150 results on '"Selleng, K."'
Search Results
2. Heparininduzierte Thrombozytopenie
- Author
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Greinacher, A. and Selleng, K.
- Published
- 2018
- Full Text
- View/download PDF
3. A novel, homozygous mutation in GFI1B causing inherited thrombocytopenia with Glanzmann-like platelet dysfunction
- Author
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Zaninetti, C, additional, Selleng, K, additional, Thiele, T, additional, Wesche, J, additional, Rath, M, additional, Felbor, U, additional, and Greinacher, A, additional
- Published
- 2023
- Full Text
- View/download PDF
4. Hämorrhagische Diathesen
- Author
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Pötzsch, B., Madlener, K., Kiefel, V., Selleng, K., Greinacher, A., Oldenburg, J., Brackmann, H.-H., Schneppenheim, R., Budde, U., Schindewolf, M., Lindhoff-Last, E., Spannagl, M., Pötzsch, Bernd, editor, and Madlener, Katharina, editor
- Published
- 2010
- Full Text
- View/download PDF
5. Tolerance of platelet concentrates treated with UVC-light only for pathogen reduction – a phase I clinical trial
- Author
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Thiele, T., Pohler, P., Kohlmann, T., Sümnig, A., Aurich, K., Selleng, K., Westphal, A., Bakchoul, T., Petersmann, A., Müller, T. H., Greinacher, A., and Seltsam, A.
- Published
- 2015
- Full Text
- View/download PDF
6. False‐positive tests for heparin‐induced thrombocytopenia in patients with antiphospholipid syndrome and systemic lupus erythematosus
- Author
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PAUZNER, R., GREINACHER, A., SELLENG, K., ALTHAUS, K., SHENKMAN, B., and SELIGSOHN, U.
- Published
- 2009
- Full Text
- View/download PDF
7. Therapierefraktäre Thrombozytopenie bei einem 28-jährigen Patienten
- Author
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Sauter, D., Ostermann, H., Selleng, K., and Spiekermann, K.
- Published
- 2011
- Full Text
- View/download PDF
8. Heparin-induced thrombocytopenia in patients requiring prolonged intensive care unit treatment after cardiopulmonary bypass
- Author
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SELLENG, S., SELLENG, K., WOLLERT, H.-G., MUELLEJANS, B., LIETZ, T., WARKENTIN, T.E., and GREINACHER, A.
- Published
- 2008
- Full Text
- View/download PDF
9. Heparin‐induced thrombocytopenia: a prospective study on the incidence, platelet‐activating capacity and clinical significance of antiplatelet factor 4/heparin antibodies of the IgG, IgM, and IgA classes
- Author
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GREINACHER, A., JUHL, D., STROBEL, U., WESSEL, A., LUBENOW, N., SELLENG, K., EICHLER, P., and WARKENTIN, T.E.
- Published
- 2007
- Full Text
- View/download PDF
10. PROTEIN A IMMUNOADSORPTION IN SEVERE ESCHERICHIA COLI O104: H4 - ASSOCIATED HEMOLYTIC UREMIC SYNDROME WITH NEUROLOGICAL COMPLICATIONS: O124 (S.3-3)
- Author
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Stracke, S., Ernst, F., Dressel, A., Friesecke, S., Abel, P., Selleng, K., Fiene, M., Weissen born, K., Schmidt, B. M.W., Schiffer, M., Felic, S. B., Lerch, M. M., Mayerle, J., Kielstein, J. T., and Greinacher, A.
- Published
- 2012
11. Coombsʼ crossmatch after negative antibody screening - a retrospective observational study comparing the tube test and the microcolumn technology
- Author
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Lange, J., Selleng, K., Heddle, N. M., Traore, A., and Greinacher, A.
- Published
- 2010
- Full Text
- View/download PDF
12. Management of emergency cardiac surgery in a patient with alloanti-Ge2
- Author
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Selleng, S., Selleng, K., Zawadzinski, C., Wollert, H.-G., Yürek, S., and Greinacher, A.
- Published
- 2009
- Full Text
- View/download PDF
13. Mistransfusion in the emergency room
- Author
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Selleng, S., Selleng, K., Friesecke, S., Haupt, B., and Greinacher, A.
- Published
- 2007
14. Increased expression of CTLA-4 (CD152) by T and B lymphocytes in Wegenerʼs granulomatosis
- Author
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Steiner, K., Moosig, F., Csernok, E., Selleng, K., Gross, W. L., Fleischer, B., and Bröker, B. M.
- Published
- 2001
15. International Forum on typing and matching strategies in patients on anti-CD38 monoclonal therapy
- Author
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De Vooght, K. M.K., Lozano, M., Bueno, J. L., Alarcón, A., Romera, I., Suzuki, K., Zhiburt, E., Holbro, A., Infanti, L., Buser, A., Hustinx, H., Deneys, V., Frélik, A., Thiry, C., Murphy, M., Staves, J., Selleng, K., Greinacher, A., Kutner, J. M., Bonet Bub, C., Castilho, L., Kaufman, R. M., Colling, M. E., Perseghin, P., Incontri, A., Dassi, M., Brilhante, D., Macédo, A., Cserti-Gazdewich, C., Pendergrast, J. M., Hawes, J., Lundgren, M. N., Storry, J. R., Jain, A., Marwaha, N., Sharma, R. R., De Vooght, K. M.K., Lozano, M., Bueno, J. L., Alarcón, A., Romera, I., Suzuki, K., Zhiburt, E., Holbro, A., Infanti, L., Buser, A., Hustinx, H., Deneys, V., Frélik, A., Thiry, C., Murphy, M., Staves, J., Selleng, K., Greinacher, A., Kutner, J. M., Bonet Bub, C., Castilho, L., Kaufman, R. M., Colling, M. E., Perseghin, P., Incontri, A., Dassi, M., Brilhante, D., Macédo, A., Cserti-Gazdewich, C., Pendergrast, J. M., Hawes, J., Lundgren, M. N., Storry, J. R., Jain, A., Marwaha, N., and Sharma, R. R.
- Published
- 2018
16. International Forum on typing and matching strategies in patients on anti-CD38 monoclonal therapy.
- Author
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UCL - (MGD) Centre de transfusion sanguine, UCL - SSS/IREC/MONT - Pôle Mont Godinne, De Vooght, K M K, Lozano, M, Bueno, J-L, Alarcón, A, Romera, I, Suzuki, K, Zhiburt, E, Holbro, A, Infanti, L, Buser, A, Hustinx, H, Deneys, Véronique, Frélik, A, Thiry, C, Murphy, M, Staves, J, Selleng, K, Greinacher, A, Kutner, J M, Bonet Bub, C, Castilho, L, Kaufman, R M, Colling, M E, Perseghin, P, Incontri, A, Dassi, M, Brilhante, D, Macédo, A, Cserti-Gazdewich, C, Pendergrast, J M, Hawes, J, Lundgren, M N, Storry, J R, Jain, A, Marwaha, N, Sharma, R R, UCL - (MGD) Centre de transfusion sanguine, UCL - SSS/IREC/MONT - Pôle Mont Godinne, De Vooght, K M K, Lozano, M, Bueno, J-L, Alarcón, A, Romera, I, Suzuki, K, Zhiburt, E, Holbro, A, Infanti, L, Buser, A, Hustinx, H, Deneys, Véronique, Frélik, A, Thiry, C, Murphy, M, Staves, J, Selleng, K, Greinacher, A, Kutner, J M, Bonet Bub, C, Castilho, L, Kaufman, R M, Colling, M E, Perseghin, P, Incontri, A, Dassi, M, Brilhante, D, Macédo, A, Cserti-Gazdewich, C, Pendergrast, J M, Hawes, J, Lundgren, M N, Storry, J R, Jain, A, Marwaha, N, and Sharma, R R
- Published
- 2018
17. International Forum on typing and matching strategies in patients on anti-CD38 monoclonal therapy
- Author
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CDL Staf Patiëntenzorg KC, Other research (not in main researchprogram), De Vooght, K. M.K., Lozano, M., Bueno, J. L., Alarcón, A., Romera, I., Suzuki, K., Zhiburt, E., Holbro, A., Infanti, L., Buser, A., Hustinx, H., Deneys, V., Frélik, A., Thiry, C., Murphy, M., Staves, J., Selleng, K., Greinacher, A., Kutner, J. M., Bonet Bub, C., Castilho, L., Kaufman, R. M., Colling, M. E., Perseghin, P., Incontri, A., Dassi, M., Brilhante, D., Macédo, A., Cserti-Gazdewich, C., Pendergrast, J. M., Hawes, J., Lundgren, M. N., Storry, J. R., Jain, A., Marwaha, N., Sharma, R. R., CDL Staf Patiëntenzorg KC, Other research (not in main researchprogram), De Vooght, K. M.K., Lozano, M., Bueno, J. L., Alarcón, A., Romera, I., Suzuki, K., Zhiburt, E., Holbro, A., Infanti, L., Buser, A., Hustinx, H., Deneys, V., Frélik, A., Thiry, C., Murphy, M., Staves, J., Selleng, K., Greinacher, A., Kutner, J. M., Bonet Bub, C., Castilho, L., Kaufman, R. M., Colling, M. E., Perseghin, P., Incontri, A., Dassi, M., Brilhante, D., Macédo, A., Cserti-Gazdewich, C., Pendergrast, J. M., Hawes, J., Lundgren, M. N., Storry, J. R., Jain, A., Marwaha, N., and Sharma, R. R.
