Maria L. Avila

Postthrombotic syndrome following upper extremity deep vein thrombosis in children

Despite its relatively estimated high occurrence, the characterization of pediatric upper extremity deep vein thrombosis (UE-DVT) and of UE postthrombotic syndrome (PTS) is still lacking. We investigated the occurrence, characteristics, and predictors of UE-PTS in a cohort of children with objectively confirmed UE-DVT. Patients were analyzed in 3 groups according to DVT pathogenesis and neonatal status: primary (G1), secondary neonates (G2neonates), and non-neonates (G2non-neonates). A total of 158 children (23 G1, 25 G2neonates, and 110 G2non-neonates) were included. The most common triggering factors were effort-related (87%) in G1 and central lines in G2neonates (100%) and in G2non-neonates (92%). PTS scores ≥1, as per the Modified Villalta Scale, were identified in 87% of primary patients, 16% of G2neonates, and 49% of G2non-neonates. Survival analysis showed that the time to PTS score ≥1 significantly differed among group (log-rank test P < .0001). A multivariable logistic regression showed that DVT pathogenesis and imaging-determined degree of thrombus resolution at the end of therapy were independent predictors of a PTS score ≥2. In conclusion, pediatric UE-PTS frequency and severity depend on UE-DVT pathogenesis (primary/secondary) and, within the secondary group, on patients age. Line-related UE-PTS has a more benign course, particularly in neonates.

Normal Values for Segmental Bioimpedance Spectroscopy in Pediatric Patients

INTRODUCTION Localized limb edema is a clinically relevant sign in diseases such as post-thrombotic syndrome and lymphedema. Quantitative evaluation of localized edema in children is mainly done by measuring the absolute difference in limb circumference, which includes fat and fat-free mass. Bioimpedance spectroscopy (BIS) provides information on the fluid volume of a body segment. Our objective was to determine normal ranges for segmental (arm and leg) BIS measurements in healthy children. Additionally, we determined the normal ranges for the difference in arm and ankle circumference and explored the influence of handedness and the correlation between techniques. METHODS Healthy children aged 1-18 years were recruited. The ratio of extracellular fluid content between contralateral limbs (estimated as the inter-arm and inter-leg extracellular impedance ratio), and the ratio of extracellular to intracellular fluid content for each limb (estimated as the intracellular to extracellular impedance ratio) were determined with a bioimpedance spectrometer. Arm and ankle circumference was determined with a Gulick II tape. RESULTS We recruited 223 healthy children (48 infants, 54 preschoolers, 66 school-aged children, and 55 teenagers). Normal values for arm and leg BIS measurements, and for the difference in arm and ankle circumference were estimated for each age category. No influence of handedness was found. We found a statistically significant correlation between extracellular impedance ratio and circumference difference for arms among teenagers. CONCLUSION We determined normal BIS ranges for arms and legs and for the difference in circumference between arms and between ankles in children. There was no statistically significant correlation between extracellular impedance ratio and difference in circumference, except in the case of arms in adolescents. This may indicate that limb circumference measures quantities other than fluid, challenging the adequacy of this technique to determine the presence of localized edema in most age groups.

Postthrombotic syndrome and other outcomes of lower extremity deep vein thrombosis in children

