Turner syndrome may be associated with hepatic adenoma.

Turner syndrome, caused by complete or partial loss of an X chromosome, is marked by a range of clinical manifestations including short stature, cardiovascular and renal disease. Hepatic involvement is an increasingly recognized concern. Steatosis and elevated transaminases are commonly observed in this population, but case reports have also described hepatic adenoma. Hepatic adenomas are rare, occurring in one per million people in the general population. They are typically benign but malignant transformation or rupture can occur. We sought to investigate whether Turner syndrome is associated with hepatic adenoma. Patients with Turner syndrome encountered at a single, academic institution between 2006 and 2020 were identified using ICD-10 codes and demographic, medication, laboratory, and imaging data were analyzed. Of the 228 patients identified, 46.9% had liver function testing, which were abnormal in 48.6%. Five of 77 patients with hepatic imaging had abnormalities. Three patients (1.3%) had hepatic adenoma, one after presenting in hemorrhagic shock due to rupture. These findings suggest that patients with Turner syndrome may have an increased risk for developing hepatic adenoma. Annual monitoring of liver function tests is already recommended in Turner syndrome. The addition of periodic hepatic imaging may also be beneficial.

Gabapentin Can Improve Irritability and Feeding Tolerance in Single Ventricle Interstage Patients: A Case Series.

Visceral hyperalgesia is common among children with complex medical conditions. Infants with complex congenital heart disease, specifically single ventricle interstage patients, are often found to have feeding intolerance and irritability. Gabapentin treatment has shown promise for symptomatic improvement for visceral hyperalgesia in some patients. We present a case series of five patients in which four of the five patients showed improvement within 48 h of starting gabapentin. The use of gabapentin in single ventricle interstage patients to treat visceral hyperalgesia shows promise based on our case series, but future multi-center prospective studies would be beneficial.

COVID-19-Related Thrombotic and Bleeding Events in Adults With Congenital Heart Disease.

Background: Altered coagulation is a striking feature of COVID-19. Adult patients with congenital heart disease (ACHD) are prone to thromboembolic (TE) and bleeding complications. Objectives: The purpose of this study was to investigate the prevalence and risk factors for COVID-19 TE/bleeding complications in ACHD patients. Methods: COVID-19-positive ACHD patients were included between May 2020 and November 2021. TE events included ischemic cerebrovascular accident, systemic and pulmonary embolism, deep venous thrombosis, myocardial infarction, and intracardiac thrombosis. Major bleeding included cases with hemoglobin drop >2 g/dl, involvement of critical sites, or fatal bleeding. Severe infection was defined as need for intensive care unit, endotracheal intubation, renal replacement therapy, extracorporeal membrane oxygenation, or death. Patients with TE/bleeding were compared to those without events. Factors associated with TE/bleeding were determined using logistic regression. Results: Of 1,988 patients (age 32 [IQR: 25-42] years, 47% male, 59 ACHD centers), 30 (1.5%) had significant TE/bleeding: 12 TE events, 12 major bleeds, and 6 with both TE and bleeding. Patients with TE/bleeding had higher in-hospital mortality compared to the remainder cohort (33% vs 1.7%; P < 0.0001) and were in more advanced physiological stage (P = 0.032) and NYHA functional class (P = 0.01), had lower baseline oxygen saturation (P = 0.0001), and more frequently had a history of atrial arrhythmia (P < 0.0001), previous hospitalization for heart failure (P < 0.0007), and were more likely hospitalized for COVID-19 (P < 0.0001). By multivariable logistic regression, prior anticoagulation (OR: 4.92; 95% CI: 2-11.76; P = 0.0003), cardiac injury (OR: 5.34; 95% CI: 1.98-14.76; P = 0.0009), and severe COVID-19 (OR: 17.39; 95% CI: 6.67-45.32; P < 0.0001) were independently associated with increased risk of TE/bleeding complications. Conclusions: ACHD patients with TE/bleeding during COVID-19 infection have a higher in-hospital mortality from the illness. Risk of coagulation disorders is related to severe COVID-19, cardiac injury during infection, and use of anticoagulants.

Optimizing efficiency of a custom clinical decision support tool improves adult congenital heart disease care.

