Primary prophylaxis of venous thromboembolism in children

Venous thromboembolism (VTE) is rare in children and young adolescents, and occurs predominantly in those with congenital heart disease in whom guidelines exist for VTE prophylaxis. For other paediatric patients, the rarity of the event makes writing an evidence‐based clinical practice guideline difficult because each of the known risk factors contributes only a small increase in risk. Thrombophilia screening is controversial because few results assist with prediction of likely thrombosis and may not alter recommendations for prophylaxis. Recent publications highlight the importance of non‐pharmacological prevention of VTE in children and adolescents undergoing surgery and the importance of liaison among surgeon, anaesthetist and haematologist. This annotation was written with the aim of collating current evidence for VTE prophylaxis and emphasising the need for further research in vulnerable subgroups.     

Prothrombotic risk factors in children with hemiplegic cerebral palsy

BACKGROUND: The purpose of the present paper was to investigate the prevalence of prothrombotic risk factors associated with hemiplegic cerebral palsy (CP). METHODS: Twenty-three hemiplegic CP patients were tested for inherited and acquired prothrombotic risk factors, except methylene tetrahydrofolate reductase (MTFR) polymorphism. RESULTS: A total of 56.5% of patients had at least one coagulation abnormality and 13% of them had two. Four patients (8.7%) had infection and congenital heart disease, who also had additional coagulopathy risk factors. Obstetric problems were detected in 56.5%. Coagulopathy risk factors were factor V Leiden mutation (21.7%), protein C deficiency (21.7%), elevated lipoprotein-a (13%), G20210A mutation of prothrombin (8.7%), and protein S deficiency (4.3%). CONCLUSION: Children with hemiplegic CP need to be evaluated for coagulopathic abnormalities.     

Contrast-enhanced MR angiography of pulmonary venous abnormalities in children

BACKGROUND: Echocardiography and X-ray angiography have been considered as gold standards for evaluation of pulmonary venous abnormalities. However, each technique has its own limitations, such as limitation in visualization of the pulmonary veins within the lungs by echocardiography, and the invasive nature of and use of ionizing radiation in X-ray angiography. Contrast-enhanced MR angiography (MRA) is a fast noninvasive method of visualization of the vessels including the pulmonary arteries and veins. OBJECTIVES: To evaluate the utility of contrast-enhanced MRA in the evaluation of pulmonary venous abnormalities in pediatric patients and to compare its diagnostic accuracy with that of transthoracic echocardiography. MATERIALS AND METHODS: In 30 pediatric patients 31 contrast-enhanced MRA studies were performed for evaluation of pulmonary venous abnormalities. Each of 124 pulmonary veins was evaluated for site of connection, course within the lung, presence of obstruction, and topographic relationship with the adjacent structures. The findings of MRA were compared with echocardiographic findings for 116 veins in 29 studies in 28 patients. RESULTS: Contrast-enhanced MRA visualized 99% (123 of 124) of the pulmonary veins investigated, while echocardiography visualized 89% (103 of 116). Exact agreement was found between the two methods in 72% of the veins with a weighted kappa of 0.60 (0.47-0.73, 95% CI). Echocardiography failed to diagnose an abnormal connection in 2 of 15 pulmonary veins, a discrete stenosis in 2 of 19 veins, and diffuse hypoplasia in 10 of 14 veins. In 29% of patients, MRA made the uncertain echocardiographic findings clear. In another 29%, MRA provided a new diagnosis. CONCLUSIONS: Contrast-enhanced MRA is a powerful, safe, and accurate fast-imaging technique for the anatomical evaluation of pulmonary venous abnormalities. MRA may obviate the need for conventional X-ray angiography. Cardiac catheterization may be reserved for those patients in whom pulmonary vascular resistance needs to be determined.     

