P Ffrench

Hôpital Louis Pradel, Lyons, Rhône-Alpes, France

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Publications (50)153.94 Total impact

  • Thrombosis Research 11/2012; · 3.13 Impact Factor
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    ABSTRACT: Analyses of site-directed fibrinogen mutants expressed in several recombinant models have previously shown that both inter- and intra-chain disulfide bonds are critical for fibrinogen assembly and secretion. Four naturally occurring mutations on AαCys36 and AαCys45 residues are reported here to be associated with decreased fibrinogen levels. This confirms the main role of the AαCys36-BβCys65 and AαCys45-γCys23 disulfide bonds in reaching a normal fibrinogen plasma level. Decreased coagulant/antigen ratios indicate abnormal species secretion in heterozygous subjects which varies between individuals. However, in contrast to overexpression in experimental models, disruption of the AαCys36-BβCys65 disulfide bond did not result in the appearance of Aα-Bβ-γ moieties in vivo. A 188 kDa molecule reacting only with anti Aα and anti Bβ chains was found in the plasma of the AαCys45Tyr variant. Heterozygous carriers of Aα chain mutations usually have normal fibrinogen levels, in contrast to the AαCys36Gly, AαCys36Arg and AαCys45Tyr variants that are shown here to cause hypofibrinogenemia.
    Haematologica 04/2011; 96(8):1226-30. · 5.94 Impact Factor
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    ABSTRACT: To evaluate whether intensivists would accept to optimize their orderings of biological samplings, x-rays and target drugs and to assess the consequence on patient's outcome. Monocentric evaluation of medical economic procedure. Meetings of consultants, registrars and residents started on Dec 21, 2006 with two to three sessions a year in order to evaluate the process of medical ordering. The physicians and pharmacists gave the results of orderings at each meeting. Orderings of systematic samplings, bedside x-rays and unjustified expansive drugs were discouraged, but target samplings and lung ultrasonography were encouraged. New residents were systematically taught about this programme. Meanwhile, monthly morbidity-mortality meetings were pursued in order to assess the consequences of this politics. While ICU total production increased by 3.4% and potentially evitable deaths decreased by 34%, annual expenses decreased by approximatively € 777,000 from 2006 to 2008. This was due to decreased orderings in biology by 30%, bedside x-rays by 10%, computed tomographic scans by 16% and target drugs by 35%. However, an increased ordering in four target drugs was observed in 2008 as compared with 2007. Multidisciplinary optimization of medical ordering can be efficient in ICU. However, a profit-sharing with ordering physicians would be necessary to prolong these effects.
    Annales francaises d'anesthesie et de reanimation 10/2010; 29(10):682-6. · 0.77 Impact Factor
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    ABSTRACT: Objectives To evaluate whether intensivists would accept to optimize their orderings of biological samplings, x-rays and target drugs and to assess the consequence on patient's outcome.
    Annales Francaises D Anesthesie Et De Reanimation - ANN FR ANESTH REANIM. 01/2010; 29(10):682-686.
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    ABSTRACT: Danaparoid is a safe and effective drug for the treatment of heparin-induced thrombocytopenia (HIT). We describe an uncommon complication: danaparoid cross-reactivity with HIT antibodies. A retrospective observational multicenter study on HIT was conducted in France. In this study concerning HIT patients treated with lepirudin, 12 patients were treated with lepirudin because danaparoid cross-reacted with the heparin-dependent antibodies. Three groups of situations can be separated. In a first group, four patients received a short course of danaparoid until their initial functional HIT assay showed a cross-reactivity between danaparoid and HIT antibodies. One patient presented a fatal thrombotic complication but the relationship between this thrombotic complication and danaparoid cross-reactivity cannot be certain. In a second group, four patients received for 4 days at least a danaparoid treatment while the initial functional test did not show any danaparoid cross-reactivity. During danaparoid treatment, no significant increase of platelet count was observed and two patients presented a fatal thrombotic complication. In a third group, cross-reactivity between danaparoid and HIT antibodies was not checked before danaparoid therapy. During danaparoid treatment, no significant increase of platelet count was observed and the four patients developed a venous thromboembolic complication. Absence of any increase in platelet count after 3 to 5 days of danaparoid therapy and/or the occurrence of a new thrombotic event should lead to danaparoid cross-reactivity suspicion. However, before attributing thrombotic complications to danaparoid cross-reactivity, it is crucial to verify that the patients received the recommended danaparoid dosage regimen.
