Introduction Haemophilia A is an inherited bleeding disorder characterised by factor VIII (FVIII) deficiency. In patients with non-severe haemophilia A, surgery and bleeding are the main... Show moreIntroduction Haemophilia A is an inherited bleeding disorder characterised by factor VIII (FVIII) deficiency. In patients with non-severe haemophilia A, surgery and bleeding are the main indications for treatment with FVIII concentrate. A recent study reported that standard dosing frequently results in FVIII levels (FVIII: C) below or above FVIII target ranges, leading to respectively a bleeding risk or excessive costs. In addition, FVIII concentrate treatment carries a risk of development of neutralising antibodies. An alternative is desmopressin, which releases endogenous FVIII and von Willebrand factor. In most patients with non-severe haemophilia A, desmopressin alone is not enough to achieve FVIII target levels during surgery or bleeding. We hypothesise that combined pharmacokinetic (PK)-guided administration of desmopressin and FVIII concentrate may improve dosing accuracy and reduces FVIII concentrate consumption.Methods and analysis In the DAVID study, 50 patients with non-severe haemophilia A (FVIII: C >= 0.01 IU/mL) with a bleeding episode or undergoing surgery will receive desmopressin and FVIII concentrate combination treatment. The necessary dose of FVIII concentrate to reach FVIII target levels after desmopressin administration will be calculated with a population PK model. The primary endpoint is the proportion of patients reaching FVIII target levels during the first 72 hours after start of the combination treatment. This approach was successfully tested in one pilot patient who received perioperative combination treatment.Ethics and dissemination The DAVID study was approved by the medical ethics committee of the Erasmus MC. Results of the study will be communicated trough publication in international scientific journals and presentation at (inter) national conferences. Show less
Limperg, P.F.; Maurice-Stam, H.; Haverman, L.; Coppens, M.; Kruip, M.J.H.A.; Eikenboom, J.; ... ; Peters, M. 2019
Introduction and Aim Suboptimal health-related quality of life and lowered employment rates found in a previous study in young adults (YA) with congenital coagulation disorders (CCD) in the... Show moreIntroduction and Aim Suboptimal health-related quality of life and lowered employment rates found in a previous study in young adults (YA) with congenital coagulation disorders (CCD) in the Netherlands underline the need for more insight into professional functioning of YA with CCD and into determinants of professional functioning. Methods Young adults (18-30 years) with CCD participated in a cross-sectional study. Professional functioning was assessed with the Work Productivity and Activity Impairment questionnaire (WPAI). Potential determinants were assessed with the Course of Life Questionnaire (CoLQ), Pediatric Quality of Life Inventory Young Adult version (PedsQL_YA), Illness Cognition Questionnaire (ICQ) and Haemophilia Activities List (HAL). Logistic regression analyses were performed in the complete sample of YA with CCD, and in YA men with haemophilia separately, to examine determinants of WPAI outcomes. Results Ninety-four YA (77 men; mean age 24.1 years, SD 3.5 and 17 women; mean age 24.5 years, SD 3.8) with CCD (74% haemophilia A/B) participated. 74.5% of YA were paid employed for on average 30 hours per week. Of these, more than a quarter reported work impairment. Older age and a non-severe type of haemophilia (in the sample of YA men with haemophilia) were associated with successful (paid) employment. No variables were associated with professional functioning (expressed as Presenteeism and Overall work impairment) in patients with CCD or haemophilia. Conclusion Three-quarters of YA with CCD were successful in finding paid employment. Though absenteeism was low, YA with paid employment needs attention as a considerable part experienced work impairment. Show less
Pol, L.M. van der; Tromeur, C.; Bistervels, I.M.; Ni Ainle, F.; Bemmel, T. van; Bertoletti, L.; ... ; Artemis Study Investigators 2019
