Implementation of a tier system for IVIG indications to address IVIG shortage at a tertiary care pediatric medical center.

BACKGROUND: Drug shortages are a common issue that healthcare systems face and can result in adverse health outcomes for patients requiring inferior alternate treatment. The United States recently experienced a national drug shortage of intravenous immunoglobulin (IVIG). Several reported strategies to address the IVIG and other drug shortages have been proposed; however, there is a lack of evidence-based methods for protocol development and implementation. OBJECTIVE: To evaluate the efficacy of introducing a multidisciplinary task force and tier system of indications and to minimize adverse effects during a shortage of IVIG. METHODS: Faculty members across disciplines with expertise in IVIG use were invited to participate in a task force to address the shortage and ensure adequate supply for emergent indications. A tier system of IVIG indications was established according to the severity of diagnosis, urgency of indication, and quality of supporting evidence. Based on inventory, indications in selected tiers were auto-approved. Orders that could not be automatically approved were escalated for task force review. RESULTS: Overall, there were 342 distinct requests for IVIG during the study period (August 1, 2019 to December 31, 2019). All Tier 1 indications were approved. Of all requests, only 2.6% (9) of requests were denied, none of which resulted in adverse effects based on retrospective chart review. Seven patients who regularly receive IVIG had possible adverse effects due to dose reduction or spacing of treatment; however, each complication was multifactorial and not attributed to the shortage or tier system implementation alone. CONCLUSION: Implementation of a multidisciplinary task force and tier system to appropriately triage high-priority indications for limited pharmaceutical agents should be considered in health institutions faced with a drug shortage.

Clinical Impact of a Standardized Risk-Stratified Thromboprophylaxis Protocol for Multisystem Inflammatory Syndrome in Children.

OBJECTIVE: To evaluate the clinical impact of an institutional thromboprophylaxis protocol in patients with multisystem inflammatory syndrome in children (MIS-C), who are at increased risk for thromboembolism (TE). STUDY DESIGN: We conducted a single-center retrospective cohort study of children less than 18 years between March 2020 and December 2021. Eligible patients were confirmed with MIS-C and were managed with a standardized multidisciplinary treatment approach that included a thromboprophylaxis protocol to guide and unify clinical practice. For high-risk patients, prophylactic dose enoxaparin (target anti-Factor Xa 0.1-0.3 U/mL) was added. In high-risk patients with TE risk factors persistent at hospital discharge, thromboprophylaxis was prescribed for an additional 30 days. RESULTS: Of 135 patients with MIS-C, 124 (92%) required intensive care unit stay and 64 (47%) required a central venous catheter for a median duration of 5 days (IQR, 4-7). Prophylactic dose enoxaparin was initiated in 116 out of 121 patients (96%) deemed high-risk per our protocol at a median of 1 day after admission [IQR, 0-3] achieving target levels at a median of 1 day [IQR, 1-2]. The median initial anti-Factor Xa level was 0.13 u/mL [IQR, 0.05-0.19]. One patient (0.7%) developed symptomatic noncatheter related superficial vein thrombosis requiring therapeutic anticoagulation. Thromboprophylaxis was extended for 30 days after discharge in 108 out of 135 patients (80%). Bleeding events occurred in 5 patients during hospitalization (4.2%). All bleeding events were clinically relevant nonmajor bleeding. There were no deaths. CONCLUSIONS: Implementation of an institutional standardized thromboprophylaxis protocol in MIS-C was feasible and led to timely initiation of prophylactic anticoagulation and low rates of TEs and bleeding complications.

Medich Giant Platelet Syndrome: An Evolving Qualitative and Quantitative Platelet Disorder.

Qualitative platelet disorders remain rare and varied. We describe here 2 additional patients with giant platelets, thrombocytopenia, deficiency in alpha granules and the presence of membranous inclusions within the cytoplasm. Collectively known as Medich syndrome, we further elucidated structural and clinical features of this rare syndrome. Platelets obtained from 2 patients with macro-thrombocytopenia were evaluated by electron microscopy. Structural findings were correlated with clinical characteristics. The defining morphologic feature found in the platelets of these patients is the presence of long, tubular inclusions consisting of several layers of membrane wrapped around a core of cytoplasm. These inclusions may deform the discoid shape of the platelet. In addition, abnormal giant alpha granules are present. Clinically all patients in the current report and review of the literature had mucosal bleeding and were often misdiagnosed as having immune related thrombocytopenia. To date five cases of Medich giant platelet syndrome have been reported. The cases are unified by the ultrastructural findings of abnormal alpha granules and unusual cytoplasmic scrolls. All patients experienced mucosal bleeding, however many clinical, biologic and genetic characteristics of this rare disorder remain to be determined.

