Prospective observational study of the effect of dual antiplatelet therapy with tranexamic acid treatment on platelet function and bleeding after cardiac surgery.

BACKGROUND: The bleeding impact of dual antiplatelet therapy (DAPT), aspirin and clopidogrel, maintained until coronary artery bypass graft surgery (CABG), is still a matter of debate. The lack of preoperative antiplatelet activity measurement and heterogeneity of antifibrinolytic protocols in prior studies make the conclusions questionable. The aim of this prospective study was to determine, after preoperative antiplatelet activity measurement, if the maintenance of DAPT until CABG increases bleeding in patients treated with tranexamic acid (TA). METHODS: This observational study included 150 consecutive patients, 89 treated with aspirin and 61 treated with DAPT, undergoing a first-time planned on-pump CABG with TA treatment. Antiplatelet activity was measured with platelet aggregation tests and quantification of VASP phosphorylation. Postoperative bleeding at 24 h was recorded and propensity score analysis was performed. RESULTS: Based on VASP assay, 54% of patients showed high on-clopidogrel platelet activity inhibition. Postoperative bleeding at 24 h increased by 22% in the DAPT group, compared with the aspirin group (680 [95% CI: 360-1670] vs 558 [95%CI: 267-1270] ml, P < 0.01), consistent with increased blood transfusion (21% vs 7%, P = 0.01); a higher incidence of mediastinitis did not reach statistical significance (15% vs 4%, P = 0.05). Bleeding correlated with the extent of clopidogrel antiplatelet effect, with the best correlation for the VASP assay. CONCLUSIONS: Maintenance of DAPT until the day of CABG in patients treated with TA, increased postoperative bleeding at 24 h in parallel with preoperative antiplatelet activity induced by clopidogrel.

[Incidence of sample storage temperature on HbA 1c determination by high performance liquid chromatography method]. / Influence de la température de conservation sur le dosage d'HbA 1c par méthode de chromatographie liquide haute performance.

We have evaluated the conservation prior to HbA(1c) determination of three whole blood samples stored at -80 degrees C, -20 degrees C, 4 degrees C and 20 degrees C, for a maximal duration of one year. HbA(1c) was measured by an ion-exchange high performance liquid chromatography (HPLC) method (Variant II). We have analyzed the HbA(1c) value and the quality of the chromatographic separation for each sample. Storage of whole blood samples at -80 degrees C is good for at least one year. Storage at 4 degrees C is correct for two weeks, without major sample degradation. A more important and earlier degradation occurs at -20 degrees C. The conservation at 20 degrees C (room temperature) is very short. In conclusion, the temperatures of 4 and -80 degrees C are of interest for whole blood storage before HbA(1c) measurement, respectively for short and long term conservations. The temperatures of 20 and -20 degrees C are not recommended.

[Evaluation of Variant II analyzer equipped with the new 270-2101 NU kit (Bio-Rad) for HbA 1c assay]. / Evaluation de l'analyseur Variant II équipé de la nouvelle trousse 270-2101 NU (Bio-Rad) pour le dosage de l'HbA 1c.

HbA(1c) represents a key parameter in the follow-up of glycemic balance in diabetic patients. It may be assayed by different methods, among which high-pressure liquid chromatography (HPLC). We have evaluated a new method available on HPLC Variant II analyzer (BioRad) equipped with the new kit 270-2101 NU. Chromatographic separation is improved, allowing a better identification of peaks. Intra- and inter-assay coefficients of variation are respectively lower than 1.1% and 1.8%. Linearity is excellent from 3.2% to more than 18%. The correlation with the previous method (kit 270-2101) is good: y (% HbA(1c) new kit) = 0.944x (% HbA(1c) previous kit) + 0.299, r(2) = 0.995. There is no inter-sample contamination. This method is less sensitive to interferences frequently found in practice (labile glycated hemoglobin, carbamylated haemoglobin) than the previous one. Validation is possible in more circumstances when an abnormal hemoglobin is present (especially in case of hemoglobin D or E). As the control of analytic quality is a major element for validation and clinical use of HbA(1c) results, the characteristics of this new method make it a well-suited tool for daily laboratory practice.

[Interference of labile glycated hemoglobin on HbA(1c) assay by a high pressure liquid chromatography method]. / Interférence de l'hémoglobine glyquée labile sur le dosage de l'HbA(1c) par une méthode de chromatographie liquide haute performance.

HbA(1c) assay by high pressure liquid chromatography remains submitted to interferences, among which that of labile HbA(1c) in 1 to 2% of samples. We have evaluated the interference of labile HbA(1c) on HbA(1c) assay using Variant II analyzer (Biorad), by in vitro formation of labile glycated haemoglobin and by evaluation of two protocols of elimination of labile HbA(1c) (wash and incubation of red blood cells in saline solution, or incubation in the wash/dilution solution of the analyzer). Levels of labile HbA(1c) higher than 4.5 % lead to underestimation of HbA(1c). The different protocols tested proved efficient and were adapted to routine conditions. The fastest method is the incubation of red blood cells in the wash/dilution solution for at least two hours, or more if labile fraction is unusually high.

[Proton pump inhibitors and clopidogrel: a hazardous association?]. / Inhibiteurs de la pompe à protons et clopidogrel (Plavix®): une liaison dangereuse ?

Proton pump inhibitors (PPI) and antiplatelet agents, especially aspirin and clopidogrel, are among the most prescribed medications worldwide. Their co-administration is justified by the increased risk of gastrointestinal bleeding related to the antiplatelet therapy. The issue of the interaction between PPI and clopidogrel has been raised with the emergence of the concept of "high on-clopidogrel platelet reactivity" (or "clopidogrel resistance") together with the discovery of the role of CYP2C19 isoform in the pharmacokinetics of those two medications. Indeed, CYP2C19 is involved in the conversion of the clopidogrel pro-drug into its active metabolite and is involved in the metabolisation of PPI into inactive metabolites, acting as substrates/inhibitors of CYP2C19. Despite their heterogeneity, most pharmacodynamic studies have shown a decreased clopidogrel antiplatelet effect when associated to PPI, especially those with the highest CYP2C19 inhibiting activity (omeprazole, lansoprazole, rabeprazole). On the other hand, clinical studies are inconclusive. Retrospective studies have shown an increased risk of major cardiovascular events or mortality when clopidogrel and PPI are associated in comparison with clopidogrel alone, particularly in the patients with the higher cardiovascular risk. However, the two prospective randomized studies published so far did not find any interaction and confirmed the benefit of PPI on the gastrointestinal bleeding. As a conclusion, as the clinical studies are not conclusive, the French health authorities have recently removed the alert about this interaction. PPI and clopidogrel can thus be co-prescribed.

[Hydroxychloroquine: a new therapeutic approach to the thrombotic manifestations of antiphospholipid syndrome]. / Hydroxychloroquine: une nouvelle approche thérapeutique des manifestations thrombotiques du syndrome des antiphospholipides.

Studies have shown a protective effect of hydroxychloroquine on thrombosis in systemic lupus erythematosus patients. Recent in vitro studies have demonstrated that this molecule was able to restore the anticoagulant action of annexin A5, which is reduced in presence of antiphospholipid antibodies. Hydroxychloroquine use may be a new approach of the prevention of thrombosis in the antiphospholipid syndrome, which remains to be validated by well-conducted clinical trials.