- Published
- 2018
18. An international investigation into O red blood cell unit administration in hospitals
- Author
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Zeller, M.P., Barty, R., Aandahl, A., Apelseth, T.O., Callum, J., Dunbar, N.M., Elahie, A., Garritsen, H., Hancock, H., Kutner, J.M., Manukian, B., Mizuta, S., Okuda, M., Pagano, M.B., Poglód, R., Rushford, K., Selleng, K., Sørensen, C.H., Sprogøe, U., Staves, J., Weiland, T., Wendel, S., Wood, E.M., Watering, L. van de, Wordragen‐Vlaswinkel, M. van, Ziman, A., Zwaginga, J.J., Murphy, M.F., Heddle, N.M., Yazerm, M.H., and Publica
- Abstract
Background: Transfusion of group O blood to non‐O recipients, or transfusion of D- blood to D+ recipients, can result in shortages of group O or D- blood, respectively. This study investigated RBC utilization patterns at hospitals around the world and explored the context and policies that guide ABO blood group and D type selection practices. Study design and methods: This was a retrospective study on transfusion data from the 2013 calendar year. This study included a survey component that asked about hospital RBC selection and transfusion practices and a data collection component where participants submitted information on RBC unit disposition including blood group and D type of unit and recipient. Units administered to recipients of unknown ABO or D group were excluded. Results: Thirty‐eight hospitals in 11 countries responded to the survey, 30 of which provided specific RBC unit disposition data. Overall, 11.1% (21,235/191,397) of group O units were transfused to non‐O recipients; 22.6% (8777/38,911) of group O D- RBC units were transfused to O D+ recipients, and 43.2% (16,800/38,911) of group O D- RBC units were transfused to recipients that were not group O D-. Disposition of units and hospital transfusion policy varied within and across hospitals of different sizes, with transfusion of group O D- units to non‐group O D- patients ranging from 0% to 33%. Conclusion: A significant proportion of group O and D- RBC units were transfused to compatible, nonidentical recipients, although the frequency of this practice varied across sites.
- Published
- 2017
19. International Forum on typing and matching strategies in patients on anti-CD38 monoclonal therapy
- Author
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De Vooght, K. M. K., primary, Lozano, M., additional, Bueno, J-L., additional, Alarcón, A., additional, Romera, I., additional, Suzuki, K., additional, Zhiburt, E., additional, Holbro, A., additional, Infanti, L., additional, Buser, A., additional, Hustinx, H., additional, Deneys, V., additional, Frélik, A., additional, Thiry, C., additional, Murphy, M., additional, Staves, J., additional, Selleng, K., additional, Greinacher, A., additional, Kutner, J. M., additional, Bonet Bub, C., additional, Castilho, L., additional, Kaufman, R. M., additional, Colling, M. E., additional, Perseghin, P., additional, Incontri, A., additional, Dassi, M., additional, Brilhante, D., additional, Macédo, A., additional, Cserti-Gazdewich, C., additional, Pendergrast, J. M., additional, Hawes, J., additional, Lundgren, M. N., additional, Storry, J. R., additional, Jain, A., additional, Marwaha, N., additional, and Sharma, R. R., additional
- Published
- 2018
- Full Text
- View/download PDF
20. Vox Sanguinis International Forum on typing and matching strategies in patients on anti-CD38 monoclonal therapy: summary
- Author
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de Vooght, K. M. K., primary, Lozano, M., additional, Bueno, J-L., additional, Alarcón, A., additional, Romera, I., additional, Suzuki, K., additional, Zhiburt, E., additional, Holbro, A., additional, Infanti, L., additional, Buser, A., additional, Hustinx, H., additional, Deneys, V., additional, Frélik, A., additional, Thiry, C., additional, Murphy, M., additional, Staves, J., additional, Selleng, K., additional, Greinacher, A., additional, Kutner, J.M., additional, Bonet Bub, C., additional, Castilho, L., additional, Kaufman, R., additional, Colling, M.E., additional, Perseghin, P., additional, Incontri, A., additional, Dassi, M., additional, Brilhante, D., additional, Macêdo, A., additional, Cserti-Gazdewich, C., additional, Pendergrast, J.M., additional, Hawes, J., additional, Lundgren, M.N., additional, Storry, J.R., additional, Jain, A., additional, Marwaha, N., additional, and Sharma, R.R., additional
- Published
- 2018
- Full Text
- View/download PDF
21. Group O utilization patterns: The GROUP study.
- Author
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Ziman A., Weiland T., Wendel S., Heddle N.M., Yazer M.H., Zeller M., Aandahl A., Apelseth T., Callum J., Dunbar N.M., Garritsen H., Hancock H., Kutner J., Manukian B., Mizuta S., Okuda M., Pagano M.B., Poglod R., Rushford K., Selleng K., Sorensen C., Sprogoe U., Staves J., Van Wordragen M., Ziman A., Weiland T., Wendel S., Heddle N.M., Yazer M.H., Zeller M., Aandahl A., Apelseth T., Callum J., Dunbar N.M., Garritsen H., Hancock H., Kutner J., Manukian B., Mizuta S., Okuda M., Pagano M.B., Poglod R., Rushford K., Selleng K., Sorensen C., Sprogoe U., Staves J., and Van Wordragen M.
- Abstract
Background/Case Studies: Group O red blood cells (RBCs) are the universal donor red cells; they can be given to a recipient with any other blood group. Although it is usually the standard practice to select ABO group specific blood as the first choice for patients requiring transfusion, there are many situations where group O blood is given to non-O recipients. Transfu-sion of group O blood to non-O recipients, or the transfusion of Rh negative (D-) blood to Rh positive (D1) recipients, can result in shortages of O or D-blood, respectively. Current patterns of group O and D- blood utilization are not well understood. Study Design/Methods: Hospital transfusion services collected ABO and Rh groups of transfused RBC units and of recipients during the 2013 calendar year. Units administered to recipients of unknown ABO or Rh group were excluded. Two analyses were performed: How often group O RBCs were transfused to non-O recipients, and how often D- units (of any ABO group) were transfused to D1 recipients. The hospitals were divided into 3 categories: Small (<250 beds), medium (250-1000 beds), and large (>1000 beds). Results/Findings: Data was received from 30 centers in 9 countries. There were 7 small, 17 medium and 6 large hospital respondents. In total, these 30 centers transfused a total of 415,696 RBC units, of which 2257 (0.5%) were units excluded from the D mismatch analysis because the D type of the recipient was unknown. The ABO groups of all recipients were known. Overall 11.1% of the O units were transfused to non-O recipients. The percentage of O RBCs transfused to non-O recipients was similar among the small, medium and large sized hospital respondents (12.4, 12.8 and 8.5%, respectively). The rate of group O RBC transfusion to non-O recipients at the small hospitals ranged from 0-33.0%, at the medium hospitals from 0-22.0%, and at the large hospitals from 5.0-10.0%. In terms of D- RBC transfusion to D1 recipients, overall 29.8% of the D- units were transfus
- Published
- 2017
22. An international investigation into O red blood cell unit administration in hospitals: the GRoup O Utilization Patterns (GROUP) study.
