• Cincinnati Children's Hospital Medical Center. Evidence-based care guideline for prevention of thromboembolism after cavopulmonary anastomosis (bidirectional Glenn and Fontan operations). Cincinnati (OH): Cincinnati Children's Hospital Medical Center; 2006 May. 14 p. [34 references]

This is the current release of the guideline.

This guideline updates a previous version: Cincinnati Children's Hospital Medical Center. Evidence based clinical practice guideline for prevention of thromboembolism after cavopulmonary anastomosis (bidirectional Glenn and Fontan operations). Cincinnati (OH): Cincinnati Children's Hospital Medical Center; 2001 May 29. 10 p.

Once the guideline has been in place for four years, the development team reconvenes to explore the continued validity of the guideline. This phase can be initiated at any point that evidence indicates a critical change is needed.

Thromboembolism after cavopulmonary anastomosis

Evaluation
Prevention
Risk Assessment
Treatment

Cardiology
Critical Care
Pediatrics
Surgery

Advanced Practice Nurses
Nurses
Physician Assistants
Physicians
Respiratory Care Practitioners

To provide a guideline for the effective prevention of thromboembolism after cavopulmonary anastomosis

These guidelines are intended for use in infants and children who have undergone the bidirectional Glenn or modified Fontan operation.

The guidelines do not address all considerations needed to manage those with the following:

• Coagulopathy
• Salicylate allergy

Assessment

1. Preoperative history and physical exam, including family history or physical findings suggestive of coagulopathy
2. Laboratory evaluation, including preoperative complete blood count (CBC) with platelets and coagulation studies if abnormalities suspected

Prevention/Treatment

1. Antithrombotic aspirin therapy
2. Warfarin therapy in high-risk patients
3. Alternative antithrombotic therapy when aspirin therapy is temporarily contraindicated

• Intravascular and/or intracardiac thrombus formation and thromboembolic complications
• Hemodynamic stability
• Length of stay in the Cardiac Intensive Care Unit (CICU)

Searches of Electronic Databases

To select evidence for critical appraisal by the group for the update of this guideline, the Medline, EmBase and the Cochrane databases were searched. Evidence from 2000 and before was verified for inclusion in the guidelines. Evidence from 2001 to the January, 2006 were reviewed to generate an unrefined, "combined evidence" database using a search strategy focused on answering clinical questions relevant to prevention of thromboembolism or anticoagulation following cavopulmonary anastomosis and employing a combination of Boolean searching on human-indexed thesaurus terms (MeSH headings using an OVID Medline interface) and "natural language" searching on searching on human-indexed thesaurus terms (MeSH headings using an OVID Medline interface) and "natural language" searching on words in the title, abstract, and indexing terms. The citations were reduced by: eliminating duplicates, non-English articles, and adult articles. The resulting abstracts were reviewed by a methodologist to eliminate low quality and irrelevant citations. During the course of the guideline development, additional clinical questions were generated and subjected to the search process, and some relevant review articles were identified. December, 2000 was the last date for which literature was reviewed for the previous version of this guideline. The details of that review strategy are not documented. However, all previous citations were reviewed for appropriateness to this revision.

Not stated

Not stated

Not applicable

Review of Published Meta-Analyses
Systematic Review

Not stated

Expert Consensus

The recommendations contained in this guideline were formulated by an interdisciplinary working group which performed systematic and critical literature reviews, using a grading scale, and examined current local clinical practices.

Recommendations have been formulated by a consensus process directed by best evidence, patient and family preference and clinical expertise. During formulation of these guidelines, the team members have remained cognizant of controversies and disagreements over the management of these patients. They have tried to resolve controversial issues by consensus where possible and, when not possible, to offer optional approaches to care in the form of information that includes best supporting evidence of efficacy for alternative choices.

Not applicable

A formal cost analysis was not performed and published cost analyses were not reviewed.

Internal Peer Review

Experience with the implementation of earlier publications of this guideline has provided information which has been incorporated into this revision.

The guidelines have been reviewed by clinical experts not involved in the development process, senior management, and other individuals as appropriate to their intended purposes. The guideline is based in part on three independent reviews performed by members of Evidence-Based Care Group of Health Policy & Clinical Effectiveness at Cincinnati Children's Hospital and Medical Center (CCHMC) using AGREE criteria (Appraisal of Guidelines for Research and Evaluation).

