Suzan Williams

Clinical features and outcome of pulmonary embolism in children

Pulmonary embolism (PE) is rare in childhood but evidence suggests it is under‐recognised. Children diagnosed with PE at a large tertiary centre over an 8‐year period were retrospectively reviewed. Fifty‐six children with radiologically proven PE were identified, 31 males and 25 females, median age 12 years. Eighty‐four per cent had symptoms of PE. Risk factors for thromboembolism were present in 54 patients (96·4%); most commonly immobility (58·9%), central venous line (35·7%) and recent surgery (28·6%). Investigation revealed a thrombophilic abnormality in 14/40 patients (35%). Concurrent deep vein thrombosis was confirmed in 31 patients (55·4%), predominantly lower limb. D dimer was elevated at presentation in 26/30 patients (86·7%). Eight patients underwent systemic thrombolysis. An inferior vena cava filter was placed in five patients. Therapy was complicated by major haemorrhage in 12 patients (21·4%). The majority (82·1%) had complete or partial resolution of PE following a median of 3 months anticoagulation. Seven patients had a recurrent thromboembolic event and 12 patients died (mortality 21·4%); five due to thromboembolism (8·9%) and two due to haemorrhage. Risk factors for PE in children are distinct from adults and morbidity and mortality is significant. Multicentre prospective studies are required to determine optimal treatment and long‐term outcome of childhood PE.

Risk, Clinical Features, and Outcomes of Thrombosis Associated With Pediatric Cardiac Surgery

Background— Thrombosis, usually considered a serious but rare complication of pediatric cardiac surgery, has not been a major clinical and/or research focus in the past. Methods and Results— We noted 444 thrombi (66% occlusive, 60% symptomatic) in 171 of 1542 surgeries (11%). Factors associated with increased odds of thrombosis were age <31 days (odds ratio [OR], 2.0; P=0.002), baseline oxygen saturation <85% (OR, 2.0; P=0.001), previous thrombosis (OR, 2.6; P=0.001), heart transplantation (OR, 4.1; P<0.001), use of deep hypothermic circulatory arrest (OR, 1.9 P=0.01), longer cumulative time with central lines (OR, 1.2 per 5-day equivalent; P<0.001), and postoperative use of extracorporeal support (OR, 5.2; P<0.001). Serious complications of thrombosis occurred with 64 of 444 thrombi (14%) in 47 of 171 patients (28%), and were associated with thrombus location (intrathoracic, 45%; extrathoracic arterial, 19%; extrathoracic venous, 8%; P<0.001), symptomatic thrombi (OR, 8.0; P=0.02), and partially/fully occluding thrombi (OR, 14.3; P=0.001); indwelling access line in vessel (versus no access line) was associated with lower risk of serious complications (OR, 0.4; P=0.05). Thrombosis was associated with longer intensive care unit (+10.0 days; P<0.001) and hospital stay (+15.2 days; P<0.001); higher odds of cardiac arrest (OR, 4.9; P<0.001), catheter reintervention (OR, 3.3; P=0.002), and reoperation (OR, 2.5; P=0.003); and increased mortality (OR, 5.1; P<0.001). Long-term outcome assessment was possible for 316 thrombi in 129 patients. Of those, 197 (62%) had resolved at the last follow-up. Factors associated with increased odds of thrombus resolution were location (intrathoracic, 75%; extrathoracic arterial, 89%; extrathoracic venous, 60%; P<0.001), nonocclusive thrombi (OR, 2.2; P=0.01), older age at surgery (OR, 1.2 per year; P=0.04), higher white blood cell count (OR, 1.1/109 cells per 1 mL; P=0.002), and lower fibrinogen (OR, 1.4/g/L; P=0.02) after surgery. Conclusions— Thrombosis affects a high proportion of children undergoing cardiac surgery and is associated with suboptimal outcomes. Increased awareness and effective prevention and detection strategies are needed.

