Publications by authors named "Laurence Camoin-Jau"

64 Publications

Can hydroxychloroquine be protective against COVID-19-associated thrombotic events ?

J Microbiol Immunol Infect 2021 Feb 5;54(1):37-45. Epub 2021 Jan 5.

Aix-Marseille Univ, IRD, APHM, MEPHI, IHU-Méditerranée Infection, Marseille, France.

Although SARS-CoV-2 is considered a lung-tropic virus, severe COVID-19 is not just a viral pulmonary infection, clinically it is a multi-organ pathology with major coagulation abnormalities and thromboembolism events. Recently, antiphospholipid (aPL) antibodies were found increased in a large number of COVID-19 patients. Elevated aPL have been well documented in antiphospholipid syndrome (APS), a systemic autoimmune disorder characterized by recurrent venous or arterial thrombosis and/or obstetrical morbidity. Among treatment regimen of APS, hydroxychloroquine (HCQ) is one of the molecules proposed in the primary prevention of thrombosis and obstetrical morbidity in those patients. Due to its antithrombotic properties documented in APS therapy, HCQ could be considered a good candidate for the prevention of thrombotic events in COVID-19 patients in association with anticoagulant and its repurposing deserves further evaluation.
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http://dx.doi.org/10.1016/j.jmii.2020.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783458PMC
February 2021

Dabigatran Level Before Reversal Can Predict Hemostatic Effectiveness of Idarucizumab in a Real-World Setting.

Front Med (Lausanne) 2020 16;7:599626. Epub 2020 Dec 16.

Université de Paris, Innovative Therapies in Haemostasis, INSERM, Paris, France.

Idarucizumab has been included in guidelines for the management of bleeding or surgical procedure in dabigatran-treated patients without need for biological monitoring. The aim of the study was to assess the prognostic value of dabigatran plasma level before reversal to test the hemostatic efficacy of idarucizumab. The secondary objectives were (i) to analyze plasma dabigatran level according to the risk of rebound and (ii) to evaluate the incidence of post-reversal non-favorable clinical outcomes (including thromboembolism, bleeding, antithrombotic, and death) and antithrombotic resumption. This was an observational multicentric cohort study, which included all French patients who required idarucizumab for dabigatran reversal. Between May 2016 and April 2019, 87 patients from 21 French centers were enrolled. Patients received idarucizumab for overt bleeding ( = 61), urgent procedures ( = 24), or overdose without bleeding ( = 2). Among patients with major bleeding ( = 57), treatment with idarucizumab was considered effective in 44 (77.2%) of them. Patients who did not achieve effective hemostasis after reversal had a significantly higher mean level of plasma dabigatran at baseline (524.5 ± 386 vs. 252.8 ng/mL ± 235, = 0.033). Furthermore, patients who did not achieve effective hemostasis after reversal had less favorable outcomes during follow-up (46.2 vs. 81.8%, = 0.027). ROC curve identified a cutoff of 264 ng/mL for dabigatran level at admission to be predictive of ineffective hemostasis. No plasma dabigatran rebound was observed after reversal in patients with dabigatran plasma level < 264 ng/mL at baseline. This retrospective study shows that dabigatran level before reversal could predict hemostatic effectiveness and dabigatran plasma rebound after idarucizumab injection.
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http://dx.doi.org/10.3389/fmed.2020.599626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772865PMC
December 2020

Clinical validation of immunoassay HemosIL® AcuStar HIT-IgG (PF4-H) in the diagnosis of Heparin-induced thrombocytopenia.

J Thromb Thrombolysis 2021 Jan 1. Epub 2021 Jan 1.

Laboratoire d'Hématologie, La Timone Hospital, APHM, Boulevard Jean- Moulin, 13005, Marseille, France.

Heparin induced thrombocytopenia (HIT) is a life and limb-threatening complication of heparin exposure. The misdiagnosis of this disease can have major consequences on the patients. The objective of this study was to evaluate a diagnostic strategy that combines the 4Ts score with the result of HemosIL® AcuStar HIT-IgG (PF4-H) to confirm the diagnosis of HIT. Citrated plasmas from 1300 patients with suspicion of HIT were analyzed with a fully automated quantitative chemiluminescent immunoassay (HemosIL® AcuStar HIT-IgG (PF4/H)). If the IgG anti-PF4/H antibodies were positive (cut-off, 1 U/mL), HIT diagnosis was confirmed using functional tests. In total, 1300 samples of consecutive patients were enrolled, 94 (7.2%) of which gave positive results in HemosIL® AcuStar-IgG. HIT was diagnosed in 65 out of these patients, corresponding to a prevalence of 5%. Using ROC curve analysis, patients were divided into three groups according to their titer of antibodies. Higher values of the IgG (PF4-H) were associated with increased probability of HIT, and the diagnostic specificity was greatly increased using the combination of a 4Ts score > 3 and a positive titer ≥ 3.25 U/mL. Importantly, the diagnostic specificity is 100% when the titer is > 12.40 U/mL. We demonstrated that higher values of Anti PF4/H Antibodies were associated with a high probability of having HIT. A titer of HemosIL® IgG (PF4-H) > 12.40 U/mL has a specificity of 100% which should no require a functional test to confirm the diagnosis of HIT.
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http://dx.doi.org/10.1007/s11239-020-02349-4DOI Listing
January 2021

Natural history of COVID-19 and therapeutic options.

Expert Rev Clin Immunol 2020 12 24;16(12):1159-1184. Epub 2020 Dec 24.

Institut Hospitalo-Universitaire Méditerranée Infection , Marseille, France.

: COVID-19 presents benign forms in young patients who frequently present with anosmia. Infants are rarely infected, while severe forms occur in patients over 65 years of age with comorbidities, including hypertension and diabetes. Lymphopenia, eosinopenia, thrombopenia, increased lactate dehydrogenase, troponin, C-reactive protein, D-dimers and low zinc levels are associated with severity.: The authors review the literature and provide an overview of the current state of knowledge regarding the natural history of and therapeutic options for COVID-19. : Diagnosis should rely on PCR and not on clinical presumption. Because of discrepancies between clinical symptoms, oxygen saturation or radiological signs on CT scans, pulse oximetry, and radiological investigation should be systematic. The disease evolves in successive phases: an acute virological phase, and, in some patients, a cytokine storm phase; an uncontrolled coagulopathy; and an acute respiratory distress syndrome. Therapeutic options include antivirals, oxygen therapy, immunomodulators, anticoagulants and prolonged mechanical treatment. Early diagnosis, care, and implementation of an antiviral treatment; the use of immunomodulators at a later stage; and the quality of intensive care are critical regarding mortality rates. The higher mortality observed in Western countries remains unexplained. Pulmonary fibrosis may occur in some patients. Its future is unpredictable.
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http://dx.doi.org/10.1080/1744666X.2021.1847640DOI Listing
December 2020

Different pattern of the second outbreak of COVID-19 in Marseille, France.