- Author
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Heddle N.M., van Wordragen-Vlaswinkel M., Ziman A., Jan Zwaginga J., Murphy M.F., Yazer M.H., Zeller M.P., Barty R., Aandahl A., Apelseth T.O., Callum J., Dunbar N.M., Elahie A., Garritsen H., Hancock H., Kutner J.M., Manukian B., Mizuta S., Okuda M., Pagano M.B., Poglod R., Rushford K., Selleng K., Sorensen C.H., Sprogoe U., Staves J., Weiland T., Wendel S., Wood E.M., van de Watering L., Heddle N.M., van Wordragen-Vlaswinkel M., Ziman A., Jan Zwaginga J., Murphy M.F., Yazer M.H., Zeller M.P., Barty R., Aandahl A., Apelseth T.O., Callum J., Dunbar N.M., Elahie A., Garritsen H., Hancock H., Kutner J.M., Manukian B., Mizuta S., Okuda M., Pagano M.B., Poglod R., Rushford K., Selleng K., Sorensen C.H., Sprogoe U., Staves J., Weiland T., Wendel S., Wood E.M., and van de Watering L.
- Abstract
BACKGROUND: Transfusion of group O blood to non-O recipients, or transfusion of D- blood to D+ recipients, can result in shortages of group O or D- blood, respectively. This study investigated RBC utilization patterns at hospitals around the world and explored the context and policies that guide ABO blood group and D type selection practices. STUDY DESIGN AND METHODS: This was a retrospective study on transfusion data from the 2013 calendar year. This study included a survey component that asked about hospital RBC selection and transfusion practices and a data collection component where participants submitted information on RBC unit disposition including blood group and D type of unit and recipient. Units administered to recipients of unknown ABO or D group were excluded. RESULT(S): Thirty-eight hospitals in 11 countries responded to the survey, 30 of which provided specific RBC unit disposition data. Overall, 11.1% (21,235/191,397) of group O units were transfused to non-O recipients; 22.6% (8777/38,911) of group O D- RBC units were transfused to O D+ recipients, and 43.2% (16,800/38,911) of group O D- RBC units were transfused to recipients that were not group O D-. Disposition of units and hospital transfusion policy varied within and across hospitals of different sizes, with transfusion of group O D- units to non-group O D- patients ranging from 0% to 33%. CONCLUSION(S): A significant proportion of group O and D- RBC units were transfused to compatible, nonidentical recipients, although the frequency of this practice varied across sites.Copyright © 2017 AABB
- Published
- 2017
23. Development of RBC transfusion indications and the collection of patient-specific pre-transfusion information.
- Author
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Lin Y., Okazaki H., Ikeda T., Nagura Y., Zwaginga J.J., Poglod R., Rosiek A., Letowska M., Yuen J., Cid J., Harm S.K., Adhikari P., Yazer M.H., van de Watering L., Lozano M., Sirdesai S., Rushford K., Wood E.M., Yokoyama A.P., Kutner J.M., Callum J., Cserti-Gazdewich C., Lieberman L., Pendergrast J., Pendry K., Murphy M.F., Selleng K., Greinacher A., Marwaha N., Sharma R., Jain A., Orlin Y., Yahalom V., Perseghin P., Incontri A., Masera N., Lin Y., Okazaki H., Ikeda T., Nagura Y., Zwaginga J.J., Poglod R., Rosiek A., Letowska M., Yuen J., Cid J., Harm S.K., Adhikari P., Yazer M.H., van de Watering L., Lozano M., Sirdesai S., Rushford K., Wood E.M., Yokoyama A.P., Kutner J.M., Callum J., Cserti-Gazdewich C., Lieberman L., Pendergrast J., Pendry K., Murphy M.F., Selleng K., Greinacher A., Marwaha N., Sharma R., Jain A., Orlin Y., Yahalom V., Perseghin P., Incontri A., and Masera N.
- Published
- 2017
24. Development of RBC transfusion indications and the collection of patient-specific pre-transfusion information
- Author
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Yazer, M. H., primary, van de Watering, L., additional, Lozano, M., additional, Sirdesai, S., additional, Rushford, K., additional, Wood, E. M., additional, Yokoyama, A. P., additional, Kutner, J. M., additional, Lin, Y., additional, Callum, J., additional, Cserti-Gazdewich, C., additional, Lieberman, L., additional, Pendergrast, J., additional, Pendry, K., additional, Murphy, M. F., additional, Selleng, K., additional, Greinacher, A., additional, Marwaha, N., additional, Sharma, R., additional, Jain, A., additional, Orlin, Y., additional, Yahalom, V., additional, Perseghin, P., additional, Incontri, A., additional, Masera, N., additional, Okazaki, H., additional, Ikeda, T., additional, Nagura, Y., additional, Zwaginga, J. J., additional, Pogłod, R., additional, Rosiek, A., additional, Letowska, M., additional, Yuen, J., additional, Cid, J., additional, Harm, S. K., additional, and Adhikari, P., additional
- Published
- 2017
- Full Text
- View/download PDF
25. Rezidivierende Thrombembolien trotz Vollantikoagulation bei Patientin mit Antiphospholipidsyndrom
- Author
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Wernicke, S., primary, Selleng, K., additional, Felix, S. B., additional, Greinacher, A., additional, and Hammer, F., additional
- Published
- 2017
- Full Text
- View/download PDF
26. T-24-08: A novel, homozygous mutation in GFI1B causing inherited thrombocytopenia with Glanzmann-like platelet dysfunction.
- Author
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Zaninetti, C., Selleng, K., Thiele, T., Wesche, J., Rath, M., Felbor, U., and Greinacher, A.
- Published
- 2023
- Full Text
- View/download PDF
27. Prolongierte low-dose systemische Thrombolyse bei ausgedehnter Sinus-/Hirnvenenthrombose
- Author
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Khaw, AV, Gaida-Hommernick, B, Sehm, B, Kirsch, M, and Selleng, K
- Published
- 2024
- Full Text
- View/download PDF
28. Cellano-Antikörper als seltene Ursache eines Morbus haemolyticus neonatorum
- Author
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Orlowski, N, Dombrowski, F, Selleng, K, Heckmann, M, and Hirsch, T
- Subjects
ddc: 610 ,610 Medical sciences ,Medicine - Abstract
Einleitung: Der Morbus haemolyticus neonatorum bezeichnet die fetale Schädigung durch maternale IgG-Antikörper gegen fetale Erythrozyten-Antigene. Seit der Einführung der anti-D- Immunglobulin-Injektion wird die Rh-Inkompatibilität insgesamt seltener beobachtet und neben dem ABO-System[for full text, please go to the a.m. URL], Süddeutscher Kongress für Kinder- und Jugendmedizin; 63. Jahrestagung der Süddeutschen Gesellschaft für Kinder- und Jugendmedizin gemeinsam mit der Süddeutschen Gesellschaft für Kinderchirurgie und dem Berufsverband der Kinder- und Jugendärzte e.V. – Landesverband Baden-Württemberg
- Published
- 2014
- Full Text
- View/download PDF
29. Positiver indirekter Antihumanglobulintest durch Daratumumab – Strategien für die transfusionsmedizinische Versorgung
- Author
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Selleng, K., additional
- Published
- 2016
- Full Text
- View/download PDF
30. Behandlung einer Patientin mit dekompensierter autoimmunhämolytischer Anämie nach Stammzelltransplantation
- Author
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Czekay, S., additional, Kietz, S., additional, Dickau, K., additional, Sümnig, A., additional, Selleng, K., additional, Salama, A., additional, Kiefel, V., additional, Greinacher, A., additional, Lode, H., additional, and Bakchoul, T., additional
- Published
- 2015
- Full Text
- View/download PDF
31. Heparin-induced thrombocytopenia : a prospective study on the incidence, platelet-activating capacity and clinical significance of antiplatelet factor 4/heparin antibodies of the IgG, IgM, and IgA classes.