Each recommendation is followed by evidence grades identifying the type of supporting evidence. Definitions of the evidence grades are presented at the end of the "Major Recommendations" field.

Assessment

1. Preoperative history and physical exam
   • Patient or family history of coagulopathy, salicylate allergy, or viral exposures
   • Physical findings suggestive of coagulopathy (e.g., petechiae, purpura)

2. Laboratory assessment
   • Preoperative complete blood count (CBC) with platelets
   • Coagulation studies if history or physical suggests abnormalities and prior to initiation of warfarin

     Note: Available evidence does not support routine screening for coagulopathies.

Treatment Recommendations

1. It is recommended that patients begin antithrombotic aspirin therapy upon resuming oral intake following the bidirectional Glenn or Fontan operation. (Jacobs et al., 2002 [C/D]; Barker et al., 2005 [D]); Local Expert Consensus (E))

   Note: Both aspirin and warfarin reduce the risk of thromboembolism. Although the choice of pharmacologic regimen remains controversial, the risk of hemorrhagic complications in children, compounded by the difficulties of monitoring and maintaining appropriate anticoagulation on warfarin, favors the use of aspirin for antithrombotic therapy (Barker et al., 2005 [D]). The two appear equivalent in the prevention of myocardial infarction and stroke in the setting of atherosclerosis (Anand & Yusuf, 1999 [M]); however, in pediatric and adult populations, the risk of hemorrhagic complications is higher with warfarin therapy (Anand & Yusuf, 1999 [M]; Hart et al., 1999 [M]; Rao et al., 1989 [D]; Bradley et al., 1985 [D])

2. It is recommended that warfarin therapy be considered in patients at higher risk due to the following factors:
   • Previous thromboembolic complications (Kaulitz et al., 2005 [D])
   • Poor ventricular function (Kaulitz et al., 2005 [D]; Al-Khadra et al., 1998 [D])
   • Extracardiac Fontan connections (Shirai et al., 1998[D]; Petrossian et al., 1999 [E]; Laschinger et al., 1996 [E])
   • Pulmonary stump (Oski et al., 1996) [D])
   • Atrial tachyarrhythmias (Cheung et al., 2005; Kaulitz et al., 2005 [D])

   Note: Children with Fontan operations require a lower warfarin dosage than children receiving warfarin after other types of congenital heart surgery for a similar degree of anticoagulation (Streif et al.,1999 [C]). The recommended starting dose is 0.1 mg/kg to maintain a target international normalized ratio (INR) range of 2.0 to 3.0.

3. It is recommended that alternative antithrombotic therapy be considered during periods when aspirin therapy is temporarily contraindicated (reference See note).

   Note: Examples of aspirin contraindications may include exposure to influenza or varicella, receipt of varicella vaccine (American Academy of Pediatrics, 2003 [O]), and elective surgical or dental procedures associated with bleeding. Risks of discontinuation of aspirin versus the risk of Reye's syndrome or bleeding associated with dental or surgical procedures must be considered by the clinician and family on an individual basis.

Definitions:

Evidence Based Grading Scale

M: Meta-analysis or systematic review
A: Randomized controlled trial: large sample
B: Randomized controlled trial: small sample
C: Prospective trial or large case series
D: Retrospective analysis
S: Review article
O: Other evidence
E: Expert opinion or consensus
F: Basic laboratory research
L: Legal requirement
Q: Decision analysis
X: No evidence

None provided

The type of evidence is identified and classified for each recommendation (see "Major Recommendations") using the following scheme:

Evidence Based Grading Scale:

M: Meta-analysis or systematic review
A: Randomized controlled trial: large sample
B: Randomized controlled trial: small sample
C: Prospective trial or large case series
D: Retrospective analysis
S: Review article
O: Other evidence
E: Expert opinion or consensus
F: Basic laboratory research
L: Legal requirement
Q: Decision analysis
X: No evidence

Decreased risk of intravascular and/or intracardiac thrombus formation and thromboembolic complications