Int J Infect Dis 2021 Jan 7;102:17-19. Epub 2020 Oct 7.

IHU Méditerranée Infection, 19-21 boulevard Jean Moulin, 13005 Marseille, France; Aix-Marseille Univ., Institut de Recherche pour le Développement (IRD), Assistance Publique - Hôpitaux de Marseille (AP-HM), Microbes Evolution Phylogeny and Infections (MEPHI), 27 boulevard Jean Moulin, 13005 Marseille, France. Electronic address:

Objective: To describe the characteristics of COVID-19 patients seen in March-April and June-August 2020 in Marseille, France with the aim to investigate possible changes in the disease between these two time periods.

Methods: Demographics, hospitalization rate, transfer to intensive care unit (ICU), lethality, clinical and biological parameters were investigated.

Results: Compared to those seen in March-April, COVID-19 patients seen in June-August were significantly younger (39.2 vs. 45.3 years), more likely to be male (52.9% vs. 45.6%), and less likely to be hospitalized (10.7 vs. 18.0%), to be transferred to ICU (0.9% vs. 1.8%) and to die (0.1% vs. 1.1%). Their mean fibrinogen and D-dimer blood levels were lower (1.0 vs. 1.5 g/L and 0.6 vs. 1.1 μg/mL, respectively). By contrast, their viral load was higher (cycle threshold ≤16 = 5.1% vs. 3.7%).

Conclusions: Patients in the two periods did not present marked age and sex differences, but markers of severity were undoubtedly less prevalent in the summer period, associating with a 10 times decrease in the lethality rate.
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http://dx.doi.org/10.1016/j.ijid.2020.10.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539893PMC
January 2021

Heparin-Induced Thrombocytopenia in Severe COVID-19.

Circulation 2020 11 29;142(19):1875-1877. Epub 2020 Sep 29.

Aix-Marseille Université, Hôpital Nord, and Laboratoire d'Hématologie, Hôpital de la Timone (L.C.-J.), Assistance Publique-Hôpitaux de Marseille, France.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.049015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643786PMC
November 2020

A Novel Approach for Detecting Unique Variations among Infectious Bacterial Species in Endocarditic Cardiac Valve Vegetation.

Cells 2020 08 13;9(8). Epub 2020 Aug 13.

Aix Marseille Univ, IRD, APHM, MEPHI, IHU Méditerranée Infection, 13005 Marseille, France.

Infectious endocarditis (IE) remains one of the deadliest heart diseases with a high death rate, generally following thrombo-embolic events. Today, therapy is based on surgery and antibiotic therapy. When thromboembolic complications in IE patients persist, this is often due to our lack of knowledge regarding the pathophysiological development and organization of cells in the vegetation, most notably the primordial role of platelets and further triggered hemostasis, which is related to the diversity of infectious microorganisms involved. Our objective was to study the organization of IE vegetations due to different bacteria species in order to understand the related pathophysiological mechanism of vegetation development. We present an approach for ultrastructural analysis of whole-infected heart valve tissue based on scanning electron microscopy and energy-dispersive X-ray spectroscopy. Our approach allowed us to detect differences in cell organization between the analyzed vegetations and revealed a distinct chemical feature in ones. Our results illustrate the benefits that such an approach may bring for guiding therapy, considering the germ involved for each IE patient.
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http://dx.doi.org/10.3390/cells9081899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464176PMC
August 2020

Ultrastructure of a late-stage bacterial endocarditis valve vegetation.

J Thromb Thrombolysis 2021 Apr;51(3):821-826

Aix Marseille Univ, IRD, APHM, MEPHI, IHU Méditerranée Infection, 19-21 Boulevard Jean Moulin, 13385, Marseille Cedex 05, France.

Infective endocarditis (IE) remains a severe illness with high mortality rate, despite advances in antibiotic therapy and cardiac surgery. If infectious bacteria and platelets are two key players of human IE vegetation developmental process, their interactions and respective roles in fully developed late-stage IE vegetations remain obscure. The objective of this study was to better understand the organization of the different components of the IE vegetation and to provide a detailed description of this vegetation ultrastructure. A late stage Staphylococcal endocarditic vegetation was provided from a 13 years teenager patient. After reception of the surgical piece, we carried out a histological study using routine methods, notably the hematoxylin-eosin-saffron staining. Labeling with the anti-CD 61 antibody was also carried out. In a second step, we used transmission electron microscopy to describe the different regions making up the vegetation. Our ultrastructural study revealed vegetation was clearly composed by three different regions and identified the specific location of the bacteria and platelets in the vegetation tissues. Histological analysis showed that platelets and Staphylococcus aureus were not co-localized. Electron microscopy study confirmed that S. aureus were found at distance from platelets, as well from immune cells, embedded in a biofilm and/or a necrotic area. These results reveal a development of a deep bacteria-only niche in vegetation, raising questions about medication access to these microorganisms. Vegetation composed of three regions: a region rich in bacteria incorporated into the necrotic tissue, the second region composed of fibrin filaments and the third region rich in platelets and free of bacteria.
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http://dx.doi.org/10.1007/s11239-020-02232-2DOI Listing
April 2021

Statins potentiate the antibacterial effect of platelets on .

Platelets 2020 Jul 14:1-6. Epub 2020 Jul 14.

IHU Méditerranée Infection, Aix Marseille University, IRD, APHM, MEPHI , Marseille, France.