- Author
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Greinacher, A, Juhl, D, Strobel, U, Wessel, A, Lubenow, Norbert, Selleng, K, Eichler, P, Warkentin, T E, Greinacher, A, Juhl, D, Strobel, U, Wessel, A, Lubenow, Norbert, Selleng, K, Eichler, P, and Warkentin, T E
- Abstract
INTRODUCTION: Platelet-activating antiplatelet factor 4/heparin (anti-PF4/heparin) antibodies are the major cause of heparin-induced thrombocytopenia (HIT). However, the relative utility of functional (platelet activation) vs. antigen [enzyme-immunoassay (EIA)] assays, and the significance of assay discrepancies remain unresolved. METHODS: Consecutive patient sera (n = 1650) referred for diagnostic HIT testing were screened prospectively by both the heparin-induced platelet activation (HIPA) test and anti-PF4/heparin EIA - including individual classes (IgG, IgA, IgM) - with clinical correlations studied. Platelet microparticle and annexin-V-binding properties of the sera were also investigated. RESULTS: Only 205 (12.4%) sera tested positive in either the HIPA and/or EIA: 95 (46.3%) were positive in both, 109 (53.1%) were only EIA-positive, and, notably, only one serum was HIPA-positive/EIA-negative. Of 185 EIA-positive sera, only 17.6% had detectable IgM and/or IgA without detectable IgG. Among sera positive for EIA IgG, optical density values were higher when the sera were HIPA-positive (1.117 vs. 0.768; P < 0.0001), with widely overlapping values. Two HIPA-positive but EIA-IgG-negative sera became HIPA-negative following IgG depletion, suggesting platelet-activating antibodies against non-PF4-dependent antigens. Clinical correlations showed that HIPA-negative/EIA-positive patients did not develop thrombosis and had reasons other than HIT to explain thrombocytopenia. IgM/A antibodies did not increase microparticle penetration, but increased annexin-V binding. CONCLUSIONS: The anti-PF4/heparin EIA has high ( approximately 99%) sensitivity for HIT. However, only about half of EIA-positive patients are likely to have HIT. Anti-PF4/heparin antibodies of IgM/A class and non-PF4-dependent antigens have only a minor role in HIT.
- Published
- 2007
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- View/download PDF
32. Hemorrhage in Long-term Ventilated Critically ill Patients Treated with Citalopram: Report of Four Cases
- Author
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Boesche, M, primary, Kähler, C, additional, Friesecke, S, additional, Selleng, K, additional, and Ewert, R, additional
- Published
- 2011
- Full Text
- View/download PDF
33. Therapierefraktäre Thrombozytopenie bei einem 28-jährigen Patienten
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Sauter, D., primary, Ostermann, H., additional, Selleng, K., additional, and Spiekermann, K., additional
- Published
- 2010
- Full Text
- View/download PDF
34. Glucosamine sulfate does not crossreact with the antibodies of patients with heparin-induced thrombocytopenia.
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Weimann, G, Lubenow, Norbert, Selleng, K, Eichler, P, Albrecht, D, Greinacher, A, Weimann, G, Lubenow, Norbert, Selleng, K, Eichler, P, Albrecht, D, and Greinacher, A
- Abstract
OBJECTIVE: To assess the crossreactivity of glucosamine sulfate, used for treatment of degenerative joint disease with antibodies induced in heparin-induced thrombocytopenia (HIT). BACKGROUND: HIT is a severe adverse effect of heparin therapy induced by an immunological mechanism. The antibodies in HIT are induced by a complex of heparin and, in most cases, platelet factor 4. Hereby generation of the antigen is not strictly dependent on heparin. Heparin can be substituted by a variety of polysulfated carbohydrates. In vitro and in vivo crossreactivity of HIT antibodies has been demonstrated for a chemically polysulfated chondroitin-like substance (Arteparon, Luitpoldwerke, Munich, Germany), formerly used for chondroprotection. Another drug widely used in the treatment of degenerative joint disease is glucosamine sulfate. Glucosamine is a building block of glycosaminoglycans, of which heparin is the clinically most important. Many patients with degenerative joint disease use glucosamine sulfate. This group is also at the highest risk to develop HIT following joint replacement surgery. METHODS: We examined the interactions of glucosamine sulfate (DONA 200-S, Opfermann, Wiehl, Germany) with platelets and antibodies of patients with HIT in and without the presence of heparin. Sera of 5 HIT patients and platelets of 4 healthy donors were used. The binding of HIT antibodies to PF4/glucosamine sulfate complexes was assessed by an ELISA. RESULTS: HIT antibodies did not activate platelets in the presence of glucosamine sulfate in a serotonin-release assay. Preincubation with glucosamine sulfate did not inhibit platelet activation by HIT antibodies in the presence of heparin (0.2 IU/ml). Antibodies bonded to PF4/heparin but not to PF4/glucosamine sulfate complexes. CONCLUSIONS: In contrast to sulfated glycosaminoglycans, there is no evidence for an immunological crossreactivity of HIT antibodies between heparin and glucosamine sulfate.
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- 2001
35. 4A.2 HIT update: new tests, old tests, useful tests?
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Greinacher, A., primary and Selleng, K., additional
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- 2007
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36. Prolongierte low-dose systemische Thrombolyse bei ausgedehnter Sinus-/Hirnvenenthrombose
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Khaw, AV, primary, Gaida-Hommernick, B, additional, Sehm, B, additional, Kirsch, M, additional, and Selleng, K, additional
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- 2007
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37. Heparin-induced thrombocytopenia in intensive care patients.
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Selleng K, Warkentin TE, Greinacher A, Selleng, Kathleen, Warkentin, Theodore E, and Greinacher, Andreas
- Abstract
Objective: To summarize new information on frequency of heparin-induced thrombocytopenia (HIT) in patients treated in intensive care units (ICU), developments in the interpretation of assays for detecting anti-PF4/heparin antibodies, and treatment of HIT patients.Study Selection: All data on the frequency of laboratory-confirmed HIT in ICU patients were included; for laboratory testing of HIT and treatment of patients, this review focuses on recent data that became available in 2005 and 2006.Data Extraction and Synthesis: HIT is a potentially life-threatening adverse effect of heparin treatment caused by platelet-activating antibodies of immunoglobulin G class usually recognizing complexes of platelet factor 4 and heparin. HIT is more often caused by unfractionated heparin than low-molecular-weight heparin and is more common in postsurgical than in medical patients. In the ICU setting, HIT is uncommon (0.3-0.5%), whereas thrombocytopenia from other causes is very common (30-50%). For laboratory diagnosis of HIT antibodies, both antigen assays and functional (platelet activation) assays are available. Both tests are very sensitive (high negative predictive value) but specificity is problematic, especially for the antigen assays, which also detect nonpathogenic immunoglobulin M and immunoglobulin A class antibodies. Detection of immunoglobulin M or immunoglobulin A antibodies could potentially lead to adverse events such as bleeding if a false diagnosis of HIT prompts replacement of heparin by an alternative anticoagulant. For treatment of HIT, three alternative anticoagulants are approved: the direct thrombin inhibitors, lepirudin and argatroban, and the heparinoid, danaparoid (not approved in the United States). Recent data indicate that the approved dosing regimens of the direct thrombin inhibitors are too high, especially in ICU patients.Conclusions: HIT affects <1% of ICU patients even though 30-50% develop thrombocytopenia. The choice of the optimal alternative anticoagulant depends on patient characteristics. Many ICU patients require lower doses of alternative anticoagulant than those recommended by the manufacturer. [ABSTRACT FROM AUTHOR]- Published
- 2007
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38. Treatment of severe neurological deficits with IgG depletion through immunoadsorption in patients with Escherichia coli O104:H4-associated haemolytic uraemic syndrome: a prospective trial.
