Retrospective Comparison of Recombinant Activated Factor VII Versus 4-Factor Prothrombin Complex Concentrate in Cardiac Surgical Patients.

OBJECTIVES: To compare the incidences of postoperative thrombotic complications, transfusion of blood products, and chest tube output in congenital cardiac surgical patients who received either recombinant activated factor VII (rFVIIa) or 4-factor prothrombin complex concentrate (4F-PCC). DESIGN: We performed a retrospective study. SETTING: Patients who underwent surgery at a tertiary academic hospital. PARTICIPANTS: Pediatric patients who underwent cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were obtained from the Society of Thoracic Surgeons and the Pediatric Cardiac Critical Care Consortium databases, as well as from manual chart review. Adjusted p values were obtained from multivariate regression using age (days), surgeon (number), cardiopulmonary bypass time (minutes), and need for deep hypothermic circulatory arrest (yes/no). A total of 55 patients were included in the 4F-PCC group, and 89 in the rFVIIa group. The median dose of rFVIIa was 77 mcg/kg (46-88), and the median dose of 4F-PCC was 31 IU/kg (24-43). The incidences of thrombotic complications were 8% in the 4F-PCC group and 30% in the rFVIIa group (adjusted p = 0.023). No difference was reported between the groups regarding chest tube output on days 1 and 2 or transfusion of blood products. Using a sensitivity analysis with propensity matching, the incidence of thrombosis was 10% in the 4F-PCC group (n = 38), and 31% in the rFVIIa group (n = 39) (p = 0.036). No difference was reported in terms of bleeding or transfusion. CONCLUSIONS: This retrospective study suggested that the administration of rFVIIa was associated with a higher risk of thrombotic complications when compared to 4F-PCC, without benefits in terms of bleeding and transfusions.

Anticoagulation practices associated with bleeding and thrombosis in pediatric extracorporeal membrane oxygenation; a multi-center secondary analysis.

To determine associations between anticoagulation practices and bleeding and thrombosis during pediatric extracorporeal membrane oxygenation (ECMO), we performed a secondary analysis of prospectively collected data which included 481 children (<19 years), between January 2012 and September 2014. The primary outcome was bleeding or thrombotic events. Bleeding events included a blood product transfusion >80 ml/kg on any day, pulmonary hemorrhage, or intracranial bleeding, Thrombotic events included pulmonary emboli, intracranial clot, limb ischemia, cardiac clot, and arterial cannula or entire circuit change. Bleeding occurred in 42% of patients. Five percent of subjects thrombosed, of which 89% also bled. Daily bleeding odds were independently associated with day prior activated clotting time (ACT) (OR 1.03, 95% CI= 1.00, 1.05, p=0.047) and fibrinogen levels (OR 0.90, 95% CI 0.84, 0.96, p <0.001). Thrombosis odds decreased with increased day prior heparin dose (OR 0.88, 95% CI 0.81, 0.97, p=0.006). Lower ACT values and increased fibrinogen levels may be considered to decrease the odds of bleeding. Use of this single measure, however, may not be sufficient alone to guide optimal anticoagulation practice during ECMO.

Coagulation profiles and viscoelastic testing in multisystem inflammatory syndrome in children.

OBJECTIVE: To characterize viscoelastic testing profiles of children with multisystem inflammatory syndrome in children (MIS-C). METHODS: This single-center retrospective review included 30 patients diagnosed with MIS-C from March 1 to September 1, 2020. Thromboelastography (TEG) with platelet mapping was performed in 19 (63%) patients and compared to age- and sex-matched controls prior to cardiac surgery. Relationships between TEG parameters and inflammatory markers were assessed using correlation. RESULTS: Patients with MIS-C had abnormal TEG results compared to controls, including decreased kinetic (K) time (1.1 vs. 1.7 minutes, p < .01), increased alpha angle (75.0° vs. 65.7°, p < .01), increased maximum amplitude (70.8 vs. 58.3 mm, p < .01), and decreased lysis in 30 minutes (Ly30) (1.1% vs. 3.7%, p = .03); consistent with increased clot formation rate and strength, and reduced fibrinolysis. TEG maximum amplitude was moderately correlated with erythrocyte sedimentation rate (ESR) (r = 0.60, p = .02), initial platelet count (r = 0.67, p < .01), and peak platelet count (r = 0.51, p = .03). TEG alpha angle was moderately correlated with peak platelet count (r = 0.54, p = .02). Seventeen (57%) patients received aspirin (ASA) and anticoagulation, five (17%) received only ASA, and three (10%) received only anticoagulation. No patients had a symptomatic thrombotic event. Six (20%) patients had a bleeding event, none of which was major. CONCLUSIONS: Patients with MIS-C had evidence of hypercoagulability on TEG. Increased ESR and platelets were associated with higher clot strength. Patients were prophylactically treated with ASA or anticoagulation with no symptomatic thrombosis or major bleeding. Further multicenter study is required to characterize the rate of thrombosis and optimal thromboprophylaxis algorithm in this patient population.

