Platelet Dysfunction in Thrombosis Patients Treated with Vitamin K Antagonists and Recurrent Bleeding

Meijden, Paola E. J. van der; Bouman, A.C.; Feijge, Marion A.H.; Oerle, René van; Spronk, Henri M. H.; Hamulyák, Karly; Cate‐Hoek, Arina J. ten; Cate, Hugo Ten; Heemskerk, Johan W. M.

doi:10.1371/journal.pone.0064112

Cited by 9 publications

(10 citation statements)

References 34 publications

(32 reference statements)

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“…Genetic factors have not been extensively characterized yet. Biochemically, there is no indication of impaired platelet function in those who bleed versus nonbleeding VKA users [20]. At the same time, impaired whole blood thrombin generation may indicate an underlying hemostatic impairment in VKA users (Bloemen S, de Laat, ten Cate-Hoek et al, unpublished).…”

Section: The Benchmark Anticoagulant: Warfarinmentioning

confidence: 99%

Upstream versus downstream thrombin inhibition

Gulpen¹,

Cate‐Hoek²,

Cate³

2016

Expert Review of Cardiovascular Therapy

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Introduction: For a long time, vitamin K antagonists (VKA) have been the preferred drugs for the anticoagulation management of both atrial fibrillation and venous thromboembolism. Hereby, the major purpose is to attenuate the onset of thrombosis without affecting hemostasis. Areas covered: Nowadays, non-vitamin K anticoagulants (NOAC), a new class of oral anticoagulants is available for the above-mentioned indications. NOAC are at least as effective and safer with regard to intracranial bleedings compared to VKA, but major bleedings still occur. For this reason, the search for safer anticoagulants is still ongoing. Expert commentary: There are several unmet needs in NOAC management, including selection of optimal drug and dose, uncertainty on specific conditions and lack of drug persistence. There remains to be an important need for safer anticoagulants; 'upstream' anticoagulants including inhibitors of factor XIa may provide additional benefit related to fewer bleeding complications. ARTICLE HISTORY

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Section: The Benchmark Anticoagulant: Warfarinmentioning

confidence: 99%

Upstream versus downstream thrombin inhibition

Gulpen¹,

Cate‐Hoek²,

Cate³

2016

Expert Review of Cardiovascular Therapy

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“…31 Aggregation of platelets in whole blood was measured by Multiplate impedance aggregometry (Roche Diagnostics, Basel, Switzerland) as described.…”

Section: Platelet Aggregationmentioning

confidence: 99%

“…31 Aggregation of platelets in whole blood was measured by Multiplate impedance aggregometry (Roche Diagnostics, Basel, Switzerland) as described. 32 Ticagrelor (1 mM), being more potent than prasugrel, 33 was added in vitro to block residual P2Y 12 activity, where indicated.…”

Section: Platelet Aggregationmentioning

confidence: 99%

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Gradual increase in thrombogenicity of juvenile platelets formed upon offset of prasugrel medication