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Greinacher A, Friesecke S, Abel P, Dressel A, Stracke S, Fiene M, Ernst F, Selleng K, Weissenborn K, Schmidt BM, Schiffer M, Felix SB, Lerch MM, Kielstein JT, and Mayerle J
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- 2011
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39. Improving quality of blood transfusion practices in Nigeria.
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Gwarzo D, Selleng K, Ismail H, Sulaiman K, Reichelt S, Asare R, Greinacher A, and Kuliya-Gwarzo A
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- Humans, Nigeria, Blood Transfusion, Blood Banks
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- 2024
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40. Laboratory and demographic predictors of functional assay positive status in suspected heparin-induced thrombocytopenia: A multicenter retrospective cohort study.
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Giles JB, Rollin J, Martinez KL, Selleng K, Thiele T, Pouplard C, Sheppard JI, Heddle NM, Phillips EJ, Roden DM, Gruel Y, Warkentin TE, Greinacher A, and Karnes JH
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- Humans, Female, Retrospective Studies, Heparin adverse effects, Anticoagulants adverse effects, Immunoglobulin A, Platelet Factor 4, Immunoglobulin G, Demography, Thrombocytopenia chemically induced, Thrombocytopenia diagnosis
- Abstract
Heparin-induced thrombocytopenia (HIT) is an antibody-mediated immune response against platelet factor 4 (PF4) bound to heparin anticoagulants. A priori identification of patients at-risk for HIT remains elusive and a number of risk factors have been identified, but these associations and their effect sizes have limited validation in large cohorts of suspected HIT patients. The aim of this study was to investigate existing anti-PF4/heparin antibody thresholds and model the relationship of demographic variables and anti-PF4/heparin antibody levels with functional assay positivity across multiple institutions in the absence of detailed clinical data. In a large collection of suspected HIT patients (n = 8904), we tested for associations between laboratory and demographic variables and functional assay positive status as well as anti-PF4/heparin antibody levels. We also tested for correlation between IgG-specific and polyspecific (IgG/IgA/IgM) anti-PF4/heparin antibody values and their ability to predict functional assay positive status using area under the receiver operating characteristic (AUROC). Logistic regression identified increasing anti-PF4/heparin antibody OD levels (OR = 51.84 [37.27-74.34], p < 2.0 × 10
-16 ) and female sex (OR = 1.47 [1.19-1.82], p = 3.5 × 10-4 ) as risk factors for positive functional assay in the largest cohort with consistent effect sizes in two other cohorts. In a subset of 1175 patients, polyspecific and IgG-specific anti-PF4/heparin antibody values were heterogeneous (mean coefficient of variation = 31.9 %), but strongly correlated (rho = 0.878; p < 2 × 10-16 ) with similar prediction of functional assay positivity (polyspecific AUROC = 0.976 and IgG-specific AUROC = 0.980). Thus, we recapitulate previously identified risk factors of functional assay positivity, providing precise effect sizes in a large observational population of suspected HIT patients. Our data reinforce the necessity of functional assay confirmation and suggest that, despite heterogeneity, polyspecific and IgG-specific anti-PF4/heparin antibody assays predict functional assay positive status similarly, even in the absence of 4Ts scores and detailed clinical data., Competing Interests: Declaration of competing interest Theodore (Ted) E. Warkentin, MD, has received lecture honoraria from Instrumentation Laboratory, and royalties from Informa (Taylor & Francis) and UptoDate (Wolters Kluwer); has provided consulting services to Aspen Canada, Aspen Global, CSL Behring, Ergomed, Paradigm Pharmaceuticals, Octapharma, and Veralox Therapeutics; has received research funding from Instrumentation Laboratory; and has provided expert witness testimony relating to heparin-induced thrombocytopenia (HIT) and non-HIT thrombocytopenic and coagulopathic disorders. Andreas Greinacher reports grants and non-financial support from Aspen, Boehringer Ingelheim, MSD, Bristol Myers Squibb (BMS), Paringenix, Bayer Healthcare, Gore Inc., Rovi, Sagent, Biomarin/Prosensa, personal fees from Aspen, Boehringer Ingelheim, MSD, Macopharma, BMS, Chromatec, Instrumentation Laboratory, non-financial support from Boehringer Ingelheim, Portola, Ergomed, GTH e.V. outside the submitted work. Kathleen Selleng reports a research funding from Immucor, personal fees from Aspen and Viatris and non-financial support from SOBI outside the submitted work. There are no other conflicts., (Copyright © 2023 Elsevier Ltd. All rights reserved.)- Published
- 2023
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41. Long-term outcome in vaccine-induced immune thrombocytopenia and thrombosis.
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Schönborn L, Seck SE, Thiele T, Kaderali L, Hoffmann T, Hlinka A, Lindhoff-Last E, Völker U, Selleng K, Buoninfante A, Cavaleri M, and Greinacher A
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- Humans, COVID-19 Vaccines adverse effects, Longitudinal Studies, Prospective Studies, SARS-CoV-2, Purpura, Thrombocytopenic, Idiopathic chemically induced, Purpura, Thrombocytopenic, Idiopathic diagnosis, COVID-19, Thrombocytopenia chemically induced, Thrombosis etiology, Influenza Vaccines
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Background: Rapid diagnosis and treatment has improved outcome of patients with vaccine-induced immune thrombocytopenia and thrombosis (VITT). However, after the acute episode, many questions on long-term management of VITT remained unanswered., Objectives: To analyze, in patients with VITT, the long-term course of anti-platelet factor 4 (PF4) antibodies; clinical outcomes, including risk of recurrent thrombosis and/or thrombocytopenia; and the effects of new vaccinations., Methods: 71 patients with serologically confirmed VITT in Germany were enrolled into a prospective longitudinal study and followed for a mean of 79 weeks from March 2021 to January 2023. The course of anti-PF4 antibodies was analyzed by consecutive anti-PF4/heparin immunoglobulin G enzyme-linked immunosorbent assay and PF4-enhanced platelet activation assay., Results: Platelet-activating anti-PF4 antibodies became undetectable in 62 of 71 patients (87.3%; 95% CI, 77.6%-93.2%). In 6 patients (8.5%), platelet-activating anti-PF4 antibodies persisted for >18 months. Five of 71 patients (7.0%) showed recurrent episodes of thrombocytopenia and/or thrombosis; in 4 of them (80.0%), alternative explanations beside VITT were present. After further COVID-19 vaccination with a messenger RNA vaccine, no reactivation of platelet-activating anti-PF4 antibodies or new thrombosis was observed. No adverse events occurred in our patients subsequently vaccinated against influenza, tick-borne encephalitis, varicella, tetanus, diphtheria, pertussis, and polio. No new thrombosis occurred in the 24 patients (33.8%) who developed symptomatic SARS-CoV-2 infection following recovery from acute VITT., Conclusion: Once the acute episode of VITT has passed, patients appear to be at low risk for recurrent thrombosis and/or thrombocytopenia., Competing Interests: Declaration Of Competing Interests A.G. reports grants and nonfinancial support from Aspen, Boehringer Ingelheim, Merck-Sharp and Dome, Bristol-Myers Squibb (BMS), Paringenix, Bayer Healthcare, Gore Inc, Rovi, Sagent, and Biomarin/Prosensa; personal fees from Aspen, Boehringer Ingelheim, Merck-Sharp and Dome, Macopharma, BMS, Chromatec, and Instrumentation Laboratory; and nonfinancial support from Boehringer Ingelheim, Portola, Ergomed, and GTH e.V., outside the submitted work. T.T. reports personal fees and other from BMS, personal fees and other from Pfizer, personal fees from Bayer, personal fees and other from Chugai Pharma, other from Novo Nordisk, personal fees from Novartis, other from Daichii Sankyo, and other from Laboratoire français du Fractionnement et des Biotechnologies, outside the submitted work. E.L.-L. has received lecture honoraria and advisory fees from Bayer AG, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, Portola, CSL Behring, Viatris, Werfen, Norgine, and Aspen and institutional research support from Bayer AG, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, and CSL Behring for a different research project. L.S. receives a young investigator grant of the medical faculty of the Universitätsmedizin Greifswald. There are no other competing interests to disclose., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)
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- 2023
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42. Genome-wide association study of platelet factor 4/heparin antibodies in heparin-induced thrombocytopenia.
