Pilot study assesses TEG applications in pediatric population

By Robert N. Chaplin, MD, and Nancy Ghanayem, MD, clinical director, Cardiac Critical Care, Children's Hospital of Wisconsin; Associate Professor, Medical College of Wisconsin; member of Children's Specialty Group

To better assess thromobelastography applications in a pediatric population, a pilot study is underway at Children's Hospital of Wisconsin in patients undergoing cardiothoracic surgery requiring cardiopulmonary bypass. TEG results will be obtained perioperatively and analyzed to assess whether current transfusion practices could be improved upon with TEG. Physicians will treat patients based on current practices and will be blinded to TEG results until after analysis.

TEG is a technology that originated in 1948 for assessment of abnormalities within the clotting system, and it has seen a resurgence in the past 5-10 years, especially in the area of cardiothoracic surgery. It monitors hemostasis as a dynamic process and measures the kinetics of clot formation and degradation, including both strength and stability. This information allows the clinician to determine the ability of the blood to provide hemostasis, the presence of clotting factors and platelet function available for clot formation. These results allow for better evaluation of the entire clotting process, as opposed to measuring the standard hematology values of prothrombin time, activated partial thromboplastin time, activated clotting time, platelet count, and other aspects of a DIC panel.

Adult studies have found this instrument to be of great benefit for monitoring a patient's coagulation system prior to surgery, as well as for evaluation of ongoing bleeding during and after the procedure. Literature in pediatrics is more limited, however studies are ongoing. This technology is not an inexpensive tool and presently is under evaluation to assess a potential cost benefit for patients. In theory, if the reasons for bleeding can be determined or a prediction made as to which patients may be at a higher risk for bleeding, specific abnormalities related to the coagulation cascade can be corrected more accurately. Ultimately, if effective, blood product usage can be reduced, with the added benefit of a reduced strain on the nation's limited blood supply.

TEG analysis consists of placing a blood sample into a small cup, which oscillates around a pin inserted into the blood sample. As the blood clot forms, it attaches to both the pin and the cup, creating a torsion effect on the pin. The stronger the clot, the more torsion forces are applied to the pin. Data is captured by a computer program for future analysis.

Following analysis, the properties and kinetics of the clot are presented in graph form as a representation of the clotting system in that patient. The graph is interpreted to determine what actions, if any, will be undertaken.

Phases of clot formation
A straight line that eventually splits represents the first phase of clot formation. The time from the beginning of the test until the split is the clotting time, which is the time required to begin the formation of fibrin strands. This time is reduced with hypercoagulable states, and increases with factor deficiency and/or presence of anticoagulants like heparin. This also is called the enzymatic phase.

The splitting of the tracing represents the second, or kinetic, phase. This represents the kinetics of clot formation, essentially the buildup and crosslinking of fibrin strands. Both the time to reach a specific strength and the angle of the buildup are assessed in this phase.

The point where the split lines are at their farthest distance from each other marks the end of the kinetic phase. This is known as the maximum amplitude. This point is determined essentially by platelet function.

The final phase is that of thrombolysis or clot resolution.

TEG allows clinical staff to evaluate the entire process from clot formation through resolution, helping to determine which areas have deficiencies. Based on TEG results, staff will be able to target therapies to those specific problems. The research team is hopeful that this technology may begin to make an impact on the way coagulation is looked at in cardiovascular surgery patients and lead to improved therapies while reducing costs.

Fetal Cardiac Program: identifying, treating defects

By Maura Flynn-Galganski, RN, Children's Hospital of Wisconsin

The Fetal Cardiac Program, part of Herma Heart Center at Children's Hospital of Wisconsin, provides comprehensive assessment and care of fetal cardiac disease while supporting and educating each family. Patients referred to the program have an identified cardiac abnormality detected on an obstetric ultrasound or risk factors that predispose them to having children with cardiac disease. This includes mothers with a history of diabetes mellitus, systemic lupus and congenital heart disease.

If a fetus has a chromosomal defect, such as Trisomy 21, or an extracardiac anomaly such as diaphragmatic hernia, an advanced cardiac ultrasound is conducted. Mothers also are evaluated when they have had a previous child with congenital heart disease.

Herma Heart Center services include a fetal echocardiogram with comprehensive imaging of the heart structure and function. Fetal arrhythmias also can be evaluated using Doppler echocardiography. A doctor and nurse coordinator provide counseling and education, and a social worker offers valuable information on insurance, financial issues and other outside services. Families also may meet with a cardiothoracic surgeon prior to delivery. If the fetus has complex congenital heart disease necessitating neonatal surgery, a meeting with a cardiac-focused critical care physician is coordinated.

Herma Heart Center is one of the nation's top programs for medical and surgical treatment of congenital heart defects and children's heart disease. Diagnosing infants before birth improves care, since needs are anticipated and plans for care can be made in advance. Research shows that outcomes improve when the delivery and operating rooms are in close proximity. The Froedtert and Medical College of Wisconsin Birth Center, located inside Children's Hospital, makes it easier for the mother to breastfeed, bond with the baby and talk with care providers.

