Definite diagnosis of plasma prekallikrein deficiency should not be based exclusively on shortening of the aPTT upon prolonged pre‐incubation

Adenaeuer, Anke; Trinchero, Alice; Lackner, Karl J.; Lämmle, Bernhard; Rossmann, Heidi

doi:10.1111/ijlh.13841

Int J Lab Hematology

2022

DOI: 10.1111/ijlh.13841

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Definite diagnosis of plasma prekallikrein deficiency should not be based exclusively on shortening of the aPTT upon prolonged pre‐incubation

Anke Adenaeuer

Alice Trinchero²,

Karl J. Lackner

et al.

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2023

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Cited by 2 publications

(2 citation statements)

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confidence: 99%

“…11 Individuals with FXII or PK deficiency do not appear to have distinct symptoms or clinical phenotypes, other than an often incidentally detected prolonged activated partial thromboplastin time (aPTT). 12,13 Conversely, those born with hyperactive FXII (HAE-FXII) are prone to bradykinin-induced complications. 2,14 Taking the function of these coagulation factors into consideration, inhibiting the contact pathway presents a promising clinical strategy for reducing hemorrhagic or inflammatory complications in patients requiring the use of medical devices.…”

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

Goel

Tathireddy

Wang

et al. 2023

Semin Thromb Hemost

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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.

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confidence: 99%

mentioning

confidence: 99%

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

Goel

Tathireddy

Wang

et al. 2023

Semin Thromb Hemost

View full text Add to dashboard Cite

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Severe high-molecular-weight kininogen deficiency: clinical characteristics, deficiency–causing KNG1 variants, and estimated prevalence

Adenaeuer¹,

Trinchero²,

Krutmann³

et al. 2023

Journal of Thrombosis and Haemostasis

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Definite diagnosis of plasma prekallikrein deficiency should not be based exclusively on shortening of the aPTT upon prolonged pre‐incubation

Cited by 2 publications

References 9 publications

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

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

Severe high-molecular-weight kininogen deficiency: clinical characteristics, deficiency–causing KNG1 variants, and estimated prevalence

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