    European Journal of Intensive Care Medicine 05/2009; 35(8):1449-53. · 5.17 Impact Factor
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    ABSTRACT: We report the case of a 70-year-old patient, with two drug-eluting stents (DES), scheduled for a complete gastrectomy for a gastric cancer. This case underlines management problems regarding a patient with a high risk of DES thrombosis in case of AAP withdrawal and a high risk of bleeding in case of AAP maintenance. At this time, no evidence-based recommendation is available for clinicians to manage these patients. Our strategy was therefore based on platelet function monitoring test, which is however neither available in clinical practice nor validated to predict haemorrhagic risk. Several biologic tests are under study; they could be useful to guide perioperative management of antiplatelet therapy in the clinical setting of surgical patients with DES.
    Annales Francaises D Anesthesie Et De Reanimation - ANN FR ANESTH REANIM. 01/2009; 28(1):78-81.
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    ABSTRACT: We report the case of a 70-year-old patient, with two drug-eluting stents (DES), scheduled for a complete gastrectomy for a gastric cancer. This case underlines management problems regarding a patient with a high risk of DES thrombosis in case of AAP withdrawal and a high risk of bleeding in case of AAP maintenance. At this time, no evidence-based recommendation is available for clinicians to manage these patients. Our strategy was therefore based on platelet function monitoring test, which is however neither available in clinical practice nor validated to predict haemorrhagic risk. Several biologic tests are under study; they could be useful to guide perioperative management of antiplatelet therapy in the clinical setting of surgical patients with DES.
    Annales francaises d'anesthesie et de reanimation 01/2009; 28(1):78-81. · 0.77 Impact Factor
  • Journal of Thrombosis and Haemostasis 06/2008; 6(8):1422-4. · 6.08 Impact Factor
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    ABSTRACT: During extracorporeal membrane oxygenation, anticoagulation therapy is usually achieved with unfractionated heparin. We report on an extracorporeal membrane oxygenation with danaparoid sodium for a patient with severe respiratory failure due to massive pulmonary embolism and suspected type 2 heparin-induced thrombocytopenia. Danaparoid, a low molecular weight heparinoid, is an alternative to heparin for patients who develop type 2 heparin-induced thrombocytopenia. Danaparoid was given at 400 IU/h with an objective of antifactor Xa activity of 0.6-0.8 U/mL, which was monitored twice a day. No excessive bleeding or clotting of the circuit was noted. The patient was weaned from extracorporeal membrane oxygenation after 9 days of treatment.
    Anesthesia and analgesia 05/2008; 106(4):1101-3, table of contents. · 3.08 Impact Factor
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    ABSTRACT: A multicentre retrospective study was performed to assess the efficacy/safety of a French purified plasma-derived protein C (PC) concentrate in inherited PC deficiency. Nine patients were enrolled, five children aged < 5 weeks, among whom four with a severe deficiency were homozygous, and four patients < 37 years with PC levels ranging 14-25%, including one compound heterozygous. Thirty replacement therapy courses were recorded with mean PC dosages ranging between 24-90 IU/kg/day for prophylactic courses and 51-209 IU/kg/day for treatment courses. Recoveries varied between 0.8 and 1.12% IU/kg in preventive situations and between 1.09 and 1.91% IU/kg for treatment courses; 23 treatment courses were performed in patients aged 1 day to 18 years, 19 out of 23 treatments resulted in complete recovery with no sequelae. Treatment efficacy was difficult to assess in four out of 23 cases because the thrombotic event was not confirmed in one case and due to late treatment initiation in the three other cases. Seven prophylactic treatments were used either in association of vitamin K antagonists or to prevent thrombotic events due to vitamin K antagonist introduction or withdrawal. The safety assessed during 914 infusions was excellent. No abnormal bleeding was reported, including with high doses, during surgery, with heparin therapy. Replacement therapy with this French PC concentrate is safe and effective in patients with inherited PC deficiency.