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Giles JB, Steiner HE, Rollin J, Shaffer CM, Momozawa Y, Mushiroda T, Inai C, Selleng K, Thiele T, Pouplard C, Heddle NM, Kubo M, Miller EC, Martinez KL, Phillips EJ, Warkentin TE, Gruel Y, Greinacher A, Roden DM, and Karnes JH
- Subjects
- Antibodies, Genome-Wide Association Study, Heparin adverse effects, Humans, Immunologic Factors adverse effects, Platelet Factor 4 genetics, Thrombocytopenia chemically induced, Thrombocytopenia genetics
- Abstract
Heparin, a widely used anticoagulant, carries the risk of an antibody-mediated adverse drug reaction, heparin-induced thrombocytopenia (HIT). A subset of heparin-treated patients produces detectable levels of antibodies against complexes of heparin bound to circulating platelet factor 4 (PF4). Using a genome-wide association study (GWAS) approach, we aimed to identify genetic variants associated with anti-PF4/heparin antibodies that account for the variable antibody response seen in HIT. We performed a GWAS on anti-PF4/heparin antibody levels determined via polyclonal enzyme-linked immunosorbent assays. Our discovery cohort (n = 4237) and replication cohort (n = 807) constituted patients with European ancestry and clinical suspicion of HIT, with cases confirmed via functional assay. Genome-wide significance was considered at α = 5 × 10-8. No variants were significantly associated with anti-PF4/heparin antibody levels in the discovery cohort at a genome-wide significant level. Secondary GWAS analyses included the identification of variants with suggestive associations in the discovery cohort (α = 1 × 10-4). The top variant in both cohorts was rs1555175145 (discovery β = -0.112 [0.018], P = 2.50 × 10-5; replication β = -0.104 [0.051], P = .041). In gene set enrichment analysis, 3 gene sets reached false discovery rate-adjusted significance (q < 0.05) in both discovery and replication cohorts: "Leukocyte Transendothelial Migration," "Innate Immune Response," and "Lyase Activity." Our results indicate that genomic variation is not significantly associated with anti-PF4/heparin antibody levels. Given our power to identify variants with moderate frequencies and effect sizes, this evidence suggests genetic variation is not a primary driver of variable antibody response in heparin-treated patients with European ancestry., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2022
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43. ABO O blood group as a risk factor for platelet reactivity in heparin-induced thrombocytopenia.
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Karnes JH, Rollin J, Giles JB, Martinez KL, Steiner HE, Shaffer CM, Momozawa Y, Inai C, Bombin A, Shi M, Mosley JD, Stanaway I, Selleng K, Thiele T, Mushiroda T, Pouplard C, Heddle NM, Kubo M, Phillips EJ, Warkentin TE, Gruel Y, Greinacher A, and Roden DM
- Subjects
- ABO Blood-Group System genetics, Anticoagulants adverse effects, Female, Heparin adverse effects, Humans, Immunoglobulin G, Male, Platelet Factor 4 genetics, Risk Factors, Genome-Wide Association Study, Thrombocytopenia chemically induced, Thrombocytopenia genetics
- Abstract
Heparin-induced thrombocytopenia (HIT) is an unpredictable, potentially catastrophic adverse effect resulting from an immune response to platelet factor 4 (PF4)/heparin complexes. We performed a genome-wide association study (GWAS) with positive functional assay as the outcome in a large discovery cohort of patients divided into 3 groups: (1) functional assay-positive cases (n = 1269), (2) antibody-positive (functional assay-negative) controls (n = 1131), and (3) antibody-negative controls (n = 1766). Significant associations (α = 5 × 10-8) were investigated in a replication cohort (α = 0.05) of functional assay-confirmed HIT cases (n = 177), antibody-positive (function assay-negative) controls (n = 258), and antibody-negative controls (n = 351). We observed a strong association for positive functional assay with increasing PF4/heparin immunoglobulin-G (IgG) level (odds ratio [OR], 16.53; 95% confidence interval [CI], 13.83-19.74; P = 1.51 × 10-209) and female sex (OR, 1.15; 95% CI, 1.01-1.32; P = .034). The rs8176719 C insertion variant in ABO was significantly associated with positive functional assay status in the discovery cohort (frequency = 0.41; OR, 0.751; 95% CI, 0.682-0.828; P = 7.80 × 10-9) and in the replication cohort (OR, 0.467; 95% CI, 0.228-0.954; P = .0367). The rs8176719 C insertion, which encodes all non-O blood group alleles, had a protective effect, indicating that the rs8176719 C deletion and the O blood group were risk factors for HIT (O blood group OR, 1.42; 95% CI, 1.26-1.61; P = 3.09 × 10-8). Meta-analyses indicated that the ABO association was independent of PF4/heparin IgG levels and was stronger when functional assay-positive cases were compared with antibody-positive (functional assay-negative) controls than with antibody-negative controls. Sequencing and fine-mapping of ABO demonstrated that rs8176719 was the causal single nucleotide polymorphism (SNP). Our results clarify the biology underlying HIT pathogenesis with ramifications for prediction and may have important implications for related conditions, such as vaccine-induced thrombotic thrombocytopenia., (© 2022 by The American Society of Hematology.)
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- 2022
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44. Most anti-PF4 antibodies in vaccine-induced immune thrombotic thrombocytopenia are transient.
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Schönborn L, Thiele T, Kaderali L, Günther A, Hoffmann T, Seck SE, Selleng K, and Greinacher A
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- COVID-19 Vaccines adverse effects, ChAdOx1 nCoV-19, Female, Heparin adverse effects, Humans, Immunoglobulin G, Platelet Factor 4, COVID-19 prevention & control, Thrombocytopenia chemically induced, Thrombosis, Vaccines adverse effects
- Abstract
Vaccine-induced thrombotic thrombocytopenia (VITT) is triggered by vaccination against COVID-19 with adenovirus vector vaccines (ChAdOx1 nCoV-19; Ad26.COV2-S). In this observational study, we followed VITT patients for changes in their reactivity of platelet-activating antiplatelet factor 4 (PF4) immunoglobulin G (IgG) antibodies by an anti-PF4/heparin IgG enzyme immunoassay (EIA) and a functional test for PF4-dependent, platelet-activating antibodies, and new thrombotic complications. Sixty-five VITT patients (41 females; median, 51 years; range, 18-80 years) were followed for a median of 25 weeks (range, 3-36 weeks). In 48/65 patients (73.8%; CI, 62.0% to 83.0%) the functional assay became negative. The median time to negative functional test result was 15.5 weeks (range, 5-28 weeks). In parallel, EIA optical density (OD) values decreased from median 3.12 to 1.52 (P < .0001), but seroreversion to a negative result was seen in only 14 (21.5%) patients. Five (7.5%) patients showed persistent platelet-activating antibodies and high EIA ODs for >11 weeks. None of the 29 VITT patients who received a second vaccination dose with an mRNA COVID-19 vaccine developed new thromboses or relevant increase in anti-PF4/heparin IgG EIA OD, regardless of whether PF4-dependent platelet-activating antibodies were still present. PF4-dependent platelet-activating antibodies are transient in most patients with VITT. VITT patients can safely receive a second COVID-19 mRNA-vaccine shot., (© 2022 by The American Society of Hematology.)
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- 2022
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45. Insights in ChAdOx1 nCoV-19 vaccine-induced immune thrombotic thrombocytopenia.
