Technical Feasibility and Clinical Efficacy of Iliac Vein Stent Placement in Adolescents and Young Adults with May-Thurner Syndrome.

PURPOSE: To report technical feasibility and clinical efficacy of iliac vein stent placement in adolescent patients with May-Thurner Syndrome (MTS). MATERIALS AND METHODS: Single-institution retrospective review of the medical record between 2014 and 2021 found 63 symptomatic patients (F = 40/63; mean age 16.1 years, 12-20 years) who underwent left common iliac vein (LCIV) stent placement for treatment of LCIV compression from an overriding right common iliac artery, or equivalent (n = 1, left IVC). 32/63 (50.7%) patients presented with non-thrombotic iliac vein lesions (NIVL). 31/63 (49.2%) patients presented with deep vein thrombosis of the lower extremity and required catheter-directed thrombolysis after stent placement (tMTS). Outcomes include technically successful stent placement with resolution of anatomic compression and symptom improvement. Stent patency was monitored with Kaplan-Meier analysis at 3, 6, 12, 24, and 36 months. Anticoagulation and antiplatelet (AC/AP) regimens were reported. RESULTS: Technical success rate was 98.4%. 74 bare-metal self-expanding stents were placed in 63 patients. Primary patency at 12, and 24-months was 93.5%, and 88.9% for the NIVL group and 84.4% and 84.4% for the tMTS group for the same period. Overall patency for the same time intervals was 100%, and 95.4% for the NIVL group and 96.9%, and 96.9% for the tMTS group. Procedural complication rate was 3.2% (2/63) with no thrombolysis-related bleeding complications. Clinical success was achieved in 30/32 (93.8%) and 29/31 (93.5%) patients with tMTS and NIVL groups, respectively. CONCLUSION: CIV stent placement in the setting of tMTS and NIVL is technically feasible and clinically efficacious in young patients with excellent patency rates and a favorable safety profile.

Incidence and Timing of Thrombosis After the Norwood Procedure in the Single-Ventricle Reconstruction Trial.

Background Thrombosis is common in infants undergoing staged surgeries for single-ventricle congenital heart disease. The reported incidence and timing of thrombosis varies widely, making it difficult to understand the burden of thrombosis and develop approaches for prevention. We aimed to determine the timing and cumulative incidence of thrombosis following the stage I Norwood procedure and identify clinical characteristics associated with thrombosis. Methods and Results We analyzed data from the Pediatric Heart Network Single Ventricle Reconstruction trial from 2005 to 2009 and identified infants with first-time thrombotic events. In 549 infants, the cumulative incidence of thrombosis was 21.2% (n=57) from stage I through stage II. Most events occurred during stage I (n=35/57, 65%), with a median time to thrombosis of 15 days. We used a Cox proportional hazards model to estimate the association of clinical variables with thrombosis. After adjusting for baseline variables, boys had a higher hazard of thrombosis (adjusted hazard ratio [HR], 2.69; 95% CI, 1.44-5.05; P=0.002), non-hypoplastic left heart syndrome cardiac anatomy was associated with a higher early hazard of thrombosis (adjusted HR, 3.93; 95% CI, 1.89-8.17; P<0.001), and longer cardiopulmonary bypass time was also associated with thrombosis (per 10-minute increase, adjusted HR, 1.07; 95% CI, 1.01-1.12; P=0.02). Lower oxygen saturation after the Norwood procedure increased the hazard for thrombosis in the unadjusted model (HR, 1.08; 95% CI, 1.02-1.14; P=0.011). Conclusions Thrombosis affects 1 in 5 infants through Stage II discharge, with most events occurring during stage I. Male sex, non-hypoplastic left heart syndrome anatomy, longer cardiopulmonary bypass time, and lower stage I oxygen saturation were associated with thrombosis.

Catheter-Directed Pharmacologic Thrombolysis for Acute Submassive and Massive Pulmonary Emboli in Children and Adolescents-An Exploratory Report.