Pediatric lower extremity deep vein thrombosis (LE-DVT) can lead to postthrombotic syndrome (PTS) and other adverse events. We investigated the outcomes of LE-DVT in children. Three groups were compared: non-line-related (Non-LR) DVT, LR DVT in neonates (LRneonates), and LR DVT in non-neonates (LRnon-neonates). A total of 339 children were included (Non-LR, n = 56; LRneonates, n = 95; and LRnon-neonates, n = 188). We found a statistically significant difference in the frequency of PTS (P = .04; 62.5%, 40.0%, and 46.3% in Non-LR, LRneonates, and LRnon-neonates, respectively), of recurrent LE-DVT (P = .001; 10.7% and 2.0% in Non-LR and LRnon-neonates, respectively), and pulmonary embolism (PE) (P < .001; 19.6% and 3.2% in Non-LR and LRnon-neonates, respectively) among groups. There was no difference in DVT resolution (P = .41). Multivariable analysis showed that DVT resolution, triggering event, and sex predicted Modified Villalta Scale (MVS; for pediatric PTS) scores >1; there was an interaction between DVT triggering event and sex. The time to reach an MVS >1 was significantly different when comparing groups (log-rank test, P < .001). Moreover, we found a significant difference in baseline MVS scores among groups, but the difference did not appear to change over time. In conclusion, LR LE-DVT had more benign outcomes than Non-LR DVT. Sex, DVT triggering event, and DVT resolution predicted LE-PTS in our cohort.

Assessment of the outcomes associated with periprocedural anticoagulation management in children with acute lymphoblastic leukemia.

OBJECTIVE To report the outcomes of an institutional protocol for periprocedural anticoagulant (AC) management in children with acute lymphoblastic leukemia (ALL). STUDY DESIGN Children being treated for ALL who received full-dose (therapeutic) anticoagulation before undergoing at least 1 lumbar puncture (LP) were included in this retrospective cohort study. The main outcome was the risk of traumatic LP; exploratory analysis included the risks of symptomatic spinal hematoma and progression/recurrence of the thrombotic event. Analyses were conducted using logistic regression analysis with a generalized estimating equation approach. RESULTS Twenty-two children with ALL receiving an AC underwent a total of 396 LPs. Although traumatic LP was associated with full-dose AC therapy in univariable analysis, a multiple logistic regression model controlling for other risk factors for traumatic LP showed that AC therapy was not significantly associated with the risk of traumatic LP when the ACs were held as per the institutional protocol. No patient developed symptomatic spinal hematoma. Exploratory analysis revealed that AC dose, a likely marker of thrombus burden, was significantly associated with progression/recurrence of the thrombotic event in univariable analysis. CONCLUSION In our cohort, recent AC therapy was not statistically associated with an increased risk of bleeding after LP when following a specific protocol for periprocedural AC management. The risk associated with the progression/recurrence of thromboembolic events requires further evaluation.

Pediatric post-thrombotic syndrome in children: Toward the development of a new diagnostic and evaluative measurement tool

OBJECTIVE Our goal was to conduct the item generation and piloting phases of a new discriminative and evaluative tool for pediatric post-thrombotic syndrome. METHODS We followed a formative model for the development of the tool, focusing on the signs/symptoms (items) that define post-thrombotic syndrome. For item generation, pediatric thrombosis experts and subjects diagnosed with extremity post-thrombotic syndrome during childhood nominated items. In the piloting phase, items were cross-sectionally measured in children with limb deep vein thrombosis to examine item performance. RESULT Twenty-three experts and 16 subjects listed 34 items, which were then measured in 140 subjects with previous diagnosis of limb deep vein thrombosis (70 upper extremity and 70 lower extremity). The items with strongest correlation with post-thrombotic syndrome severity and largest area under the curve were pain (in older children), paresthesia, and swollen limb for the upper extremity group, and pain (in older children), tired limb, heaviness, tightness and paresthesia for the lower extremity group. CONCLUSION The diagnostic properties of the items and their correlations with post-thrombotic syndrome severity varied according to the assessed venous territory. The information gathered in this study will help experts decide which item should be considered for inclusion in the new tool.

A critical review of scoring options for clinical measurement tools.

