Mary Bauman

The 2013 International Society for Heart and Lung Transplantation Guidelines for mechanical circulatory support: Executive summary

Institutional Affiliations Co-chairs Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, Georgia Institute of Technology and Morehouse School of Medicine; Pamboukian SV: University of Alabama at Birmingham, Birmingham, Alabama; Teuteberg JJ: University of Pittsburgh, Pittsburgh, Pennsylvania Task force chairs Birks E: University of Louisville, Louisville, Kentucky; Lietz K: Loyola University, Chicago, Maywood, Illinois; Moore SA: Massachusetts General Hospital, Boston, Massachusetts; Morgan JA: Henry Ford Hospital, Detroit, Michigan Contributing writers Arabia F: Mayo Clinic Arizona, Phoenix, Arizona; Bauman ME: University of Alberta, Alberta, Canada; Buchholz HW: University of Alberta, Stollery Children’s Hospital and Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada; Deng M: University of California at Los Angeles, Los Angeles, California; Dickstein ML: Columbia University, New York, New York; El-Banayosy A: Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania; Elliot T: Inova Fairfax, Falls Church, Virginia; Goldstein DJ: Montefiore Medical Center, New York, New York; Grady KL: Northwestern University, Chicago, Illinois; Jones K: Alfred Hospital, Melbourne, Australia; Hryniewicz K: Minneapolis Heart Institute, Minneapolis, Minnesota; John R: University of Minnesota, Minneapolis, Minnesota; Kaan A: St. Paul’s Hospital, Vancouver, British Columbia, Canada; Kusne S: Mayo Clinic Arizona, Phoenix, Arizona; Loebe M: Methodist Hospital, Houston, Texas; Massicotte P: University of Alberta, Stollery Children’s Hospital, Edmonton, Alberta, Canada; Moazami N: Minneapolis Heart Institute, Minneapolis, Minnesota; Mohacsi P: University Hospital, Bern, Switzerland; Mooney M: Sentara Norfolk, Virginia Beach, Virginia; Nelson T: Mayo Clinic Arizona, Phoenix, Arizona; Pagani F: University of Michigan, Ann Arbor, Michigan; Perry W: Integris Baptist Health Care, Oklahoma City, Oklahoma; Potapov EV: Deutsches Herzzentrum Berlin, Berlin, Germany; Rame JE: University of Pennsylvania, Philadelphia, Pennsylvania; Russell SD: Johns Hopkins, Baltimore, Maryland; Sorensen EN: University of Maryland, Baltimore, Maryland; Sun B: Minneapolis Heart Institute, Minneapolis, Minnesota; Strueber M: Hannover Medical School, Hanover, Germany Independent reviewers Mangi AA: Yale University School of Medicine, New Haven, Connecticut; Petty MG: University of Minnesota Medical Center, Fairview, Minneapolis, Minnesota; Rogers J: Duke University Medical Center, Durham, North Carolina

Prothrombotic conditions in an unselected cohort of children with venous thromboembolic disease

Summary.  Venous thromboembolic events (VTEs) in children are usually associated with underlying clinical conditions. The added contribution of prothrombotic conditions to the occurrence of VTEs in children is not clear. This study reports the prevalence of prothrombotic conditions in 171 consecutive children with VTE followed in the Hospital for Sick Children Thrombosis Outpatient Clinic. The median age of the children at the time of VTE was 2.3 months (range 1 day to 16.5 years). An underlying medical condition and a central venous line (CVL) were present in 156 (91%) and 132 (77%) of 171 children, respectively. A positive family history was present in 8% of children. The prevalence of factor V Leiden was 4.7%, prothrombin G20210A polymorphism was 2.3%, protein S deficiency was 1.2%, protein C deficiency was 0.6% and increased plasma lipoprotein (a) concentration (>30 mg dL−1) was 7.5% (tested in 107 children). The overall frequency of inherited prothrombotic coagulation proteins was 13% (95% confidence interval 7 to 19%) and the frequency was not significantly different between neonates and older children with VTE. Inherited prothrombotic coagulation proteins were not associated with gender, CVL‐related VTE, a positive family history of thrombosis or spontaneous VTE in neonates. Increased frequency of inherited prothrombotic coagulation proteins was, however, found in older children with spontaneous VTE (60%) compared with older children with VTEs secondary to an underlying medical condition (10%) (P = 0.02). In conclusion, this study indicates that inherited prothrombotic coagulation proteins do not contribute significantly to the pathogenesis of VTEs in neonates and children, in whom the most significant etiological factors are the presence of a CVL and/or other medical conditions.