• Risk of hemorrhagic complications is higher with warfarin therapy than with aspirin therapy
• There is a risk of Reye's syndrome with aspirin therapy

Potential temporary contraindications for aspirin therapy in the following patients:

• Exposure to influenza or varicella or receipt of varicella vaccine
• Elective surgical or dental procedures associated with bleeding

• Unfortunately, although the problem of thromboembolism has been recognized, clinicians have not systematically evaluated the use of antithrombotic therapy. A controversy exists with respect to the most appropriate choice of pharmacologic regimen. To date, no prospective, randomized controlled trials have addressed this question. Monotherapy with either aspirin or warfarin is most commonly implemented. In developing this guideline, the working group recognized the paucity of large-scale studies with direct bearing on this particular pediatric population.
• The specific recommendations in this guideline are drawn from directly applicable studies where possible, but are largely extrapolated from smaller studies and from studies more indirectly related to the present issues.
• These recommendations result from review of literature and practices current at the time of their formulations. This guideline does not preclude using care modalities proven efficacious in studies published subsequent to the current revision of this document. This document is not intended to impose standards of care preventing selective variances from the guidelines to meet the specific and unique requirements of individual patients. Adherence to this guideline is voluntary. The physician in light of the individual circumstances presented by the patient must make the ultimate judgment regarding the priority of any specific procedure.

Appropriate companion documents have been developed to assist in the effective dissemination and implementation of the guideline.

Getting Better
Living with Illness
Staying Healthy

Effectiveness
Patient-centeredness
Safety

• Cincinnati Children's Hospital Medical Center. Evidence-based care guideline for prevention of thromboembolism after cavopulmonary anastomosis (bidirectional Glenn and Fontan operations). Cincinnati (OH): Cincinnati Children's Hospital Medical Center; 2006 May. 14 p. [34 references]

Not applicable: The guideline was not adapted from another source.

2001 May 29 (revised 2006 May)

Cincinnati Children's Hospital Medical Center - Hospital/Medical Center

Cincinnati Children's Hospital Medical Center

Cardiac Guideline Development Team 2006

Cincinnati Children's Hospital Medical Center Physicians: Peter Manning , MD, Cardiac Surgery; Catherine Dent, MD, Cardiac Intensive Care; William Border, MD, Cardiology; James Spaeth, MD, Anesthesia; Michael Alice Moga, MD, Cardiology/Fellow

Patient Services: Karen Uzark, PhD, CPNP, Cardiology; Susan Ryckman, MS, CPNP, Cardiac Services; Betsy Adler, MS, PNP, Cardiac Surgery; Christa Barlow, CNP, Cardiac Surgery; Karen Jones, MS, PNP, Cardiac Surgery; Melissa Magness, RN, Cardiac ICU; Tammy Lingsch, RN, A6 Central; Cynthia Wedekind, Pharm D, Clinical Pharmacy; Martha Willis, CNP, Cardiac Surgery; Jenni Raake, RRT, Respiratory Care

Division of Health Policy & Clinical Effectiveness Support: Eloise Clark, MPH; Danette Stanko, MA, MPH, Epidemiologist; Kate Rich, Lead Decision Support Analyst; Carol Frese, RN, Medical Reviewer; Eduardo Mendez, RN, MPH, Dir. Evidence-Based Care

This guideline was developed without external funding.

This is the current release of the guideline.

This guideline updates a previous version: Cincinnati Children's Hospital Medical Center. Evidence based clinical practice guideline for prevention of thromboembolism after cavopulmonary anastomosis (bidirectional Glenn and Fontan operations). Cincinnati (OH): Cincinnati Children's Hospital Medical Center; 2001 May 29. 10 p.

Once the guideline has been in place for four years, the development team reconvenes to explore the continued validity of the guideline. This phase can be initiated at any point that evidence indicates a critical change is needed.

None available

This NGC summary was completed by ECRI on March 11, 2004. The information was verified by the guideline developer on December 19, 2006. This summary was updated by ECRI on March 6, 2007 following the U.S. Food and Drug Administration (FDA) advisory on Coumadin (warfarin sodium). This summary was updated by ECRI Institute on September 7, 2007 following the revised U.S. Food and Drug Administration (FDA) advisory on Coumadin (warfarin).