Cerebral Sinus Venous Thrombosis in Infants after Surgery for Congenital Heart Disease.

OBJECTIVE: To determine the prevalence of and risk factors for cerebral sinus venous thrombosis (CSVT) in neonates undergoing congenital heart disease (CHD) repair. STUDY DESIGN: Neonates who had CHD repair with cardiopulmonary bypass and postoperative brain magnetic resonance imaging (MRI) between 2013 and 2019 at a single tertiary care center were identified from institutional databases. Demographic, clinical, and surgical data were abstracted from these databases and from the medical record; 278 neonates with CHD had cardiopulmonary bypass, 184 of whom had a postoperative brain MRI. RESULTS: Eight patients (4.3%) had a CSVT. Transposition of the great arteries with an intact ventricular septum (P < .01) and interrupted aortic arch (P = .02) were associated with an increased risk for CSVT. Other risk factors for CSVT included cross-clamp time (98 [IQR, 77.5-120] minutes vs 67 [IQR, 44-102] minutes; P = .03), units of platelets (3.63 [IQR, 3-4] vs 2.17 [IQR, 1-4]; P < .01) and packed red blood cells (0.81 [IQR, 0.25-1] vs 1.21 [IQR, 1-1]; P = .03) transfused intraoperatively, and time between surgery and MRI (10 [IQR, 7-12.5] days vs 20 [IQR, 12-35] days; P < .01). Five patients (62.5%) were treated with anticoagulation. All patients had complete or partial resolution of their CSVT, regardless of treatment. CONCLUSIONS: Brain MRI after cardiopulmonary bypass in neonates revealed a low prevalence of CSVT (4.3%). Further studies are needed to establish best practices for surveillance, prevention, and treatment of CSVT in this population.

Hospital-Associated Venous Thromboembolism in a Pediatric Cardiac ICU: A Multivariable Predictive Algorithm to Identify Children at High Risk.

OBJECTIVES: Critically ill children with cardiac disease are at significant risk for hospital-associated venous thromboembolism, which is associated with increased morbidity, hospital length of stay, and cost. Currently, there are no widely accepted guidelines for prevention of hospital-associated venous thromboembolism in pediatrics. We aimed to develop a predictive algorithm for identifying critically ill children with cardiac disease who are at increased risk for hospital-associated venous thromboembolism as a first step to reducing hospital-associated venous thromboembolism in this population. DESIGN: This is a prospective observational single-center study. SETTING: Tertiary care referral children's hospital cardiac ICU. PATIENTS: Children less than or equal to18 years old admitted to the cardiac ICU who developed a hospital-associated venous thromboembolism from December 2013 to June 2017 were included. Odds ratios and 95% CIs are reported for multivariable predictors. MEASUREMENTS AND MAIN RESULTS: A total of 2,204 separate cardiac ICU encounters were evaluated with 56 hospital-associated venous thromboembolisms identified in 52 unique patients, yielding an overall prevalence of 25 hospital-associated venous thromboembolism per 1,000 cardiac ICU encounters. We were able to create a predictive algorithm with good internal validity that performs well at predicting hospital-associated venous thromboembolism. The presence of a central venous catheter (odds ratio, 4.76; 95% CI, 2.0-11.1), sepsis (odds ratio, 3.5; 95% CI, 1.5-8.0), single ventricle disease (odds ratio, 2.2; 95% CI, 1.2-3.9), and extracorporeal membrane oxygenation support (odds ratio, 2.7; 95% CI, 1.2-5.7) were independent risk factors for hospital-associated venous thromboembolism. Encounters with hospital-associated venous thromboembolism were associated with a higher rate of stroke (17% vs 1.2%; p < 0.001). CONCLUSIONS: We developed a multivariable predictive algorithm to help identify children who may be at high risk of hospital-associated venous thromboembolism in the pediatric cardiac ICU.

Characteristics and outcomes of osteomyelitis in children with sickle cell disease: A 10-year single-center experience.

