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8 results on '"Reitter-Pfoertner, S.E."'

2. Inhibitor development and mortality in non‐severe hemophilia A

Author

Eckhardt, C.L., Loomans, J.I., van Velzen, A.S., Peters, M., Mauser‐Bunschoten, E.P., Schwaab, R., Mazzucconi, M.G., Tagliaferri, A., Siegmund, B., Reitter‐Pfoertner, S.E., van der Bom, J.G., Fijnvandraat, K., Kamphuisen, P.W., Peerlinck, K., Oldenburg, J., Santagostino, E., Astermark, J., Eckhardt, C.L, van Velzen, A.S, Streefkerk, N., Loomans, J.L., van Eijkelenburg, A., Jansen, A.J., Kruijt, C.C., van Tienoven, B., van Baar, A.C.G., Corten, I.W., Meijer, K., Nijziel, M.R., Dors, N., Hamulyak, K., Beckers, E., Brons, P.P., Laros‐van Gorkom, B.A.P., van Heerde, W.L., Leebeek, F., Kruip, M., Cnossen, M.H., Mauser‐Bunschoten, E., Fischer, K., Smiers, F.J., Hermans, C., Klamroth, R., Escuriola‐Ettingshausen, C., Königs, C., Petrini, P., Holmström, M., Mäkipernaa, A., Male, C., Pabinger, I., Keenan, R.D., Liesner, R., Khair, K., Yee, T.T., Hart, D.P., Rangarajan, S., Mitchell, M., Thompson, G., Haya, S., Moret, A., Cid, A.R., Jimenez‐Yuste, V., Mancuso, M.E., Mazzuconni, M.G., Santoro, C., Morfini, M., Castaman, G., Schinco, P., Rivolta, G.F., Platokouki, H., and McRae, S.

Published
2015
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3. Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia A

Author

Eckhardt, C.L., Velzen, A.S. van, Peters, M., Astermark, J., Brons, P.P., Castaman, G., Cnossen, M.H., Dors, N., Escuriola-Ettingshausen, C., Hamulyak, K., Hart, D.P., Hay, C.R.M., Haya, S., Heerde, W.L. van, Hermans, C., Holmstrom, M., Jimenez-Yuste, V., Keenan, R.D., Klamroth, R., Gorkom, B.A.P., Leebeek, F.W.G., Liesner, R., Makipernaa, A., Male, C., Mauser-Bunschoten, E., Mazzucconi, M.G., Mcrae, S., Meijer, K., Mitchell, M., Morfini, M., Nijziel, M., Oldenburg, J., Peerlinck, K., Petrini, P., Platokouki, H., Reitter-Pfoertner, S.E., Santagostino, E., Schinco, P., Smiers, F.J., Siegmund, B., Tagliaferri, A., Yee, T.T., Kamphuisen, P.W., Bom, J.G. van der, Fijnvandraat, K., INSIGHT Study Grp, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Service d'hématologie, UCL - (SLuc) Centre de malformations vasculaires congénitales, Cardiovascular Centre (CVC), Vascular Ageing Programme (VAP), RS: CARIM School for Cardiovascular Diseases, Biochemie, Interne Geneeskunde, Pediatrics, Hematology, Epidemiology, Other departments, Paediatric Infectious Diseases / Rheumatology / Immunology, ACS - Amsterdam Cardiovascular Sciences, and AII - Amsterdam institute for Infection and Immunity

Subjects
Invasive mycoses and compromised host Translational research [N4i 2], Adult, medicine.medical_specialty, Age-related aspects of cancer [ONCOL 2], Time Factors, Adolescent, Genotype, Immunology, Mutation, Missense, Kaplan-Meier Estimate, Hemophilia A, DIAGNOSIS, Biochemistry, Gastroenterology, Young Adult, Interquartile range, Risk Factors, Internal medicine, medicine, Missense mutation, Humans, Cumulative incidence, Desmopressin, Genotyping, POLYMORPHISMS, Retrospective Studies, Hematology, Factor VIII, Cardiovascular diseases [NCEBP 14], business.industry, Incidence (epidemiology), DESMOPRESSIN, Cell Biology, Middle Aged, MILD, Antibodies, Neutralizing, Confidence interval, Treatment Outcome, business, medicine.drug, Follow-Up Studies
Abstract

