• Monagle P, Chalmers E, Chan A, DeVeber G, Kirkham F, Massicotte P, Michelson AD. Antithrombotic therapy in neonates and children: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008 Jun;133(6 Suppl):887S-968S. [561 references] PubMed

• February 28, 2008, Heparin Sodium Injection: The U.S. Food and Drug Administration (FDA) informed the public that Baxter Healthcare Corporation has voluntarily recalled all of their multi-dose and single-use vials of heparin sodium for injection and their heparin lock flush solutions. Alternate heparin manufacturers are expected to be able to increase heparin production sufficiently to supply the U.S. market. There have been reports of serious adverse events including allergic or hypersensitivity-type reactions, with symptoms of oral swelling, nausea, vomiting, sweating, shortness of breath, and cases of severe hypotension.

Remark: Depending on the age of the patient, it may be more appropriate to follow adult guidelines for management of VTE in the setting of APLAs. (See the National Guideline Clearinghouse (NGC) summary of the American College of Chest Physicians [ACCP] chapter Antithrombotic Therapy for Venous Thromboembolic Disease by Kearon et al.).

Neonatal RVT

1. For neonates or children with unilateral renal vein thrombosis (RVT) in the absence of renal impairment or extension into the IVC, the guideline developers suggest supportive care with monitoring of the RVT for extension or anticoagulation with UFH/LMWH or LMWH in therapeutic doses; the guideline developers suggest continuation for 3 months (Grade 2C).
2. For unilateral RVT that extends into the IVC, the guideline developers suggest anticoagulation with UFH/LMWH or LMWH for 3 months (Grade 2C).
3. For bilateral RVT with various degrees of renal failure, the guideline developers suggest anticoagulation with UFH and initial thrombolytic therapy with tPA, followed by anticoagulation with UFH/LMWH (Grade 2C).

   Remark: LMWH therapy requires careful monitoring in the presence of significant renal impairment.

Primary Antithrombotic Prophylaxis for CVL in Neonates and Children

1. In children with CVLs, the guideline developers recommend against the use of routine systemic thromboprophylaxis (Grade 1B).
2. In children receiving long-term home total parenteral nutrition, the guideline developers suggest thromboprophylaxis with VKAs with a target INR of 2.5 (range 2.0–3.0) (Grade 2C).
3. For blocked CVLs, the guideline developers suggest tPA or recombinant urokinase (UK) to restore patency (Grade 2C). If after at least 30 min following local thrombolytic instillation CVL patency is not restored, the guideline developers suggest a second dose be administered. If the CVL remains blocked following two doses of local thrombolytic agent, the guideline developers suggest investigations to rule out a CVL-related thrombosis be initiated (Grade 2C).

Primary Prophylaxis for Blalock-Taussig Shunts

For pediatric patients having a modified Blalock-Taussig shunt (MBTS), the guideline developers suggest intraoperative therapy with UFH followed by either aspirin (1–5 mg/kg/d) or no further antithrombotic therapy compared to prolonged LMWH or VKAs (Grade 2C).

Primary Prophylaxis for Stage 1 Norwoods in Neonates

For patients who underwent the Norwood procedure, the guideline developers suggest UFH immediately after the procedure, with or without ongoing antiplatelet therapy (Grade 2C).

Primary Prophylaxis for Glenn or Bilateral Cavopulmonary Shunts (BCPS) in Children

In patients who have bilateral cavopulmonary shunts, the guideline developers suggest postoperative UFH (Grade 2C). (For additional information, see Section 1.11 in the original guideline document titled "Primary Prophylaxis for Glenn or Bilateral Cavopulmonary Shunts in Children").

Primary Prophylaxis for Fontan Surgery in Children

For children after Fontan surgery, the guideline developers recommend aspirin (1–5 mg/kg/d) or therapeutic UFH followed by VKAs to achieve a target INR of 2.5 (range, 2.0 to 3.0) (Grade 1B).