Enoxaparin for neonatal thrombosis: A call for a higher dose for neonates

INTRODUCTION Enoxaparin is the current anticoagulant of choice for neonatal thrombosis. Present neonatal treatment guidelines of 1.5 mg/kg every 12 hours (q12 h) are extrapolated primarily from an earlier study with 9 infants less than 2 months of age. More recent studies indicate an increased dose requirement for neonates. MATERIALS AND METHODS Relevant data from articles and abstracts were identified by searching MEDLINE and pediatric and hematology conference proceedings. RESULTS Publications between 1996 and 2007 included 8 papers, 4 abstracts and 1 review article with primary research documenting enoxaparin use in 240 neonates. The mean maintenance dose of enoxaparin ranged from 1.48 to 2.27 mg/kg q12 h for all infants, but was higher for preterm neonates at 1.9-2.27 mg/kg q12 h. The efficacy of enoxaparin, causing either complete or partial resolution was between 59 and 100%. Minor side effects were common and adverse events (major bleeding) occurred in 12 patients (0-19%). CONCLUSIONS Increased experience with enoxaparin use in neonates in the past decade has indicated higher doses to achieve accepted target anti-factor Xa values. The long-term use of indwelling catheters (Insuflon catheter) for enoxaparin administration may need to be reevaluated in ELBW infants. Suggested starting doses of enoxaparin are 1.7 mg/kg q12 h for term neonates and 2.0 mg/kg q12 h for preterm neonates if there is no considerable bleeding risk. However, further prospective studies are needed to validate an increased initial dose of enoxaparin.

Clinical probability score and D‐dimer estimation lack utility in the diagnosis of childhood pulmonary embolism

Summary.  Background: Childhood pulmonary embolism (PE) causes significant mortality and evidence suggests that it is under‐diagnosed. Clinical probability scores and D‐dimer estimation to assess pre‐test probability have not been studied in children with suspected PE. Patients/Methods: This retrospective cohort study evaluated Wells simplified probability score for PE in 50 children with PE and 25 PE negative control patients, and D‐dimer values in 27 PE positive and 12 PE negative children. Results: PE positive and PE negative groups had similar rates of risk factors for venous thromboembolism (VTE). Wells simplified probability score showed a small difference between PE positive and PE negative children (median score: PE positive, 4.5; PE negative, 4; P = 0.009), children with PE are more likely to obtain a ‘PE likely’ score (score > 4), P = 0.012. The difference was of slightly greater significance when the Wells score was adjusted to account for pediatric normal ranges for heart rate, P = 0.007, and signs/symptoms of upper limb DVT, P = 0.006. Children with PE were as likely as PE negative patients to have a D‐dimer value within the normal range (PE positive, 15%; PE negative, 25%; P = 0.654). A combination of a ‘PE unlikely’ score and normal D‐dimer value occurred in 1/12 (8%) of PE negative children. Conclusions: The Wells clinical probability score and D‐dimer estimation may lack utility in the determination of pre‐test probability of PE in children. Validation of a pediatric clinical probability score, incorporating D‐dimer estimation, by prospective study, would be difficult as a result of the rarity of childhood PE.

Unfractionated heparin dosing in young infants: clinical outcomes in a cohort monitored with anti‐factor Xa levels

Summary.  Background: Unfractionated heparin (UFH) is a widely used anticoagulant. Current American College of Chest Physicians guidelines for infants extrapolated from adults recommend 28 U kg−1 h−1 of UFH to achieve an anti‐factor Xa level of 0.35–0.7 IU mL−1. Objective: To assess the profile of anti‐FXa‐based UFH dosing guidelines in infants. Patients/Methods: We included all infants aged < 6 months treated with per‐protocol intravenous UFH at the Hospital for Sick Children, Toronto, over a 3.5‐year period. Results: Of 100 infants, 11% achieved sustained therapeutic anti‐FXa levels with current dose recommendations. Only 15% achieved target anti‐FXa levels within 24 h with per‐protocol dose escalations. Seventeen per cent of patients never achieved therapeutic anti‐FXa levels, despite up to 60 days of therapy and triple the recommended dose. The median dose needed to achieve therapeutic anti‐FXa levels in the remaining 83 infants was 33 U kg−1 h−1 (interquartile range, 30–36). Two in three infants had decreased thrombus size at completion of therapy and no thrombus progression/recurrence, and 11/100 infants suffered major bleeding. Without exclusion of extracorporeal membrane oxygenation patients, an activated partial thromboplastin time (APTT) of > 180 s was detected as a risk factor for major bleeding. Conclusions: UFH monitoring is challenging in infants. Despite their delay in reaching therapeutic anti‐FXa levels, infants monitored with the adult‐based anti‐FXa range have a high thrombus resolution rate, no thrombus progression, but a relatively high bleeding rate. Extreme APTT elevation may contribute to this bleeding risk, particularly in critically ill patients. Current UFH guidelines for young infants may still be inadequate, and laboratory methods with age‐appropriate ranges may be required to further improve clinical outcomes within this population.

