Manco-Johnson highlights Broderick et al's study on the association of vigorous sports with bleeding rate in 104 children and adolescents with moderate or severe hemophilia. The study results ...indicate that the risk of bleeding events requiring acute factor replacement was increased following collision sports, with an odds ratio of 2.7 for category 2 activities (such as basketball or baseball) and 3.7 for category 3 activities (such as wrestling or US football). However, because exposure time to the higher-risk activities was a small percentage of total life hours and because the annual rate of bleeding was low, the absolute increase in risk was low. Additional statistical modeling, in which factor level was inferred from infusion schedule and known recovery and half-life, revealed that each 1% increase in plasma factor activity was associated with a 2% lower bleeding risk, thus suggesting therapeutic strategies that might further reduce the bleeding risk associated with collision sports.
In 82 children with thrombosis who were followed for up to five years, elevation of factor VIII, D-dimer, or both at diagnosis or persistent elevation during follow-up predicted a lack of thrombus ...resolution, recurrent thrombosis, or the post-thrombotic syndrome.
Elevation of factor VIII, D-dimer, or both predicted a lack of thrombus resolution and recurrent thrombosis.
Thrombosis is an increasing concern in pediatrics, but few prospective studies have evaluated the outcome in children. Congenital deficiencies of protein C, protein S, and antithrombin are known risk factors for recurrent thromboembolism in children, and it is often assumed that idiopathic thrombosis carries the same risk of recurrence in adults and children. Little is known, however, about factors that underlie the risk of recurrent thromboembolism and adverse long-term sequelae of thrombosis in children.
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Recurrent venous thromboembolism and the post-thrombotic syndrome develop in approximately 25 percent and 28 percent, respectively, of unselected adults by five years of follow-up
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The safety and efficacy of a full-length sucrose-formulated recombinant factor VIII product (rFVIII-FS; Kogenate FS; Kogenate Bayer) was evaluated in previously untreated (PUPs) and minimally treated ...(MTP) patients with severe haemophilia A (FVIII <2%). Patients (37 PUPs; 24 MTPs) aged 0.1-25.7 months were treated with rFVIII-FS for a cumulative of 9,141 exposure days (EDs), median 114 EDs (range 4-478), on prophylactic or on-demand therapy. Eighty-nine percent of all treated bleeding episodes were successfully treated with 1 (74%) or 2 (15%) infusions. Clinical response to first infusion for each bleeding episode was rated as 'excellent' in 58%, or 'good' in 33%, of all cases. Recombinant FVIII-FS was used in 27 surgical procedures, mainly catheter implantations, which were all conducted without bleeding complications. FVIII recovery mean values (approximately 2%/kg/IU) were as expected for any licensed FVIII concentrate. FVIII neutralizing antibody formation was 15% (9/60). Aside from inhibitor formation, three adverse events were rated as 'at least possibly drug-related' for a total drug-related adverse event rate of 0.14%. No viral seroconversions were observed. Overall, excellent safety and efficacy were demonstrated with rFVIII-FS for therapy of young children with severe haemophilia A.
We sought to determine joint outcomes relative to impact level of athletic participation among school-aged children who had hemophilia and were taking prophylactic factor replacement, as well as to ...investigate prognostic factors for joint outcomes.
School-aged boys with severe hemophilia A or B at a single center were included in the study. Clinical data on baseline joint status, BMI, hemophilia treatment, bleeding episodes, joint assessments, athletic participation, and injuries were retrospectively reviewed. Data on athletic participation were supplemented, when incomplete in the medical record, via structured telephone interview.
Among 37 children with severe hemophilia A or B receiving factor prophylaxis, 73% participated in high-impact activities, whereas 27% participated in exclusively low-impact activities. The frequency of joint hemorrhages and new injuries did not appreciably differ between high- and low-impact athletics. In most instances, children developed <1 bleed or injury per season. A new target joint developed in 1 (3%) child. Sixteen percent of children met established BMI criteria for overweight, and 3% were obese. In logistic regression analyses with adjustment for prophylaxis frequency, level of athletic participation was not a significant prognostic factor for joint hemorrhage.
In the setting of regular prophylaxis and adult coaching and supervision, significant bleeding complications were uncommon and level of impact of athletic participation was not a prognostic factor for joint outcomes. Athletic participation with appropriate supervision and precautions should be encouraged in children with hemophilia receiving prophylaxis, given potential health benefits in an increasingly overweight pediatric population.
Type 1 von Willebrand disease (VWD) is characterized by a partial quantitative deficiency of von Willebrand factor (VWF). Few VWF gene mutations have been identified that cause dominant type 1 VWD. ...The decreased survival of VWF in plasma has recently been identified as a novel mechanism for type 1 VWD. We report 4 families with moderately severe type 1 VWD characterized by low plasma VWF:Ag and FVIII:C levels, proportionately low VWF:RCo, and dominant inheritance. A decreased survival of VWF in affected individuals was identified with VWF half-lives of 1 to 3 hours, whereas the half-life of VWF propeptide (VWFpp) was normal. DNA sequencing revealed a single (heterozygous) VWF mutation in affected individuals, S2179F in 2 families, and W1144G in 2 families, neither of which has been previously reported. We show that the ratio of steady-state plasma VWFpp to VWF:Ag can be used to identify patients with a shortened VWF half-life. An increased ratio distinguished affected from unaffected individuals in all families. A significantly increased VWFpp/VWF:Ag ratio together with reduced VWF:Ag may indicate the presence of a true genetic defect and decreased VWF survival phenotype. This phenotype may require an altered clinical therapeutic approach, and we propose to refer to this phenotype as type-1C VWD.