et al. 2015

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© F e r r a t a S t o r t i F o u n d a t i o nfunction of platelets recovers after discontinuation of prasugrel treatment. We hypothesized an immediate recovery of newly formed, juvenile platelets to the level of untreated platelets. Our data provide evidence for a critical role of the juvenile platelets in the regained aggregation of platelets and thrombus formation, and also show that these platelets gradually increase in responsiveness. Methods Patients and control subjectsThis study was approved by the local medical ethics committee . All patients and healthy volunteers gave written informed consent to participate in the study according to the Declaration of Helsinki. Sixteen patients were studied who were treated with prasugrel (10 mg/day) for one year and long-term aspirin (80-100 mg/day) due to a myocardial infarction with ST elevation. After one year of prasugrel treatment, blood was collected on the last treatment day, and at 1, 2, 5 and 30 days later. From 2 patients, blood samples were also collected after 12 days to better understand the delayed regain of platelet function. Patients with a malignancy, active infection or a known platelet disorder were not included. Blood was obtained by venipuncture into Vacuette tubes, containing K2-EDTA, for measurement of hemostatic variables and immature platelet fraction (IPF) using a Sysmex XN-9000 analyzer (Sysmex, Chuo-ku Kobe, Japan); 3.2% (w/v) trisodium citrate for platelet function measurements, or hirudin for whole blood platelet aggregation. Control experiments were performed with blood drawn from healthy volunteers collected in trisodium citrate or acidic citrate dextrose. 28 Preparation of platelet-rich plasma, platelets and red cellsPlatelet-rich plasma (PRP), platelet-free plasma and washed platelets were prepared as described. 29 Platelet counts were determined with a thrombocounter XP300 Sysmex analyzer (Sysmex, Chuo-ku Kobe, Japan). Washed red blood cells were prepared as previously shown. 30Irreversible P2Y 12 inhibition in vitro PRP from healthy donors was treated with lysine aspirin. 28 The platelets were incubated with the active metabolite of clopidogrel (CAM) or vehicle medium. Mixtures of washed CAM-treated and vehicle-treated platelets were used for measurement of platelet aggregation, integrin α IIb β 3 activation by flow cytometry and perfusion experiments with reconstituted whole blood. Platelet aggregationAggregation of platelets in PRP was measured using a Chronolog aggregometer (Stago, Asnières sur Seine Cedex, France). 31 Aggregation of platelets in whole blood was measured by Multiplate impedance aggregometry (Roche Diagnostics, Basel, Switzerland) as described.32 Ticagrelor (1 mM), being more potent than prasugrel, 33 was added in vitro to block residual P2Y 12 activity, where indicated. Flow cytometric analysis of platelet subpopulationsFlow cytometry was performed on an Accuri C6 flow cytometer with CFlow Plus software (Becton-Dickinson Bioscience). To check for integrin α IIb β 3 activation, platelets were activated ...

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“…[ 11 ] Whereas, its deficiency has been linked with platelet dysfunction and hypercoagulability state in individuals at risk of CVD. [ 12 , 13 ] Although a recent meta-analysis showed that vitamin K supplementation could significantly reduce vascular calcification in clinical settings, [ 14 ] it remains relatively unknown how this cofactor impacts CVD-related complications in patients with T2D. Thus, due to its emerging role in protecting against diabetes-associated complications, [ 11 ] the current systematic review and meta-analysis will explore available evidence reporting on how vitamin K supplementation affects CVD-related parameters in patients with T2D.…”

Section: Introductionmentioning

confidence: 99%

The prophylactic effects of vitamin K supplementation on coagulopathies associated with type 2 diabetes mellitus

2020

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Background: The impact of vitamin K in ameliorating diabetes-associated complications, especially those linked with platelet activation and coagulation remains unclear. The current study aims to systematically explore and discuss the available evidence on the impact of vitamin K on the diabetes-cardiovascular disease (CVD)-associated complications. Methods: A systematic review of studies published on the MEDLINE (PubMed), EMBASE, and Google Scholar electronic database will be conducted. The review will include studies published from inception until May 25, 2020, reporting on the effect of vitamin K on CVD-related markers, especially coagulation factors and platelet activation in type 2 diabetes mellitus. Before the full-text screening, all studies will be screened by title, abstract, and keywords. The Downs and Black checklist will be used to assess the quality of the studies. Additionally, the Cochrane collaboration tool will also be used to evaluate the risk of bias across the included studies. Kappa Cohen's calculator will be used to assess the level of agreement between the authors. Discussions: This systematic review will not require ethical approval, and the results will be distributed through conference and peer-reviewed publications. Our results will assist current and future research scientists on the potential use of vitamin K as a protective therapy against CVD-related complications. Systematic review registration: This protocol is registered on the International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42020151667.

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Platelet Dysfunction in Thrombosis Patients Treated with Vitamin K Antagonists and Recurrent Bleeding

Cited by 9 publications

References 34 publications

Upstream versus downstream thrombin inhibition

Upstream versus downstream thrombin inhibition

Gradual increase in thrombogenicity of juvenile platelets formed upon offset of prasugrel medication

The prophylactic effects of vitamin K supplementation on coagulopathies associated with type 2 diabetes mellitus

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