Biventricular Impella use in pediatric patients with severe graft dysfunction from acute rejection after heart transplantation.

Rejection with severe hemodynamic compromise is a significant source of morbidity and mortality for pediatric heart transplant patients. Traditionally, treatment for these patients includes inotropes and escalation to extracorporeal membrane oxygenation (ECMO) when necessary. There is increasing interest in using percutaneous ventricular assistive devices in the pediatric population as a less invasive alternative to ECMO. We report the largest case series to date of biventricular support using percutaneous Impella devices. Retrospective case series was performed by chart review. Hemodynamics, left ventricular ejection fraction (LVEF), and indices of end organ function were collected before and after Impella placement. A 14-year-old male, 18-year-old male, and 19-year-old female, all status post heart transplant, presented with severely decreased biventricular function due to presumed clinical rejection, requiring maximal inotropic support without improvement. In all the three cases, simultaneous Impella CP and RP devices were placed percutaneously. Prior to implantation, LVEFs were 40%, 23%, and 25%, respectively. Hemodynamics measured invasively prior to device placement showed elevated filling pressures. Adverse events while on support included bleeding, hemolysis, and right femoral arterial dissection during implantation. All patients were successfully weaned from the devices and survived to discharge. The average time of right-sided support and total support was 11 days and 13 days, respectively. After device removal, right-sided pressures and echocardiographic measurements showed improvement in all patients. Bilateral Impella configuration (BiPella) is a viable option for temporary mechanical circulatory support in pediatric patients with significant graft dysfunction.

Left Ventricular Strain Normalizes After Balloon Aortic Valvuloplasty in Infants with Congenital Aortic Stenosis.

Severe aortic stenosis (AS) causes left ventricular (LV) afterload and subendocardial ischemia. Despite this, most infants with AS have normal LV ejection fraction (EF). Strain analysis using two-dimensional speckle tracking echocardiography (2DSTE) may identify more sensitive markers of systolic dysfunction. We sought to show changes in LV strain after balloon aortic valvuloplasty (BAV) in infants with AS. Twenty-seven infants ≤ 1 year of age with AS who underwent BAV from 2007 to 2017 were included. Echocardiograms before/after BAV were retrospectively analyzed with 2DSTE. Median age was 29 days (interquartile range 3-52) and LV EF was 64 ± 10%. Global longitudinal strain (GLS) significantly improved post-BAV (- 17 ± 5 vs. - 20 ± 4%, p = 0.001) with no difference in global circumferential strain. Peak longitudinal strain was abnormal at the inferoseptal base and mid-ventricle (- 15 ± 6 and - 17 ± 5 = 7%, respectively) and significantly improved in the basal and mid-anterolateral segments (- 17 ± 5 vs. - 21 ± 5%, p < 0.01; - 17 ± 6% vs. - 20 ± 5%, p = 0.01, respectively). Five (20%) patients underwent reintervention, and had significantly higher peak-to-peak pre and post-BAV AS gradients (86 ± 14 vs. 61 ± 20 mmHg, p = 0.02; 33 ± 17 vs. 21 ± 10 mmHg, p = 0.04, respectively). In conclusion, longitudinal strain is abnormal in infants with AS and improves to previously published normal values after BAV.

Early Thromboprophylaxis Initiation is Associated With Reduced Fontan Thromboses in the Early Postoperative Period.

Fontan circuit thrombosis is a significant cause of early postoperative morbidity and mortality. Thrombosis incidence and relationship to thromboprophylaxis choice and timing of initiation are not well established. We sought to evaluate the incidence of Fontan circuit thrombosis in the first 30 postoperative days and its relationship to thromboprophylaxis choice and timing. Patients undergoing Fontan surgery, 2006-2016, were reviewed. Fontan circuit thrombosis was defined by sonographic detection of intracardiac or deep venous thrombi. Logistic regression was used to assess relationships between thromboprophylaxis characteristics and thrombosis. One hundred ninety-two patients underwent Fontan. Fontan thrombosis occurred in 19 (10%) patients. 54% were started on aspirin, 27% coumadin, 4% heparin, and 7% none. There was no relationship between thrombosis and baseline anatomy, Fontan type or fenestration. Median time to thromboprophylaxis initiation was 4 days (interquartile range 2-6). Patients not started on thromboprophylaxis had 44.8 times the odds of thrombosis as those on thromboprophylaxis (confidence interval 6.4-311.7, P < 0.01); no children starting thromboprophylaxis before postoperative day 2 developed thromboses. For every day that thromboprophylaxis was delayed, odds of thrombosis increased by 30% (odds ratio 1.3; CI 1.1-1.6, P < 0.01). There was no difference in the odds of thrombosis between children taking aspirin vs other thromboprophylaxis types. Odds of early postoperative Fontan circuit thrombosis are increased in patients in whom thromboprophylaxis is delayed beyond the second postoperative day, with no difference in the odds of thrombosis between patients initiated on aspirin vs other thromboprophylaxis. Early aspirin institution post Fontan is recommended to reduce morbidity. Ultra-mini-Abstract: Odds of early postoperative Fontan circuit thrombosis are increased in patients in whom thromboprophylaxis is delayed beyond the second postoperative day, with no difference in the odds of thrombosis between patients initiated on aspirin vs other thromboprophylaxis. Early aspirin institution post Fontan is recommended to reduce morbidity and resource utilization.

