The incidence of venous thromboembolism in thrombophilic children: a prospective cohort study

Antithrombin and protein C and S defects, factor V Leiden mutation, and G20210A prothrombin gene mutation are well-recognized risk factors for venous thromboembolism (VTE) in adults, especially during circumstantial situations such as trauma, immobilization, surgery, or oral contraceptive treatment. The relevance of these defects in predisposing children to VTE is still undefined. In a prospective cohort study we assessed the incidence of spontaneous and risk period–related VTE in asymptomatic children (aged 1-14 years), who were family members of a proband with an objectively diagnosed venous thromboembolic event and a documented single thrombophilic abnormality. We enrolled 143 children from 63 families. Of them, 81 (56.6%) were carriers of an inherited defect, whereas the remaining 62 were free from known genetic or acquired causes of thrombophilia. The mean observation period was 5 years (range, 1-8 years) in each group. Thirty-one risk periods occurred in the carriers group and 20 in noncarriers. Neither spontaneous nor risk period–related VTE occurred in either group during 395 and 296 observation years, respectively. However, circumstances where most of the pediatric thromboses occur (insertion of central venous lines, cancer, and cardiovascular surgery) were not encountered. In conclusion, the thrombotic risk in otherwise healthy children with a single identified thrombophilic defect appears to be very low. Common triggering conditions for VTE in thrombophilic adults do not seem to increase the thrombotic risk in children carrying the same inherited defect. Accordingly, screening for thrombophilia in otherwise healthy children younger than 15 years who belong to families with inherited defects predisposing to thrombosis seems unjustified.

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Incidence of VTE in asymptomatic children with deficiencies of antithrombin, protein C, and protein S: a prospective cohort study

Blood Advances ◽

10.1182/bloodadvances.2020002781 ◽

2020 ◽

Vol 4 (21) ◽

pp. 5442-5448

Author(s):

Daniela Tormene ◽

Elena Campello ◽

Chiara Simion ◽

Giacomo Turatti ◽

Michelangelo Marobin ◽

...

Keyword(s):

Cohort Study ◽

Confidence Interval ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Protein C ◽

Protein S ◽

Healthy Children ◽

Thrombotic Risk ◽

Asymptomatic Children ◽

Risk Period

Abstract Although antithrombin, protein C, and protein S defects are well-recognized inherited risk factors for venous thromboembolism (VTE) in adults, whether they predispose children to these vascular disorders as well is undefined. In a prospective cohort study, we assessed the incidence of spontaneous and risk period–related VTE in children who were family members of adults who, after an episode of symptomatic VTE, had then been identified as carriers of these abnormalities. A total of 134 children from 87 families were enrolled. Seventy (51.5%) of these children were carriers of an inherited defect, and the remaining 64 were not; the mean observation period was 4 years (range, 1-16 years) and 3.9 years (range, 1-13), respectively. Sixteen risk periods were experienced by carriers, and 9 by noncarriers. Six VTE occurred in the 70 carriers during 287 observation-years, accounting for an annual incidence of 2.09% patient-years (95% confidence interval, 0.8-4.5), compared with none in the 64 noncarriers during 248 observation-years. Of the 14 children with thrombophilia who experienced a risk period for thrombosis, 4 (28.6%) developed a VTE episode. The overall incidence of risk-related VTE was 25% per risk period (95% confidence interval, 6.8-64). In conclusion, the thrombotic risk in otherwise healthy children with severe inherited thrombophilia does not seem to differ from that reported for adults with the same defects. Screening for thrombophilia in children who belong to families with these defects seems justified to identify those who may benefit from thromboprophylaxis during risk periods for thrombosis.

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Incidence of venous thromboembolism in asymptomatic family members who are carriers of factor V Leiden: a prospective cohort study

Blood ◽

10.1182/blood.v99.6.1938 ◽

2002 ◽

Vol 99 (6) ◽

pp. 1938-1942 ◽

Cited By ~ 58

Author(s):

Paolo Simioni ◽

Daniela Tormene ◽

Paolo Prandoni ◽

Patrizia Zerbinati ◽

Sabrina Gavasso ◽

...