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Greinacher A, Selleng K, Palankar R, Wesche J, Handtke S, Wolff M, Aurich K, Lalk M, Methling K, Völker U, Hentschker C, Michalik S, Steil L, Reder A, Schönborn L, Beer M, Franzke K, Büttner A, Fehse B, Stavrou EX, Rangaswamy C, Mailer RK, Englert H, Frye M, Thiele T, Kochanek S, Krutzke L, Siegerist F, Endlich N, Warkentin TE, and Renné T
- Subjects
- Adenoviridae immunology, Animals, Antigen-Antibody Complex ultrastructure, Autoantibodies biosynthesis, Capillary Leak Syndrome etiology, Capsid Proteins immunology, Cell Line, Transformed, ChAdOx1 nCoV-19 chemistry, ChAdOx1 nCoV-19 immunology, ChAdOx1 nCoV-19 toxicity, Dynamic Light Scattering, Epitopes chemistry, Epitopes immunology, Extracellular Traps immunology, Extravasation of Diagnostic and Therapeutic Materials etiology, Genetic Vectors immunology, HEK293 Cells chemistry, Humans, Imaging, Three-Dimensional, Immunoglobulin G biosynthesis, Inflammation, Mice, Microscopy methods, Platelet Activation, Proteomics, Purpura, Thrombocytopenic, Idiopathic blood, Purpura, Thrombocytopenic, Idiopathic immunology, Sinus Thrombosis, Intracranial diagnostic imaging, Sinus Thrombosis, Intracranial immunology, Spike Glycoprotein, Coronavirus immunology, Virus Cultivation, Antigen-Antibody Complex immunology, Autoantibodies immunology, COVID-19 prevention & control, Capsid Proteins adverse effects, ChAdOx1 nCoV-19 adverse effects, Drug Contamination, Genetic Vectors adverse effects, HEK293 Cells immunology, Immunoglobulin G immunology, Platelet Factor 4 immunology, Purpura, Thrombocytopenic, Idiopathic etiology, SARS-CoV-2, Spike Glycoprotein, Coronavirus adverse effects
- Abstract
SARS-CoV-2 vaccine ChAdOx1 nCoV-19 (AstraZeneca) causes a thromboembolic complication termed vaccine-induced immune thrombotic thrombocytopenia (VITT). Using biophysical techniques, mouse models, and analysis of VITT patient samples, we identified determinants of this vaccine-induced adverse reaction. Super-resolution microscopy visualized vaccine components forming antigenic complexes with platelet factor 4 (PF4) on platelet surfaces to which anti-PF4 antibodies obtained from VITT patients bound. PF4/vaccine complex formation was charge-driven and increased by addition of DNA. Proteomics identified substantial amounts of virus production-derived T-REx HEK293 proteins in the ethylenediaminetetraacetic acid (EDTA)-containing vaccine. Injected vaccine increased vascular leakage in mice, leading to systemic dissemination of vaccine components known to stimulate immune responses. Together, PF4/vaccine complex formation and the vaccine-stimulated proinflammatory milieu trigger a pronounced B-cell response that results in the formation of high-avidity anti-PF4 antibodies in VITT patients. The resulting high-titer anti-PF4 antibodies potently activated platelets in the presence of PF4 or DNA and polyphosphate polyanions. Anti-PF4 VITT patient antibodies also stimulated neutrophils to release neutrophil extracellular traps (NETs) in a platelet PF4-dependent manner. Biomarkers of procoagulant NETs were elevated in VITT patient serum, and NETs were visualized in abundance by immunohistochemistry in cerebral vein thrombi obtained from VITT patients. Together, vaccine-induced PF4/adenovirus aggregates and proinflammatory reactions stimulate pathologic anti-PF4 antibody production that drives thrombosis in VITT. The data support a 2-step mechanism underlying VITT that resembles the pathogenesis of (autoimmune) heparin-induced thrombocytopenia., (© 2021 by The American Society of Hematology.)
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- 2021
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46. Blood Product Supply for a Helicopter Emergency Medical Service.
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Selleng K, Baschin M, Henkel B, Jenichen G, Thies KC, Rudolph M, Reifferscheid F, Braun J, Hannich M, Winter T, Hahnenkamp K, and Greinacher A
- Abstract
Background: Long patient transport times to trauma centers are a well-known problem in sparsely populated regions with a low hospital density. Transfusion of red blood cell concentrates (RBC) and plasma improves outcome of trauma patients with severe bleeding. Helicopter emergency services (HEMS) are frequently employed to provide early advanced medical care and to reduce time to hospital admission. Supplying HEMS with blood products allows prehospital transfusion and may help to prevent exsanguination or prolonged hemorrhagic shock. We have investigated the maintenance of blood product quality under air transport conditions and the logistical steps to introduce a HEMS blood depot into routine practice., Methods: A risk analysis was performed and a validation plan developed. A special, commercially available transport container for blood products was identified. Maintenance of temperature conditions between 2 and 6°C in the box were monitored at ambient temperatures up to 35°C over 48 h. Quality of blood products before and after helicopter air transport were evaluated including (1) for RBCs: hemoglobin, hematocrit, hemolysis rate; (2) for thawed plasma: aPTT, INR, single clotting factor activities. The logistics for blood supply of the regional HEMS were developed by the transfusion service of the Greifswald University Hospital in collaboration with the in-hospital transport team, the HEMS team, and the HEMS operator., Results: The transport container maintained a temperature below 6°C up to 36 h at 35°C ambient temperature. Vibration during helicopter operation did not impair quality of RBC and thawed plasma. To provide blood products for HEMS at least two transport containers and an additional set of cooling tiles is needed as the cooling tiles need a special temperature priming over 20 h. The two boxes were used at alternate days. To reduce wastage, RBCs and thawed plasmas were exchanged every fourth day and reintegrated into the blood bank inventory for further in-hospital use., Conclusions: Supplying HEMS with RBCs and plasma is feasible. Helicopter transport has no negative impact on blood product quality. The logistic challenges require close collaboration between the HEMS team and the blood transfusion service., Competing Interests: M.B. and K.-C.T. are members of the scientific working group of the DRF Luftrettung. M.R., F.R., J.B. are employees of the DRF Luftrettung. K.S. received research funding from Immucor, traveling support from SOBI and consultant fees from Aspen. A.G. received research funding from Ergomed, Boehringer Ingelheim, Rovi, Sagent, Macopharma, Portola, Biokit, Blau Farmaceutics, Prosensa/Biomarin, DRK-BSD NSTOB, DRK-BSD Baden-Württemberg/Hessen, travel support, speakers and consulting fees from Roche, GTH e.V., Sanofi-Aventis, Macopharma, Chromatec, Instrumentation Laboratory, Bayer Vital and Aspen. B.H., G.J., M.H., T.W., K.H. declare no conflict of interest., (Copyright © 2021 by S. Karger AG, Basel.)
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- 2021
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47. 10 Years of Experience with the First Thawed Plasma Bank in Germany.
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Selleng K and Greinacher A
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Background: Plasma is stored at -30°C, which requires thawing before transfusion, causing a time delay between ordering and issuing of at least 30 min. In case of bleeding emergencies, guidelines strongly recommend a 2:1 transfusion ratio of RBCs and plasma. In addition, each minute delay in issuing of blood products in bleeding emergencies increases the mortality risk. To provide plasma in time in bleeding emergencies, a thawed plasma bank was introduced in 2011., Summary: The thawed plasma bank of University Medicine Greifswald has provided 18,924 thawed stored plasma units between 2011 and 2020. The workflow in the laboratory as well as in the emergency room, the operating room, and the intensive care unit have been optimized by thawed stored plasma. In case of emergencies, the stress factor for the transfusion medicine laboratory staff has been reduced substantially. The thawed plasma bank allows to transfuse patients with massive transfusion demand at a 2:1 ratio of RBCs and plasma according to guidelines. To reduce storage time, we issue all plasma requests from the thawed plasma bank except for pediatric patients. This results in a median storage time in the thawed plasma bank of 24 h. The "just in time" availability of plasma within the entire hospital based on the thawed plasma bank has reduced precautionary ordering of plasma, and hereby the unnecessary use of plasma. After introduction of the thawed plasma bank, plasma usage decreased substantially by 24% within the first year and by 60% compared to 2019/2020. However, as the overall approach to using blood products has changed over the last 10 years due to the patient blood management initiative, quantification of the effects of the thawed plasma bank in reduction of plasma transfusion is difficult., Key Messages: (1) A thawed plasma bank for the routine supply of blood products in a large hospital is feasible in Germany. (2) The thawed plasma bank allows to supply RBCs and plasma in a 2:1 ratio in bleeding emergencies. (3) The beneficial logistical effects of the thawed plasma bank are optimal if all plasma requests are supplied from the thawed plasma bank. This results in a median storage time of 24 h for thawed plasma., Competing Interests: K. Selleng received research funding from Immucor, traveling support from SOBI, and consultant fees from Aspen outside the submitted work. A. Greinacher reports grants and nonfinancial support from Aspen, Boehringer Ingelheim, MSD, Bristol Myers Squibb, Bayer Healthcare, Instrumentation Laboratory; personal fees from Aspen, MSD, Macopharma, Bristol Myers Squibb, Chromatec, Instrumentation Laboratory; and nonfinancial support from Portola, Ergomed, and Biokit outside the submitted work., (Copyright © 2021 by S. Karger AG, Basel.)
