Targeting the Contact Pathway of Coagulation for the Prevention and Management of Medical Device-Associated Thrombosis

Abhishek Goel; Harsha Tathireddy; Si-Han Wang; Helen H. Vu; Cristina Puy; Monica T. Hinds; David Zonies; Owen J.T. McCarty; Joseph J. Shatzel

doi:10.1055/s-0043-57011

Seminars in Thrombosis and Hemostasis, Inhaltsverzeichnis

Semin Thromb Hemost 2024; 50(07): 989-997
DOI: 10.1055/s-0043-57011

Review Article

Targeting the Contact Pathway of Coagulation for the Prevention and Management of Medical Device-Associated Thrombosis

Abhishek Goel

¹Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon

,

Harsha Tathireddy

¹Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon

,

Si-Han Wang

²Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon

,

Helen H. Vu

²Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon

,

Cristina Puy

²Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon

,

Monica T. Hinds

²Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon

,

David Zonies

³Department of Surgery, Oregon Health and Science University, Portland, Oregon

,

Owen J.T. McCarty

¹Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon

²Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon

,

Joseph J. Shatzel

¹Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon

²Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon

› Institutsangaben

Abstract

Hemorrhage remains a major complication of anticoagulants, with bleeding leading to serious and even life-threatening outcomes in rare settings. Currently available anticoagulants target either multiple coagulation factors or specifically coagulation factor (F) Xa or thrombin; however, inhibiting these pathways universally impairs hemostasis. Bleeding complications are especially salient in the medically complex population who benefit from medical devices. Extracorporeal devices—such as extracorporeal membrane oxygenation, hemodialysis, and cardiac bypass—require anticoagulation for optimal use. Nonetheless, bleeding complications are common, and with certain devices, highly morbid. Likewise, pharmacologic prophylaxis to prevent thrombosis is not commonly used with many medical devices like central venous catheters due to high rates of bleeding. The contact pathway members FXI, FXII, and prekallikrein serve as a nexus, connecting biomaterial surface-mediated thrombin generation and inflammation, and may represent safe, druggable targets to improve medical device hemocompatibility and thrombogenicity. Recent in vivo and clinical data suggest that selectively targeting the contact pathway of coagulation through the inhibition of FXI and FXII can reduce the incidence of medical device-associated thrombotic events, and potentially systemic inflammation, without impairing hemostasis. In the following review, we will outline the current in vivo and clinical data encompassing the mechanism of action of drugs targeting the contact pathway. This new class of inhibitors has the potential to herald a new era of effective and low-risk anticoagulation for the management of patients requiring the use of medical devices.

Keywords

medical device - anticoagulation - thrombosis - contact pathway - factor XI

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Referenzen

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