Background Pulmonary embolism is one of the leading causes of maternal death in the Western world. Because of the low specificity and sensitivity of the d-dimer test, all pregnant women with... Show moreBackground Pulmonary embolism is one of the leading causes of maternal death in the Western world. Because of the low specificity and sensitivity of the d-dimer test, all pregnant women with suspected pulmonary embolism undergo computed tomographic (CT) pulmonary angiography or ventilation-perfusion scanning, both of which involve radiation exposure to the mother and fetus. Whether a pregnancy-adapted algorithm could be used to safely avoid diagnostic imaging in pregnant women with suspected pulmonary embolism is unknown. Methods In a prospective study involving pregnant women with suspected pulmonary embolism, we assessed three criteria from the YEARS algorithm (clinical signs of deep-vein thrombosis, hemoptysis, and pulmonary embolism as the most likely diagnosis) and measured the d-dimer level. Pulmonary embolism was ruled out if none of the three criteria were met and the d-dimer level was less than 1000 ng per milliliter or if one or more of the three criteria were met and the d-dimer level was less than 500 ng per milliliter. Adaptation of the YEARS algorithm for pregnant women involved compression ultrasonography for women with symptoms of deep-vein thrombosis; if the results were positive (i.e., a clot was present), CT pulmonary angiography was not performed. All patients in whom pulmonary embolism had not been ruled out underwent CT pulmonary angiography. The primary outcome was the incidence of venous thromboembolism at 3 months. The secondary outcome was the proportion of patients in whom CT pulmonary angiography was not indicated to safely rule out pulmonary embolism. Results A total of 510 women were screened, of whom 12 (2.4%) were excluded. Pulmonary embolism was diagnosed in 20 patients (4.0%) at baseline. During follow-up, popliteal deep-vein thrombosis was diagnosed in 1 patient (0.21%; 95% confidence interval [CI], 0.04 to 1.2); no patient had pulmonary embolism. CT pulmonary angiography was not indicated, and thus was avoided, in 195 patients (39%; 95% CI, 35 to 44). The efficiency of the algorithm was highest during the first trimester of pregnancy and lowest during the third trimester; CT pulmonary angiography was avoided in 65% of patients who began the study in the first trimester and in 32% who began the study in the third trimester. Conclusions Pulmonary embolism was safely ruled out by the pregnancy-adapted YEARS diagnostic algorithm across all trimesters of pregnancy. CT pulmonary angiography was avoided in 32 to 65% of patients. Show less
Wall, S.J. van der; Rein, N. van; Bemt, B. van den; Kruip, M.J.H.A.; Meijer, K.; Boome, L.C.J. te; ... ; Huisman, M. 2019
Aims Because practice-based data on the usage of idarucizumab for urgent dabigatran reversal is unavailable, we evaluated the appropriateness of idarucizumab usage, its haemostatic effectiveness... Show moreAims Because practice-based data on the usage of idarucizumab for urgent dabigatran reversal is unavailable, we evaluated the appropriateness of idarucizumab usage, its haemostatic effectiveness and clinical outcomes.Methods and results An observational cohort study was performed including consecutive patients who were treated with idarucizumab between 2016 and 2018. Appropriate usage was assessed with predefined criteria. Post-reversal effectiveness was evaluated according to International Society on Thrombosis and Haemostasis (ISTH) recommendations. Patients were followed for 90 days for occurrence of thromboembolism, (re-) bleeding and death. Idarucizumab was used in 88 patients, of whom 53 (60%) presented with severe bleeding (20 gastrointestinal and 18 intracranial) and 35 (40%) requiring urgent surgical intervention. Use of idarucizumab was judged inappropriate in 25 patients (28%). Effective haemostasis was achieved in 32 of 48 (67%) bleeding patients in whom assessment was possible. Seven of 16 patients with major bleeding who did not achieve effective haemostasis (five intracranial) died, compared with two of 32 patients with effective haemostasis (relative risk 7.0, 95% confidence interval 1.6-30). Four patients (4.2%) developed thromboembolism [2 (2.1%) within 30 days] and four patients (4.2%) re-bleeding, all within 10 days. Seventeen patients (19%) died; 10 (11%) within 5 days.Conclusion In this practice-based cohort, idarucizumab use was considered inappropriate in 28% of patients. Effective haemostasis was achieved in two-third of bleeding patients and was associated with lower mortality risk. Clinical outcomes were similar to those observed in the RE-VERSE AD trial, comprising re-bleeds and thromboembolism, and a high-mortality rate. Show less