Neutralizing antibodies (inhibitors) toward factor VIII form a severe complication in nonsevere hemophilia A, profoundly aggravating the bleeding pattern. Identification of high-risk patients is hampered by lack of data that take exposure days to therapeutic factor VIII concentrates into account. In the INSIGHT study, we analyzed the association between F8 mutation and inhibitor development in patients with nonsevere hemophilia A (factor VIII 2-40 IU/dL). This analysis included 1112 non-severe hemophilia A patients from 14 centers in Europe and Australia that had genotyped at least 70% of their patients. Inhibitor risk was calculated as Kaplan-Meier incidence with cumulative number of exposure days as the time variable. During 44 800 exposure days (median, 24 exposure days per patient; interquartile range [IQR], 7-90), 59 of the 1112 patients developed an inhibitor; cumulative incidence of 5.3% (95% confidence interval [CI], 4.0-6.6) after a median of 28 exposure days (IQR, 12-71). The inhibitor risk at 50 exposure days was 6.7% (95% CI, 4.5-8.9) and at 100 exposure days the risk further increased to 13.3% (95% CI, 9.6-17.0). Among a total of 214 different F8 missense mutations 19 were associated with inhibitor development. These results emphasize the importance of F8 genotyping in nonsevere hemophilia A. ( Blood . 2013; 122(11):1954-1962) © 2013 by The American Society of Hematology.

Published
2013
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4. Prediction of DDAVP response in 850 non-severe hemophilia A patients

Author

Loomans, J.I., Velzen, A.S. van, Eckhardt, C.L., Peters, M., Astermark, J., Brons, P.P., Carcao, M.D., Castaman, G., Cnossen, M.H., Dors, N., Escuriola-Ettingshausen, C., Hamulyak, K., Hart, D.P., Haya, S., Heerde, W.L. van, Hermans, C., Holmstrom, M., Jackson, S.C., Jimenez-Yuste, V., Keenan, R.D., Klamroth, R., Konigs, C., Kruip, M.J.H.A., Laros-Van Gorkom, B.A.P., Leebeek, F.W.G., Makipernaa, A., Male, C., Mauser-Bunschoten, E., Mazzucconi, M.G., Mcrae, S., Meijer, K., Mitchell, M., Morfini, M., Nance, D., Nijziel, M., Oldenburg, J., Peerlinck, K., Petrini, P., Platokouki, H., Rangarajan, S., Reitter-Pfoertner, S.E., Santagostino, E., Schinco, P., Tagliaferri, A., Yee, T.T., Kamphuisen, P.W., Bom, J.G. van der, Fijnvandraat, K., and Rise Study Grp

Published
2014

5. Von Willebrand Factor antigen and age explain variation in baseline FVIII:C among nonsevere hemophilia A patients with the same F8 genotype (Arg593Cys and Asn618Ser)

Author

Loomans, J.I., Velzen, A.S. van, Eckhardt, C.L., Peters, M., Astermark, J., Brons, P.P., Castaman, G., Cnossen, M.H., Dors, N., Escuriola-Ettingshausen, C., Hamulyak, K., Hart, D.P., Hay, C.R.M., Haya, S., Heerde, W.L. van, Hermans, C., Holmstroom, M., Jimenez-Yuste, V., Keenan, R.D., Klamroth, R., Konigs, C., Kruip, M.J.H.A., Laros-Van Gorkom, B.A.P., Leebeek, F.W.G., Liesner, R., Makipernaa, A., Male, C., Mauser-Bunschoten, E., Mazzucconi, M.G., Mcrae, S., Meijer, K., Mitchell, M., Morfini, M., Nijziel, M., Oldenburg, J., Peerlinck, K., Petrini, P., Platokouki, H., Rangarajan, S., Reitter-Pfoertner, S.E., Santagostino, E., Schinco, P., Smiers, F.J., Siegmund, B., Tagliaferri, A., Yee, T.T., Kamphuisen, P.W., Bom, J.G. van der, Fijnvandraat, K., and Insight Rise Study Grp

Published
2014

6. Clinical presentation of inhibitor development in non-severe hemophilia A: half of patients have high titer inhibitors and present with bleeding complications