Study objective: Improve the efficiency of an inpatient clinical decision support tool (CDS) for patients with adult congenital heart disease (ACHD). Design: The efficiency of a CDS was evaluated across two time periods and compared. Setting: An academic, tertiary care center. Participants: ACHD patients roomed in an inpatient setting. Intervention: Plan-Do-Study-Act (PDSA) methods were applied starting in 2021 and included refinement of diagnostic codes and the addition of department encounter codes. Main outcome measures: True positive and false positive CDS alerts. Results: Baseline data from 2017 had a median (IQR) of 38 (17) and 2019 baseline data had 65 (19) total alerts per month. Combining both baseline data years, the median true positive CDS alerts was 47.3 %. There were 71 (6) total alerts per month for the 2021-2022 time period and with ongoing PDSA cycles and optimization in the CDS the true positive alerts improved substantially resulting in a shifting of the median to 78.9 % within 9 months. Conclusion: CDS can efficiently notify providers when an ACHD patient is encountered. The use of ICD 10 codes alone to identify ACHD patients has limited accuracy with a high proportion of false positives. Ongoing revision of the CDS system methods is important to improving efficiency and minimizing provider alert fatigue.

New-Onset Accelerated Idioventricular Rhythm During Dental Rehabilitation.

Accelerated idioventricular rhythm has been documented in several cases involving the induction of general anesthesia; however, it has not previously been known to occur during reversal of neuromuscular blockade with neostigmine and glycopyrrolate. The current understanding of the pathophysiology of accelerated idioventricular rhythm involves enhanced automaticity of ventricular myocardium in the setting of increased vagal tone suppressing sinoatrial node pace making. We present the case of an 8-year-old boy who developed accelerated idioventricular rhythm during dental rehabilitation. In this case, accelerated idioventricular rhythm developed immediately upon reversal of neuromuscular blockade with neostigmine and glycopyrrolate and recurred intermittently during his recovery in the postanesthesia care unit. This was a benign occurrence in our patient who remained asymptomatic and hemodynamically stable, and his arrhythmia eventually subsided without intervention after several hours of telemetry. This case suggests that reversal of neuromuscular blockade with neostigmine and glycopyrrolate may induce accelerated idioventricular rhythm in certain patients without known cardiovascular disease.

Impact of the COVID-19 pandemic on cardiometabolic health parameters in children with preexisting dyslipidemia.

BACKGROUND: The COVID-19 pandemic has raised concerns for worsening cardiometabolic health in children. OBJECTIVE: This study evaluates the impact of the COVID-19 pandemic and subsequent social restrictions on pediatric cardiometabolic health factors. METHODS: Retrospective review of patients in a pediatric lipid clinic in the year prior to (3/18/2019-3/17/2020) and during (3/18/2020-3/17/2021) the COVID-19 pandemic was performed. Physical findings (body mass index [BMI], waist circumference [WC], and blood pressure), laboratory markers of cardiometabolic health (lipid panel, insulin resistance, and liver transaminases), self-reported exercise time, and lipid-lowering medications (metformin, statin, omega-3 fatty acids, fenofibrate) were compared. RESULTS: 297 subjects met inclusion criteria. Among subjects prescribed no medications or on stable medication doses (n=241), there were few changes in lipid panels. Among subjects with new or increased medication doses between pre-pandemic and pandemic intervals (n=62), there were increases in triglycerides (p= 0.019) and HgbA1c (p=0.046). There was no change in z-scores for both BMI and WC for either group. CONCLUSION: We observed concerning trends in markers of cardiovascular disease health (dyslipidemia, insulin resistance, and diabetes), independent of changes in weight, in at-risk children during the recent COVID pandemic. Our findings suggest that this vulnerable population may benefit from more frequent monitoring and intense management during such events.

Is Porcine Small Intestinal Submucosal Extracellular Matrix (ECM) a Suitable Material for Right Ventricular Outflow Tract Reconstruction in Association With Pulmonary Valve Replacement?

Pulmonary valve replacement (PVR) with right ventricular outflow tract (RVOT) reconstruction is a common congenital cardiac operation. Porcine submucosal intestinal-derived extracellular matrix (ECM) patches have been used for RVOT reconstruction. We present 2 adult patients with Tetralogy of Fallot who underwent PVR with RVOT reconstruction utilizing ECM. Both cases required reoperation due to patch dehiscence causing a large paravalvular leak. One patient also had a pseudoaneurysm associated with ECM dehiscence. There may be a propensity for ECM dehiscence in this application and, based on these cases, we recommend avoidance of ECM in RVOT reconstruction with PVR. PVR patients repaired with ECM should be monitored for this complication.