Infants will often have other special needs, as cardiac defects often are associated with chromosomal syndromes or extracardiac abnormalities. The Fetal Cardiac Program works with the Fetal Concerns Program, which is designed to provide a full range of care when there are pregnancy concerns. The only program of its kind in Wisconsin, the Fetal Concerns Program offers services such as:

• Fetal diagnosis of birth defects.
• Counseling regarding the specific diagnosis.
• Access to prenatal treatments.
• Medical care of the infant.
• Linking families to support services.
• Specially trained nurse who helps schedule services.
• Help creating palliative care plans, when appropriate.

Coordinators of both programs manage family follow-up visits. Following a diagnosis of congenital heart disease, patients usually are seen every four weeks to monitor the baby's growth and observe any developmental changes. If the referring physician is unable to continue following the mother and/or assist in the delivery, a perinatologist will provide continuity of care.

Future plans for the Fetal Cardiac Program include developing research protocols with other fetal centers to improve fetal outcomes and preparing for the exciting field of fetal intervention. For more information about Herma Heart Center and the Fetal Cardiac Program, visit the Children's Hospital Web site at www.chw.org.

New cardiac surgeon, researcher join Herma Heart Center

Kimberly Gandy, MD, PhD, has joined Herma Heart Center. She is a pediatric cardiothoracic surgeon at Children's Hospital of Wisconsin and associate professor of Surgery (Cardiothoracic) at the Medical College of Wisconsin. She is also a member of Children's Specialty Group.

Dr. Gandy earned her medical degree from Northwestern University in Evanston, Ill., and completed residencies in Surgery and Cardiothoracic Surgery at Duke University Medical Center in Durham, N.C. She completed her fellowship in Pediatric Cardiothoracic Surgery at Stanford University School of Medicine in Palo Alto, Calif. She is board certified in Surgery and Thoracic Surgery. Dr. Gandy also earned a doctorate in Immunology from Stanford.

She and her husband, Jos Domen, PhD, conduct research in a number of areas, including myocardial rescue of congenital cardiomyopathy with blood cells, and tolerance induction for organ transplantation using hematopoietic stem cells. Dr. Domen is an assistant professor of Surgery (Cardiothoracic) at the Medical College of Wisconsin.

Pilot study supports healthy cardiovascular lifestyle

By Pamela S. Cava, DO, director, Pediatric Cardiology, Children's Hospital of Wisconsin Clinics-Gurnee; pediatric cardiologist, Children's Hospital of Wisconsin Clinics-Kenosha and Racine; assistant professor, Pediatrics (Cardiology), Medical College of Wisconsin; and Susan Hovis, RN, BSN, project coordinator, F4Kids, Medical College of Wisconsin

Empowering children to act as change agents to support a healthy cardiovascular lifestyle is the goal of a pilot study at the Medical College of Wisconsin called F4Kids = A Healthier Future. Currently in the first stage of development, the study includes four components: food, fun, fitness and feelings. The F4Kids study will be piloted in the implementation phase with a fourth-grade class at Lincoln Elementary School in Cudahy, Wis.

More children are developing preventable risk factors for cardiovascular disease, including hypertension, smoking, high cholesterol, inactivity, diabetes, obesity and metabolic syndrome. CVD ranks as the number two cause of death for children younger than age 15. The Wisconsin Nutrition and Physical Activity State Plan reports 26 percent of high school students are at risk of becoming or are overweight. Over the past decade, nearly 50 percent of Wisconsin's youngest children, ages 2-4 years, also have joined this risk group.

Modeled after the Health Ahead/Heart Smart program, F4Kids will create an individualized wellness curriculum that infuses age-appropriate cardiovascular intervention materials into all subject areas, including music, art, math, science and physical education.

Through the F4Kids program, children from key at-risk groups will be reached through a three stage process:

Stage 1
Existing school curricula will be analyzed to develop a new interdisciplinary wellness curriculum developed that is individualized for school districts based on their needs. This effort will be funded by the Healthier Wisconsin Partnership Program, a component of the Advancing a Healthier Wisconsin endowment at the Medical College of Wisconsin. As this process is carried out at the pilot school and future schools, this stage ensures that the unique needs of the local school community are met.

Stage one of the F4Kids study has four objectives:

Objective 1: An F4Kids Core Curriculum Committee will review and assess the current school curriculum and identify cardiovascular health components from Health Ahead/Heart Smart that complement it. The committee will be made up of the F4Kids medical director, program director, curriculum expert, and experts in nutrition and exercise physiology.

Objective 2: A school community needs assessment will be completed. Researchers will conduct a community needs survey of the key stakeholders of the project, including families, teachers and students, to determine attitudes and beliefs about cardiovascular health and the role of schools. Three focus groups, including students, teachers and parents, then will be conducted. Information will be analyzed, reported and used for program development.