Prothrombotic risk factors in childhood stroke and venous thrombosis

Many studies have shown a high percentage of venous thromboses in children to be associated with haematological disorders. However, studies assessing the influence of haemostaseological disorders on paediatric stroke are rare. We compared 26 children with cerebral infarction (median age 2 months, range 0-16.2 years) and 17 with venous thrombosis (median age 4.5 years, range 0-17 years) with regard to prothrombotic risk factors. Prothrombotic disorders were found in 8 out of 26 patients with cerebral infarction (FV Leiden mutation: n = 4; protein C deficiency: n = 1; FV Leiden mutation + protein C deficiency: n = 2; prothrombin mutation G20210A: n = 1) and in 13 out of 17 with venous thrombosis (FV Leiden mutation n = 3; protein C deficiency n = 5; elevated HRGP + PAI: n = 1; combined deficiency of AT, protein C and plasminogen: n = 1; F XII deficiency: n = 1; lupus anticoagulans n = 1; FV Leiden + F XII deficiency + lupus anticoagulans + PAI: n = 1). Comparison of these prevalences with those of 150 healthy paediatric controls showed in children with FV Leiden mutation and/or protein C deficiency an increased risk of cerebral infarction (patients vs. controls: 26.9% vs. 6%; OR 5.77; 95%-CI 1.92-17.3; P = 0.0031) as well as of venous thrombosis (53% vs. 5.3% 19.9; 95%-CI 6-65.6; P < 0.0001). This result is in contrast with reports on thrombophilia in cerebral infarction in adult patients. Conclusion Our results indicate that FV Leiden mutation and protein C deficiency may contribute to the multifactorial aetiology of stroke in early childhood.     

Quality improvement program reduces venous thromboembolism in infants and children with long-gap esophageal atresia (LGEA)

Purpose

Patients with long-gap esophageal atresia (LGEA) treated with the Foker process are at increased risk of venous thromboembolism (VTE). An institutional quality improvement program to decrease VTE risk factor exposure and utilize prophylactic anticoagulation was implemented. We aim to evaluate the efficacy and safety of a VTE risk-reduction program in patients with LGEA.

Methods

Implementation and evaluation of a VTE risk-reduction program in patients with LGEA from 2012 to 2015 was performed. Symptomatic VTE with radiographic confirmation were defined as events. Post-program characteristics were evaluated and compared to a historical cohort.

Results

Sixty-seven patients were identified. Two developed VTE (7 %) post-program implementation; compared to 13/40 (33 %) VTE incidence in the historical cohort (p = 0.018). Baseline demographics were similar, including age, esophageal atresia type and gap length. Post-protocol patients had fewer paralysis episodes (p = 0.004), paralysis days (p = 0.003), central venous catheters (p = 0.003), thoracotomies (p < 0.001), ventilator hours (p = 0.02), and decreased hospital (p < 0.001) and ICU stay (p < 0.001). All patients in the VTE risk-reduction program were exposed to prophylactic anticoagulation. No bleeding complications and/or thrombosis-related mortality occurred.

Conclusion

VTE risk-reduction program implementation decreased symptomatic VTE incidence with associated decreases in ICU and hospital length of stay. Prophylactic anticoagulation can be utilized safely in a complicated pediatric surgical population.

     

Risk of venous thromboembolism in pediatric patients with brain tumors

BACKGROUND: Venous thromboembolism (VTE) is a common event in adults with malignant brain tumors approaching 24% throughout the course of the disease. The high morbidity and mortality of this complication yielded several protocols for prevention of the disease in adults undergoing neurosurgery for brain tumors and possible primary prevention afterwards. We investigated the incidence and complications of VTE in pediatric neuro-oncology patients. PROCEDURE: We analyzed, retrospectively, the files of all consecutive patients under the age of 18 years who were hospitalized for the treatment of brain tumors between the years 1990 and 2003 in two leading, closely related, Israeli neuro-oncology centers. RESULTS: A total of 462 children were analyzed. Three hundred eighty-four patients underwent surgery and 78 were treated medically. Only three (0.64%) of the patients developed clinical episodes of VTE that were treated conservatively. Two of these patients developed intracranial bleeding while on secondary prevention for the disease. CONCLUSIONS: Although this study has considerable limitations in terms of retrospective design, heterogeneous group of patients and diagnoses, the changing awareness for thrombosis over the last 14 years and the inclusion of symptomatic VTE events only, our surprising data suggest that, as opposed to adults, the risk of clinically significant VTE in children with brain tumors may be exceedingly low. These findings set the stage for future forthcoming evaluations in view of the prospective studies that were done in adults and the possible significant implications for the prevention and possible etiologies of the disease.     