COVID-19 in Adults With Congenital Heart Disease.

BACKGROUND: Adults with congenital heart disease (CHD) have been considered potentially high risk for novel coronavirus disease-19 (COVID-19) mortality or other complications. OBJECTIVES: This study sought to define the impact of COVID-19 in adults with CHD and to identify risk factors associated with adverse outcomes. METHODS: Adults (age 18 years or older) with CHD and with confirmed or clinically suspected COVID-19 were included from CHD centers worldwide. Data collection included anatomic diagnosis and subsequent interventions, comorbidities, medications, echocardiographic findings, presenting symptoms, course of illness, and outcomes. Predictors of death or severe infection were determined. RESULTS: From 58 adult CHD centers, the study included 1,044 infected patients (age: 35.1 ± 13.0 years; range 18 to 86 years; 51% women), 87% of whom had laboratory-confirmed coronavirus infection. The cohort included 118 (11%) patients with single ventricle and/or Fontan physiology, 87 (8%) patients with cyanosis, and 73 (7%) patients with pulmonary hypertension. There were 24 COVID-related deaths (case/fatality: 2.3%; 95% confidence interval: 1.4% to 3.2%). Factors associated with death included male sex, diabetes, cyanosis, pulmonary hypertension, renal insufficiency, and previous hospital admission for heart failure. Worse physiological stage was associated with mortality (p = 0.001), whereas anatomic complexity or defect group were not. CONCLUSIONS: COVID-19 mortality in adults with CHD is commensurate with the general population. The most vulnerable patients are those with worse physiological stage, such as cyanosis and pulmonary hypertension, whereas anatomic complexity does not appear to predict infection severity.

Prevalence and Long-Term Outcomes of Solid Organ Transplant in Children with Intellectual Disability.

OBJECTIVES: To describe the prevalence and long-term outcomes of kidney, liver, and heart transplant for children with an intellectual disability. STUDY DESIGN: We performed a retrospective cohort analysis of children receiving a first kidney, liver, or heart-alone transplant in the United Network for Organ Sharing dataset from 2008 to 2017. Recipients with definite intellectual disability were compared with those possible/no intellectual disability. Kaplan-Meier survival estimates were calculated for graft and patient survival. Cox proportional hazard models were used to estimate the association between intellectual disability and graft and patient survival. RESULTS: Over the study period, children with definite intellectual disability accounted for 594 of 6747 (9%) first pediatric kidney-alone, 318 of 4566 (7%) first pediatric liver-alone, and 324 of 3722 (9%) first pediatric heart-alone transplant recipients. Intellectual disability was not significantly associated with patient or graft survival among liver and heart transplant recipients. Among kidney transplant recipients, definite intellectual disability was significantly associated with higher graft survival and lower patient survival, but the absolute differences were small. CONCLUSIONS: Children with intellectual disability account for 7%-9% of pediatric transplant recipients with comparable long-term outcomes to other pediatric recipients. These findings provide important empirical support for policies that include children with intellectual disability as transplant candidates.

Technical Performance Score Predicts Perioperative Outcomes in Complex Congenital Heart Surgery Performed in a Small-to-Medium-Volume Program.

As the quality of surgical outcomes depend on many factors, the development of validated tools to assess the different aspects of complex multidisciplinary teams' performance is crucial. The Technical Performance Score (TPS) has only been validated to correlate with outcomes in large-volume surgical programs. Here we assess the utility of TPS in correlation to perioperative outcomes for complex congenital heart surgeries (CHS) performed in a small-to-medium-volume program. 673 patients underwent CHS from 4/2012 to 12/2017 at our institution. Of those, 122 were STAT 4 and STAT 5. TPS was determined for each STAT 4 and STAT 5 operation using discharge echocardiogram: 1 = optimal, 2 = adequate, 3 = inadequate. Patient outcomes were compared including mortality, length of stay, ventilation times, and adverse events. 69 patients (57%) were neonates, 32 (26%) were infants, 17 (14%) were children, 4 (3%) were adults. TPS class 1 was assigned to 85 (70%) operations, TPS class 2 was assigned to 25 (20%) operations, and TPS class 3 was assigned to 12 (10%) operations. TPS was associated with re-intubation, ICU length of stay, postoperative length of stay, and mortality. TPS did not correlate with unplanned 30-day readmissions, need for reoperation, and inotropic score. Technical performance score was associated with perioperative outcomes and is a useful tool to assess the adequacy of repair for high complexity CHS in a small-to-medium-volume surgical program. TPS should be a part of program review in congenital heart programs of all sizes to identify strategies that may reduce postoperative morbidity and potentially improve long-term outcomes.