Objective 3: A school-specific, interdisciplinary wellness curriculum will be created that infuses age-appropriate cardiovascular intervention materials into major subject areas. The F4Kids Steering Committee will develop the individualized health promotion curriculum for the school. The committee includes representatives from the Medical College of Wisconsin and Children's Health Alliance of Wisconsin. The Cudahy Health Department will provide statistical information related to Cudahy schools and build community awareness. A nutritionist will give recommendations on school and home nutrition and provide access to community food resources. Representatives from the University of Wisconsin-Milwaukee will offer community engagement and evaluation tools.

Objective 4: Researchers will evaluate the partnership,
curriculum review process and development of the new curriculum. Online evaluations and questionnaires will be submitted at routine intervals to evaluate ongoing strengths and limitations of the partnerships. One month after participation, focus groups will be asked to complete an evaluation survey regarding their experience. Throughout the development phase, researchers routinely will assess feedback from all partners to allow for continuous improvement of the curriculum development process.

Stage 2
Teachers and school staff will be trained on the incorporation of the newly enhanced curriculum.

Stage 3
The curriculum will be evaluated and modifications reserved for future implementation.
Because of documented outcomes, the F4Kids research study is based on components of the HealthAhead/Heart Smart program, which holds strong ties to the Bogalusa Heart Study (Berenson, 1972). These outcomes include:

• Positive changes in school cafeteria food selection.
• Participation in physical activity.
• Data supported improvement in prevention factors for cardiovascular disease.

After successful pilot implementation, the process will be expanded througout the Milwaukee Public Schools system and other interested communities. Statewide and potential national implementation of the F4Kids program is the ultimate goal.

Daily AT3 testing speeds results, decreases costs

By Beth A. Trost, MD, technical director, Hematology/Coagulation Laboratory; and Jane Kegel, medical technologists, Children's Hospital of Wisconsin

Components	Ages	Normal Ranges
Antithrombin 3 Activity	0-5 D	39-87 IU/dL
	5D-1M	41-93 IU/dL
	1M-3M	48-108 IU/dL
	3M-6M	73-121 IU/dL
	>6M	85-119 IU/dL

Children's Hospital of Wisconsin Hematology La boratory now offers daily in-house antithrombin III testing to provide quicker results and decrease specimen handling costs.

AT3 is a glycoprotein synthesized in the liver that exerts an inhibitory effect on thrombin, enhanced in the presence of heparin. Thrombin is the necessary component in the final step of the formation of blood clots, and therefore, AT3 plays a considerable role in thromboembolic disorders.

In the pediatric population, there are several different scenarios where testing to determine AT3 levels may be helpful. Both hereditary and acquired deficiencies
of AT3 occur, and the test can be useful in the evaluation of children presenting with clots. While hereditary deficiencies are rare, in the hospital setting the majority of the testing involves patients at risk for an acquired AT3 deficiency.

Acquired AT3 deficiencies occur frequently in the contexts of severe sepsis, trauma, burns, liver disease, nephrotic syndrome, L-asparaginase treatment and extracorporeal circulation. These disorders either have a consumptive coagulopathy or an acute inflammatory component in common. AT3 levels decline because of consumption in the coagulation process and can develop a functional decline due to release of activated neutrophilic enzymes, which cleave the active portion of the AT3 molecule.

AT3 levels are known to decrease profoundly during cardiopulmonary bypass. While hemodilution contributes to this decrease, evidence also exists for a consumptive component. Plasma levels below 60-70 percent of normal are generally the critical point in the pathogenesis of thrombosis.

Thrombin is pathologically generated on the large surfaces of extracorporeal circuits during cardiopulmonary bypass. Heparin, while prolonging activated clotting times, does not prevent sub-clinical intravascular coagulation. In addition, some patients still may not exhibit adequate prolongation of the activated clotting time even after high doses of heparin. Low AT3 levels have been suggested as the underlying
etiology. Thus knowledge of AT3 levels may help guide appropriate supplementation, possibly decreasing heparin and blood usage.

The specimen should be collected in a sodium citrate tube. Short draws, clotted or hemolyzed samples are not acceptable as they may yield incorrect results. The specimen is centrifuged upon receipt in the lab, and the plasma is drawn off for testing. The plasma either is tested immediately or frozen and saved for later testing.

The principle of the test involves incubating plasma with an excess of thrombin in the presence of heparin. The residual thrombin is then quantitated. The thrombin level is inversely proportional to the AT3 level. The level is not affected by therapeutic doses of heparin. Results are reported as a percentage of normal. Children younger than 6 months old normally have low levels of AT3, assisted in part by the presence of a2 macro-globulin. Reference ranges will not change and are listed with the results.

Specimens will be accepted for testing daily from 6 a.m. to 2:30 p.m. Specimens received after hours will be saved and run during the next available test cycle. For more information, contact Children's Hospital Hematology/Coagulation Laboratory at (414) 266-2513.