Prevention and Treatment of Thrombosis in Pediatric and Congenital Heart Disease A Scientific Statement From the American Heart Association

Thrombosis has long been recognized as a potentially life-threatening complication in children with congenital heart disease (CHD), children with acquired heart disease, and in adults with CHD. High-risk groups include patients with shunt- dependent single ventricles (shunt thrombosis, 8%–12%; 4%

Accuracy of the CoaguChek XS for point-of-care international normalized ratio (INR) measurement in children requiring warfarin

Point-of-care INR (POC INR) meters can provide a safe and effective method for monitoring oral vitamin K antagonists (VKAs) in children. Stollery Childrens Hospital has a large POC INR meter loan program for children requiring oral VKAs. Our protocol requires that POC INR results be compared to the standard laboratory INR for each child on several consecutive tests to ensure accuracy of CoaguChek XS (Roche Diagnostics, Basel Switzerland) meter. It was the objective of the study to determine the accuracy of the CoaguChek XS by comparing whole blood INR results from the CoaguChek XS to plasma INR results from the standard laboratory in children. POC INR meter validations were performed on plasma samples from two time points from 62 children receiving warfarin by drawing a venous blood sample for laboratory prothrombin (PT)-INR measurements and simultaneous INR determinations using the POC-INR meter. Agreement between CoaguChek XS INR and laboratory INR was assessed using Bland-Altman plots. Bland-Altmans 95% limits of agreement were 0.11 (-0.20; 0.42) and 0.13 (-0.22; 0.48) at the two time points, respectively. In conclusion, the CoaguChek XS meter appraisal generates an accurate and precise INR measure in children when compared to laboratory INR test results.

Evaluation of enoxaparin dosing requirements in infants and children - Better dosing to achieve therapeutic levels

Increasing the starting dose of enoxaparin results in the early achievement of therapeutic anti-factor Xa levels in children receiving enoxaparin which is critical for effective therapy and the reduction of venipunctures. The aim of this study was: i) to determine the enoxaparin dose required to achieve therapeutic anti-factor Xa levels in infants and children, and ii) to establish whether increasing the starting dose of enoxaparin influenced the time required to reach the therapeutic range and the number of venipunctures required for dose-adjustment, and iii) the radiographic outcome of the thrombosis, where applicable. A retrospective chart review of children who received enoxaparin was carried out at the Stollery Childrens Hospital, Edmonton, Alberta, Canada. Patients treated with standard-dose enoxaparin (1.5 mg/kg for children < or =3 months of age, 1.0 mg/kg for children > or =3 months of age), were compared with children who received a higher initial starting dose of enoxaparin (1.7 mg/kg for children > or =3 months of age, 1.2 mg/kg for children > or =3 months of age). Infants <3 months required an enoxaparin dose of 1.83 mg/kg, and those who received an increased initial enoxaparin dose resulted in faster attainment of therapeutic anti-factor Xa levels requiring significantly fewer venipunctures. Similarly, infants > or =3-12 months, 1-5 years, and 6-18 years, require enoxaparin 1.48 mg/kg, 1.23 mg/kg and 1.13 mg/kg, respectively, in order to achieve a therapeutic anti-factor Xa level. In conclusion, increasing the starting dose of enoxaparin may result in more rapid attainment of therapeutic range with fewer venipunctures, dose adjustments, and without an increase in adverse events.

Prevalence of post-thrombotic syndrome following asymptomatic thrombosis in survivors of acute lymphoblastic leukemia.

Summary.  Background: Deep vein thrombosis (DVT) is a complication of treatment of acute lymphoblastic leukemia (ALL) in children but little is known about the long‐term outcomes of these DVT. Objective: To determine the incidence of post‐thrombotic syndrome (PTS) in (i) children with ALL diagnosed with asymptomatic DVT using radiographic testing and (ii) an unselected group of ALL survivors. Methods: Cross‐sectional study in two populations. Group I comprised children in the Prophylactic Antithrombin Replacement in Kids with ALL treated with L‐Asparaginase (PARKAA) study diagnosed with DVT by radiographic tests. Group II consisted of non‐selected childhood ALL survivors <21 years. PTS was assessed using a standardized scoring sheet. Results: Group I: 13 PARKAA patients (median age 12 years) were assessed, and 7 had PTS (54%; 95% CI, 25–81). All patients had collaterals, three also had increased arm circumference. Group II: 41 patients (median age 13 years) with a history of ALL were enrolled, and 10 had PTS (24%; 95% CI, 11–38). All patients had collaterals; five also had increased arm circumference. Conclusion: There is a high incidence of PTS in survivors of childhood ALL with radiographically diagnosed asymptomatic DVT. A significant proportion of ALL survivors develop PTS, indicating previously undiagnosed DVT.

Decompressive Hemicraniectomy in Children With Severe Ischemic Stroke and Life-Threatening Cerebral Edema

Decompressive hemicraniectomy has been discussed as a treatment option that increases survival in adults with malignant stroke. This approach has not been studied extensively in children. From a prospective cohort, we identified 4 children who underwent decompressive hemicraniectomy for malignant infarctions with life-threatening cerebral edema within 72 hours of their stroke. All 4 children had different causes for their stroke and experienced severe cerebral edema with increasing intracranial pressure and an impending fatal outcome. Despite massive cerebral infarction, all patients were ambulant and able to speak at the time of follow-up. Although a limited experience, decompressive hemicraniectomy is a life-saving approach for malignant stroke in children.

