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The risk factors associated with the probability of central venous access device (CVAD)-associated deep vein thrombosis (DVT) resolution have been hardly evaluated in children. Current guidelines suggest anticoagulation for a maximum of 3 months in patients with provoked DVT if the provoking factor is resolved. To know if the thrombus will resolve after anticoagulant therapy will help to choose whether to initiate and/or continue this treatment or not. We did a retrospective study of 85 pediatric patients (45 girls, 40 boys) with CVAD-associated DVT to examine the risk factors associated with lack of thrombus resolution in the first 6 months after diagnosis. Sixty-two children had their thrombosis resolved after a median of 50 days (p25-p75 25-97) since diagnosis. In multivariate analysis, variables significantly associated with no resolution were total occlusion (OR 12.50, 95% CI 2.99-52.14, p=.001), location in upper extremity, head, and neck veins (OR 17.70, 95% CI 1.64-191.43, p=.018); collateral circulation in the first 45 days after diagnosis (OR 33.55, 95% CI 2.42-464.71, p=.009); and having between 0 and 3 prothrombotic risk factors at diagnosis (OR 6.20, 95% CI 1.21-31.75, p=.029).Conclusion: CVAD-associated DVT resolution in children in the first 6 months since diagnosis was significantly lower if the thrombosis was occlusive, if it was located in the upper extremity, head, and neck veins; if collateral circulation was seen on ultrasound in the first 45 days; and/or when the patient showed less prothrombotic risk factors at diagnosis. What is Known: • The risk factors associated with central venous access device-associated deep vein thrombosis resolution have been hardly evaluated in children. • Current guidelines suggest anticoagulation for a maximum of 3 months in provoked vein thrombosis if the provoking factor is resolved. What is New: • Thrombus resolution was lower if it was occlusive, located in the upper extremity veins, if collateral circulation was seen, and with less prothrombotic risk factors at diagnosis. • To know if the thrombus will resolve after anticoagulation will help to choose whether to initiate and/or continue it or not.

INTRODUCTION: We present the first registry of patients with congenital bleeding disorders and COVID-19. The study has been carried out in the Community of Madrid, which has the highest number of cases in Spain. The objective is to understand the incidence of COVID-19, the course of the disease if it occurs and the psychosocial and occupational impact on this population. METHODS: We included 345 patients (246 of haemophilia, 69 of von Willebrand Disease, two rare bleeding disorders and 28 carriers of haemophilia). A telephone survey was used to collect the data. RESULTS: Forty-two patients presented symptoms suggestive of infection by COVID-19, and in six cases, the disease was confirmed by RT-PCR. The cumulative incidence of our series was 1.73%. It is worth noting the complexity of the management of COVID-19 in two patients on prophylaxis with non-factor replacement therapy. Adherence to the prescribed treatment was maintained by 95.5% of patients. Although 94% were independent for daily living activities, 42.4% had a recognized disability and 58% required assistance, provided by the Madrid Haemophilia Association (Ashemadrid) in 75% of cases. Only 4.4% of consultations were held in person. CONCLUSIONS: Patients with congenital bleeding disorders infected with SARS-CoV-2 presented a mild course of the disease that did not require admission. Their identification and treatment by a specialist team from a Haemophilia Treatment Center are essential to make a correct assessment of the risk of haemorrhage/thrombosis. COVID-19 had a major impact on the psychosocial aspects of these patients which must be remedied with recovery plans.

