Cefazolin and coagulation disorders: a case report

Barthel, Anne; Rouzic, N.; Henriot, Basile; Quélennec, Baptiste; Lorléac’h, A.; Prades, Nathalie; Schmitt, François

doi:10.1684/abc.2017.1314

Cited by 5 publications

(2 citation statements)

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“…As most bleeding disorders are associated with the dysfunction of coagulation factors and increasing drug-induced bleeding complications have been reported to off-target the vitamin K cycle, 25,[30][31][32] the goal of this study was to functionally screen drugs that affect the biosynthesis of VKD coagulation factors. We first tested the feasibility of using our recently established cellbased assay 33 as a high-throughput screening approach to identifying drugs that may target VKD carboxylation.…”

Section: Introductionmentioning

confidence: 99%

A cell-based high-throughput screen identifies drugs that cause bleeding disorders by off-targeting the vitamin K cycle

Chen

Jin

et al. 2020

Blood

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Drug-induced bleeding disorders contribute to substantial morbidity and mortality. Antithrombotic agents that cause unintended bleeding with obvious reasons are relatively easy to control. However, the mechanisms of most drug-induced bleeding disorders are poorly understood which makes intervention more difficult. As most bleeding disorders are associated with the dysfunction of coagulation factors, we adapted our recently established cell-based assay to identify drugs that impact the biosynthesis of active vitamin K-dependent (VKD) coagulation factors with possible off-target effects. The NIH Clinical Collection (NCC) library containing 727 drugs was screened and 9 drugs, including the most commonly prescribed anticoagulant warfarin, were identified. Bleeding complications associated with most of these drugs have been clinically reported, but the pathogenic mechanisms remain unclear. Further characterization of the 9 top-hit drugs on the inhibition of VKD carboxylation suggests that warfarin, lansoprazole, and nitazoxanide mainly target vitamin K epoxide reductase (VKOR), while idebenone, clofazimine, and AM404 mainly target vitamin K reductase (VKR) in vitamin K redox cycling. The other three drugs mainly affect vitamin K availability within the cells. The molecular mechanisms underlying the inactivation of VKOR and VKR by these drugs are clarified. Results from both cell-based and animal model studies suggest that the anticoagulation effect of drugs targeting VKOR, but not VKR, can be rescued by the administration of vitamin K. These findings provide insights into the prevention and management of drug-induced bleeding disorders. The established cell-based high-throughput screening approach provides a powerful tool for identifying new vitamin K antagonists that function as anticoagulants.

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Section: Introductionmentioning

confidence: 99%

A cell-based high-throughput screen identifies drugs that cause bleeding disorders by off-targeting the vitamin K cycle

Chen

Jin

et al. 2020

Blood

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“…Those anomalies contribute to hemostasis disorders. They are mostly observed with certain cephalosporins (cefamandole, cefoperazone and moxalactam), whose nucleus carries a 1-methyltetrazole-5-thiol (MTT) group (Lipsky, 1983).…”

Section: Discussionmentioning

confidence: 99%

Coagulation disorders during treatment with cefazolin and rifampicin: rare but dangerous

Kouki

Montagner

Mauhin

et al. 2021

J. Bone Joint Infect.

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Abstract. We describe a 79-year-old man with spondylodiscitis and unknown pathogen, treated with cefazolin and rifampicin. He developed a massive digestive hemorrhage. Prothrombin time was prolonged with severe vitamin-K-dependent clotting-factor deficiency. Severe bleeding can occur during cefazolin and rifampicin use. This deficiency should be assessed before prescribing cefazolin–rifampicin and prothrombin time monitored.

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Impact of genetic and clinical factors on warfarin therapy in patients early after heart valve replacement surgery

Liu

Wang

et al. 2019

Eur J Clin Pharmacol

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Cefazolin and coagulation disorders: a case report

Cited by 5 publications

References 0 publications

A cell-based high-throughput screen identifies drugs that cause bleeding disorders by off-targeting the vitamin K cycle

A cell-based high-throughput screen identifies drugs that cause bleeding disorders by off-targeting the vitamin K cycle

Coagulation disorders during treatment with cefazolin and rifampicin: rare but dangerous

Impact of genetic and clinical factors on warfarin therapy in patients early after heart valve replacement surgery

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