Sex-Specific Differences in Ventricular Dimensions in Repaired Tetralogy of Fallot: A Retrospective Study.

The timing of pulmonary valve replacement (PVR) in asymptomatic patients with repaired tetralogy of Fallot (TOF) is typically based on cardiac magnetic resonance imaging-derived ventricular volume measurements. Current criteria do not account for sex-based differences in chamber size. The purpose of this study was to compare male and female ventricular volumes and function in TOF patients with a hypothesis that females are less likely to meet common-indexed right ventricular end-diastolic volume (RVEDVi) and right ventricular end-systolic volume (RVESVi) criteria for PVR. Cardiac magnetic resonance data from 17 females (age 31.7 ± 15.4 years) and 23 males (30.7 ± 15.4 years) with TOF were retrospectively analyzed. Demographic and imaging data were recorded. Differences in sex-based means and standard deviations were evaluated using the Wilcoxon rank-sum test with continuity correction. Age and pulmonary regurgitant fraction were similar in females and males. RVEDVi was lower in females than in males, but the difference was not statistically significant. Differences in RVESVi, LVEDVi, LVESVi, and left ventricular ejection fraction were statistically significant, while the difference in right ventricular ejection fraction was not. RVEDVi was greater than 150 mL/m2 in 3/17 (17.6%) females and 10/23 (43.5%) males (OR 3.6). RVESVi was greater than 82 mL/m2 in 2/17 females and 8/23 males (OR 4.0). Sex-specific differences in right ventricular and left ventricular volumes and function are present in patients with TOF despite similar pulmonary regurgitation. These differences may need to be considered when evaluating patients for PVR.

Analysis of cavopulmonary and cardiac flow characteristics in fontan Patients: Comparison with healthy volunteers.

BACKGROUND: Characterizing the flow of the Fontan circuit, and correlating flow characteristics with the development of complications, is an important clinical challenge. Past work has analyzed the flow characteristics of Fontan circulation on a component-by-component basis. 4D flow MRI with radial projections allows for large volumetric coverage, and therefore can be used to analyze the flow through many codependent cardiovascular components in a single imaging session. PURPOSE: To describe flow characteristics across the entire Fontan circuit and to compare these with the flow characteristics in healthy volunteers. STUDY TYPE: Prospective. SUBJECTS: Eleven single ventricle patients with a Fontan connection and 15 healthy controls. SEQUENCE: Phase contrast with vastly undersampled isotropic projection reconstruction (PC-VIPR) at a field strength of 3 T. ASSESSMENT: Cavopulmonary and ventricular flow distributions, blood flow kinetic energy, vorticities, efficiency indices, and other flow parameters were analyzed using Ensight and MatLab. STATISTICAL TESTS: The results were compared across Fontan subjects, between respiratory phases, and between Fontan subjects and healthy volunteers using a Student's t-test for unequal sample sizes and linear regression. RESULTS: Cava-specific pulmonary flow distributions of Fontan patients varied significantly between respiratory phases (P < 0.05). Ventricular kinetic energy (KE) was significantly higher in Fontan patients than it was in healthy controls, leading to a lower cardiac efficiency metric in the Fontan group. A significant diastolic KE time-shift was also observed in the Fontan patient group. Peak diastolic KE was significantly higher in the single ventricle of patients with right ventricle morphology than it was in left ventricle morphology patients. DATA CONCLUSION: Radial 4D flow MRI can be used for comprehensive analysis of single ventricle Fontan flow characteristics. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019.

Geleophysic dysplasia: 48 year clinical update with emphasis on cardiac care.