Remark: The optimal duration of therapy is unknown. Whether patients with fenestrations require more intensive therapy until fenestration closure is unknown.

Primary Prophylaxis for Endovascular Stents in Children

For children having endovascular stents inserted, the guideline developers suggest administration of UFH perioperatively (Grade 2C).

Primary Prophylaxis for Dilated Cardiomyopathy in Neonates and Children

The guideline developers suggest that pediatric patients with cardiomyopathy receive VKAs to achieve a target INR of 2.5 (range, 2.0 to 3.0) no later than their activation on a cardiac transplant waiting list (Grade 2C).

Underlying values and preferences: The guideline developer's suggestion for administration of VKAs places a high value on avoiding thrombotic complications, and a relatively low value on avoiding the inconvenience, discomfort and limitations of anticoagulant monitoring, in children who are eligible for transplant, which is a potentially curative therapy.

Primary Pulmonary Hypertension

In children with primary pulmonary hypertension, the guideline developers suggest anticoagulation with VKAs commencing when other medical therapy is commenced (Grade 2C).

Biological Prosthetic Heart Valves

For children with biological prosthetic heart valves, the guideline developers recommend that clinicians follow the relevant recommendations from the adult population (See the NGC summary of the ACCP chapter Valvular and Structural Heart Disease by Salem et al.)

Mechanical Prosthetic Heart Valves

1. For children with mechanical prosthetic heart valves, the guideline developers recommend that clinicians follow the relevant recommendations from the adult population with respect to the intensity of anticoagulation therapy. (See the NGC summary of the ACCP chapter Valvular and Structural Heart Disease by Salem et al.)
2. For children with mechanical prosthetic heart valves who have had thrombotic events while on therapeutic antithrombotic therapy or in patients in whom there is a contraindication to full-dose VKAs, the guideline developers suggest adding aspirin therapy (Grade 2C).

Ventricular Assist Devices (VADs)

1. Following ventricular assist device (VAD) placement, in the absence of bleeding the guideline developers suggest administration of UFH targeted to an anti-factor Xa of 0.35 to 0.7 u/mL (Grade 2C). The guideline developers suggest starting UFH between 8 hours and 48 hours following implantation (Grade 2C).
2. The guideline developers suggest antiplatelet therapy (either aspirin, 1 to 5 mg/kg/d, and/or dipyridamole, 3 to 10 mg/kg/d) to commence within 72 hours of VAD placement (Grade 2C).
3. The guideline developers suggest that once clinically stable, pediatric patients be weaned from UFH to either LMWH (target anti-FXa 0.5–1.0 U/mL) or VKA (target INR, 3.0; range, 2.5–3.5) until transplanted or weaned from VAD (Grade 2C).

Cardiac Catheterization (CC)

1. For neonates and children requiring CC via an artery, the guideline developers recommend administration of IV UFH prophylaxis (Grade 1A).
2. The guideline developers recommend the use of UFH doses of 100 to 150 U/kg as a bolus (Grade 1B). The guideline developers suggest further doses of UFH rather than no further therapy in prolonged procedures (Grade 2B).
3. The guideline developers recommend against the use of aspirin therapy for prophylaxis for CC (Grade 1B).

Therapy of Femoral Artery Thrombosis

1. For pediatric patients with a femoral artery thrombosis, the guideline developers recommend therapeutic doses of IV UFH (Grade 1B). The guideline developers suggest treatment for at least 5 to 7 days (Grade 2C).
2. The guideline developers recommend administration of thrombolytic therapy for pediatric patients 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 (Grade 1B).
3. For children with femoral artery thrombosis, the guideline developers suggest surgical intervention when there is a contraindication to thrombolytic therapy and organ or limb death is imminent (Grade 2C).
4. The guideline developers suggest that for children in whom thrombolysis or surgery is not required, conversion to LMWH to complete 5 to 7 days of treatment (Grade 2C).