EMPoWarMENT: Edmonton pediatric warfarin self-management pilot study in children with primarily cardiac disease.

UNLABELLED Increasing numbers of children require warfarin thromboprophylaxis. Home INR testing by the patient (PST) has revolutionized warfarin management. However, the family/patient must contact the health team for guidance for warfarin dosing. Patient self management(PSM) prepares a patient performing PST to take an active role in warfarin dosing. Adult studies demonstrate that PSM is safe and effective with improved adherence and treatment satisfaction quality of life (QOL). OBJECTIVE To estimate the safety and efficacy in children performing PSM or PST, to evaluate warfarin dose decision making in PSM, and warfarin related QOL. METHODS Warfarinized children performing PST for >3m were randomized to PST or PSM. The PSM group underwent warfarin management education and assumed independent warfarin management. INRs were collected for a year prior to and for 1 year of study to determine TTR and warfarin decision making. QOL was assessed through inventory completion and interviews. RESULTS 28 children were randomized and followed for 12 months. TTR was (83.9% pre/ post), and 77.7% pre to 83.0% post for PST and PSM (p=0.312). Appropriate warfarin decision making was 90% with no major bleeding episodes and no thromboembolic events. PSM was preferred by families. CONCLUSIONS PSM for children may be a safe and effective management strategy for warfarinized children. Clinical studies with larger sample size are required.

Central venous catheter sampling of low molecular heparin levels: An approach to increasing result reliability

Background: The low molecular weight heparin effect in children is monitored using the anti-factor Xa level. Venipuncture is recommended; however, central venous catheter blood sampling is often necessary. Heparin infused through central venous catheters may contaminate central venous catheter blood samples, preventing reliable anti-factor Xa level measurement. Simultaneous anti-factor Xa/partial thromboplastin time measurement with central venous catheter blood sampling may predict anti-factor Xa reliability. Objectives: To determine the prevalence of heparin contamination as measured by the partial thromboplastin time/anti-factor Xa in central venous catheter blood samples and whether careful sampling could minimize heparin contamination of anti-factor Xa levels from central venous catheter blood sampling. Methods: Simultaneous partial thromboplastin time/anti-factor Xa measurements from central venous catheter blood sampling determined the prevalence of heparin contamination of central venous catheter blood samples. In phase II, children receiving low molecular weight heparin had routine central venous catheter blood sampling to measure the peak anti-factor Xa and the simultaneous partial thromboplastin time. Anti-factor Xa levels with a partial thromboplastin time of >40 secs (pair 1) were identified; there was no low molecular weight heparin dose change, and the paired sample was repeated using a careful sampling technique (pair 2). Pairs 1 and 2 were compared to determine the efficiency of the sampling technique in removing heparin from the central venous catheter blood samples. Results: In phase I, 100 children had 485 paired anti-factor Xa/partial thromboplastin time central venous catheter blood samples with 29% ± 4.1% (95% confidence interval 25% to 33%) anti-factor Xa with partial thromboplastin times of >40 secs. In phase II, 43 children had 129 paired anti-factor Xa/partial thromboplastin time samples with partial thromboplastin times of >40 secs. The pair 1 mean partial thromboplastin times/anti-factor Xa levels were 109.8 secs (SD 53.1, range 34.0 to >200 secs) and 1.03 units/mL (SD 0.56, range 0.26–4.2 units/mL). Repeated partial thromboplastin times/anti-factor Xa levels (pair 2) were significantly decreased from those of pair 1 (p < .001) with means of 58.5 secs (SD 21.2, range 22–152 secs) vs. 109.8 secs (SD 53.1, range 34.0 to > 200 secs, p < .001) and 0.63 unit/mL (SD 0.30, range 0.02–1.77 units/mL) vs. 1.03 units/mL (SD 0.56, range 0.26–4.2 units/mL), respectively. Conclusions: Measurement of the partial thromboplastin time performed in combination with that of the anti-factor Xa level can be used to assist health practitioners to identify unfractionated heparin contamination of anti-factor Xa levels drawn from central venous catheters. A careful sampling technique may minimize heparin contamination in central venous catheter blood samples.

Point-of-care INR measurement in children requiring warfarin: what has been evaluated and future directions

Many children are surviving primary illnesses and now require thromboprophylaxis as a result of advances in management. Vitamin K antagonists are commonly prescribed to prevent or treat thrombosis. These agents are far more challenging to effectively manage in children. As a result of these challenges, frequent blood monitoring to measure international normalized ratio (INR) values is required. Point-of-care (POC) INR monitors use a capillary blood sample that has been expressed as a solution to improve effective management of vitamin K antagonist therapy. POC INR meters have been demonstrated to be accurate and precise in measuring INRs. Implementation of a standardized education program prior to patient use of POC meters results in differences between measured laboratory INRs and POC INR comparisons that meet criteria for clinical relevance. This indicates that POC INR meters are safe and effective for use in children.