Haemostaseology

 

 

Project management:

PD Dr. med. Sonja Werwitzke, PhD,

In cooperation with Prof. Dr. med. Andreas Tiede, PhD,

Clinical Department of Hematology

 

Contact:

PD Dr. Sonja Werwitzke
Phone: 0511 532 8377
email: werwitzke.sonja@mh-hannover.de


Research focus:

Laboratory analytical investigations in the context of clinical studies, also in the function of the Central Laboratory of multicenter studies, for the research of new primarily immunological and hemostaseological assays (e.g. functional emicizumab activity; anti-drug antibodies of innovative therapeutics), which allow a better assessment of disease and therapy. Development of new biomarkers that support risk assessment (e.g. prognostic markers for the risk of bleeding in autoimmune acquired haemophilia A) and can better predict the course of the disease and the response to therapy in terms of individual precision diagnostics.


The focus of basic research is on investigating the pathophysiology of the immune response against coagulation factor VIII (FVIII). The development of a neutralizing antibody against FVIII (so-called inhibitor) can occur in congenital haemophilia A under FVIII substitution therapy or as part of an autoimmune process (loss of tolerance to FVIII) in acquired haemophilia A, whereby both disease entities show clinically very different bleeding tendencies. The inhibitors form immune complexes with FVIII as antigen, which interact with effector molecules (e.g. Fc gamma receptors, complement components) and can subsequently modulate the immune response. Immune complexes can also functionally intervene in hemostasis. The role of immune complexes on primary hemostasis and platelet function will be characterized in the flow chamber model (Figure 1) and other assays (e.g. cell culture) to better understand the severe bleeding tendency in acquired hemophilia A.

 

 

 

 

 

Funding:

GTH study group "Acquired Hemophilia"
Gesellschaft für Thrombose- und Hämostaseforschung (GTH): Early Career Investigator Award
Günther-Landbeck-Excellence Award
Roche Pharma AG (Investigator-Initiated Study GTH-AHA-EMI)
Octapharma AG (preclinical research)

 

Selected publications:

  • Emicizumab versus immunosuppressive therapy for the management of acquired hemophilia A. Hart C, Klamroth R, Sachs UJ, Greil R, Knoebl P, Oldenburg J, Miesbach W, Pfrepper C, Trautmann-Grill K, Pekrul I, Holstein K, Eichler H, Weigt C, Schipp D, Werwitzke S, Tiede A. J Thromb Haemost. 2024 Oct;22(10):2692-2701.
  • Emicizumab prophylaxis in patients with acquired haemophilia A (GTH-AHA-EMI): an open-label, single-arm, multicentre, phase 2 study. Tiede A, Hart C, Knöbl P, Greil R, Oldenburg J, Sachs UJ, Miesbach W, Pfrepper C, Trautmann-Grill K, Holstein K, Pilch J, Möhnle P, Schindler C, Weigt C, Schipp D, May M, Dobbelstein C, Pelzer FJ, Werwitzke S, Klamroth R. Lancet Haematol. 2023 Nov;10(11):e913-e921.
  • Microembolic signal monitoring in patients with HeartMate 3 and HeartWare left ventricular assist devices: Association with antithrombotic treatment and cerebrovascular events. Ravenberg KK, Gabriel MM, Leotescu A, Tran AT, Grosse GM, Schuppner R, Ernst J, Lichtinghagen R, Tiede A, Werwitzke S, Bara CL, Schmitto JD, Weissenborn K, Hanke JS, Worthmann H. Artif Organs. 2023 Feb;47(2):370-379.
  • Targets of autoantibodies in acquired hemophilia A are not restricted to factor VIII: data from the GTH-AH 01/2010 study. Oleshko O, Werwitzke S, Klingberg A, Witte T, Eichler H, Klamroth R, Holstein K, Hart C, Pfrepper C, Knöbl P, Greil R, Neumeister P, Reipert BM, Tiede A. Blood Adv. 2023 Jan 10;7(1):122-130.
  • Prothrombotic immune thrombocytopenia after COVID-19 vaccination. Tiede A, Sachs UJ, Czwalinna A, Werwitzke S, Bikker R, Krauss JK, Donnerstag F, Weißenborn K, Höglinger G, Maasoumy B, Wedemeyer H, Ganser A. Blood. 2021 Jul 29;138(4):350-353.
  • Anti-factor VIII IgA as a potential marker of poor prognosis in acquired hemophilia A: results from the GTH-AH 01/2010 study. Tiede A, Hofbauer CJ, Werwitzke S, Knöbl P, Gottstein S, Scharf RE, Heinz J, Groß J, Holstein K, Dobbelstein C, Scheiflinger F, Koch A, Reipert BM. Blood. 2016 May 12;127(19):2289-97.