Keyword(s):

Cohort Study ◽

Venous Thromboembolism ◽

Family Members ◽

Factor V Leiden ◽

Annual Incidence ◽

Factor V ◽

Factor V Leiden Mutation ◽

Risk Period ◽

Heterozygous Carriers

Abstract In a prospective cohort study, we assessed the incidence of spontaneous and risk period–related venous thromboembolism (VTE) in asymptomatic family members of patients who experienced VTE and had the factor V Leiden mutation. In all, 561 family members of 131 probands were included, 313 of whom were carriers (299 heterozygous and 14 homozygous) and 248 of whom were noncarriers of the factor V Leiden mutation. Average follow-up was 4 years (range, 4 months-6 years). There were 1255 and 984 observation-years of follow-up in carriers and noncarriers, respectively. Eight episodes of VTE occurred in heterozygous carriers, resulting in an annual incidence of 0.67% (95% confidence interval [CI], 0.29-1.33). Two events occurred in the absence of associated risk factors, determining an annual incidence of spontaneous VTE of 0.17% (95% CI, 0.02-0.6). Only one VTE (risk period–related) occurred in noncarriers, with an annual incidence of 0.1% (95% CI, 0.003-0.56). Relative risk for VTE in heterozygous carriers compared with noncarriers of the factor V Leiden mutation was 6.6 (95% CI, 1.1-39.8). Risk period–related VTE occurred with an incidence of 18% and 5% per risk period in heterozygous carriers and in noncarriers, respectively. Thus, the low rate of VTE in asymptomatic family members carrying the mutation did not justify continuous anticoagulant prophylaxis. Screening families of symptomatic probands with the factor V Leiden mutation has the potential to identify those asymptomatic carriers who might benefit from thromboprophylaxis during risk periods.

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Fibrinolytic Variables in Patients with Recurrent Venous Thrombosis: a Prospective Cohort Study

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615594 ◽

2001 ◽

Vol 85 (03) ◽

pp. 390-394 ◽

Cited By ~ 49

Author(s):

Jeremy Roberts ◽

Robin Roberts ◽

Marilyn Johnston ◽

Pamela Stevens ◽

Peter Skingley ◽

...

Keyword(s):

Cohort Study ◽

Venous Thromboembolism ◽

Venous Thrombosis ◽

Plasminogen Activator ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Clot Lysis ◽

First Episode ◽

Thrombotic Risk ◽

Recurrent Venous Thrombosis

SummaryTo determine whether fibrinolytic testing predicts recurrent venous thrombosis, we have performed a prospective cohort study in which 303 patients with a first episode of venous thromboembolism underwent comprehensive fibrinolytic testing while receiving oral anticoagulants, and after anticoagulants had been discontinued. They were then followed for up to 3 years for recurrent venous thrombosis. No systematic differences in the levels or activity of type 1 plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (tPA) or euglobulin clot lysis times were detected between patients who did, or did not, suffer recurrent thrombosis. There were also no differences in these variables when patients whose initial thrombosis was idiopathic were compared to patients whose thrombosis occurred in the setting of a known thrombotic risk factor. Based on these results, neither measuring fibrinolytic parameters in patients with venous thromboembolism, nor modification of treatment based on the results of such testing, are justified. Our study also confirms that patients with idiopathic venous thromboembolism have a high risk of recurrence.

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SARS‐CoV‐2 infection and venous thromboembolism after surgery: an international prospective cohort study

Anaesthesia ◽

10.1111/anae.15563 ◽

2021 ◽

Author(s):

◽

Keyword(s):

Cohort Study ◽

Venous Thromboembolism ◽

Prospective Cohort Study ◽

Prospective Cohort

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Inter-observer reliability of a risk assessment model for venous thromboembolism in acutely-ill medical hospitalized patients: Results from a prospective cohort study

Phlebology The Journal of Venous Disease ◽

10.1177/02683555211021226 ◽

2021 ◽

pp. 026835552110212

Author(s):

Cassia RL Ferreira ◽

Marcos de Bastos ◽

Mirella L Diniz ◽

Renan A Mancini ◽

Yan S Raposo ◽

...