Introduction: Idarucizumab is a humanized monoclonal antibody fragment that binds to dabigatran and reverses its anticoagulant activity. It has been available in Spain since June 2016 and is indicated for imminent surgery or invasive procedures and life-threatening bleeding. The aim of the study was to describe the actual experience with idarucizumab in different centers in Madrid. Methods: Patients with electronic prescription of idarucizumab between June 2016 and July 2021 were included. Demographic information, comorbidities, laboratory parameters, dabigatran indication, anticoagulation resumption, adverse events related to idarucizumab and death within 30 days were collected from medical records. Qualitative data are presented as frequencies and percentages. Quantitative data are presented as mean ± standard deviation (SD) or median (interquartile range -IQR-). Cumulative survival was calculated by dividing the number of patients alive by the number of patients in each indication category for idarucizumab in a 30-day post-infusion period. Results: A total of 69 patients from 8 hospitals in Madrid were included. Ninety-six percent received dabigatran for prevention of stroke and embolism in nonvalvular atrial fibrillation and 4% received it for the treatment of thromboembolic disease. The mean age was 73.5 ± 13.9 years, and 55.6% were men. Median aPTT was 45.6 seconds and was prolonged in 72.1% (49). Patient characteristics, concomitant conditions and laboratory parameters are reviewed in Table 1. The main indication for idarucizumab was reversal of anticoagulation for persistent bleeding (46.4%), followed by surgery (44.9%). Fibrinolysis due to ischemic stroke was performed in 3 patients (4.3%), dabigatran intoxication occurred in 3 patients due to acute renal failure (4.3%). Gastrointestinal bleeding was the most common type of bleeding. Two of the patients intoxicated with dabigatran also had gastrointestinal bleeding. Cardiac surgery was the most common type of intervention, with heart transplant being a common indication (9/13). Minor surgical procedures included 2 lumbar punctures and 1 central venous catheterization. In one case, the type of surgery was not available. Figure 1 A and B summarize the bleeding location and type of surgery. The median time between infusion of idarucizumab and cessation of bleeding or onset of surgery was 3 hours, however this information was only available in 43 patients. No reports of excessive bleeding during surgery or after fibrinolysis were noted. One patient with dabigatran intoxication was reported to have an episode of persistent melena in which the trough plasma level was 1178.1 ng/mL. This patient died of an aggressive lymphoproliferative disorder that couldn´t be biopsied due to altered coagulation. A case of auricular thrombosis occurred in a patient with a heart transplant due to hyperthophic cardiomiopathy and end-stage heart failure requiring thrombectomy. The patient required a biventricular assistance and died of myocardial infarction. Full 30-day follow-up was available for 68 patients, during this period 11 died. Five patients in the bleeding group died, 3 from hypovolemic shock, 1 from intraparenchymal hemorrhage and data were missing for 1. Two patients who received a heart transplant died, one as described previously 10 days after the transplant and the other 2 days after the transplant from hemorrhagic shock. Three patients who underwent abdominal surgery died of septic shock. One patient with dabigatran intoxication died. Cumulative survival after a follow-up period of 30 days was 86% (Figure 2). Seventy-seven percent (53) resumed anticoagulation after a median of 3 days (0-180), and 62.3% (33) were bridged with low molecular weight heparin (LMWH) at prophylactic doses. Finally, 75% (40) maintained LMWH (7) or restarted dabigatran or another direct oral anticoagulant (33). A total of 13 patients didn´t resume any anticoagulation. Conclusions: Idarucizumab is an effective drug for reversal of dabigatran anticoagulation in bleeding or imminent surgery/invasive procedures. In this cohort it was used safely in patients awaiting a heart transplant. No cases of bleeding after infusion or during surgery were reported, except for a single case of auricular thrombosis. Most patients resumed anticoagulation at discharge. The experience described confirms the safety of idarucizumab in daily clinical practice. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Aim: To evaluate the influence of two variants of P450 oxidoreductase (POR), rs2868177 and POR*28, on the stable dosage of acenocoumarol. Patients & methods: For this observational, cross-sectional study, patients were undergone stable anticoagulant treatment with acenocoumarol. Univariate and multiple regression analyses were performed to assess the influence of POR polymorphisms. Results: About 340 patients were enrolled. Multiple regression had a coefficient of determination (R2) of 51.5% and an Akaike information criterion of 234.22. The inclusion of POR*28 polymorphisms increased the R2 to 52.0% and reduced the Akaike information criteria to 230.58. The POR*28 heterozygote showed statistical significance in the algorithm. Conclusion: The POR*28 heterozygote appears to be associated with the stable dose of acenocoumarol, but its clinical contribution to the prediction of the dosing of this drug is minimal.