Platelets have largely demonstrated their implication in anti-infectious immunity. This effect is ensured by the secreted molecules stored mostly in platelet alpha granules. Previous studies have reported that showed sensitivity to this antibacterial effect of platelets. Statins, for their part, have shown a modulating effect on platelet activation. Furthermore, several studies have reported a protective effect of statins in staphylococcal endocarditis. The aim of this study was to investigate the influence of statins on the antibacterial effect of washed platelets. Blood samples were collected from healthy donors (n = 35). PRP was prepared according to the ISTH recommendation. Bacteria were incubated for four hours with untreated-washed platelets, or rather treated by statins and/or GPIIbIIIa antagonists. In order to evaluate the antibacterial effect, the platelet-bacteria mix was spread on the blood agar to count the number of colonies after 18 hours of incubation. Measurement of CD 41 and CD62P expression by flow cytometry was performed to evaluate the effect of statin on bacterial-induced platelet activation. Statins have shown a potentiation of the antibacterial effect of washed platelets ( < .01 for Atorvastatin and Rosuvastatin and < .001 for Fluvastatin untreated washed platelets condition). This effect of statins was dose-dependent and was more significant at 20 μM. The addition of Fluvastatin to platelet-bacterial mix significantly increased the expression of platelet CD41 and CD62P ( < .05 and < .01 vs resting washed platelets, respectively). Tirofiban, GPIIbIIIa antagonist, reversed the antibacterial effect of washed platelets and suppressed the potentiating effect of statins. Our study demonstrated that statins potentiate the anti-staphylococcal effect of washed platelets. This result may explain the beneficial effect of statins on infective endocarditis. Further studies are therefore required to explain this effect at the molecular level and to assess its impact .
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http://dx.doi.org/10.1080/09537104.2020.1792434DOI Listing
July 2020

Antiplatelet Agents Have a Distinct Efficacy on Platelet Aggregation Induced by Infectious Bacteria.

Front Pharmacol 2020 5;11:863. Epub 2020 Jun 5.

Aix Marseille Univ, IRD, APHM, MEPHI, IHU Méditerranée infection, Marseille, France.

Platelets are the cornerstone of hemostasis. However, their exaggerated aggregation induces deleterious consequences. In several diseases, such as infectious endocarditis and sepsis, the interaction between platelets and bacteria leads to platelet aggregation. Despite platelet involvement, no antiplatelet therapy is currently recommended in these infectious diseases. We aimed here, to evaluate, , the effect of antiplatelet drugs on platelet aggregation induced by two of the bacterial pathogens most involved in infectious endocarditis, and . Blood samples were collected from healthy donors (n = 43). Treated platelet rich plasmas were incubated with three bacterial strains of each species tested. Platelet aggregation was evaluated by Light Transmission Aggregometry. CD62P surface exposure was evaluated by flow cytometry. Aggregate organizations were analyzed by scanning electron microscopy. All the strains tested induced a strong platelet aggregation. Antiplatelet drugs showed distinct effects depending on the bacterial species involved with different magnitude between strains of the same species. Ticagrelor exhibited the highest inhibitory effect on platelet activation (p <0.001) and aggregation (p <0.01) induced by . In the case of , platelet activation and aggregation were better inhibited using the combination of both aspirin and ticagrelor (p <0.05 and p <0.001 respectively). Aggregates ultrastructure and effect of antiplatelet drugs observed by scanning electron microscopy depended on the species involved. Our results highlighted that the effect of antiplatelet drugs depended on the bacterial species involved. We might recommend therefore to consider the germ involved before introduction of an optimal antiplatelet therapy.
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http://dx.doi.org/10.3389/fphar.2020.00863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291881PMC
June 2020

Spondylodiscitis complicating infective endocarditis.

Heart 2020 Dec 28;106(24):1914-1918. Epub 2020 May 28.

Cardiology Department, APHM, La Timone Hospital, Marseille, France

Objective: The primary objective was to assess the characteristics and prognosis of pyogenic spondylodiscitis (PS) in patients with infective endocarditis (IE). The secondary objectives were to assess the factors associated with occurrence of PS.

Methods: Prospective case-control bi-centre study of 1755 patients with definite IE with (n=150) or without (n=1605) PS. Clinical, microbiological and prognostic variables were recorded.

Results: Patients with PS were older (mean age 69.7±18 vs 66.2±14; p=0.004) and had more arterial hypertension (48% vs 34.5%; p<0.001) and autoimmune disease (5% vs 2%; p=0.03) than patients without PS. The lumbar vertebrae were the most frequently involved (84 patients, 66%), especially L4-L5. Neurological symptoms were observed in 59% of patients. Enterococci and were more frequent (24% vs 12% and 24% vs 11%; p<0001, respectively) in the PS group. The diagnosis of PS was based on contrast-enhanced MRI in 92 patients, bone CT in 88 patients and F-FDG PET/CT in 56 patients. In-hospital (16% vs 13.5%, p=0.38) and 1-year (21% vs 22%, p=0.82) mortalities did not differ between patients with or without PS.

Conclusions: PS is a frequent complication of IE (8.5% of IE), is observed in older hypertensive patients with enterococcal or IE, and has a similar prognosis than other forms of IE. Since PS is associated with specific management, multimodality imaging including MRI, CT and PET/CT should be used for early diagnosis of this complication of endocarditis.
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http://dx.doi.org/10.1136/heartjnl-2019-316492DOI Listing
December 2020

Effect of antiplatelet agents on platelet antistaphylococcal capacity: An in vitro study.

Int J Antimicrob Agents 2020 Mar 7;55(3):105890. Epub 2020 Jan 7.

Aix-Marseille Université, IRD, APHM, MEPHI, IHU Méditerranée Infection, Marseille, France; Laboratoire d'hématologie, Hôpital de la Timone, APHM, boulevard Jean Moulin, 13005 Marseille, France. Electronic address:

The involvement of platelets in anti-infectious immunity has been widely demonstrated. Molecules secreted mainly by α-granules are involved in reducing the growth of certain bacterial species. However, the effect of antiplatelet treatments on the platelet antibacterial ability remains poorly understood. This study aimed to evaluate the platelet antibacterial effect against Staphylococcus aureus and to evaluate the influence of antiplatelet drugs on this effect. Blood samples were collected from healthy donors or patients treated with antiplatelet therapy. Six S. aureus strains were included. Bacteria were incubated with platelets for 4 h. Colonies were counted on blood agar. The supernatant's effect was evaluated. The effect of in vitro antiplatelet agents and salicylic acid was also tested. The CD62P expression rate was evaluated under different conditions of infection and platelet treatment. Platelets slowed the growth of the six S. aureus strains (P = 0.006 for P6134, P = 0.001 for P6170 and P6138, and P = 0.003 for the other strains versus bacteria alone). The supernatant of platelets pre-infected with bacteria and that of platelets pre-treated with TRAP retained this antibacterial effect (platelet-bacteria supernatant, P = 0.018; TRAP, P = 0.011 versus bacteria alone). Treatment of platelets by antiplatelet drugs significantly decreased this antibacterial effect (aspirin, P = 0.027; ticagrelor, P = 0.0263; combination, P = 0.0092 versus untreated platelets). Salicylic acid also induced inhibition of this antibacterial effect (P = 0.042 versus untreated platelets). This study showed that antiplatelet agents decreased the antibacterial effect of platelets against S. aureus.
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http://dx.doi.org/10.1016/j.ijantimicag.2020.105890DOI Listing
March 2020

The distinct effects of aspirin on platelet aggregation induced by infectious bacteria.