    Vox Sanguinis 10/2007; 93(3):233-40. · 2.85 Impact Factor
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    ABSTRACT: The coronary stents are widely used to prevent coronary restenosis after percutaneous coronary intervention. Dual antiplatelet therapy (acetyl salicylic acid and a thienopyridine-clopidogrel or ticlopidine) are prescribed at least during six weeks after conventional stent and six months after drug eluting stent insertion to prevent stent thrombosis. When an invasive procedure is required, a risk of stent thrombosis arises after stopping antiplatelet therapy and a risk of bleeding when continuing this treatment. Therefore, cardiologists should choose carefully the type of coronary stent before insertion and concerned physicians (anaesthesiologists, surgeons, cardiologists) should decide a perioperative strategy in these high-risk patients.
    Annales francaises d'anesthesie et de reanimation 10/2007; 26(9):784-90. · 0.77 Impact Factor
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    ABSTRACT: The negative predictive value of D-dimer (DD) assay in patients with venous thromboembolic disease is well established for deep vein thrombosis and pulmonary embolism. Little is known about the value of DD assay in patients with superficial thrombophlebitis (ST). The purpose of this study was to assess the value of DD assay in patients with ST of the lower limb. The study group was composed of 100 consecutive patients, irrespective of age. Patients with clinical manifestations suggestive of ST of the lower limbs with positive duplex color Doppler evidence confirming the diagnosis and DD assay results (Vidas D-Dimer Exclusion) within 24 hours were included in the study. Patients with thrombosis in another site in addition to the superficial vein of the lower limb, those taking anticoagulants for more than 48 hours, and those with a condition known to potentially elevate DD levels were excluded. The volume of the thrombus was determined echographically and reported as mean diameter and length. Sixty-two women and 38 men were included. Mean age (+/- 5) was 58 years +/- 13.48 (range 18-90; median: 57). The ST involved the Great saphenous (n=74), the small saphenous (n=11) or another vein (n=15). Mean thrombus volume was 4453 mm(3) +/- 7101 (range 94-38484; median: 1751). Mean DD level was 829 ng/ml +/- 516.72 (range 100-2567; median: 715.5). DD assay was negative (<500 ng/ml) in 32 patients (32%) and positive in 68 (68%). For these three items, there was no significant difference between ST with and without varicose veins. DD assay was always positive (>or=500 ng/ml) in all patients aged over 70 years (n=22). In patients aged less than 70 years (n=78), DD assay was positive in 46 (59%) and negative in 32 (41%). DD level was positively correlated with thrombus volume in patients aged less than 70 years (P<0.0001). ROC analysis, sensitivity as a function of specificity by thrombus volume for the entire population, determined the usefulness of a negative DD assay. Considering the critical threshold at 5914 mm(3), sensitivity was 1.0 (95CI 0.89-1.0), with 0.29 specificity (95CI 0.19-0.42), 1.00 negative predictive value and 0.75 positive predictive value. However, the thrombus volume was less than this threshold value in three of the nine cases of ST with extension to the terminal portion of the saphenous. A positive DD assay was observed in 68% of patients with ST, with no significant difference with or without varicose veins. The test was positive in all patients aged over 70 years and in 59% of those aged under 70 years. There was a correlation between DD level and thrombus volume, yielding a threshold volume (5914 m(3)) above which all DD tests were positive. Nevertheless, this threshold volume was too great to include all ST extending to the terminal portion of the saphenous. Measurement of DD level is thus not contributive to the diagnosis of ST.
    Journal des Maladies Vasculaires 05/2007; 32(2):90-5. · 0.24 Impact Factor
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    ABSTRACT: The coronary stents are widely used to prevent coronary restenosis after percutaneous coronary intervention. Dual antiplatelet therapy (acetyl salicylic acid and a thienopyridine-clopidogrel or ticlopidine) are prescribed at least during six weeks after conventional stent and six months after drug eluting stent insertion to prevent stent thrombosis. When an invasive procedure is required, a risk of stent thrombosis arises after stopping antiplatelet therapy and a risk of bleeding when continuing this treatment. Therefore, cardiologists should choose carefully the type of coronary stent before insertion and concerned physicians (anaesthesiologists, surgeons, cardiologists) should decide a perioperative strategy in these high-risk patients.