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.There is a strong association between genetic polymorphisms and the acenocoumarol dosage requirements. Genotyping the polymorphisms involved in the pharmacokinetics and pharmacodynamics of acenocoumarol before starting anticoagulant therapy would result in a better quality of life and a more efficient use of healthcare resources. The objective of this study is to develop a new algorithm that includes clinical and genetic variables to predict the most appropriate acenocoumarol dosage for stable anticoagulation in a wide range of patients. We recruited 685 patients from 2 Spanish hospitals and 1 primary healthcare center. We randomly chose 80% of the patients (n = 556), considering an equitable distribution of genotypes to form the generation cohort. The remaining 20% (n = 129) formed the validation cohort. Multiple linear regression was used to generate the algorithm using the acenocoumarol stable dosage as the dependent variable and the clinical and genotypic variables as the independent variables. The variables included in the algorithm were age, weight, amiodarone use, enzyme inducer status, international normalized ratio target range and the presence of CYP2C9∗2 (rs1799853), CYP2C9∗3 (rs1057910), VKORC1 (rs9923231) and CYP4F2 (rs2108622). The coefficient of determination (R2) explained by the algorithm was 52.8% in the generation cohort and 64% in the validation cohort. The following R2 values were evaluated by pathology: atrial fibrillation, 57.4%; valve replacement, 56.3%; and venous thromboembolic disease, 51.5%. When the patients were classified into 3 dosage groups according to the stable dosage (21 mg/week), the percentage of correctly classified patients was higher in the intermediate group, whereas differences between pharmacogenetic and clinical algorithms increased in the extreme dosage groups. Our algorithm could improve acenocoumarol dosage selection for patients who will begin treatment with this drug, especially in extreme-dosage patients. The predictability of the pharmacogenetic algorithm did not vary significantly between diseases., This study was funded by a grant from the Spanish Ministry of Health and Social Policy (Instituto de Salud Carlos III, PI07/0710) and the Andalusian Regional Ministry of Health (Progress and Health Foundation, PI-0717-2013)

Our goal was to analyze the association of the level of antiphospholipid antibodies (aPLs) with stroke severity and outcome in patients with antiphospholipid syndrome (APS).Observational study included consecutive patients with ischemic stroke younger than 55 years (2007-2012). We analyzed serum levels of aPLs, including anticardiolipin (aCL) antibodies, anti-β2-glycoprotein I antibodies (anti-β2GPI) and antiprothrombin antibodies (aPS/PT) within the first 48 h after admission, and again, in the case of a positive result, at least 12 weeks after the first measurement. Stroke severity was measured by the National Institutes of Health Stroke Scale (NIHSS), and the three-month stroke outcome by the modified Rankin Scale (mRS). Multiple linear regression models were used to analyze the correlation between the aPLs and stroke severity and outcome.Overall 255 stroke patients were included, 22 (8.6%) with APS. Among them, a positive correlation was found between immunoglobulin M (IgM) aCL levels within 48 h and NIHSS (rho = 0.471; p = 0.027), as well as a tendency toward a positive correlation between immunoglobulin G (IgG) anti-β2GPI levels within 48 h and three-month mRS (rho = 0.364; p = 0.096). Multiple linear regression analyses showed a positive correlation between levels of IgM aCL 48 h and the NIHSS (β-coefficient [standard error; SE] = 0.127 [0.044]), as well as the levels of IgG anti-β2GPIwithin 48 h and the three-month mRS (β-coefficient [SE] = 0.034 [0.011]).In young stroke patients with APS, serum levels of IgM aCL within 48 h are correlated with stroke severity and levels of IgG anti-β2GPI within 48 h are correlated with three-month outcomes.