Platelets 2020 Nov 19;31(8):1028-1038. Epub 2019 Dec 19.

Département d'infectiologie, MEPHI, IHU Méditerranée infection, Aix Marseille Univ, IRD, AP-HM , Marseille, France.

Bacteria induce platelet aggregation triggered by several mechanisms. The goal of this work was to characterize platelet aggregates induced by different bacterial strains and to quantify the effect of aspirin treatment using aggregation tests, as well as a novel approach based on confocal analysis. Blood samples were obtained from either healthy donors (n = 27) or patients treated with long-term aspirin (n = 15). The bacterial species included were , and . The different aggregate's ultrastructures depending on the bacterial strain were analyzed using Scanning electron microscopy. Quantification of the size of the platelet aggregates, their mean number as well as the bacterial impregnation within the aggregates was performed using confocal laser scanning light microscopy. Light Transmission Aggregometry was also performed. Our results reported distinct characteristics of platelet aggregates depending on the bacterial strain. Using confocal analysis, we have shown that aspirin significantly reduced platelet aggregation induced by ( = .003) and ( = .006) with no effect in the case of ( = .529). The results of the aggregometry were concordant with those of the confocal technique in the case of and . Interestingly, aggregation induced by was detected only with confocal analysis. In conclusion, our confocal scanning microscopy allowed a detailed study of the platelet aggregation induced by bacteria. We showed that aspirin acts on bacterial-induced platelet aggregation depending on the species. These results are in favor of the use of aspirin considering the species and the bacterial strain involved.
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http://dx.doi.org/10.1080/09537104.2019.1704717DOI Listing
November 2020

Aspirin Effect on -Platelet Interactions During Infectious Endocarditis.

Front Med (Lausanne) 2019 15;6:217. Epub 2019 Oct 15.

Aix Marseille Univ, IRD, APHM, MEPHI, IHU Méditerranée Infection, Marseille, France.

Infectious endocarditis (IE) is a rare disease associated with high mortality and morbidity rate. The platelet-bacterial interaction presents the cornerstone of the development of endocardial vegetation. The epidemiology of IE has undergone profound changes between the last and the new decade, with becoming the main incriminated species. Despite improvements in antibiotic and surgical therapies, embolic disorders remain highly associated with IE that can be fatal. Antiplatelet drugs have been widely proposed to overcome embolic events associated with IE. This proposal has been supported by numerous , experimental, and clinical studies. However, other studies have yielded conflicting results. In this review, we focus on the effect of aspirin on the genesis of endocarditic vegetation, as well as on the management of embolic and hemorrhagic events related to it, starting by its influence on the platelet-bacteria interaction.
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http://dx.doi.org/10.3389/fmed.2019.00217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803506PMC
October 2019

Comparing two blood culture systems for the detection of bacterial contamination in platelet concentrates.

Transfusion 2018 11 7;58(11):2604-2610. Epub 2018 Oct 7.

Aix-Marseille Université, Microbes, Evolution, Phylogeny and Infection (MEPHI) MEPHI, Institut de Recherche pour le Développement (IRD) IRD 198, Marseille, France.

Background: The transfusion of platelet concentrates (PCs) contaminated with bacteria may cause serious, and even fatal, septic reactions in patients. The aim of this study was to compare the VersaTREK with the BACTEC FX automated culture systems for screening bacterial contamination, directly after the delay of 24 hours of preparation to obtain the final pooled buffy coat PCs, to prevent transfusion-transmitted bacterial infections.

Study Design And Methods: Seven bacterial strains were each inoculated into five replicate pooled buffy coat PCs at approximately 100 colony-forming units/unit, and 5- or 10-mL samples were inoculated into duplicate aerobic culture bottles. The time and detection rates were compared between BACTEC FX, as a reference method, and VersaTREK.

Results: Time to detection was significantly shorter using VersaTREK for most species detected by both systems for the volumes tested. Of 70 VersaTREK cultures, 69 (98.57% detection rate) were positive after 24 hours of incubation with the 5-mL sample. In contrast, the BACTEC FX system detected all positive samples in PCs for the volume of 10 mL, although seven samples were false negatives for the 5-mL volume.

Conclusion: The VersaTREK system compared favorably to the BACTEC FX system for 5-mL volumes (p < 0.05) and could be considered a potential method for detecting bacterial contamination in PC samples directly after 24 hours of preparation of the final pooled buffy coat PCs.
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http://dx.doi.org/10.1111/trf.14911DOI Listing
November 2018

The hidden side of oral thrombin inhibitors.

Int J Cardiol 2019 01 6;274:186-187. Epub 2018 Sep 6.

Aix-Marseille University, APHM, Cardiology Department, Hospital Nord, Marseille, France.

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http://dx.doi.org/10.1016/j.ijcard.2018.09.001DOI Listing
January 2019

Intracranial haemorrhage in infective endocarditis.

Arch Cardiovasc Dis 2018 Dec 5;111(12):712-721. Epub 2018 Jun 5.

Cardiology Department, la Timone Hospital, AP-HM, boulevard Jean-Moulin, 13005 Marseille, France; MEPHI, IRD, IHU-Méditerranée Infection, Aix Marseille University, AP-HM, 13005 Marseille, France.

Background: Although intracranial cerebral haemorrhage (ICH) complicating infective endocarditis (IE) is a critical clinical issue, its characteristics, impact, and prognosis remain poorly known.

Aims: To assess the incidence, mechanisms, risk factors and prognosis of ICH complicating left-sided IE.

Methods: In this single-centre study, 963 patients with possible or definite left-sided IE were included from January 2000 to December 2015.