Geleophysic dysplasia is a rare skeletal dysplasia often complicated by progressive cardiac disease. Information about long-term outcomes is limited. A clinical update of the oldest surviving patient described with geleophysic dysplasia type 1 is provided. Special note is made in relation to the cardiac disease and interventions. Genetic testing of ADAMTSL2 revealed a previously reported missense mutation as well as a novel nonsense mutation, which can be added to the list of causative mutations in geleophysic dysplasia.

Disparities in Wait-List Outcomes for Adults With Congenital Heart Disease Listed for Heart Transplantation Before and Since Revision of Status I Listing.

Medical and surgical advances in the late 20th century that allowed the majority of children born with congenital heart disease (CHD) to survive have resulted in a shift of the burden of morbidity and mortality into adulthood. Heart failure is the leading cause of death in adults with CHD. This study aimed to address the gap in understanding of outcomes of adults with CHD who have heart failure and are listed for heart transplantation compared with those without CHD. The study analyzed data from the US Scientific Registry of Transplant Recipients database, categorized by the listing era (on/before or after January 19, 1999). The primary combined outcome was death while waiting for an organ or delisting due to worsening clinical condition. Overall, there was a significant decrease in the probability of the primary outcome in the current compared with the early era for both adults with CHD (13.2% vs 18.6%, p = 0.01) and non-CHD (12.1% vs 15.9%, p < 0.0001). However, this improvement was only observed among adults with CHD listed in Status I, whereas adults without CHD saw significant improvement in both statuses I and II. Furthermore in the current era, when compared with their non-CHD counterparts, adults with CHD continue to have worse wait-list outcomes irrespective of listing status. In conclusion, outcomes for adults with CHD listed for heart transplantation have improved since the revision of Status I listing in 1999. Despite such improvements there continues to be a significant disparity in wait-list outcomes between adults with compared with those without CHD.

Prevalence and outcomes of heart transplantation in children with intellectual disability.

Heart transplantation in children with intellectual disability is a controversial issue. We sought to describe the prevalence and outcomes of heart transplantation in children with intellectual disability and hypothesized that recipients with intellectual disability have comparable short-term outcomes compared to recipients without intellectual disability. We performed a retrospective cohort analysis of children receiving a first heart-alone transplant in the UNOS STAR database from 2008 to 2013. Recipients with intellectual disability were compared to those without using chi-square tests. Kaplan-Meier curves were constructed for patient and graft survival. Cox proportional hazard models were used to estimate the association between intellectual disability and graft failure and patient survival. Over the study period, 107 children with intellectual disability underwent initial heart transplantation, accounting for 8.9% of first pediatric heart transplants (total=1204). There was no difference in the incidence of acute rejection between groups in the first year after transplant. Mean functional status scores at follow-up improved in both groups after transplantation, but tended to be lower among children with intellectual disability than children without. Log-rank tests did not suggest significant differences in graft survival between those with and without intellectual disability during the first 4 years following transplantation. Children with intellectual disability constitute a significant portion of total heart transplants with short-term outcomes comparable to children without intellectual disability.

Minimally Invasive Esophagectomy in a Patient With Tetralogy of Fallot and Right-Sided Aortic Arch.

Improvements in surgical technique and perioperative care have resulted in increased long-term survival for patients with congenital heart disease. As these patients begin to reach their later years, clinicians are challenged with determining optimal management of noncardiac diseases in this complex patient population, including surgically treatable malignancies. We present a case of esophageal cancer in a patient with previously repaired tetralogy of Fallot and right-sided aortic arch, treated with neoadjuvant therapy followed by laparoscopic and left thoracoscopic esophagectomy.

Neonatal Enterovirus Infection: Case Series of Clinical Sepsis and Positive Cerebrospinal Fluid Polymerase Chain Reaction Test with Myocarditis and Cerebral White Matter Injury Complications.

Objective We describe five neonates with enteroviral (EV) infection to demonstrate central nervous system (CNS) and cardiac complications and report successful treatment of myocarditis with immunoglobulin intravenous (IVIG) in two. Study Design Case series identified during three enteroviral seasons in one neonatal intensive care unit (NICU) by cerebral spinal fluid (CSF) reverse transcriptase polymerase chain reaction (PCR) testing for EV in neonates suspected to have sepsis, but with sterile bacterial cultures. Results Cases were identified in each of three sequential years in a NICU with 800 to 900 admissions/year. Two cases were likely acquired perinatally; all were symptomatic with lethargy and poor feeding by age 5 to 10 days. All had signs of sepsis and/or meningitis; one progressed to periventricular leukomalacia and encephalomalacia. Two recovered from myocarditis after treatment that included IVIG 3 to 5 g/kg. Conclusion Neonates who appear septic without bacterial etiology may have EV CNS infections that can be diagnosed rapidly by CSF PCR testing. Cases may be underdiagnosed in the early neonatal period if specific testing is not performed. Neonates with EV infection should be investigated for evidence of periventricular leukomalacia, screened for myocarditis, and considered for IVIG treatment.