Peripheral Arterial Catheter Thrombosis in Neonates and Children

1. For pediatric patients with peripheral arterial catheters in situ, the guideline developers recommend UFH through the catheter, preferably by continuous infusion (5 U/mL at 1 mL/h) (Grade 1A).
2. For children with a peripheral arterial catheter-related thromboembolism (TE), the guideline developers suggest immediate removal of the catheter (Grade 1B). The guideline developers suggest UFH anticoagulation with or without thrombolysis, or surgical thrombectomy (Grade 2C).

Neonatal Aortic Thrombosis: UAC Related

1. To maintain umbilical artery catheter (UAC) patency, the guideline developers suggest prophylaxis with a low-dose UFH infusion via the UAC (heparin concentration of 0.25–1 U/mL) (Grade 2A).
2. For neonates with UAC-related thrombosis, the guideline developers suggest therapy with UFH or LMWH for at least 10 days (Grade 2C).
3. For neonates with UAC-related thrombosis, the guideline developers recommend UAC removal (Grade 1B).
4. For neonates with UAC-related thrombosis with potentially life-, limb-, or organ-threatening symptoms, the guideline developers suggest thrombolysis with tPA. When thrombolysis is contraindicated, the guideline developers suggest surgical thrombectomy (Grade 2C).

UAC-Related Thrombosis: Effect of Catheter Location

The guideline developers suggest UACs placement in a high position rather than a low position (Grade 2B).

Primary Prophylaxis for Venous Access Related to Hemodialysis

In patients undergoing hemodialysis, the guideline developers suggest against routine use of VKAs or LMWH for prevention of thrombosis related to central venous lines or fistulas (Grade 2C).

Use of UFH or LMWH for Hemodialysis

The guideline developers suggest the use of UFH or LMWH in hemodialysis (Grade 2C).

Kawasaki Disease

1. In children with Kawasaki disease, the guideline developers recommend aspirin in high doses (80 to 100 mg/kg/d during the acute phase, for up to 14 days) as an anti-inflammatory agent, then in lower doses (1 to 5 mg/kg/d for 6 to 8 weeks) as an antiplatelet agent (Grade 1B).
2. In children with Kawasaki disease, the guideline developers suggest against concomitant use of ibuprofen or other nonsteroidal anti-inflammatory drugs during aspirin therapy (Grade 2C).
3. In children with Kawasaki disease, the guideline developers recommend IV gamma globulin (2 g/kg, single dose) within 10 days of the onset of symptoms (Grade 1A).
4. In children with giant coronary aneurysms following Kawasaki disease, the guideline developers suggest warfarin (target INR, 2.5; INR range, 2.0 to 3.0) in addition to therapy with low-dose aspirin be given as primary thromboprophylaxis (Grade 2C).

Neonatal Sinovenous Thrombosis

1. For neonates with cerebral sinovenous thrombosis (CSVT) without significant intracranial hemorrhage (ICH), the guideline developers suggest anticoagulation, initially with UFH, or LMWH and subsequently with LMWH or VKA for a minimum of 6 weeks, and no longer than 3 months (Grade 2C).
2. For children with cerebral sinovenous thrombosis (CSVT) with significant hemorrhage, the guideline developers suggest radiologic monitoring of the thrombosis at 5 to 7 days and anticoagulation if thrombus propagation is noted (Grade 2C).

Childhood CSVT

1. For children with cerebral sinovenous thrombosis (CSVT), without significant intracranial hemorrhage (ICH), the guideline developers recommend anticoagulation initially with UFH or LMWH and subsequently with LMWH or VKA for a minimum of 3 months relative to no anticoagulation (Grade 1B).
2. The guideline developers suggest that if after 3 months of therapy there is incomplete radiologic recanalisation of CSVT or ongoing symptoms, administration of a further 3 months of anticoagulation (Grade 2C).
3. For children with CSVT with significant hemorrhage, the guideline developers suggest radiologic monitoring of the thrombosis at 5 to 7 days. If thrombus propagation is noted at that time, the guideline developers suggest anticoagulation (Grade 2C).
4. The guideline developers suggest children with CSVT in the context of a potentially recurrent risk factors (e.g., nephrotic syndrome, L-asparaginase therapy) should receive prophylactic anticoagulation at times of risk factor recurrence (Grade 2C).
5. The guideline developers suggest thrombolysis thrombectomy or surgical decompression only in children with severe CSVT in whom there is no improvement with initial UFH therapy (Grade 2C).