Results: Sixty-eight (7%) patients had an ICH (mean age 57±13 years; 75% male). ICH was classified into three groups according to mechanism: ruptured mycotic aneurysm (n=22; 32%); haemorrhage after ischaemic stroke (n=27; 40%); and undetermined aetiology (n=19; 28%). Five variables were independently associated with ICH: platelet count<150×10/L (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.01-5.4; P=0.049); severe valve regurgitation (OR 3.2, 95% CI 1.3-7.6; P=0.008); ischaemic stroke (OR 4.2, 95% CI 1.9-9.4; P<0.001); other symptomatic systemic embolism (OR 14.1, 95% CI 5.1-38.9; P<0.001); and presence of mycotic aneurysm (OR 100.2, 95% CI 29.2-343.7; P<0.001). Overall, 237 (24.6%) patients died within 2.3 (0.7-10.4) months of follow-up. ICH was not associated with increased mortality (P not significant). However, the 1-year mortality rate differed according to ICH mechanism: 14%, 15% and 45% in patients with ruptured mycotic aneurysm, haemorrhage after ischaemic stroke and undetermined aetiology, respectively (P=0.03). In patients with an ICH, mortality was higher in non-operated versus operated patients when cardiac surgery was indicated (P=0.005). No operated patient had neurological deterioration.

Conclusions: ICH is a common complication of left-sided IE. The impact on prognosis is dependent on mechanism (haemorrhage of undetermined aetiology). We observed a higher mortality rate in patients who had conservative treatment when cardiac surgery was indicated compared with in those who underwent cardiac surgery.
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http://dx.doi.org/10.1016/j.acvd.2018.03.009DOI Listing
December 2018

Benefit of Switching Dual Antiplatelet Therapy After Acute Coronary Syndrome According to On-Treatment Platelet Reactivity: The TOPIC-VASP Pre-Specified Analysis of the TOPIC Randomized Study.

JACC Cardiovasc Interv 2017 12;10(24):2560-2570

Département de Cardiologie, CHU Timone, Marseille, France; "Nutrition, Obesity and Risk of Thrombosis," UMR1062, INSERM, Marseille, France; Faculté de Médecine, Aix-Marseille Université, Marseille, France. Electronic address:

Objectives: This study sought to evaluate the impact of initial platelet reactivity on the benefit of switched strategy.

Background: TOPIC (Timing Of Platelet Inhibition after acute Coronary Syndrome) study suggested that switched dual antiplatelet therapy (DAPT) could improve net clinical benefit after acute coronary syndrome by preventing bleeding.

Methods: Acute coronary syndrome patients, 1 month after coronary stenting and event free, were randomly assigned to aspirin and clopidogrel (switched DAPT) or continuation of drug regimen (unchanged DAPT). All patients underwent platelet function testing at this time and were classified as low on-treatment platelet reactivity (LTPR) (platelet reactivity index vasodilator-stimulated phosphoprotein ≤20%) or non-LTPR (platelet reactivity index vasodilator-stimulated phosphoprotein >20%). The primary endpoint aimed to evaluate the impact of platelet reactivity on clinical outcomes and benefit of switched DAPT strategy.

Results: A total of 645 patients were included, 305 (47%) of whom were classified as LTPR. LTPR patients were less often diabetic (p = 0.01), had lower body mass index (p < 0.01), and were more often on ticagrelor (p < 0.01). Patients defined as LTPR and randomized to unchanged DAPT were at the highest risk of primary endpoint occurrence (31%; p < 0.01). Conversely, in the switched arm, LTPR patients had no significant difference in primary outcome incidence compared with non-LTPR patients (hazard ratio [HR]: 0.78; 95% confidence interval [CI]: 0.40 to 1.49; p = 0.45). The switched strategy was associated with important reduction in primary endpoint incidence in LTPR patients (HR: 0.29; 95% CI: 0.17 to 0.51; p < 0.01) and only numerically lower incidence in non-LTPR patients (HR: 0.79; 95% CI: 0.46 to 1.35; p = 0.39).

Conclusions: Switched DAPT was superior regardless of initial platelet reactivity but the benefit was greater in LTPR patients. Indeed, the switched strategy was highly effective in this group, which had impaired prognosis with unchanged DAPT but similar prognosis after switching.
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http://dx.doi.org/10.1016/j.jcin.2017.08.044DOI Listing
December 2017

Rapid identification of microorganisms from platelet concentrates by matrix-assisted laser desorption ionization time-of-flight mass spectrometry after short-term incubation on liquid medium.

Transfusion 2018 03 28;58(3):766-773. Epub 2017 Nov 28.

Aix-Marseille Université, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), UM63, CNRS 7278, IRD 198, INSERM U1095, Marseille.

Background: Platelets (PLTs) are especially affected by the risk of bacterial contamination. Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) is an accurate method for the routine identification of bacterial isolates in microbiology laboratories. We directly applied the MALDI-TOF method to bacterial detection in PLTs. In this study, we evaluated the sensitivity, specificity, and speed of a direct MALDI-TOF approach compared to the conventional method BACTEC.

Study Design And Methods: Eight bacteria associated with PLT contamination, cited by the ISBT on transfusion-transmitted infectious diseases, were spiked into PLTs for a final concentration of approximately 100 CFU/bag (n = 5 for each strain). The PLTs were then agitated for 24 hours. One milliliter of PLTs was incubated in a shaker incubator for 8 hours at 37°C with 1 mL of trypticase soy broth (TSB). The spectra were analyzed using the MALDI Biotyper software. As a control, 8 mL of PLTs incubated into BACTEC bottles and a positive bottle were subcultured to ensure identification of bacterial growth.

Results: Regardless of the strain of PLTs tested, MALDI-TOF analysis made detection and early identification possible at 8 hours. Analysis by BACTEC of PLTs infected with Escherichia coli, Bacillus cereus, and Providencia stuartii made early identification possible. For the remaining bacteria, the detection time by BACTEC was significantly longer than 8 hours.

Conclusion: We demonstrated the possibility of detecting bacteria in PLTs using a standardized culture step in TSB with MALDI-TOF, regardless of the strain, with the same specificity and analytical sensitivity and with a time to results of 12 hours. This direct method presented rapid and reliable results.
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http://dx.doi.org/10.1111/trf.14430DOI Listing
March 2018

Antithrombotic efficacy of bivalirudin compared to unfractionated heparin during percutaneous coronary intervention for acute coronary syndrome.

Platelets 2019 27;30(1):105-111. Epub 2017 Nov 27.

b Aix-Marseille Université, INSERM UMR-S 1076 , Vascular Research Center of Marseille , Marseille , France.