OBJECTIVES: The objective of this study is to report a single-center experience of the safety and efficacy of pulmonary artery catheter-directed thrombolysis for both massive and submassive pulmonary emboli in the pediatric and adolescent population. DESIGN: A 22-month retrospective review of the electronic medical record and picture archiving and communication system was performed of patients less than 21 years old, presenting with massive or submassive pulmonary emboli treated with pulmonary artery catheter-directed thrombolysis at a single, tertiary care pediatric hospital. Multiple variables were analyzed including indications, technical success, clinical efficacy, and complications. SETTING: A single, tertiary care pediatric hospital. PATIENTS: Nine patients (mean 13.9 yr; range 6-19 yr) with massive and/or submassive pulmonary emboli who underwent pulmonary artery catheter-directed thrombolysis met inclusion criteria. INTERVENTIONS: Catheter-directed thrombolysis. MEASUREMENTS AND MAIN RESULTS: Pulmonary emboli was diagnosed by CT angiography in all cases. Catheter-directed thrombolysis alone was clinically successful (defined as improved cardiopulmonary function following catheter-directed thrombolysis) in seven patients (78%) with two patients not improving following catheter-directed thrombolysis. There were no immediate bleeding complications from catheter-directed thrombolysis therapy. All patients were maintained on anticoagulation treatment following catheter-directed thrombolysis. Catheter-directed thrombolysis was technically successful (defined as successful placement of pulmonary artery infusion catheters with full or partial resolution of thrombus) in all cases. Follow-up pulmonary angiography at the cessation of catheter-directed thrombolysis revealed complete thrombus resolution in four patients (44%) and partial resolution in five patients (55%). Mean pulmonary artery pressures decreased in all patients (mean precatheter-directed thrombolysis pulmonary artery pressure = 37 ± 11 mm Hg; mean postcatheter-directed thrombolysis pulmonary artery pressure = 28 ± 10 mm Hg; p = 0.0164). CONCLUSIONS: Pulmonary artery catheter-directed thrombolysis is a technically feasible therapeutic option for children and adolescents with submassive and massive pulmonary emboli.

Acquired Hypofibrinogenemia Before Asparaginase Exposure During Induction Therapy for Pediatric Acute Lymphoblastic Leukemia: A Report of 2 Cases and Review of the Literature.

Coagulopathy in pediatric leukemia patients is typically associated with acute promyelocytic leukemia or after asparaginase use in acute lymphoblastic leukemia. Rarely seen in acute lymphoblastic leukemia, we report 2 patients who presented with normal coagulation markers, but subsequently developed severe hypofibrinogenemia and bleeding in induction before administration of asparaginase. In both cases, cryoprecipitate was administered as initial treatment for bleeding associated with the hypofibrinogenemia. One patient was refractory to cryoprecipitate replacement and required treatment with human fibrinogen concentrate due to the persistence of hypofibrinogenemia with significant bleeding. The hypofibrinogenemia was transient in both cases and resolved within a few weeks.

Tissue Plasminogen Activator Use in Children: Bleeding Complications and Thrombus Resolution.

OBJECTIVE: To review our institutional experience with tissue plasminogen activator (tPA) to determine outcomes related to bleeding complications and thrombus resolution. STUDY DESIGN: We performed a retrospective review of all patients who received systemic tPA for thrombolysis. Data points included location of thrombus, initial and maximum tPA dose, and duration of tPA. The primary endpoint was bleeding complication. RESULTS: Between 2005 and 2014, 46 patients received systemic tPA for thrombolysis: 17 (37%) were patients with a primary cardiac diagnosis, there were 17 (37%) hematology/oncology patients, and 12 (26%) patients with noncardiac, nonhematology/oncology diagnoses. The indication for tPA was central venous thrombus (n = 23), pulmonary artery thrombus (n = 9), and cardiac or aortic thrombus (n = 14). Bleeding complications occurred in 15 patients (33%). Median initial tPA dose in the bleeding complication group was 0.10 mg/kg/h vs 0.03 mg/kg/h in the group without bleeding complication group (P = .01). Cardiac patients experienced more bleeding complications (P = .01). Multivariate analysis indicated that dose of tPA (P = .01) and diagnostic category (P < .01) were associated with bleeding complication. Complete thrombus resolution occurred in 21 patients, partial in 10 patients, and no resolution in 15 patients. Complete resolution of thrombus was not associated with diagnosis, thrombus location, tPA dose, or duration. CONCLUSIONS: Cardiac patients appear to be at highest risk of bleeding complication; bleeding complications were associated with higher doses of tPA, and cardiac patients were the cohort who received the highest doses of tPA. Higher tPA doses are associated with increased risk of bleeding complication but are not associated with successful thrombus resolution.