BackgroundThe aim of this paper is twofold: (1) to describe the fundamental differences between formative and reflective measurement models, and (2) to review the options proposed in the literature to obtain overall instrument summary scores, with a particular focus on formative models.MethodsAn extensive literature search was conducted using the following databases: MEDLINE, EMBASE, PsycINFO, CINAHL and ABI/INFORM, using “formative” and “reflective” as text words; relevant articles’ reference lists were hand searched.ResultsReflective models are most frequently scored by means of simple summation, which is consistent with the theory underlying these models. However, our review suggests that formative models might be better summarized using weighted combinations of indicators, since each indicator captures unique features of the underlying construct. For this purpose, indicator weights have been obtained using choice-based, statistical, researcher-based, and combined approaches.ConclusionWhereas simple summation is a theoretically justified scoring system for reflective measurement models, formative measures likely benefit from the use of weighted scores that preserve the contribution of each of the aspects of the construct.

Development of CAPTSureTM – a new index for the assessment of pediatric postthrombotic syndrome

Essentials We developed a discriminative and evaluative index for pediatric postthrombotic syndrome (PTS). A Delphi‐survey was used for item reduction and multi‐criteria decision analysis for item weighting. The new index assesses limb PTS based on the relative severity of each sign and symptom. Higher scores related to higher odds of parental dissatisfaction with their childs condition.

Understanding the barriers in compliance to elastic compression garments in the treatment of pediatric post-thrombotic syndrome: A qualitative study

• Compliance to elastic compression stockings (ECS) can affect treatment efficacy of PTS.

Collateral circulation in pediatric post-thrombotic syndrome

Post-thrombotic syndrome (PTS) is a chronic complication of upper and lower extremity (UE/LE) deep vein thrombosis (DVT) that can affect both children and adults. Its diagnosis is essentially clinical, and is based on the presence or absence of specific signs and symptoms. The Modified Villalta Scale (MVS), and the Manco-Johnson Instrument (MJI) are the current tools used to evaluate LE-PTS in children, as recommended by the International Society of Thrombosis andHaemostasis (ISTH) [1]. These two tools are also used for the evaluation ofUE-PTS [2]. Both the MVS and MJI include an item that assesses collateral circulation, termed “venous collaterals on skin” and “dilated superficial collateral veins” [1], respectively. The Vein Prominence Scale [3], is a scoring system more recently proposed for the measurement of vein prominence in UE in children. Although visible collateral circulation is regarded as an indicator of obstruction, lack of collaterals does not rule out the presence of blood flow obstruction [4]. A study comparing ultrasound findings and collateral circulation, as detected on physical examination, in children with a history of previous central venous lines showed low sensitivity but high specificity of pathologically increased superficial veins for the detection of occlusive thrombosis or absent venous segments [5]. Besides adding to the severity of PTS by increasing the score of the MVS andMJI by one point, the implications of observing collateral circulation on the skin of a child in the setting of PTS are unknown. The present work aimed to investigate the role of collateral circulation, as assessed by physical examination, in children who sustained UE or LEDVT. To this end, we investigated the association between the results of the Vein Prominence Scale and other PTS signs and symptoms, and between the Vein Prominence Scale and functional impact of this syndrome. In addition, we investigated the inter-rater reliability of the Vein Prominence Scale, and of a simplified scoring system in UE-DVT. Our study was part of a cross-sectional study investigating the diagnostic properties of 32 signs and symptoms of UE and LE-PTS in 140 pediatric patients aged 1 to 19 years, diagnosed with unilateral UE (n = 70) or LE-DVT (n = 70), and who were therefore at risk of PTS. In the present study, we focused on the variables explained below. Collateral circulation was assessed using the Vein Prominence Scale [3] with the patient lying (whenever feasible), and both sides of the body uncovered to facilitate comparison with the unaffected

Characteristics of pain, other symptoms and function in pediatric post-thrombotic syndrome

Symptoms and function in pediatric post‐thrombotic syndrome (PTS) remain poorly characterized. Clinical features of PTS were studied in 78 children with history of limb deep vein thrombosis. Tired limb, heaviness, pain, and impaired endurance were the most frequent clinical findings. Frequency of symptoms and of impaired endurance were similar in upper and lower extremities. Pain was associated with the presence of other symptoms and impaired function.