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- 2021
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48. Anti-platelet factor 4 antibodies causing VITT do not cross-react with SARS-CoV-2 spike protein.
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Greinacher A, Selleng K, Mayerle J, Palankar R, Wesche J, Reiche S, Aebischer A, Warkentin TE, Muenchhoff M, Hellmuth JC, Keppler OT, Duerschmied D, Lother A, Rieg S, Gawaz MP, Mueller KAL, Scheer CS, Napp M, Hahnenkamp K, Lucchese G, Vogelgesang A, Flöel A, Lovreglio P, Stufano A, Marschalek R, and Thiele T
- Subjects
- Adult, Aged, Aged, 80 and over, Blood Platelets immunology, COVID-19 immunology, Cohort Studies, Epitopes immunology, Female, Heparin metabolism, Humans, Immunoglobulin G immunology, Male, Middle Aged, Protein Binding, Protein Domains, Purpura, Thrombocytopenic, Idiopathic blood, Spike Glycoprotein, Coronavirus chemistry, Young Adult, Antibodies adverse effects, COVID-19 Vaccines adverse effects, Cross Reactions immunology, Platelet Factor 4 immunology, Purpura, Thrombocytopenic, Idiopathic etiology, Purpura, Thrombocytopenic, Idiopathic immunology, Spike Glycoprotein, Coronavirus immunology
- Abstract
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe adverse effect of ChAdOx1 nCoV-19 COVID-19 vaccine (Vaxzevria) and Janssen Ad26.COV2.S COVID-19 vaccine, and it is associated with unusual thrombosis. VITT is caused by anti-platelet factor 4 (PF4) antibodies activating platelets through their FcγRIIa receptors. Antibodies that activate platelets through FcγRIIa receptors have also been identified in patients with COVID-19. These findings raise concern that vaccination-induced antibodies against anti-SARS-CoV-2 spike protein cause thrombosis by cross-reacting with PF4. Immunogenic epitopes of PF4 and SARS-CoV-2 spike protein were compared using in silico prediction tools and 3D modeling. The SARS-CoV-2 spike protein and PF4 share at least 1 similar epitope. Reactivity of purified anti-PF4 antibodies from patients with VITT was tested against recombinant SARS-CoV-2 spike protein. However, none of the affinity-purified anti-PF4 antibodies from 14 patients with VITT cross-reacted with SARS-CoV-2 spike protein. Sera from 222 polymerase chain reaction-confirmed patients with COVID-19 from 5 European centers were tested by PF4-heparin enzyme-linked immunosorbent assays and PF4-dependent platelet activation assays. We found anti-PF4 antibodies in sera from 19 (8.6%) of 222 patients with COVID-19. However, only 4 showed weak to moderate platelet activation in the presence of PF4, and none of those patients developed thrombotic complications. Among 10 (4.5%) of 222 patients who had COVID-19 with thrombosis, none showed PF4-dependent platelet-activating antibodies. In conclusion, antibodies against PF4 induced by vaccination do not cross-react with the SARS-CoV-2 spike protein, indicating that the intended vaccine-induced immune response against SARS-CoV-2 spike protein is not the trigger of VITT. PF4-reactive antibodies found in patients with COVID-19 in this study were not associated with thrombotic complications., (© 2021 by The American Society of Hematology.)
- Published
- 2021
- Full Text
- View/download PDF
49. Frequency of positive anti-PF4/polyanion antibody tests after COVID-19 vaccination with ChAdOx1 nCoV-19 and BNT162b2.
- Author
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Thiele T, Ulm L, Holtfreter S, Schönborn L, Kuhn SO, Scheer C, Warkentin TE, Bröker BM, Becker K, Aurich K, Selleng K, Hübner NO, and Greinacher A
- Subjects
- Adult, Asymptomatic Diseases, Autoantibodies blood, BNT162 Vaccine, ChAdOx1 nCoV-19, Female, Health Personnel, Humans, Immunoenzyme Techniques, Immunoglobulin G blood, Immunoglobulin G immunology, Male, Middle Aged, Platelet Activation, Purpura, Thrombotic Thrombocytopenic immunology, Seroconversion, Thrombophilia etiology, Autoantibodies immunology, COVID-19 prevention & control, COVID-19 Vaccines adverse effects, Platelet Factor 4 immunology, Polyelectrolytes, Purpura, Thrombotic Thrombocytopenic etiology, Vaccination adverse effects
- Abstract
Vaccination using the adenoviral vector COVID-19 vaccine ChAdOx1 nCoV-19 (AstraZeneca) has been associated with rare vaccine-induced immune thrombotic thrombocytopenia (VITT). Affected patients test strongly positive in platelet factor 4 (PF4)/polyanion enzyme immunoassays (EIAs), and serum-induced platelet activation is maximal in the presence of PF4. We determined the frequency of anti-PF4/polyanion antibodies in healthy vaccinees and assessed whether PF4/polyanion EIA+ sera exhibit platelet-activating properties after vaccination with ChAdOx1 nCoV-19 (n = 138) or BNT162b2 (BioNTech/Pfizer; n = 143). In total, 19 of 281 participants tested positive for anti-PF4/polyanion antibodies postvaccination (All: 6.8% [95% confidence interval (CI), 4.4-10.3]; BNT162b2: 5.6% [95% CI, 2.9-10.7]; ChAdOx1 nCoV-19: 8.0% [95% CI, 4.5% to 13.7%]). Optical densities were mostly low (between 0.5 and 1.0 units; reference range, <0.50), and none of the PF4/polyanion EIA+ samples induced platelet activation in the presence of PF4. We conclude that positive PF4/polyanion EIAs can occur after severe acute respiratory syndrome coronavirus 2 vaccination with both messenger RNA- and adenoviral vector-based vaccines, but many of these antibodies likely have minor (if any) clinical relevance. Accordingly, low-titer positive PF4/polyanion EIA results should be interpreted with caution when screening asymptomatic individuals after vaccination against COVID-19. Pathogenic platelet-activating antibodies that cause VITT do not occur commonly following vaccination., (© 2021 by The American Society of Hematology.)
- Published
- 2021
- Full Text
- View/download PDF
50. International Forum on Transfusion Practices in Haematopoietic Stem-Cell Transplantation: Responses.
- Author
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Solves P, Lozano M, Zhiburt E, Anguita Velasco J, Maria Pérez-Corral A, Monsalvo-Saornil S, Yamazaki S, Okazaki H, Selleng K, Aurich K, Krüger W, Buser A, Holbro A, Infanti L, Stehle G, Pierelli L, Matteocci A, Rigacci L, De Vooght KMK, Kuball JHE, Fielding KL, Westerman DA, Wood EM, Cohn CS, Johnson A, Koh MBC, Qadir D, Cserti-Gazdewich C, Daguindau E, Angelot-Delettre F, Tiberghien P, Wendel-Neto S, Fachini RM, Morton S, Craddock C, Lumley M, Antoniewicz-Papis J, Hałaburda K, Łętowska M, and Dunbar N
- Published
- 2021
- Full Text
- View/download PDF
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