    Annales Francaises D Anesthesie Et De Reanimation - ANN FR ANESTH REANIM. 01/2007; 26(9):784-790.
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    ABSTRACT: Objective The negative predictive value of D-dimer (DD) assay in patients with venous thromboembolic disease is well established for deep vein thrombosis and pulmonary embolism. Little is known about the value of DD assay in patients with superficial thrombophlebitis (ST). The purpose of this study was to assess the value of DD assay in patients with ST of the lower limb.
    Journal Des Maladies Vasculaires - J MAL VASCUL. 01/2007; 32(2):90-95.
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    ABSTRACT: The antithrombotic efficacy of lepirudin in patients with heparin-induced thrombocytopenia (HIT) is compromised by an increased risk for bleeding. A retrospective observational analysis in 181 patients (median age, 67 years) with confirmed HIT treated in routine practice with lepirudin was performed to identify predictive factors for thrombotic and bleeding complications. Lepirudin was administered at a mean (+/- SD) dose of 0.06 +/- 0.04 mg/kg/h (compared with a recommended initial dose of 0.15 mg/kg/h). Mean activated partial thromboplastin time was greater than 1.5 times baseline value in 99.4% of patients. Median treatment duration was 7.7 days. Until discharge from the hospital, 13.8% and 20.4% of patients experienced a thrombotic or a major bleeding event, respectively. On multivariate analysis, mean lepirudin dose was not a significant predictive factor for thrombosis. In contrast, mean lepirudin dose greater than 0.07 mg/kg/h, long duration of lepirudin treatment, and moderate to severe renal impairment were significant positive factors for major bleeding. Overall, these results suggest that the recommended dose of lepirudin in patients with HIT is too high; the use of reduced doses may be safer with regard to bleeding risk and does not compromise antithrombotic efficacy.
    Blood 10/2006; 108(5):1492-6. · 9.78 Impact Factor
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    ABSTRACT: The diagnosis and treatment of type II heparin-induced thrombocytopenia (HIT) after valvular surgery raise difficult issues due to the substitution of heparin by other anticoagulants. A 50-year-old man with hepatic cirrhosis and acute infective endocarditis underwent aortic valve replacement. On the 4th postoperative day platelet count decreased to 50 g/l. Platelet aggregation was demonstrated in vitro with unfractioned and low molecular weigh heparins and danaparoid sodium. As serum creatinine was 94 μmol/l, lepirudine (r-hirudin) was administered at recommended doses. However, six hours later hirudinaemia estimated by ecarin-clotting time was 3 mg/l and lepirudine dose had to be divided by 15 in order to reach therapeutic levels. Similarly, INR increased up to 6,7 on the 11th postoperative day after acenocoumarol 1 mg daily was administered. Despite the presence of œsophageal, gastric and duodenal lesions at risk of haemorrhage no bleeding was detected. The reasons for overdosage are discussed. The necessity of measurement or calculation of creatinine clearance before lepirudine prescription and frequent hirudinaemia during treatment is emphasized.
    Annales Francaises D Anesthesie Et De Reanimation - ANN FR ANESTH REANIM. 01/2006; 25(11):1140-1143.
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    ABSTRACT: The diagnosis and treatment of type II heparin-induced thrombocytopenia (HIT) after valvular surgery raise difficult issues due to the substitution of heparin by other anticoagulants. A 50-year-old man with hepatic cirrhosis and acute infective endocarditis underwent aortic valve replacement. On the 4th postoperative day platelet count decreased to 50 g/l. Platelet aggregation was demonstrated in vitro with unfractioned and low molecular weigh heparins and danaparoid sodium. As serum creatinine was 94 micromol/l, lepirudine (r-hirudin) was administered at recommended doses. However, six hours later hirudinaemia estimated by ecarin-clotting time was 3 mg/l and lepirudine dose had to be divided by 15 in order to reach therapeutic levels. Similarly, INR increased up to 6,7 on the 11th postoperative day after acenocoumarol 1 mg daily was administered. Despite the presence of oesophageal, gastric and duodenal lesions at risk of haemorrhage no bleeding was detected. The reasons for overdosage are discussed. The necessity of measurement or calculation of creatinine clearance before lepirudine prescription and frequent hirudinaemia during treatment is emphasized.