Bivalirudin is associated with an increased risk of acute stent thrombosis (AST) compared to unfractionated heparin (UFH) in acute coronary syndrome patients (ACS) during short-duration percutaneous coronary intervention (PCI). The mechanisms involved are unknown. We aimed to investigate the antithrombotic efficacy of bivalirudin compared to UFH during PCI. In a monocenter study, we prospectively enrolled 30 patients undergoing PCI for a non-ST elevation ACS. They were randomly assigned to a single intravenous (IV) bolus of UFH (70 IU/kg) or an IV bolus of bivalirudin 0.75 mg/kg followed by a 1.75 mg/kg/h infusion during PCI. All patients received a loading dose (LD) of 180 mg of ticagrelor at the time of PCI. The VASP index and activated partial thromboplastin time (aPTT) were used to assess the course of platelet reactivity (PR) and antithrombotic activity. The two groups were similar regarding baseline, angiographic, and interventional characteristics. There was no difference between the two groups in the course of PR following ticagrelor LD. An optimal PR inhibition was obtained 4 h after the LD of ticagrelor. The level of antithrombotic activity was significantly lower in the bivalirudin group compared to the UFH group (p < 0.001) during PCI but similar at 2 and 4 h post-PCI. We observed that, in ACS undergoing PCI, the antithrombotic efficacy of an IV bolus of bivalirudin is significantly lower than that of a 70-IU/kg UFH bolus. This could contribute to the excess in thrombotic acute events observed during short-duration PCI.
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http://dx.doi.org/10.1080/09537104.2017.1384541DOI Listing
March 2019

In vitro detection of bacterial contamination in platelet concentrates by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: a preliminary study.

J Med Microbiol 2017 Nov 6;66(11):1523-1530. Epub 2017 Oct 6.

AP-HM, Laboratoire d'Hématologie, CHU Timone, Marseille, France.

Purpose: Platelet concentrates are at risk of transfusion-related sepsis. The microbial detection methods currently available have reached their limits, as they do not completely prevent transfusion-related bacterial contamination.The aim of this study was to develop a new strategy to detect the risk of platelet transfusion-related bacterial contamination using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).

Methodology: In vitro, platelet concentrates were seeded with known concentrations of bacterial strains. Protein mass profiles were acquired by using a Microflex MALDI-TOF instrument. Dedicated 'Platelet' software was used as a spectrum subtraction tool to reveal specific peaks caused by the presence of pathogens in samples.

Results: The MALDI-TOF spectra of platelets were characterized and the reproducibility over time, regardless of the blood donor, was demonstrated with a positive predictive value of 100 %. In addition, the negative predictive value of the total number of specific peaks to predict contamination was 100 %.

Conclusion: Detecting bacteria in platelet concentrates using the MALDI-TOF approach and analysing spectra with the Platelet software present the advantage of combining the precocity of results and sufficient sensitivity (10 c.f.u. ml). Further research will be conducted to compare this novel method with the current conventional method in order to validate our results, the objective being to reduce the risk of platelet transfusion-related bacterial contamination.
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http://dx.doi.org/10.1099/jmm.0.000533DOI Listing
November 2017

Thrombosis and antiphospholipid antibody syndrome during acute Q fever: A cross-sectional study.

Medicine (Baltimore) 2017 Jul;96(29):e7578

URMITE, Aix Marseille Université, UM63, CNRS 7278, IRD 198, INSERM 1095, IHU - Méditerranée Infection Aix Marseille Univ, APHM, INSERM, VRCM, UMR_S 1076, Laboratoire d'Immunologie, Marseille Service de médecine interne Service de maladies infectieuses, Centre Hospitalier Universitaire de Grenoble, Grenoble Service de médecine interne, Centre hospitalier d'Avignon, Avignon Service de médecine interne et tropicale, Hôpital d'Instruction des Armées Laveran, Marseille Service de neurologie, Hôpital de Valence, Valence Service de maladies infectieuses, Hôpital Bretonneau, Tours Centre Hospitalier Universitaire de Nice, Nice Service de médecine interne et maladies infectieuses, CHU de Poitiers, Inserm, Poitiers Service de maladies infectieuses, CHU de Montpellier, Montpellier Centre Hospitalier Andrée-Rosemon, Cayenne, Guyane Aix Marseille Univ, INSERM, UMR912 (SESSTIM), IRD ORS PACA Laboratoire d'Hématologie, CHU Timone, APHM, Marseille, France.

Q fever is a neglected and potentially fatal disease. During acute Q fever, antiphospholipid antibodies are very prevalent and have been associated with fever, thrombocytopenia, acquired heart valve disease, and progression to chronic endocarditis. However, thrombosis, the main clinical criterion of the 2006 updated classification of the antiphospholipid syndrome, has not been assessed in this context. To test whether thrombosis is associated with antiphospholipid antibodies and whether the criteria for antiphospholipid syndrome can be met in patients with acute Q fever, we conducted a cross-sectional study at the French National Referral Center for Q fever.Patients included were diagnosed with acute Q fever in our Center between January 2007 and December 2015. Each patient's history and clinical characteristics were recorded with a standardized questionnaire. Predictive factors associated with thrombosis were assessed using a rare events logistic regression model. IgG anticardiolipin antibodies (IgG aCL) assessed by an enzyme-linked immunosorbent assay were tested on the Q fever diagnostic serum. A dose-dependent relationship between IgG aCL levels and thrombosis was tested using a receiver operating characteristic (ROC) analysis.Of the 664 patients identified for inclusion in the study, 313 (47.1%) had positive IgG aCL and 13 (1.9%) were diagnosed with thrombosis. Three patients fulfilled the antiphospholipid syndrome criteria. After multiple adjustments, only positive IgG aCL (relative risk, 14.46 [1.85-113.14], P = .011) were independently associated with thrombosis. ROC analysis identified a dose-dependent relationship between IgG aCL levels and occurrence of thrombosis (area under curve, 0.83, 95%CI [0.73-0.93], P < .001).During acute Q fever, antiphospholipid antibodies are associated with thrombosis, thrombocytopenia, and acquired valvular heart disease. Antiphospholipid antibodies should be systematically assessed in acute Q fever patients. Hydroxychloroquine, which has been previously shown to antagonize IgG aCL pathogenic properties, should be tested in acute Q fever patients with anticardiolipin antibodies to prevent antiphospholipid-associated complications.Key Point: In addition to fever, thrombocytopenia and acquired valvular heart disease, antiphospholipid antibodies are associated with thrombosis during acute Q fever.
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http://dx.doi.org/10.1097/MD.0000000000007578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5521934PMC
July 2017

Coronary events complicating infective endocarditis.