BACKGROUND: Patients with sickle cell disease (SCD) are at increased risk for osteomyelitis (OM). Diagnosis of OM in SCD is challenging as the clinical presentation is similar to a vasoocclusive crisis (VOC) with no diagnostic gold standard. We report characteristics and outcomes of OM in SCD patients treated at our center over 10-year period. DESIGN/METHOD: We conducted a retrospective analysis of patients with SCD who were treated for OM at our center over a 10-year period (2006-2016). Cases were identified utilizing radiology data mining software. Radiology reports and medical charts of potential OM cases were reviewed. RESULTS: Twenty-eight children with SCD were treated for OM at our institution. Patients treated for OM were largely similar to patients treated for a VOC. However, patients treated for OM had significantly higher C-reactive protein (10 mg/dL vs 5.58 mg/dL, P = 0.03) and erythrocyte sedimentation rate (60 mm/h vs 47 mm/h, P = 0.02). Magnetic resonance imaging (MRI) findings were consistent with OM in 18 (64%) patients and indeterminate in the remaining. Based on clinical, laboratory, and radiological findings, the diagnosis of OM was considered confirmed in 3 patients, probable in 6 patients, and presumed in 19 patients. Nontyphoidal Salmonella was isolated from cultures in 9 (32%) patients, while no organism was identified in 19 (67%) patients. All patients were treated with antibiotics. Six patients (21%) required surgical interventions. CONCLUSIONS: OM continues to pose diagnostic challenges. Most patients are treated for OM without definitive confirmation. Nontyphoidal Salmonella was the only organism identified in our cohort.

Targeted Inhibition of the Epidermal Growth Factor Receptor and Mammalian Target of Rapamycin Signaling Pathways in Olmsted Syndrome.

Importance: Olmsted syndrome is a rare and disabling genodermatosis for which no successful treatment is currently available. Objective: To evaluate the clinical response to the mammalian target of rapamycin (mTOR) inhibitor sirolimus and/or the epidermal growth factor receptor (EGFR) inhibitor erlotinib among patients with Olmsted syndrome. Design, Setting, and Participants: This case series focused on 4 children with treatment-refractory Olmsted syndrome. These children received treatments (initiated in 2017 and 2018) at the outpatient dermatology clinic at the Children's Hospital of Wisconsin in Milwaukee, Wisconsin; Children's National Hospital in Washington, DC; and Hospital Infantil Pequeno Príncipe, Curitiba in Paraná, Brazil. Exposures: Immunohistochemical analyses for mTOR and EGFR activation were performed on skin biopsy specimens from 2 patients. Oral sirolimus was administered to these 2 patients at a dosage of 0.8 mg/m2 twice daily, titrated to a goal trough whole-blood concentration of 10 to 15 ng/mL. Erlotinib was administered to all 4 patients at a dosage of 2 mg/kg/d. Main Outcomes and Measures: Clinical responses were assessed with visual analog scales for pruritus and pain and/or the Children's Dermatology Life Quality Index. Adverse effects were monitored throughout treatment. Results: Four patients (mean [SD] age, 7 [6] years; 2 boys and 2 girls) were analyzed. Lesional skin immunostaining showed increased phosphorylated ribosomal protein S6 (RPS6) and phosphorylated EGFR staining in the epidermis, indicating enhanced mTOR and EGFR signaling activation. Patients 1 and 2 were initially treated with sirolimus, displaying substantial clinical improvement in erythema and periorificial hyperkeratosis afterward. When switched to erlotinib, these patients showed substantial palmoplantar keratoderma (PPK) improvement. Patients 3 and 4 were treated with erlotinib only and later showed rapid and near complete resolution of PPK and substantial improvement in Children's Dermatology Life Quality Index scores. All 4 patients had sustained improvements in pruritus and pain. No severe adverse effects were reported. Conclusions and Relevance: This study's findings suggest that the EGFR-mTOR cascade may play a substantial role in the pathophysiological process of Olmsted syndrome and may serve as a major therapeutic target. Oral sirolimus and erlotinib may be a promising, life-altering treatment for pediatric patients with Olmsted syndrome.

Atlanto-occipital ligament calcification: a novel imaging finding in pediatric rotational vertebral artery occlusion.

We describe a 2-year-old girl with bow hunter syndrome complicated by vertebral artery dissection and multiple ischemic infarcts. Pediatric bow hunter syndrome is a rare and likely under-recognized disorder. Interestingly, our patient had atlanto-occipital ligament calcification on CT scan, an imaging finding that has not been reported in association with bow hunter syndrome and one that might help increase recognition of this dynamic disorder of the posterior circulation.

Catheter-Related Venous Thrombosis in Hospitalized Pediatric Patients with Inflammatory Bowel Disease: Incidence, Characteristics, and Role of Anticoagulant Thromboprophylaxis with Enoxaparin.

