing with normal saline or heparin or intermittent recombinant urokinase (rUK) to maintain patency as compared with no therapy. (2, C)
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For blocked CVADs, we suggest tPA or rUK to restore patency. (2, C)
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If after at least 30 min following local thrombolytic instillation CVAD patency is not restored, we suggest a second dose be administered. If the CVAD remains blocked following two doses of local thrombolytic agent, we suggest radiologic imaging to rule out a CVAD-related thrombosis. (2, C)
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For children with short- or medium-term CVADs, we recommend against the use of routine systemic thromboprophylaxis. (1, B)
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For children receiving long-term home TPN, we suggest thromboprophylaxis with VKAs. (2, C)
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Glenn Procedure or Bilateral Cavopulmonary Shunt

For children who have a BCPS, we suggest postoperative UFH. (2, C)
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Fontan Surgery

For children after Fontan surgery, we recommend aspirin or therapeutic UFH followed by VKAs over no therapy. (1, C)
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Endovascular Stents

For children having endovascular stents inserted, we suggest administration of UFH perioperatively. (2, C)
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Dilated Cardiomyopathy

For pediatric patients with cardiomyopathy, we suggest VKAs no later than their activation on a cardiac transplant waiting list. (2, C)
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Primary Pulmonary Hypertension

For children with primary pulmonary hypertension, we suggest starting anticoagulation with VKAs at the same time as other medical therapy. (2, C)
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Biologic and Mechanical Prosthetic Heart Valves

For children with VADs, we suggest administration of UFH. (2, C)
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We suggest starting UFH between 8 and 48 h following implantation. (2, C)
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In addition, we suggest antiplatelet therapy (either aspirin or aspirin and dipyridamole) to commence within 72 h of VAD placement. (2, C)
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For children with VAD, once clinically stable, we suggest switching from UFH to either LMWH or VKA (target INR, 3.0; range, 2.5-3.5) until transplanted or weaned from VAD. (2, C)
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Primary Prophylaxis for Venous Access Related to Hemodialysis

For patients undergoing hemodialysis via an arteriovenous fistula, we suggest routine use of VKAs or LMWH as fistula thromboprophylaxis as compared with no therapy. (2, C)
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For patients undergoing hemodialysis via CVAD, we suggest routine use of VKAs or LMWH for thromboprophylaxis as compared with no therapy. (2, C)
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Use of UFH or LMWH During Hemodialysis

For children having hemodialysis, we suggest the use of UFH or LMWH during hemodialysis to maintain circuit patency independent of type of vascular access. (2, C)
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Kawasaki Disease

For children with Kawasaki disease, we recommend aspirin in high doses (80-100 mg/kg per day during the acute phase for up to 14 days) as an antiinflammatory agent, then in lower doses (1-5 mg/kg per day for 6 to 8 weeks) as an antiplatelet agent. (1, B)
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For children with Kawasaki disease, we recommend IV γ-globulin (2 g/kg, single dose) within 10 days of the onset of symptoms. (1, A)
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For children with moderate or giant coronary aneurysms following Kawasaki disease, we suggest that warfarin in addition to low-dose aspirin be given as primary thromboprophylaxis. (2, C)
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For children with Kawasaki disease who have giant aneurysms and acute coronary artery thrombosis, we suggest thrombolysis or acute surgical intervention. (2, C)
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CSVT in Children

For children with CSVT without significant ICH, we recommend anticoagulation initially with UFH or LMWH and subsequently with LMWH or VKA for a minimum of 3 months relative to no anticoagulation. (1, B)
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In children who after 3 months of therapy still experience occlusion of CSVT or ongoing symptoms, we suggest administration of a further 3 months of anticoagulation. (2, C)
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For children with CSVT with signifi cant hemorrhage, we suggest initial anticoagulation as for children without hemorrhage or radiologic monitoring of the thrombosis at 5 to 7 days and anticoagulation if thrombus extension is noted at that time. (2, C)
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In children with CSVT and potentially recurrent risk factors (eg, nephrotic syndrome, asparaginase therapy), we suggest prophylactic anticoagulation at times of risk factor recurrence. (2, C)
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We suggest thrombolysis, thrombectomy, or surgical decompression only in children with severe CSVT in whom there is no improvement with initial UFH therapy. (2, C)
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AIS in Children

For children with acute AIS with or without thrombophilia, we recommend UFH or LMWH or aspirin as initial therapy until dissection and embolic causes have been excluded. (1, C)
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For children with acute AIS, we suggest, once dissection and cardioembolic causes are excluded, daily aspirin prophylaxis for a minimum of 2 years as compared with no antithrombotic therapy. (2, C)
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For children receiving aspirin who have recurrent AIS or TIAs, we suggest changing to clopidogrel or anticoagulant therapy with LMWH or VKA. (2, C)
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For children with AIS, we recommend against the use of thrombolysis (tPA) or mechanical thrombectomy outside of specific research protocols. (1, C)
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Embolic Stroke

For AIS secondary to cardioembolic causes, we suggest anticoagulant therapy with LMWH or VKAs for at least 3 months. (2, C)
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For AIS secondary to cardioembolic causes in children with demonstrated right-to-left shunts (eg, PFO), we suggest surgical closure of the shunt. (2, C)
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Dissection

For AIS secondary to dissection, we suggest anticoagulant therapy with LMWH or VKAs for at least 6 weeks. (2, C)
Ongoing treatment will depend on radiologic assessment of degree and extent of stenosis and evidence of recurrent ischemic events.
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Cerebral Vasculopathies

For children with acute AIS secondary to non-Moyamoya vasculopathy, we recommend UFH or LMWH or aspirin for 3 months as initial therapy compared with no treatment. (1, C)
For children with AIS secondary to non-Moyamoya vasculopathy, we suggest that ongoing antithrombotic therapy should be guided by repeat cerebrovascular imaging.
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Moyamoya Disease

For children with acute AIS secondary to Moyamoya, we suggest aspirin over no treatment as initial therapy. (2, C)
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For children with Moyamoya, we suggest that they be referred to an appropriate center for consideration of revascularization. (, )
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Recommendation Grading

Overview

Title

Antithrombotic Therapy In Neonates And Children

Authoring Organization

Publication Month/Year

February 1, 2012

Last Updated Month/Year

May 15, 2023

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Document Objectives

Neonates and children differ from adults in physiology, pharmacologic responses to drugs, epidemiology, and long-term consequences of thrombosis. This guideline addresses optimal strategies for the management of thrombosis in neonates and children.

Target Patient Population

Neonates and children with thrombosis risk

Inclusion Criteria

Child, Infant

Health Care Settings

Ambulatory, Childcare center, Emergency care, Hospital, Outpatient, School

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Assessment and screening, Prevention, Management, Treatment

Diseases/Conditions (MeSH)

D054556 - Venous Thromboembolism, D000925 - Anticoagulants, D010372 - Pediatrics, D013923 - Thromboembolism, D056824 - Upper Extremity Deep Vein Thrombosis, D016769 - Embolism and Thrombosis

Keywords

thromboembolism, anticoagulation, Antithrombotic Agents, Venous Thromboembolism, deep vein thrombosis, heparin, deep venous thrombosis, Anticoagulation

Supplemental Methodology Resources

Data Supplement