Neonatal Arterial Ischemic Stroke (AIS)

1. In the absence of a documented ongoing cardioembolic source, the guideline developers recommend against anticoagulation or aspirin therapy for neonates with a first arterial ischemic stroke (AIS) (Grade 1B).
2. In neonates with recurrent AIS, the guideline developers suggest anticoagulant or aspirin therapy (Grade 2C).

Childhood AIS

1. For children with non–sickle-cell disease-related acute AIS, the guideline developers recommend UFH or LMWH or aspirin (1 to 5 mg/kg/d) as initial therapy until dissection and embolic causes have been excluded (Grade 1B).
2. The guideline developers recommend, once dissection and cardioembolic causes are excluded, daily aspirin prophylaxis (1–5 mg/kg/d) for a minimum of 2 years (Grade 1B).
3. The guideline developers suggest for AIS secondary to dissection or cardioembolic causes, anticoagulant therapy with LMWH or VKAs for at least 6 weeks, with ongoing treatment dependent on radiologic assessment (Grade 2C).
4. The guideline developers recommend against the use of thrombolysis (tPA) for AIS in children, outside of specific research protocols (Grade 1B).
5. The guideline developers recommend for children with sickle-cell disease and AIS, IV hydration and exchange transfusion to reduce sickle hemoglobin levels to at least < 30% total hemoglobin (Grade 1B).
6. For children with sickle-cell disease and AIS, after initial exchange transfusion the guideline developers recommend a long-term transfusion program (Grade 1B).
7. In children with sickle-cell anemia who have transcranial Doppler velocities > 200 cm/s on screening, the guideline developers recommend regular blood transfusion, which should be continued indefinitely (Grade 1B).
8. The guideline developers recommend that children with moyamoya be referred to an appropriate center for consideration of revascularization (Grade 1B).
9. For children receiving aspirin who have recurrent AIS or transient ischemic attacks (TIAs) guideline developers suggest changing to clopidogrel or anticoagulant (LMWH or VKA) therapy (Grade 2C).

Purpura Fulminans

1. For neonates with homozygous protein C deficiency, the guideline developers recommend administration of either 10 to 20 mL/kg of fresh frozen plasma (FFP) every 12 hours (q12h) or protein C concentrate, when available, at 20 to 60 U/kg until the clinical lesions resolve (Grade 1B).
2. The guideline developers suggest long-term treatment with VKAs (Grade 2C), LMWH ((Grade 2C), protein C replacement (Grade 1B), or liver transplantation (Grade 2C).

Definitions:

*The guideline developers use the wording recommend for strong (Grade 1) recommendations and suggest for weak (Grade 2) recommendations.

• Monagle P, Chalmers E, Chan A, DeVeber G, Kirkham F, Massicotte P, Michelson AD. Antithrombotic therapy in neonates and children: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008 Jun;133(6 Suppl):887S-968S. [561 references] PubMed

Electronic copies: Available to subscribers of the Chest - The Cardiopulmonary and Critical Care Journal.

Print copies: Available from the American College of Chest Physicians, Products and Registration Division, 3300 Dundee Road, Northbrook IL 60062-2348.

Electronic copies: Available to subscribers of the Chest - The Cardiopulmonary and Critical Care Journal.

Print copies: Available from the American College of Chest Physicians, Products and Registration Division, 3300 Dundee Road, Northbrook IL 60062-2348.

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