Yaser A. Diab

Acquired von Willebrand Syndrome in a Child Following Berlin Heart EXCOR Pediatric Ventricular Assist Device Implantation Case Report and Concise Literature Review

The development of acquired von Willebrand syndrome (AVWS) after placement of a pulsatile-flow left ventricular assist device (LVAD) is rare and only recently recognized. We report the case of a young infant who was diagnosed with ventricular assist device (VAD)-related AVWS following implantation of a Berlin Heart EXCOR Pediatric Ventricular Assist Device (Berlin Heart Inc., The Woodlands, Texas, USA) for treatment of severe heart failure. Despite significant bleeding, the patient was successfully managed with von Willebrand factor-containing concentrate until VAD explantation led to definitive resolution of the AVWS. This case demonstrates that the possibility of this diagnosis should be considered in pediatric patients when extensive, nonsurgical bleeding is encountered after pulsatile-flow VAD implantation.

Acquired cytochrome C oxidase impairment in apheresis platelets during storage: a possible mechanism for depletion of metabolic adenosine triphosphate.

BACKGROUND: Intracellular adenosine triphosphate (ATP) levels decline significantly during storage of platelet (PLT) products, in part due to PLT degranulation. However, metabolic ATP stores also become depleted during storage through an unclear mechanism. Since both anaerobic glycolysis and oxidative phosphorylation are important for PLT ATP production, it is possible that the reduction in metabolic ATP reflects impaired oxidative phosphorylation. To assess this, we evaluated the kinetic activity and protein expression of cytochrome C oxidase (CcOX) in stored apheresis PLTs.

Storage of aliquots of apheresis platelets for neonatal use in syringes with and without agitation

BACKGROUND: To facilitate volume control in neonates, platelets (PLTs) are aliquoted and stored for short periods in non–gas‐permeable syringes before infusion. Although agitation of PLTs during storage in gas‐permeable bags is performed to maintain their quality, the effect of syringe agitation during storage is unknown.

IV Versus Subcutaneous Enoxaparin in Critically Ill Infants and Children: Comparison of Dosing, Anticoagulation Quality, Efficacy, and Safety Outcomes.

Objective: Subcutaneous enoxaparin is the mainstay anticoagulant in critically ill pediatric patients although it poses several challenges in this patient population. Enoxaparin infused IV over 30 minutes represents an attractive alternative, but there is limited experience with this route of administration in children. In this study, we assess dosing, anticoagulation quality, safety, and clinical efficacy of IV enoxaparin compared to subcutaneous enoxaparin in critically ill infants and children. Design: Retrospective single-center study comparing dosing, anticoagulation quality, safety, and clinical efficacy of two different routes of enoxaparin administration (IV vs subcutaneous) in critically ill infants and children. Key outcome measures included dose needed to achieve target antifactor Xa levels, time required to achieve target antifactor Xa levels, proportion of patients achieving target anticoagulation levels on initial dosing, number of dose adjustments, duration spent in the target antifactor Xa range, anticoagulation-related bleeding complications, anticoagulation failure, and radiologic response to anticoagulation. Setting: Tertiary care pediatric hospital. Patients: All children admitted to the cardiac ICU, PICU, or neonatal ICU who were prescribed enoxaparin between January 2014 and March 2016 were studied. Interventions: One hundred ten patients were identified who had received IV or subcutaneous enoxaparin and had at least one postadministration peak antifactor Xa level documented. Measurements and Main Results: Of the 139 courses of enoxaparin administered, 96 were therapeutic dose courses (40 IV and 56 subcutaneous) and 43 were prophylactic dose courses (20 IV and 23 subcutaneous). Dosing, anticoagulation quality measurements, safety, and clinical efficacy were not significantly different between the two groups. Conclusions: Our study suggests that anticoagulation with IV enoxaparin infused over 30 minutes is a safe and an equally effective alternative to subcutaneous enoxaparin in critically ill infants and children.

Acquired von Willebrand Syndrome: An Under-Recognized Cause of Major Bleeding in the Cardiac Intensive Care Unit.

Background: Acquired von Willebrand syndrome (AvWS) in the setting of congenital heart disease is an under-recognized cause of bleeding in the pediatric cardiac critical care unit. Methods: Fourteen patients diagnosed with AvWS admitted to the cardiac intensive care unit at the Children’s National Health System between December 2009 and September 2015 were identified with subsequent chart review and case analysis. Results: Of the 14 patients included in this study, 4 patients were on ventricular-assist devices, 6 patients were on extracorporeal membrane oxygenation, and 4 were patients with congenital heart disease not receiving any mechanical circulatory support. All patients identified manifested persistent severe bleeding, despite appropriate management of anticoagulation and blood product administration based on the established protocols. Detailed hemostatic testing including quantitative von Willebrand factor (vWF) multimer analysis revealed decreased high-molecular-weight multimers (HMWMs) and absent ultra-HMWM, consistent with AvWS in all patients. Eight patients received treatment with vWF concentrate, one patient with desmopressin, and five recovered without specific treatment. Bleeding ceased in all but one patient. Conclusions: Acquired von Willebrand syndrome is an uncommon but important cause of bleeding in pediatric patients with cardiac disease. A high index of clinical suspicion with knowledge of the characteristic clinical scenario in addition to low levels of vWF multimers is required to manage and diagnose AvWS. Although the optimal management of AvWS in this patient population is unclear, vWF concentrates are available and appear to be efficacious for controlling life-threatening bleeding.

Transcatheter Treatment of Thrombosis in the Single Ventricle Pathway: An Institutional Experience.