Exercise-Induced Deep Vein Thrombosis of the Upper Extremity

Paget-Schroetter syndrome or effort-related upper extremity deep vein thrombosis is a rare condition that usually afflicts young healthy individuals, most commonly males. The cause is multifactorial but almost always involves extrinsic compression of the subclavian vein at the thoracic inlet, causing venous stenosis from repetitive trauma. The diagnosis of this condition may be difficult, and its delay may contribute to potential complications including thrombosis progression, pulmonary embolism, thrombosis recurrence, and post-thrombotic syndrome. Similarly, the best therapeutic option has not been established and in the lack of evidence-based guidelines, treatment may be extremely challenging especially in children, in whom long-term complications can be particularly disabling.

Neonatal portal vein thrombosis: Diagnosis and management

Neonatal portal vein thrombosis (PVT) is an increasingly recognized event. Patients are generally asymptomatic in the neonatal period. The diagnosis is made with Doppler ultrasound. Umbilical catheterization, exchange transfusion and sepsis are risk factors for neonatal PVT. Thrombophilia is possibly a contributing risk factor. Although there are potential serious acute complications such as hepatic necrosis, the outcome is good in the majority of cases, followed up to 8 years of age. Thrombus resolution occurs in 30-70% in days to months. Liver lobe atrophy may occur following PVT, and does not appear to be associated with any impairment of liver function. Non-occlusive thrombosis is more likely to resolve than non-occlusive thrombosis. A subset of patients without resolution is at risk for developing portal hypertension over the next decade of life. There are no current defining features present during the neonatal period to enable identification of neonates at risk for portal hypertension. There is no evidence that anticoagulation therapy improves time to resolution or decreases the likelihood of portal hypertension. Anticoagulation therapy may be considered. A management algorithm is proposed.

Varied opinions on thrombolysis for venous thromboembolism in infants and children: findings from a survey of pediatric hematology-oncology specialists.

Recent guidelines discourage routine use of thrombolytic agents for treatment of venous thromboembolism (VTE) in pediatric patients, but actual practice patterns are unknown.

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.

Neonatal and childhood right atrial thrombosis: recognition and a risk-stratified treatment approach.

Pediatric literature and guidelines of treatment options for right atrial thrombosis (RAT) are lacking; thus, this review summarizes the available literature on RAT in infants and children. Medline search identified 35 publications, with 27 prospective or retrospective case series included for data analysis. A total of 122 cases of RAT were identified. The mean age of patients is 3.58 years (n = 86) with a strong predominance in the neonatal and infancy period. Ninety-one percent of cases were found to be associated with central venous catheters, 40.8% are premature neonates, 27.2% are postcardiac surgery patients, and 19.2% have underlying malignancies. Gut failure with total parenteral nutrition given via the central venous catheters occurred in 45.6% of patients. The most frequent presenting symptoms are respiratory distress and arrhythmia, and 56.8% (42 of 74) were asymptomatic. Our study defined high-risk features on echocardiogram as large size, more than 2 cm in any dimension, pedunculated, mobile, or snake-shaped, and mobile. Our result confirmed there is significant difference in the mortality for the high-risk group (16.7%; three of 18) versus the low risk group (0%; n = 32; P = 0.0416). Moreover, none of the asymptomatic patients showed progression in disease or died. Asymptomatic and hemodynamically stable patients with RAT who are at low risk are associated with good prognosis irrespective of treatment. We recommended removal of central venous line if possible, with or without anticoagulation for this group of patients. Systemic anticoagulation therapy should be given to all high-risk or symptomatic RAT patients. Surgical thrombectomy or thrombolytic therapy carries significant risk and should be considered individually.