OBJECTIVE: To describe the incidence and characteristics of central venous catheter (CVC)-related thrombosis in hospitalized pediatric patients with active inflammatory bowel disease (IBD) and report the potential usefulness of anticoagulant thromboprophylaxis (AT). STUDY DESIGN: We conducted a retrospective study of patients who were admitted to our children's hospital in the last 2 years with active IBD and required a CVC and identified all patients with an objectively confirmed symptomatic CVC-related thrombosis. To assess the usefulness of a recently implemented institutional AT protocol, we compared the frequency of CVC-related thrombosis, nadir hemoglobin, and red blood cell transfusion requirements in patients who received AT with those who did not during the study period. RESULTS: A total of 40 patients with IBD who required 47 consecutive hospitalizations were included. AT was administered during 24 of 47 hospitalizations (51%). Patients who received AT were similar to those who did not receive AT with regard to demographics, IBD phenotypes, extent of colonic involvement, and thrombotic risk factors. CVC-related thrombosis occurred in 5 of 23 hospitalizations (22%) in which AT was withheld compared with 0 of 24 hospitalizations (0%) in which patients received AT (P = .02). The red blood cell transfusion requirements and nadir hemoglobin were not significantly different between the 2 groups. CONCLUSIONS: We observed a high incidence of CVC-related thrombosis in hospitalized children with IBD. Administration of AT in our population was associated with significant reduction in CVC-related thrombosis without evidence of increased bleeding.

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.

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 center's 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.

Isolated midbrain ischemic infarct in association with hyperlipoproteinemia (a): a report of 2 adolescent patients.

Arterial ischemic strokes (AIS) localized solely to the midbrain are extremely uncommon in the pediatric population. Elevated lipoprotein (a), which promotes atherosclerosis and a prothrombotic state, has been associated with increased risk of AIS in children and adults. Here we describe a 17-year-old boy and a 15-year-old girl who presented with internuclear ophthalmoplegia secondary to an isolated midbrain AIS. Evaluation for risk factors for AIS in these otherwise healthy adolescents identified hyperlipoproteinemia (a) in combination with other potential prothrombotic conditions suggesting that hypercoagulable states such as hyperlipoproteinemia (a) may have contributed to development of small-vessel arteriopathy and localized AIS.

Coagulopathy in newborns with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia: a retrospective case-control study.

BACKGROUND: Newborns with hypoxic ischemic encephalopathy (HIE) are at risk for coagulopathy due to systemic oxygen deprivation. Additionally, therapeutic hypothermia (TH) slows enzymatic activity of the coagulation cascade, leading to constitutive prolongation of routinely assessed coagulation studies. The level of laboratory abnormality that predicts bleeding is unclear, leading to varying transfusion therapy practices. METHODS: HIE infants treated with TH between 2008-2012 were included in this retrospective study. Initial, minimum (min) and maximum (max) values of International Normalized Ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen (Fib) and platelet (PLT) count (measured twice daily during TH) were collected. Bleeding was defined as clinically significant if associated with 1) decreased hemoglobin (Hb) by 2 g/dL in 24 hours, 2) transfusion of blood products for hemostasis, or 3) involvement of a critical organ system. Laboratory data between the bleeding group (BG) and non-bleeding group (NBG) were compared. Variables that differed significantly between groups were evaluated with Receiver Operating Characteristic Curve (ROC) analyses to determine cut-points to predict bleeding. RESULTS: Laboratory and bleeding data were collected from a total of 76 HIE infants with a mean (±SD) birthweight of 3.34 ± 0.67 kg and gestational age of 38.6 ± 1.9 wks. BG included 41 infants. Bleeding sites were intracranial (n = 13), gastrointestinal (n = 19), pulmonary (n = 18), hematuria (n = 11) or other (n = 1). There were no differences between BG and NBG in baseline characteristics (p > 0.05). Both groups demonstrated INR and aPTT values beyond the acceptable reference ranges utilized for full tem newborns. BG had higher initial and max INR, initial aPTT, and lower min PLT and min Fib compared to NBG. ROC analyses revealed that platelet count <130 × 109/L, fib level <1.5 g/L, and INR >2 discriminated BG from NBG. CONCLUSIONS: Laboratory evidence of coagulopathy is universal in HIE babies undergoing TH. Transfusion strategies to maintain PLT counts >130 × 109/L, fib level >1.5 g/L, and INR <2 may prevent clinical bleeding in this high risk population.

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.