Important predictors of adverse outcomes of thrombosis in children, including postthrombotic syndrome (PTS), have recently been identified. Given this knowledge and the encouraging preliminary ...pediatric experience with systemic thrombolysis, we sought to retrospectively analyze our institutional experience with a thrombolytic regimen versus standard anticoagulation for acute, occlusive deep venous thrombosis (DVT) of the proximal lower extremities in children in whom plasma factor VIII activity and/or D-dimer concentration were elevated at diagnosis, from within a longitudinal pediatric cohort. Nine children who underwent the thrombolytic regimen and 13 who received standard anticoagulation alone were followed from time of diagnosis with serial clinical evaluation and standardized PTS outcome assessments conducted in uniform fashion. The thrombolytic regimen was associated with a markedly decreased odds of PTS at 18 to 24 months compared with standard anticoagulation alone, which persisted after adjustment for significant covariates of age and lag time to therapy (odds ratio OR = 0.018, 95% confidence interval CI = < 0.001-0.483; P = .02). Major bleeding developed in 1 child, clinically judged as not directly related to thrombolysis for DVT. These findings suggest that the use of a thrombolysis regimen may safely and substantially reduce the risk of PTS in children with occlusive lower-extremity acute DVT, providing the basis for a future clinical trial.
BACKGROUND AND PURPOSE—There are limited data about the reliability of subtype classification in childhood arterial ischemic stroke, an issue that prompted the IPSS (International Pediatric Stroke ...Study) to develop the CASCADE criteria (Childhood AIS Standardized Classification and Diagnostic Evaluation). Our purpose was to determine the CASCADE criteria’s reliability in a population of children with stroke.
METHODS—Eight raters from the IPSS reviewed neuroimaging and clinical records of 64 cases (16 cases each) randomly selected from a prospectively collected cohort of 113 children with arterial ischemic stroke and classified them using the CASCADE criteria. Clinical data abstracted included history of present illness, risk factors, and acute imaging. Agreement among raters was measured by unweighted κ statistic.
RESULTS—The CASCADE criteria demonstrated a moderate inter-rater reliability, with an overall κ statistic of 0.53 (95% confidence interval CI=0.39–0.67). Cardioembolic and bilateral cerebral arteriopathy subtypes had much higher agreement (κ=0.84; 95% CI=0.70–0.99; and κ=0.90; 95% CI=0.71–1.00, respectively) than cases of aortic/cervical arteriopathy (κ=0.36; 95% CI=0.01–0.71), unilateral focal cerebral arteriopathy of childhood (FCA; κ=0.49; 95% CI=0.23–0.76), and small vessel arteriopathy of childhood (κ=−0.012; 95% CI=−0.04 to 0.01).
CONCLUSIONS—The CASCADE criteria have moderate reliability when used by trained and experienced raters, which suggests that it can be used for classification in multicenter pediatric stroke studies. However, the moderate reliability of the arteriopathic subtypes suggests that further refinement is needed for defining subtypes. Such revisions may reduce the variability in the literature describing risk factors, recurrence, and outcomes associated with childhood arteriopathy.
Men with hemophilia were initially thought to be protected from cardiovascular disease (CVD), but it is now clear that atherothrombotic events occur. The primary objective of the CVD in Hemophilia ...study was to determine the prevalence of CVD and CVD risk factors in US older men with moderate and severe hemophilia and to compare findings with those reported in age-comparable men in the Atherosclerosis Risk in Communities (ARIC) cohort. We hypothesized if lower factor levels are protective from CVD, we would see a difference in CVD rates between more severely affected and unaffected men. Beginning in October 2012, 200 patients with moderate or severe hemophilia A or B (factor VIII or IX level ≤ 5%), aged 54 to 73 years, were enrolled at 19 US hemophilia treatment centers. Data were collected from patient interview and medical records. A fasting blood sample and electrocardiogram (ECG) were obtained and assayed and read centrally. CVD was defined as any angina, any myocardial infarction by ECG or physician diagnosis, any self-reported nonhemorrhagic stroke or transient ischemic attack verified by physicians, or any history of coronary bypass graft surgery or coronary artery angioplasty. CVD risk factors were common in the population. Compared with men of similar age in the ARIC cohort, patients with hemophilia had significantly less CVD (15% vs 25.8%; P < .001). However, on an individual patient level, CVD events occur and efforts to prevent cardiovascular events are warranted. Few men were receiving secondary prophylaxis with low-dose aspirin, despite published opinion that it can be used safely in this patient population.
•CV risk factors are common in older men with hemophilia.•Although older men with hemophilia have less CV disease than comparable unaffected men, CV events do occur and require treatment.
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