Wait-List Outcomes for Adults With Congenital Heart Disease Listed for Heart Transplantation in the U.S.

BACKGROUND: Heart failure represents a common end-stage syndrome for many adults with congenital heart disease (ACHD). These patients, however, have been excluded from most heart transplantation research. It is not known how current criteria, derived from non-ACHD populations, used to determine priority at the time of transplant listing, impact the outcomes for ACHD patients listed for heart transplantation. OBJECTIVES: The goal of this study was to investigate outcomes of ACHD in comparison to non-ACHD patients while listed for heart transplantation. METHODS: We conducted a retrospective study using the Scientific Registry of Transplant Recipients on patients ≥18 years of age listed in the United States between 1999 and 2014. The probability of mortality or delisting due to clinical worsening was estimated using cumulative incidence functions, where transplantation was a competing event. RESULTS: Among 1,290 ACHD and 38,557 non-ACHD patients listed, 237 ACHD and 6,377 non-ACHD patients died or were delisted due to clinical worsening. Death or delisting for clinical worsening was more likely for ACHD patients initially listed as status 1A (24% ACHD vs. 17% non-ACHD after 180 days; p < 0.001). There were no significant differences between ACHD and non-ACHD patients listed as status 1B or 2. In multivariable analysis, factors associated with death or delisting due to clinical worsening within 1 year in ACHD included: estimated glomerular filtration rate <60 ml/min/1.73 m(2) (hazard ratio [HR]: 1.4; 95% confidence interval [CI]: 1.0 to 1.9; p = 0.043); albumin <3.2 g/dl (HR: 2.0; 95% CI: 1.3 to 2.9; p <0.001); and hospitalization at the time of listing, whether in the intensive care unit (HR: 2.3; 95% CI: 1.6 to 3.5; p < 0.001) or not (HR: 1.9; 95% CI: 1.2 to 3.0; p = 0.006) relative to outpatients. CONCLUSIONS: Wait-list mortality or delisting due to worsening clinical status is disproportionately common for ACHD patients listed as status 1A. An allocation system that takes into account the distinctive aspects of ACHD patients may help better care for this growing population.

Hypercoagulability in adolescent girls on oral contraceptives-global coagulation profile and estrogen receptor polymorphisms.

Oral contraceptive (OCP) induced changes on coagulation are complex with high inter-individual variability. The precise reason for differences in this variability is unknown. We hypothesized that global coagulation assays better delineate these changes and variability in hypercoagulability may be the result of differences in estrogen metabolism and thrombophilia. Fifty-two adolescents initiating OCPs were prospectively enrolled; 33 subjects completed the study. Samples were analyzed prior to and after OCPs for procoagulant and anticoagulant factor activities and thrombin generation (TG) +/-thrombomodulin. Participants were genotyped for common thrombophilia and estrogen receptor-α (ESR-α) single nucleotide polymorphisms (SNPs). SNP genotypes were compared to coagulation parameters; TG parameters and differences pre and post OCPs were examined. At baseline, a striking finding was elevated FVIII levels. FVL was absent in all and F2 G20210A was present in one participant. The ESR-α polymorphism was present in heterozygous state in 59% and homozygous state in 21% participants. There were no differences in VWF levels and FVIII: C after being on OCPs. Protein S levels decreased with OCPs. Sixty percent of participants showed evidence of hypercoagulability on TG testing on OCPs. Higher thrombin peak and endogenous thrombin potential (ETP) were seen on TG after OCPs. With thrombomodulin, ETP and thrombin peak did not decrease after OCPs, signifying 'thrombomodulin resistance'. We demonstrated that OCPs induce a state of "variable" hypercoagulability in adolescents, predominantly through the protein S pathway. Genetic and nongenetic factors may account for the variable increase in hypercoagulability. Further research is needed to understand this.