BACKGROUND Shunt or conduit thrombosis in a single ventricle circuit is a life-threatening complication that requires prompt treatment to rapidly restore shunt/conduit patency. Transcatheter interventions represent an attractive alternative to systemic thrombolysis or open surgical procedures. We report our centers experience with catheter-based approaches in patients with palliated single ventricle who present with shunt/conduit thrombosis. METHODS A retrospective review was performed of all patients with palliated single ventricle physiology who were diagnosed over a 5-year period with shunt/conduit thrombosis and received catheter-based interventions. Patients were followed up to hospital discharge. RESULTS Thirteen patients were identified that were diagnosed with thrombosis of a modified Blalock-Taussig shunt (five patients), bidirectional cavopulmonary shunt (one patient), and total cavopulmonary pathway (seven patients). Shunt/conduit thrombosis occurred both early and late after palliation surgery. Catheter-based interventions included balloon angioplasty (one patient), stent implantation (12 patients), and mechanical thrombectomy (one patient). Thrombophilia was identified in seven patients. Technical and clinical success with restoration of normal shunt flow and improvement in clinical status was achieved in 12 patients. Reversible procedure-related complications occurred in three patients with no significant sequelae. CONCLUSIONS Our experience suggests that percutaneous catheter-based interventions are safe and effective in managing shunt/conduit thrombosis in infants and children with palliated single ventricle circulation.

Monitoring the Harm Associated with Use of Anticoagulants in Pediatric Populations Through Trigger-Based Automated Adverse-Event Detection

BACKGROUND The safety profile of anticoagulants, which are being used with increasing frequency in pediatric populations, is not well studied. Automatic triggers built into electronic health record systems (EHR) have been shown to be an effective way to monitor for and identify medication errors. Anticoagulant-associated adverse events were examined through the use of an anticoagulant trigger panel. METHODS In a retrospective, five-year (September 2007-September 2012) observational study, four automated triggers were used to detect anticoagulant-related adverse events: activated partial thromboplastin time (aPTT) > 100 seconds in patients on an unfractionated heparin (UFH) infusion, International Normalized Ratio (INR) > 4, anti-factor Xa (anti-FXa) >1.5U/mL for patients on enoxaparin, and the documented use of protamine. RESULTS For the 1,664 triggers evaluated, 12 were associated with the aPTT trigger, only 1 of which was preventable. Receiver operator characteristic curve analysis indicated that increasing the aPTT trigger > 140 seconds would optimize sensitivity and specificity. The INR trigger identified four outpatients with adverse events. No adverse events were associated with the anti-FXa trigger. The protamine trigger identified 12 adverse events and was associated with more severe events. Minimal overlap was found with protamine and aPTT triggers. CONCLUSION Laboratory- and medication-based triggers can be effective monitoring tools for anticoagulants. For patients receiving a UFH infusion, an aPTT cutoff value of > 140 seconds is more precise. We also found that protamine use as a trigger adds value to a trigger-based anticoagulant monitoring system. Continued improvement in the logic algorithms associated with the EHR-based trigger tool will allow expanded use of this tool in a clinical manner.

Cardiopulmonary Bypass Reduces Early Thrombosis of Systemic-to-Pulmonary Artery Shunts

Background: Shunt thrombosis is a significant cause of morbidity and mortality after systemic-to-pulmonary artery shunt (SPS) placement. Concurrent procedures with placement of SPS may require cardiopulmonary bypass (CPB). Cardiopulmonary bypass is known to cause bleeding and platelet dysfunction in infants, which may protect from early shunt thrombosis. We hypothesized that infants undergoing SPS placement on CPB have a lower incidence of early shunt thrombosis. Methods: Retrospective cohort study of infants undergoing SPS placement from January 2008 to December 2014 was performed. Patients with and without early shunt thrombosis and on or off CPB were compared using the Mann-Whitney U test or Fisher exact test. Multivariable regression analysis was performed to identify independent predictors of early shunt thrombosis and to assess effect of CPB independent of other factors. Results: Seventy-five infants underwent SPS placement during the study period (on CPB, n = 25; off CPB, n = 50). Operative mortality was 11% (8/75). Nine (12%) patients developed early shunt thrombosis, all of whom had shunt placement off CPB. Independent risk factors for early shunt thrombosis were identified to be SPS placement off CPB (P = .011), prematurity (P = .034), and competitive antegrade pulmonary blood flow (P = .038). Conclusion: Prematurity, competitive antegrade pulmonary blood flow, and shunt placement off CPB lead to higher risk of early shunt thrombosis. We speculate that the protection offered by use of CPB may be accounted for by the associated complex coagulopathy and platelet dysfunction associated with CPB.

High on Aspirin Platelet Reactivity in Pediatric Patients Undergoing the Fontan Procedure

Current guidelines recommend routine aspirin thromboprophylaxis after each stage of palliation for children with single ventricle heart disease.1 In the only randomized trial to evaluate efficacy of aspirin thromboprophylaxis after the Fontan procedure, 21% of patients still had a thromboembolism.2 One possible mechanism is suboptimal inhibition of ex vivo platelet function in response to aspirin referred to as high on aspirin platelet reactivity (HAPR). Increased platelet turnover, platelet activation, inflammation, endothelial dysfunction due to hypoxemia, cardiopulmonary bypass, and Fontan conduit surfaces may lead to impaired aspirin responsiveness in this population. We evaluated laboratory markers of aspirin responsiveness in the early postoperative period after the Fontan procedure. Twenty patients undergoing the Fontan procedure (13 males, median 33 months of age) were enrolled between August 2014 and June 2015. This study was approved by the Institutional Review Board at Children’s National Health System, and all families provided informed consent for participation. Aspirin was discontinued in all patients 5 days before their surgical procedure. After induction of anesthesia, blood was obtained for thromboelastography with platelet mapping (TEG-PM), and a urine sample was collected …