Risk Factors Associated With Bleeding in Children With Cardiac Disease Receiving Extracorporeal Membrane Oxygenation: A Multi-Center Data Linkage Analysis.

Background: Bleeding is a common complication of extracorporeal membrane oxygenation (ECMO) for pediatric cardiac patients. We aimed to identify anticoagulation practices, cardiac diagnoses, and surgical variables associated with bleeding during pediatric cardiac ECMO by combining two established databases, the Collaborative Pediatric Critical Care Research Network (CPCCRN) Bleeding and Thrombosis in ECMO (BATE) and the Extracorporeal Life Support Organization (ELSO) Registry. Methods: All children (<19 years) with a primary cardiac diagnosis managed on ECMO included in BATE from six centers were analyzed. ELSO Registry criteria for bleeding events included pulmonary or intracranial bleeding, or red blood cell transfusion >80 ml/kg on any ECMO day. Bleeding odds were assessed on ECMO Day 1 and from ECMO Day 2 onwards with multivariable logistic regression. Results: There were 187 children with 114 (61%) bleeding events in the study cohort. Biventricular congenital heart disease (94/187, 50%) and cardiac medical diagnoses (75/187, 40%) were most common, and 48 (26%) patients were cannulated directly from cardiopulmonary bypass (CPB). Bleeding events were not associated with achieving pre-specified therapeutic ranges of activated clotting time (ACT) or platelet levels. In multivariable analysis, elevated INR and fibrinogen were associated with bleeding events (OR 1.1, CI 1.0-1.3, p = 0.02; OR 0.77, CI 0.6-0.9, p = 0.004). Bleeding events were also associated with clinical site (OR 4.8, CI 2.0-11.1, p < 0.001) and central cannulation (OR 1.75, CI 1.0-3.1, p = 0.05) but not with cardiac diagnosis, surgical complexity, or cannulation from CPB. Bleeding odds on ECMO day 1 were increased in patients with central cannulation (OR 2.82, 95% CI 1.15-7.08, p = 0.023) and those cannulated directly from CPB (OR 3.32, 95% CI 1.02-11.61, p = 0.047). Conclusions: Bleeding events in children with cardiac diagnoses supported on ECMO were associated with central cannulation strategy and coagulopathy, but were not modulated by achieving pre-specified therapeutic ranges of monitoring assays.

Comorbidity, human papillomavirus infection and head and neck cancer survival in an ethnically diverse population.

OBJECTIVE: To demonstrate the importance of comorbid conditions in head and neck squamous cell carcinoma (HNSCC), we assessed the association between comorbidity and survival in an inner-city population of HNSCC patients. PATIENTS AND METHODS: Comorbid status at diagnosis was derived using medical records and the Adult Comorbidity Evaluation-27 (ACE-27) index on 288 patients with histologically confirmed HNSCC from Montefiore Medical Center in the Bronx (NY) between 2002 and 2011. The association between comorbidity, tumor human papillomavirus (HPV) status and overall and disease specific survival was assessed by Kaplan-Meier analysis and multivariable Cox regression adjusting for clinico-pathologic factors. RESULTS: The study population consisted of primary oropharyngeal (36%), laryngeal (33%) and oral cavity cancer patients (31%). Overall, 19% had no comorbidity, 43% mild comorbidity, 29% moderate comorbidity, and 9% severe comorbidity. The most common comorbid conditions were hypertension, diabetes mellitus, respiratory disease, other malignancies, and illicit drug use. Survival analyses revealed that increased comorbidity at diagnosis was significantly related to poorer overall survival (p=0.016), but not to cancer survival (p=0.369) or recurrence (p=0.652). Oropharyngeal cancer patients with HPV DNA positive tumors and lower levels of comorbidity had significantly better overall survival compared to patients with HPV negative tumors (hazard ratio=0.2, 95%CI: 0.04-0.8), however there was no significant difference in overall (or disease specific) survival by HPV status among patients with higher levels of comorbidity at diagnosis (hazard ratio=0.7, 95%CI: 0.2-2.8). CONCLUSION: In an inner-city predominantly minority population, comorbidity at HNSCC diagnosis is relatively common and associated with poor overall survival, but not cancer survival or recurrence. Interestingly, the relationship between HPV and improved survival appears to be specific to patients with low comorbidity at diagnosis.