Keyword(s):

Risk Factors ◽

Cohort Study ◽

Venous Thromboembolism ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Risk Classification ◽

Assessment Model ◽

Kappa Statistics ◽

Medical Patients ◽

Observer Reliability

Objectives To analyze the inter-observer reliability of risk for venous thromboembolism (VTE) in a population of adult acutely-ill medical patients. Methods In this prospective cohort study, we collected risk factors and risk classification for VTE using RAM IMPROVE7. Kappa statistics was used to evaluate inter-observer reliability between lead clinicians and trained researchers. We evaluated occurrence of VTE in patients with mismatched classification. Results We included 2,380 patients, median age 70 years (interquartile range [IQR], 58-79), 56.2% female. Adjusted Kappa for VTE risk factors ranged from substantial (0.64, 95% confidence interval [CI], 0.61-0.67) for “immobilization”, to almost perfect (0.98; 95% CI 0.97-0.99) for “thrombophilia”; risk classification was 0.64 (95% CI 0.60-0.67). Divergent risk classification occurred in 434 patients (18.2%) of whom seven (1.6%) developed VTE. Conclusion Despite substantial to almost perfect reliability between observers for risk factors and risk classification, lead clinicians tended to underestimate the risk for VTE.

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Commentary on: Efficacy and safety of short-term (3 days) enoxaparin in preventing venous thromboembolism after gastric cancer surgery: A single-center, prospective cohort study [Int J Surg 021 Epub ahead of Print]

International Journal of Surgery ◽

10.1016/j.ijsu.2021.106026 ◽

2021 ◽

pp. 106026

Author(s):

Marcus JW. Chong ◽

Carolyn Chiam

Keyword(s):

Gastric Cancer ◽

Cohort Study ◽

Venous Thromboembolism ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Cancer Surgery ◽

Efficacy And Safety ◽

Single Center ◽

Short Term ◽

Gastric Cancer Surgery

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5-Hydroxyvitamin D concentration in paediatric cancer patients from Scotland: a prospective cohort study

British Journal Of Nutrition ◽

10.1017/s0007114516004074 ◽

2016 ◽

Vol 116 (11) ◽

pp. 1926-1934 ◽

Cited By ~ 3

Author(s):

Raquel Revuelta Iniesta ◽

Ilenia Paciarotti ◽

Isobel Davidson ◽

Jane M. McKenzie ◽

Celia Brand ◽

...

Keyword(s):

Cohort Study ◽

Relative Risk ◽

Cancer Patients ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Vitamin D Supplementation ◽

Healthy Children ◽

Paediatric Cancer ◽

Hydroxyvitamin D ◽

Nutritional Data

AbstractChildren with cancer are potentially at a high risk of plasma 25-hydroxyvitamin D (25(OH)D) inadequacy, and despite UK vitamin D supplementation guidelines their implementation remains inconsistent. Thus, we aimed to investigate 25(OH)D concentration and factors contributing to 25(OH)D inadequacy in paediatric cancer patients. A prospective cohort study of Scottish children aged <18 years diagnosed with, and treated for, cancer (patients) between August 2010 and January 2014 was performed, with control data from Scottish healthy children (controls). Clinical and nutritional data were collected at defined periods up to 24 months. 25(OH)D status was defined by the Royal College of Paediatrics and Child Health as inadequacy (<50 nmol/l: deficiency (<25 nmol/l), insufficiency (25–50 nmol/l)), sufficiency (51–75 nmol/l) and optimal (>75 nmol/l). In all, eighty-two patients (median age 3·9, interquartile ranges (IQR) 1·9–8·8; 56 % males) and thirty-five controls (median age 6·2, IQR 4·8–9·1; 49 % males) were recruited. 25(OH)D inadequacy was highly prevalent in the controls (63 %; 22/35) and in the patients (64 %; 42/65) at both baseline and during treatment (33–50 %). Non-supplemented children had the highest prevalence of 25(OH)D inadequacy at every stage with 25(OH)D median ranging from 32·0 (IQR 21·0–46·5) to 45·0 (28·0–64·5) nmol/l. Older age at baseline (R −0·46; P<0·001), overnutrition (BMI≥85th centile) at 3 months (P=0·005; relative risk=3·1) and not being supplemented at 6 months (P=0·04; relative risk=4·3) may have contributed to lower plasma 25(OH)D. Paediatric cancer patients are not at a higher risk of 25(OH)D inadequacy than healthy children at diagnosis; however, prevalence of 25(OH)D inadequacy is still high and non-supplemented children have a higher risk. Appropriate monitoring and therapeutic supplementation should be implemented.

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