Breathing abnormalities in children with breathlessness

Dysfunctional breathing, hyperventilation and vocal cord dysfunction are frequently seen in children and adults. The prevalence is unknown. There are no standardized diagnostic criteria, and for now, effective exclusion of organic disease leaves the diagnosis of dysfunctional breathing. Therapy is mainly focussed on explanation of a benign condition and reassurance. Since dysfunctional breathing is a possible chronic condition, other therapies should be evaluated. In adults physiotherapy and breathing retraining appear beneficial. In childhood there is lack of evidence, and further research is necessary in order to optimise the outcome for children with dysfunctional breathing.     

Pulmonary thromboembolism in children

Pulmonary thromboembolism (PTE) is uncommonly diagnosed in the pediatric patient, and indeed often only discovered on autopsy. The incidence of pediatric PTE depends upon the associated underlying disease, diagnostic tests used, and index of suspicion. Multiple risk factors can be found including: peripartum asphyxia, dyspnea, haemoptysis, chest pain, dehydration, septicemia, central venous lines (CVLs), trauma, surgery, ongoing hemolysis, vascular lesions, malignancy, renal disease, foreign bodies or, uncommonly, intracranial venous sinus thrombosis, burns, or nonbacterial thrombotic endocarditis. Other types of embolism can occur uncommonly in childhood and need to be recognized, as the required treatment will vary. These include pulmonary cytolytic thrombi, foreign bodies, tumor and septic emboli, and post-traumatic fat emboli. No single noninvasive test for pulmonary embolism is both sensitive and specific. A combination of diagnostic procedures must be used to identify suspect or confirmed cases of PTE. This article reviews the risk factors, clinical presentation and treatment of pulmonary embolism in children. It also highlights the current diagnostic tools and protocols used to evaluate pulmonary embolism in pediatric patients.     

Venous thromboembolism in children

With improved pediatric survival from serious underlying illnesses, greater use of invasive vascular procedures and devices, and a growing awareness that vascular events occur among the young, venous thromboembolism (VTE) increasingly is recognized as a critical pediatric concern. This review provides background on etiology and epidemiology in this disorder, followed by an in-depth discussion of approaches to the clinical characterization, diagnostic evaluation, and management of pediatric VTE. Prognostic indicators and long-term outcomes are considered, with emphasis on available evidence underlying current knowledge and key questions for further investigation.     

Haematological abnormalities in children with tuberculosis

Over a 16 month period 307 children with suspected tuberculosis (TB) and an available full blood count (FBC) seen at Tygerberg Hospital in South Africa were evaluated and categorized as confirmed (A), probable (B), and no TB (C) according to WHO criteria. There was no difference in the mean age of the 168 group A (33.6 months), 83 group B (34.4 months), and the 56 group C (31.6 months) children. A lower mean haemoglobin (Hb 10.2 vs. 10.8 g/dl) was the only significantly different haematological parameter in children with TB compared with the comparison group (Group C). There were no differences in median total white cell count, neutrophils, lymphocytes, monocytes, platelets, or the proportion of children in each group with anaemia, microcytosis, neutrophilia, neutropenia, lymphocytosis, lymphopenia, monocytosis, thrombocytosis or thrombocytopenia. The most common haematological abnormalities in children with TB were the presence of anaemia, neutrophilia, and monocytosis but these changes were found with equal frequency in control patients. Although haematological abnormalities are fairly common in children with TB, in a developing country these abnormalities also occur frequently in children with other non-tuberculosis respiratory infections. An FBC has no diagnostic predictive value when investigating a child for TB.     

Cardiac abnormalities in children with hyperthyroidism

Summary The cardiac status of 18 hyperthyroid (HT) children (9 black and 9 white) was evaluated by echocardiography. Mitral regurgitation (MR) was diagnosed clinically in 33% (6 of the 9 blacks). None of the 9 white children had MR. Left ventricular end-diastolic diameter (LVEDD) and volume (LVEDV) did not differ from the predicted normal (PN) based on body surface area and heart rate, except in those with MR where increased LVEDD and LVEDV were noted (p<0.02). LV mass was +1.75 standard deviations (σ) of the PN (p<0.01), due to increased wall thickness or LVEDV. Left ventricular output (LVO) was +0.35σ PN (p=ns); however, when compared to that of normal children, LVO of HT was higher (p<0.001) due to the increased heart rate. Enhanced left ventricular contractility was suggested by increased rate of dimensional change during ejection (peak dD/dt-syst), with a mean value of −11.39 cm/sec as compared to the normal of −9.54 cm/sec (p<0.01). A linear multivariate regression equation differentiated the cardiac status of HT from that of normal children. Following treatment to euthyroid state, MR disappeared in 2 and became less in 4 patients. LVO, LV mass, and peak dD/dt-syst also became less. Significant cardiac changes occur in children with hyperthyroidism, which may be reversible in part after euthyroidism is restored. Supported in part by a grant (RR 305) from the General Clinical Research Centers Program of the Division of Research Resources, National Institutes of Health.     

