Monitoring hypercoagulability and hypofibrinolysis following acute venous Thromboembolism in Children: Application of the CloFAL assay in a prospective inception cohort study

Bombardier, C.; Villalobos-Menuey, Elizabeth; Ruegg, Katherine; Hathaway, William E.; Manco‐Johnson, Marilyn J.; Goldenberg, Neil A.

doi:10.1016/j.thromres.2012.03.030

Cited by 18 publications

(30 citation statements)

References 32 publications

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“…At the same, the fact that correlations of apo(a) with ELT were statistically significant but not strong may be explained by recent observations that overall plasma fibrinolytic capacity, when measured by the CloFAL assay, is strongly driven by functional fibrinogen levels. 25 A few factors may explain the difference between the present findings for Lp(a) in childhood AIS and prior work by Nowak-Göttl and colleagues. 16 Foremost among these is the fact that childhood-onset AIS cases in the German case-control study were idiopathic in nature, whereas those in this study included all potential CASCADE subtypes; our secondary analysis restricting the cases group to idiopathic AIS is more comparable to that of NowakGöttl's study, but was limited by a small sample size.…”

Section: Discussioncontrasting

confidence: 90%

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Elevated lipoprotein (a), small apolipoprotein (a), and the risk of arterial ischemic stroke in North American children

et al. 2013

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Lipoprotein (a) is a risk factor for adult cardiovascular events, in which the apolipoprotein (a) component is thought to promote atherogenesis and impair fibrinolysis. We investigated whether elevated plasma lipoprotein (a) concentration and small predominant apolipoprotein (a) isoform size (number of kringle-4 domains) are risk factors for childhood arterial ischemic stroke and correlate with plasma fibrinolytic function. Patients who had had an arterial ischemic stroke in childhood (29 days -<21 years at onset; n=43) and healthy controls (n=127) were recruited for plasma sampling and laboratory determinations. Cases were followed for recurrence in a prospective cohort study. The median lipoprotein (a) concentration did not differ between groups [cases: median 18.0 nmol/L (7.5 mg/dL) and observed range 0.9-259 nmol/L (0.38-108.0 mg/dL), controls: 20.4 nmol/L (8.5 mg/dL) and 0.2-282 nmol/L (0.08-117.5 mg/dL); P=0.62]. While odds of incident stroke were not significantly increased, risks of recurrent arterial ischemic stroke were each more than ten-times increased for lipoprotein(a) >90 th percentile of racespecific reference values and apolipoprotein (a) <10 th percentiles [odds ratio=14.0 (95% confidence interval: 1.0-184), P=0.05 and odds ratio=12.8 (1.61-101), P=0.02]. Statistically significant but weak correlations were observed between euglobulin lysis time and both lipoprotein (a) level (r=0.18, P=0.03) and apolipoprotein (a) size (r= -0.26, P=0.002). In conclusion, elevated lipoprotein (a) and small apolipoprotein (a) potently increase the risk of recurrent arterial ischemic stroke in children, with a mechanism only partially attributable to impaired fibrinolysis. Collaborative studies are warranted to investigate these findings further and, more broadly, to establish key risk factors for incident and recurrent arterial ischemic stroke in children. More recently, in a study in the USA, 17 the prevalence of elevated Lp(a) among 59 children with porencephaly or a history of perinatal or childhood onset-AIS was significantly increased compared to that of historical controls who had consisted of healthy German children (20% versus 5.4%); however, concomitant USAbased controls were lacking. Interestingly, in a French study of mother-infant diads of neonatal AIS, elevated maternal Lp(a) was not only implicated in perinatal AIS but also correlated with low birth weight in these infants, leading to a hypothesis that elevated Lp(a) may mediate placental insufficiency. Elevated lipoprotein (a), small apolipoprotein (a), and the risk of arterial ischemic stroke in North American children18 With regard to recurrent AIS in childhood, a prospective multicenter cohort study in Germany 13 demonstrated that Lp(a) >30 mg/dL was an independent risk factor for recurrent AIS (OR: 2.8; 95% CI: 1.1-7.5).In consideration of the lack of well-controlled studies of Lp(a) in childhood-onset AIS outside of Germany, and given also that apo(a) size has received little attention in pediatric AIS, we sought to determine the odds of inci...