Heart 2017 12 22;103(23):1906-1910. Epub 2017 Jun 22.

Aix-Marseille Université, Marseille, France.

Objective: Acute coronary syndromes (ACS) are a rare complication of infective endocarditis (IE). Only case reports and small studies have been published to date. We report the largest series of ACS in IE. The aim of our study was to describe the incidence and mechanisms of ACS associated with IE, to assess their prognostic impact and to describe their management.

Methods: In a bicentre prospective observational cohort study, all patients with a definite diagnosis of IE were prospectively included. The incidence, mechanism and prognosis of patients with ACS were studied.

Results: Among 1210 consecutive patients with definite IE, 26 patients (2.2%) developed an ACS. Twenty-three patients (88%) had a coronary embolism. Two patients had coronary compression by an abscess or a pseudoaneurysm and one patient had an obstruction of his bioprosthesis and left coronary ostium by a large vegetation. Nineteen (73%) patients with ACS developed heart failure and this complication was 2.5 times more frequent than in patients without ACS (p<0.0001). In the ACS population, mortality rate was twice than the population without ACS.

Conclusions: ACS is a rare complication of IE but is associated with an increased risk of heart failure and high mortality rate.
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http://dx.doi.org/10.1136/heartjnl-2017-311624DOI Listing
December 2017

Cross-Reactivity Between Heparin and Danaparoid Antibodies in Cardiac Surgery.

Ann Thorac Surg 2017 Jan;103(1):e9-e10

Aix-Marseille Université, URMITE, UM63, CNRS 7278, Inserm U1095, Faculté de Médecine, Marseille, France; Laboratoire d'Hématologie, C.H.U. La Timone, APHM, Marseille, France. Electronic address:

Management of heparin-induced thrombocytopenia (HIT) entails cessation of heparin and initiation of a nonheparin parenteral anticoagulant such as danaparoid. Danaparoid cross-reactivity with HIT antibodies is an uncommon complication of treatment of HIT. We report the case of confirmed HIT and in vivo cross-reactivity with danaparoid, complicating severe sepsis due to an infectious endocarditis treated by cardiac surgery.
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http://dx.doi.org/10.1016/j.athoracsur.2016.06.068DOI Listing
January 2017

Potential mechanism of acute stent thrombosis with bivalirudin following percutaneous coronary intervention in acute coronary syndromes.

Int J Cardiol 2016 Oct 28;220:496-500. Epub 2016 Jun 28.

Service de cardiologie, Centre hospitalo-universitaire, Aix-Marseille université, Assistance-Publique Hôpitaux de Marseille, Marseille, France; MARS cardio, Mediterranean Association for Research and Studies in Cardiology, Hôpital Nord, Marseille, France; Service d'hématologie Biologique, Centre hospitalo-universitaire Timone, Assistance-Publique Hôpitaux de Marseille, Marseille, France. Electronic address:

Background: Clinical trials have demonstrated an excess of acute stent thrombosis (AST) in acute coronary syndromes patients (ACS) undergoing percutaneous coronary intervention (PCI) with bivalirudin compared to heparin. We aimed to investigate the potential mechanisms responsible for thrombus formation under bivalirudin.

Methods: We compared heparin and bivalirudin during PCI for ACS in a prospective monocentre randomized study. Twenty patients were included after coronary angiography and received a loading dose (LD) of 180mg of ticagrelor at the time of PCI. They were randomly assigned to heparin (70UI/kg) intra-venous (IV) bolus or bivalirudin IV bolus of 0.75mg/kg followed by an infusion of 1.75mg/kg/h until the end of the PCI. The VASP index and thrombin generation test were used to assess the course of platelet reactivity (PR) and thrombin generation.

Results: Thrombin generation and PR were identical in both groups at baseline. There was no difference in the course of PR following the LD over time. An optimal PR inhibition was reached 4h after the LD of ticagrelor. Heparin and bivalirudin infusion effectively inhibited thrombin generation during PCI. However, 4h after the end of bivalirudin infusion, thrombin generation had returned to its baseline value whereas in the heparin group it remained significantly inhibited compared to baseline and to the bivalirudin group 4h after the end of the infusion (p<0.01 and p<0.02 respectively).

Conclusions: The present study suggests that the short half-life of bivalirudin and the quick restoration of thrombin activity at a time when optimal PR is not reached may be responsible for acute stent thrombosis. Clinicaltrial.gov: NCT02428725.
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http://dx.doi.org/10.1016/j.ijcard.2016.06.247DOI Listing
October 2016

Onset of optimal P2Y12-ADP receptor blockade after ticagrelor and prasugrel intake in Non-ST elevation acute coronary syndrome.

Thromb Haemost 2015 Oct 27;114(4):702-7. Epub 2015 Aug 27.

Laurent Bonello MD, PhD, Département de Cardiologie, Hôpital universitaire Nord de Marseille, INSERM UMRS 1076, Aix-Marseille Université, Chemin des Bourrely, Marseille 13015, France, Tel.: +33 491968858, Fax: +33 491968979, E-mail:

Pretreatment with a loading dose (LD) of clopidogrel or ticagrelor before percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) is supported by the guidelines, but debated following a recent meta-analysis on clopidogrel pretreatment and the ACCOAST trial. In this trial prasugrel pretreatment failed to reduce ischaemic events. The timing of optimal platelet reactivity (PR) inhibition of ticagrelor and prasugrel in non ST-elevation ACS (NSTE ACS) is yet undetermined. In the present study, we aimed to investigate the delay required to reach optimal PR inhibition in NSTE ACS following a LD of ticagrelor or prasugrel. Consecutive patients undergoing PCI for NSTE ACS were randomised in this monocentre study. The Vasodilator-phosphoprotein index (VASP) was used to measure PR before the LD and then at 30 minutes, 1, 2, 4 and 24 hours (h) post-LD. Optimal PR inhibition was defined as a VASP < 50%. We randomised 24 patients to ticagrelor or prasugrel LD. One hour after the LD, 29% of patients had a VASP > 50% (ticagrelor and prasugrel: 25 vs 33%; p=0.7). Optimal PR inhibition was obtained 2 h after the LD in both groups (12/12 with ticagrelor and 11/12 with prasugrel). At that time, the mean VASP index was 19 ± 16% (95%CI: 12-25). Maximal PR inhibition was reached after 4 h: 11 ± 10% (95%CI: 6-15). In NSTE ACS undergoing PCI a LD of ticagrelor or prasugrel given during the procedure provides optimal P2Y12-ADP receptor blockade in 2 h and maximal inhibition within 4 h.
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http://dx.doi.org/10.1160/TH15-02-0149DOI Listing
October 2015

Enhanced prevalence of plasmatic soluble MHC class I chain-related molecule in vascular pregnancy diseases.

