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Thromb Haemost 2019; 119(08): 1212-1221
DOI: 10.1055/s-0039-1687877
Theme Issue Article
Georg Thieme Verlag KG Stuttgart · New York

Btk Inhibitors as First Oral Atherothrombosis-Selective Antiplatelet Drugs?

Kristina Busygina
1   Institute for Prevention of Cardiovascular Diseases, LMU (Ludwig-Maximilians University Munich), Munich, Germany
,
Viola Denzinger
1   Institute for Prevention of Cardiovascular Diseases, LMU (Ludwig-Maximilians University Munich), Munich, Germany
,
Isabell Bernlochner
2   Medizinische Klinik und Poliklinik I, Klinikum rechts der Isar, Medizinische Fakultät, Technische Universität München, Munich, Germany
,
Christian Weber   ∗
1   Institute for Prevention of Cardiovascular Diseases, LMU (Ludwig-Maximilians University Munich), Munich, Germany
3   DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
4   Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
,
Reinhard Lorenz
1   Institute for Prevention of Cardiovascular Diseases, LMU (Ludwig-Maximilians University Munich), Munich, Germany
,
Wolfgang Siess
1   Institute for Prevention of Cardiovascular Diseases, LMU (Ludwig-Maximilians University Munich), Munich, Germany
3   DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
› Author Affiliations Funding This study was supported by grants from the Deutsche Forschungsgemeinschaft (SFB1123/B08) and the August-Lenz foundation.
Further Information

Publication History

29 September 2018

09 March 2019

Publication Date:
14 May 2019 (online)

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Abstract

Bruton's tyrosine kinase (Btk) is essential for B cell differentiation and proliferation, but also platelets express Btk. Patients with X-linked agammaglobulinemia due to hereditary Btk deficiency do not show bleeding, but a mild bleeding tendency is observed in high dose therapy of B-cell malignancies with ibrutinib and novel second-generation irreversible Btk inhibitors (acalabrutinib and ONO/GS-4059). This review discusses recent studies that may explain this apparent paradox and gives mechanistic insights that suggest a unique potential of low dose irreversible Btk inhibitors as atherothrombosis-focused antiplatelet drugs.

Keywords

Btk inhibitor - platelet - bleeding - GPVI - GPIb - X-linked agammaglobulinemia
 

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