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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
1   Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon
,
Harsha Tathireddy
1   Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon
,
Si-Han Wang
2   Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon
,
Helen H. Vu
2   Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon
,
Cristina Puy
2   Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon
,
Monica T. Hinds
2   Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon
,
David Zonies
3   Department of Surgery, Oregon Health and Science University, Portland, Oregon
,
Owen J.T. McCarty
1   Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon
2   Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon
,
Joseph J. Shatzel
1   Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon
2   Department of Biomedical Engineering, Oregon Health and Science University, Portland, Oregon
› Author Affiliations
Funding This work was supported by the National Institutes of Health (R01HL151367 to J.J.S, R01HL101972 and R01HL144113 to O.J.T.M).
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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


Publication History

Article published online:
12 April 2023

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