Author

Eckhardt, C.L., Loomans, J.I., Velzen, A.S. van, Peters, M., Astermark, J., Brons, P.P., Castaman, G., Cnossen, M.H., Dors, N., Escuriola-Ettingshausen, C., Hamulyak, K., Hart, D.P., Hay, C.R.M., Haya, S., Heerde, W.L. van, Hermans, C., Holmstrom, M., Jimenez-Yuste, V., Keenan, R.D., Klamroth, R., Laros-Gorkom, B.A.P. van, Leebeek, F.W.G., Liesner, R., Makipernaa, A., Male, C., Mauser-Bunschoten, E., Mazzucconi, M.G., Mcrae, S., Meijer, K., Mitchell, M., Morfini, M., Nijziel, M., Oldenburg, J., Peerlinck, K., Petrini, P., Platokouki, H., Rangarajan, S., Reitter-Pfoertner, S.E., Santagostino, E., Schinco, P., Smiers, F.J., Siegmund, B., Tagliaferri, A., Yee, T.T., Kamphuisen, P.W., Bom, J.G. van der, Fijnvandraat, K., and Insight Study Grp

Published
2014

7. Inhibitors increase the burden of disease in nonsevere haemophilia A patients - treatment strategies to obtain hemostasis

Author

Velzen, A.S. van, Eckhardt, C.L., Streefkerk, N., Peters, M., Astermark, J., Brons, P.P., Castaman, G., Cnossen, M.H., Dors, N., Escuriola-Ettingshausen, C., Hamulyak, K., Hart, D.P., Hay, C.R.M., Haya, S., Heerde, W.L. van, Hermans, C., Holmstrom, M., Jimenez-Yuste, V., Keenan, R.D., Klamroth, R., Gorkom, B.A.P.L. van, Leebeek, F.W.G., Liesner, R., Makipernaa, A., Male, C., Mauser-Bunschoten, E., Mazzucconi, M.G., McRae, S., Meijer, K., Morfini, M., Nijziel, M., Oldenburg, J., Peerlinck, K., Petrini, P., Platokouki, H., Rangarajan, S., Reitter-Pfoertner, S.E., Santagostino, E., Schinco, P., Smiers, F.J., Siegmund, B., Tagliaferri, A., Yee, T.T., Kamphuisen, P.W., Bom, J.G. van der, Fijnvandraat, K., and INSIGHT Study Grp

Published
2014

8. Inhibitor development and mortality in non-severe hemophilia A

Author

UCL - (SLuc) Service d'hématologie, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, Eckhardt, C.L., Loomans, J.I., van Velzen, A.S., Peters, M., Mauser-Bunschoten, E.P., Schwaab, R., Mazzucconi, M.G., Tagliaferri, A., Siegmund, B., Reitter-Pfoertner, S.E., van der Bom, J.G., Fijnvandraat, K., INSIGHT Study Group, Hermans, Cédric, UCL - (SLuc) Service d'hématologie, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, Eckhardt, C.L., Loomans, J.I., van Velzen, A.S., Peters, M., Mauser-Bunschoten, E.P., Schwaab, R., Mazzucconi, M.G., Tagliaferri, A., Siegmund, B., Reitter-Pfoertner, S.E., van der Bom, J.G., Fijnvandraat, K., INSIGHT Study Group, and Hermans, Cédric

Abstract

Background: The life expectancy of non-severe hemophilia A (HA) patients equals the life expectancy of the non-hemophilic population. However, data on the effect of inhibitor development on mortality and on hemophilia-related causes of death are scarce. The development of neutralizing factor VIII antibodies in non-severe HA patients may dramatically change their clinical outcome due to severe bleeding complications. Objectives: We assessed the association between the occurrence of inhibitors and mortality in patients with non-severe HA. Methods: In this retrospective cohort study, clinical data and vital status were collected for 2709 non-severe HA patients (107 with inhibitors) who were treated between 1980 and 2011 in 34 European and Australian centers. Mortality rates for patients with and without inhibitors were compared. Results: During 64200 patient-years of follow-up, 148 patients died (mortality rate, 2.30 per 1000 person-years; 95% confidence interval (CI), 1.96-2.70) at a median age of 64years (interquartile range [IQR], 49-76). In 62 patients (42%) the cause of death was hemophilia related. Sixteen inhibitor patients died at a median age of 71years (IQR, 60-81). In ten patients the inhibitor was present at time of death; seven of them died of severe bleeding complications. The all-cause mortality rate in inhibitor patients was >5 times increased compared with that for those without inhibitors (age-adjusted mortality rate ratio, 5.6). Conclusion: Inhibitor development in non-severe hemophilia is associated with increased mortality. High rates of hemophilia-related mortality in this study indicate that non-severe hemophilia is not mild at all and stress the importance of close follow-up for these patients.

Published
2015

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