Biomed Res Int 2014 27;2014:653161. Epub 2014 Aug 27.

Aix-Marseille Université, UMR 1076 INSERM, Vascular Research Center of Marseille, 3005 Marseille, France ; Assistance Publique Hôpitaux de Marseille, Hematology Department, Secteur de Biologie Vasculaire, Hôpital Conception, 13005 Marseille, France.

The major histocompatibility complex class I related chain (MIC) is a stress-inducible protein modulating the function of immune natural killer (NK) cells, a major leukocyte subset involved in proper trophoblast invasion and spiral artery remodeling. Aim of the study was to evaluate whether upregulation of soluble MIC (sMIC) may reflect immune disorders associated to vascular pregnancy diseases (VPD). sMIC was more frequently detected in the plasma of women with a diagnostic of VPD (32%) than in normal term-matched pregnancies (1.6%, P < 0.0001), with highest prevalence in intrauterine fetal death (IUDF, 44%) and vascular intrauterine growth restriction (IUGR, 39%). sMIC levels were higher in preeclampsia (PE) than in IUFD (P < 0.01) and vascular IUGR (P < 0.05). sMIC detection was associated with bilateral early diastolic uterine notches (P = 0.037), thrombocytopenia (P = 0.03), and high proteinuria (P = 0.03) in PE and with the vascular etiology of IUGR (P = 0.0038). Incubation of sMIC-positive PE plasma resulted in downregulation of NKG2D expression and NK cell-mediated IFN-γ production in vitro. Our work thus suggests that detection of sMIC molecule in maternal plasma may constitute a hallmark of altered maternal immune functions that contributes to vascular disorders that complicate pregnancy, notably by impairing NK-cell mediated production of IFN-γ, an essential cytokine favoring vascular modeling.
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http://dx.doi.org/10.1155/2014/653161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4160641PMC
June 2015

Ticagrelor increases adenosine plasma concentration in patients with an acute coronary syndrome.

J Am Coll Cardiol 2014 Mar 27;63(9):872-7. Epub 2013 Nov 27.

Research Unit of Physiology and Dysoxia and suractivity, UMR MD2 and Institute of Biological Research, French Defense Ministry (IRBA), Marseille, France; Laboratoire de Biochimie, Hôpital Universitaire Nord de Marseille, Assistance-Publique Hôpitaux de Marseille, Marseille, France.

Objectives: This study aimed to investigate the impact of ticagrelor on adenosine plasma concentration (APC) in acute coronary syndrome (ACS) patients.

Background: Ticagrelor is a direct-acting P2Y12-adenosine diphosphate receptor blocker. The clinical benefit of ticagrelor compared with clopidogrel in ACS patients suggests that the drug has non-platelet-directed properties. Animal and in vitro models suggested that the "pleiotropic" properties of ticagrelor may be related to an interaction with adenosine metabolism.

Methods: We prospectively randomized 60 ACS patients to receive ticagrelor or clopidogrel. The APC was measured by liquid chromatography. To assess the mechanism of APC variation, we measured adenosine deaminase concentration, adenosine uptake by red blood cells, and cyclic adenosine monophosphate production by cells overexpressing adenosine receptors. The P2Y12-adenosine diphosphate receptor blockade was assessed by the vasodilator-stimulated phosphoprotein index.

Results: Patients receiving ticagrelor had significantly higher APC than patients receiving clopidogrel (1.5 μM [interquartile range: 0.98 to 1.7 μM] vs. 0.68 μM [interquartile range: 0.49 to 0.78 μM]; p < 0.01). The APC was not correlated with vasodilator-stimulated phosphoprotein (p = 0.16). Serum-containing ticagrelor inhibited adenosine uptake by red blood cells compared with clopidogrel or controls (p < 0.01 for both comparisons). Adenosine deaminase activity was similar in serum of patients receiving clopidogrel or ticagrelor (p = 0.1). Ticagrelor and clopidogrel had no direct impact on adenosine receptors (p = not significant).

Conclusions: Ticagrelor increases APC in ACS patients compared with clopidogrel by inhibiting adenosine uptake by red blood cells.
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http://dx.doi.org/10.1016/j.jacc.2013.09.067DOI Listing
March 2014

A randomized trial of platelet reactivity monitoring-adjusted clopidogrel therapy versus prasugrel therapy to reduce high on-treatment platelet reactivity.

Int J Cardiol 2013 Oct 2;168(4):4244-8. Epub 2013 Aug 2.

Département de cardiologie, Hôpital universitaire nord, Aix-Marseille Univ., Marseille, France; INSERM UMRS 608, UFR de pharmacie, Marseille, France. Electronic address:

Background: Peri-procedural platelet reactivity (PR) inhibition is critical in patients undergoing percutaneous coronary intervention (PCI). High on-treatment PR (HTPR) was associated with recurrent ischemic events in acute coronary syndrome (ACS) patients undergoing PCI. We aimed to compare a strategy of clopidogrel loading dose-adjustment (CDA) according to PR monitoring with standard prasugrel therapy to reduce the rate of patients exhibiting HTPR.

Methods: We enrolled 177 ACS patients in a prospective multicentre randomized trial comparing CDA according to PR monitoring and prasugrel therapy. The VASP index was used to measure PR and a VASP ≥ 50% defined HTPR. The primary endpoint of the study was the rate of HTPR on discharge.

Results: Baseline characteristics of the CDA group (n = 88) and of the prasugrel group (n = 89) were similar. CDA significantly reduced PR and the rate of HTPR compared to a single LD of clopidogrel (30.9 ± 13.9%; p < 0.0001 and 43 to 2.3%; p < 0.001, respectively). Following CDA the rate of patients with HTPR was significantly lower in the CDA group compared to the prasugrel group on discharge (2.3 vs 15.7%; p = 0.005). In addition fewer patients in the CDA group had a VASP < 16% on discharge (14.7 vs 50.5%; p <0.0001).

Conclusion: In the present study, PR monitoring was superior to standard prasugrel therapy to reduce the rate of HTPR in ACS patients. In addition such strategy reduced the number of patients with very low PR.
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http://dx.doi.org/10.1016/j.ijcard.2013.07.147DOI Listing
October 2013