Venous thrombosis and thromboembolism in children with osteomyelitis

OBJECTIVE: To determine the prevalence and clinical features of deep vein thrombosis (DVT) complicating osteomyelitis during childhood. STUDY DESIGN: We retrospectively reviewed medical records of all patients with osteomyelitis admitted to Children's Medical Center Dallas between July 1, 2003 and December 31, 2004. Analysis was performed on patients with proximal upper or lower extremity, pelvic or vertebral osteomyelitis (a subgroup considered to be at highest risk for infection-related thrombosis). RESULTS: Thirty-five patients had confirmed osteomyelitis of the proximal humerus, proximal tibia/fibula, femur, pelvis, or vertebrae. Ten of these 35 children (29%) developed DVT during the acute infection based on imaging studies performed. Eight thrombi occurred adjacent to the infection and two occurred in relation to central venous catheters. Six of the 10 children with DVT also had evidence of infection disseminated to lung, brain, or heart, compared with only 1 of 25 patients without DVT (P = .001). Hospitalization was longer in those with DVT than without (33.5 v. 14.2 days, P = .001). CONCLUSION: Thromboembolic complications can occur in the setting of osteomyelitis, and affected patients may be at higher risk of disseminated infection.     

Neurologic abnormalities in children presenting with diskitis

BACKGROUND: Neurologic impairment is not considered a clinical manifestation of diskitis in children and has seldom been associated with it in the medical literature. OBJECTIVE: To describe neurologic findings and their implications in children with diskitis. STUDY DESIGN: Retrospective medical records review of children discharged with a diagnosis of diskitis between January 1992 and December 2000. The study included children in whom the diagnosis was based on the presence of clinical findings, laboratory evidence of an inflammatory process, and findings on imaging studies compatible with diskitis. RESULTS: Neurologic findings of decreased muscle strength or hyporeflexia in the lower extremities were found in 7 (41%) of 17 children who met the diagnostic criteria for diskitis. Five of the 7 underwent magnetic resonance imaging, 2 of whom demonstrated intraspinal inflammatory involvement. CONCLUSIONS: Neurologic impairment does not exclude the diagnosis of diskitis and may be a common manifestation of the disease in children. Nevertheless, when neurologic findings are present, advanced imaging studies are needed to exclude intraspinal involvement.     

Venous thromboembolism in Thai children

This is a retrospective study of 24 pediatric venous thromboembolism (VTE) patients with or without pulmonary embolism, conducted in Bangkok, Thailand, between 1981 and 2005. The incidence rate of VTE in Thai children was 3.9/10,000 hospital admissions per year. The median age was 11.7 years. Seventy-five percent of the patients had at least one associated medical condition accounting for the VTE; the two most common conditions, however, were infection and malignancy. Pulmonary embolism occurred in 29% of patients. Observed outcomes of VTE in this series included death (13%), postphlebitic syndrome (13%), and recurrence (26%). Genetic risk factors were explored in 19 patients, and no factor V Leiden or prothrombin 20210 mutations were detected. Protein C deficiency was found in 4 patients.     

Coagulation abnormalities in children with Celiac disease

We prospectively analyzed the coagulation abnormalities in 111 children with Celiac disease at diagnosis and its association with histology grade on duodenal biopsy; 27% had deranged prothrombin time. There was an increasing proportion of coagulopathy with progression of Marsh Grade on duodenal histology.     

Incidence of venous thromboembolism in infants and children: data from the National Hospital Discharge Survey

Pulmonary embolism (PE), deep venous thrombosis (DVT), and the combination were not rare in pediatric patients in the United States from 1979 to 2001. They were more frequent in infants 0 to 1 year of age and in teenagers 15 to 17 years of age than in children 2 to 14 years of age. Pregnancies doubled the rate of DVT in teenage girls.