Pathways in Anticoagulation

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Pathways in Anticoagulation

• Richard C. Becker, MD
• Professor of Medicine
• Duke University School orf Medicine
• Duke Clinical Research Institute

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Richard C. Becker, M.D. Conflicts of Interest
Grant support from AstraZeneca, BMS/Sanofi
Partnership, Johnson Johnson, Bayer, Regado
Biosciences. Honoraria from AstraZeneca and
Daiichi/Eli Lilly. Consultant for Portola
Pharmaceuticals, Regado Biosciences,
Boehringer-Ingelheim.
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extravasculature
endothelial cell
4
extravasculature
endothelial cell
PF
X
IXa
PS
IX
VIIIa
LR
II
Va
Xa
IIa
Xa
Va
VIIa
IIa
II
X
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Initiation Phase of Coagulation


ATVB 2002221381-1389.
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Propagation Phase of Coagulation
ATVB 2002221381-1389.
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A Cell-Based Model of Coagulation
and Potential Targets
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Platelet Polyphosphates and Factor XII
Activation
Muller F. Cell 2009
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Platelet Polyphosphate and Factor XII
Activation
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Anticoagulants in Development

• Factor IXa InhibitorREG-1
• Factor Xa InhibitorsRivaroxaban,apixaban,
  edoxaban
• Factor IIa InhibitorDabigatran
• PAR-1 InhibitorsVorapaxar,atapaxar

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Pathways in Anticoagulation

• Selectivity in anticoagulant therapy permits a
  hypothesis to be tested and the pathobiology of
  disease to be understood.
• Careful dose selection, coupled with adequately
  sized clinical trials remain a prerequisite for
  determining efficacy.

RC Becker 2010
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Pathways in Anticoagulation

• There is safety in selectivity if the dose is
  right, the PK and PD are well understood, the
  disease is meticulously characterized and the
  patient is carefully selected.

RC Becker 2010