Differential role of von Willebrand factor and P-selectin on microvascular thrombosis in endotoxemia.

OBJECTIVE: Endotoxin (lipopolysaccharide [LPS]) enhances microvascular thrombosis in mouse cremaster venules. Because von Willebrand factor (vWF) and P-selectin are suggested to mediate LPS-induced platelet-microvessel interactions, we determined whether vWF and P-selectin contribute to microvascular thrombosis in endotoxemia. METHODS AND RESULTS: A light/dye-induced thrombosis model was used in cremaster microvessels of saline or LPS-injected mice (wild-type, P-selectin-deficient, vWF-deficient, or littermate controls). In each strain except vWF-deficient mice, LPS enhanced thrombosis in venules, resulting in approximately 30% to 55% reduction in times to thrombotic occlusion. LPS had no effect on thrombosis in vWF-deficient mice, although these mice had similar systemic responses to LPS (tachycardia, thrombocytopenia, and plasma coagulation markers). vWF-deficient mice demonstrated prolonged times to thrombotic occlusion relative to littermates. LPS increased plasma vWF in each strain studied. While immunofluorescence in wild-type mice failed to detect LPS-induced differences in microvascular vWF expression, it revealed markedly higher vWF expression in venules relative to arterioles. CONCLUSIONS: vWF mediates light/dye-induced microvascular thrombosis and endotoxin-induced enhancement of thrombosis in mouse cremaster venules; P-selectin is not required for enhanced thrombosis in response to endotoxin. Enhanced vWF expression in venules relative to arterioles has potential implications for the differences in thrombotic responses among these microvessels.

Clinical implication of genome-wide profiling in diffuse large B-cell lymphoma and other subtypes of B-cell lymphoma.

The differentiation of lymphoid cells is tightly regulated by transcription factors at various stages during their development. During the maturation processes, different genomic alterations or aberrations such as chromosomal translocation, mutation and deletions may occur that can eventually result in distinct biological and clinical tumors. The different differentiation stages create heterogeneity in lymphoid malignancies, which can complicate the diagnosis. The initial diagnostic scheme for lymphoid diseases was coined by Rappaport followed by Revised European and American Classification of Lymphoid Neoplasms (REAL) and World Health Organization (WHO) classifications. These classification methods were based on histological, immunophenotypic and cytogenetic markers and widely accepted by pathologists and oncologists worldwide. During last several decades, great progress has been made in understanding the etiology, pathogenesis and molecular biology of malignant lymphoma. However, detailed knowledge in the molecular mechanism of lymphomagenesis is largely unknown. New therapeutic protocols based on the new classification have been on clinical trials, but with little success. Therefore, it is imperative to understand the basic biology of the tumor at molecular level. One important approach will be to measure the activity of the tumor genome and this can partly be achieved by the measurement of whole cellular mRNA. One of the key technologies to perform a high-throughput analysis is DNA microarray technology. The genome-wide transcriptional measurement, also called gene expression profile (GEP) can accurately define the biological phenotype of the tumor. In this review, important discoveries made by genome-wide GEP in understanding the biology of lymphoma and additionally the diagnostic and prognostic value of microarrays are discussed.