    Annales francaises d'anesthesie et de reanimation 01/2006; 25(11-12):1140-3. · 0.77 Impact Factor
  • Journal of Thrombosis and Haemostasis 11/2005; 3(10):2347-9. · 6.08 Impact Factor
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    ABSTRACT: In the absence of thromboprophylaxis, coronary artery bypass graft surgery (CABG), intrathoracic surgery (thoracotomy or video-assisted thoracoscopy), abdominal aortic surgery and infrainguinal vascular surgery are high-risk surgeries for the development of venous thromboembolic events (VTE). The incidence of VTE following surgery of the intrathoracic aorta, carotid endarterectomy or mediastinoscopy is unknown. Data from the litterature are lacking to draw evidence-based recommandations for venous thromboprophylaxis after these three types of surgeries, and the following guidelines are but experts'opinions (Grade D recommendations). Thromboprophylaxis is recommended after CABG (Grade D), with either subcutaneous (SC) low molecular weight heparin (LMWH) or SC or intravenous (i.v.) unfractioned heparin (UH) (PTT target = 1.1-1.5 time control value) (both grade D). This may be combined with the use of intermittent pneumatic compression device (Grade B). After valve surgery. The anticoagulation recommended to prevent valve thrombosis is sufficient in order to prevent VTE. We recommend thromboprophylaxis with either LMWH or low dose UH to prevent VTE after aortic or lower limbs infrainguinal vascular surgery (both grade B and D). Vitamine K antagonists (VKA) are not recommended in this indication (Grade D). We recommend thromprophylaxis following intrathoracic surgery via thoracotomy or videoassisted thoracoscopy (grade C). Either subcutaneous LMWH or subcutaneous or i.v. low dose UH may be used (Grade C). Efficacy of intermittent pneumatic compression device has been demonstrated in a study (grade C). VKA are not recommended (grade D). No further recommendation regarding the duration of thromboprophylaxis after these three types of surgeries can be made.
    Annales Françaises d Anesthésie et de Réanimation 09/2005; 24(8):938-46. · 0.84 Impact Factor
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    ABSTRACT: In the absence of thromboprophylaxis, coronary artery bypass graft surgery (CABG), intrathoracic surgery (thoracotomy or video-assisted thoracoscopy), abdominal aortic surgery and infrainguinal vascular surgery are high-risk surgeries for the development of venous thromboembolic events (VTE). The incidence of VTE following surgery of the intrathoracic aorta, carotid endarterectomy or mediastinoscopy is unknown. Data from the litterature are lacking to draw evidence-based recommandations for venous thromboprophylaxis after these three types of surgeries, and the following guidelines are but experts'opinions (Grade D recommendations). Thromboprophylaxis is recommended after CABG (Grade D), with either subcutaneous (SC) low molecular weight heparin (LMWH) or SC or intravenous (i.v.) unfractioned heparin (UH) (PTT target=1.1–1.5 time control value) (both grade D). This may be combined with the use of intermittent pneumatic compression device (Grade B). After valve surgery. The anticoagulation recommended to prevent valve thrombosis is sufficient in order to prevent VTE. We recommend thromboprophylaxis with either LMWH or low dose UH to prevent VTE after aortic or lower limbs infrainguinal vascular surgery (both grade B and D). Vitamine K antagonists (VKA) are not recommended in this indication (Grade D). We recommend thromprophylaxis following intrathoracic surgery via thoracotomy or videoassisted thoracoscopy (grade C). Either subcutaneous LMWH or subcutaneous or i.v. low dose UH may be used (Grade C). Efficacy of intermittent pneumatic compression device has been demonstrated in a study (grade C). VKA are not recommended (grade D). No further recommendation regarding the duration of thromboprophylaxis after these three types of surgeries can be made.
    Annales Francaises D Anesthesie Et De Reanimation - ANN FR ANESTH REANIM. 01/2005; 24(8):938-946.