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Section: Discussioncontrasting

confidence: 90%

“…[22][23][24] A recently-updated fibrinolytic index (FI 2 ) was employed. 25 ECLA was performed by an automated spectrophotometric technique as previously described, and the results are expressed as the euglobulin lysis time (ELT). 26 …”

Section: Lipoprotein (A) Apolipoprotein (A) Isoform and Global Fibrmentioning

confidence: 99%

Elevated lipoprotein (a), small apolipoprotein (a), and the risk of arterial ischemic stroke in North American children

et al. 2013

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“…The overall hemostasis potential assay uses plasma, offering distinct advantages over the thromboelastography tests, which require fresh whole blood and do not allow for pooling of samples. A similar assay to the overall hemostasis potential assay, the clot formation and lysis assay, has been used in pediatric patients to assess coagulation and fibrinolytic capacity in children with DVT [31]. In vitro studies in adults have assessed the anticoagulant effect of dabigatran using the overall hemostasis potential assay [32,33].…”

Section: Discussionmentioning

confidence: 99%

Assessing the anticoagulant effect of dabigatran in children: An in vitro study

Dietrich

Stang

Ryn

et al. 2015

Thrombosis Research

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“…After full text assessment we excluded an additional 5 papers. These studies measured global assays of plasmin generation and fibrinolysis at various time points after VTE [14], antiphospholipid antibodies in a pediatric antiphospholipid syndrome (APS) with recurrent VTE [16] and FVIII and D-dimer in subjects with recurrent VTE [17] but analyses on the association between biomarkers and outcomes were not reported. Two studies assessed inherited thrombophilia with recurrence [18, 19].…”

Section: Resultsmentioning

confidence: 99%

Markers of coagulation activation, inflammation and fibrinolysis as predictors of poor outcomes after pediatric venous thromboembolism: A systematic review and meta-analysis

Zia

Russell

Sarode

et al. 2017

Thrombosis Research

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Background Sequelae of venous thromboembolism (VTE) in children include recurrence, development of post thrombotic syndrome (PTS) when venous return from a limb is affected and chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism. Identification of laboratory-based risk factors may be useful for individualized risk assessment for VTE sequelae. Coagulation activation and inflammation may contribute to their pathophysiology. We performed a systematic review to investigate the association between biomarkers of coagulation activation, inflammation and fibrinolysis and adverse VTE outcomes in children and young adults. Methods A systematic search of electronic databases, PubMed (NIH), EMBASE (Ovid), Web of Science (Thompson Reuters), and SCOPUS (Elsevier) for studies published through November 2016 was conducted using “VTE” including MeSH terms for “coagulation activation,” “inflammation” and “fibrinolysis,” with no limit on publication date. A study was eligible for inclusion when it evaluated patients (< 21 years) with VTE and biomarkers of coagulation activation, inflammation, and fibrinolysis and assessed for their association with development of adverse thrombotic outcomes. A modified Newcastle Ottawa Scale was applied to examine the quality of included studies. Results Our search strategy yielded 200 references. A total of 3 cohort studies representing 220 patients with VTE were included. Two authors independently assessed all references for inclusion. Three studies (2 prospective cohort and one mixed cohort study) were identified that reported on biomarkers of coagulation activation, inflammation and fibrinolysis, checked at least once after VTE diagnosis and assessed association with primary outcomes of recurrent VTE, PTS and CTEPH. Studies varied with regards to definition of outcomes, the type of biomarkers measured and time point of measurement. We were unable to meta-analyze results due to marked clinical heterogeneity and <3 studies available for each biomarker. Descriptively, a significant association was found for elevated plasma levels of FVIII and D-dimer for a compound outcome of PTS, recurrence and progression in one study, and positive lupus anticoagulant at DVT diagnosis and subsequent PTS by another study. No studies were found for CTEPH. Conclusions Elevated D-dimer, FVIII and lupus anticoagulant show promise for predicting recurrent VTE and PTS in children and young adults. Further research is needed to elucidate whether these markers might be useful to predict development of adverse outcomes after VTE in children.

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Monitoring hypercoagulability and hypofibrinolysis following acute venous Thromboembolism in Children: Application of the CloFAL assay in a prospective inception cohort study

Cited by 18 publications

References 32 publications

Elevated lipoprotein (a), small apolipoprotein (a), and the risk of arterial ischemic stroke in North American children

Elevated lipoprotein (a), small apolipoprotein (a), and the risk of arterial ischemic stroke in North American children

Assessing the anticoagulant effect of dabigatran in children: An in vitro study

Markers of coagulation activation, inflammation and fibrinolysis as predictors of poor outcomes after pediatric venous thromboembolism: A systematic review and meta-analysis

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