Anticoagulation decisions in elderly patients with stroke.

Primary and secondary prevention of stroke is often a challenge in elderly patients due to the increase in both thrombotic and hemorrhagic risks with age. In some cases, there is sufficient data in the elderly population to allow recommendations or anticoagulation decisions to be made, such as for the indication of anticoagulation to prevent stroke related to atrial fibrillation (AF) or the choice of oral anticoagulant therapy in this situation. In other situations, the less robust data leave some questions; this is the case for the delay to initiate an oral anticoagulant therapy after an AF-related ischemic stroke, for the management of antithrombotic treatment after a stroke of undetermined cause or after intracranial bleeding or in a high-risk bleeding situation associated with stroke in the elderly subject. These issues will be discussed in this paper.

[Therapeutic education of elderly patients under antivitamin - K treatment: evaluation of the program after 5 years]. / Education thérapeutique de patients âges traités par AVK. Biltan d'un programme après 5 années d'existence.

INTRODUCTION: Elderly people with vitamin K antagonists (VKA) have a higher risk of potentially serious hemorrhagic complications. An education program for patients (EPP) aged > or = 75 years with VKA was set up in 2008 in a French geriatric hospital. It includes individual and group sessions conducted by a nurse and a geriatrician. OBJECTIVES: The aim of this study was to assess this EPP after 5 years. Strengths, weaknesses and difficulties of implementation were highlighted, and some improvements were proposed. METHODS: This study is an external audit conducted by a pharmacist trained in EPP. Files of consecutive patients included in the program between may 2008 and March 2013 were reviewed allowing the data collection of patients characteristics and results of the different sessions. The educational objectives were assessed by the rate of correct responses to the questionnaires during the program. The results are presented taking into account the changes made during the 5 years of the program. RESULTS: One hundred forty-three patients, mean age 83.3 +/- 6.5 years, were included in the EPP. 51 sessions were conducted (2.8 patients/session on average). 58% of selected patients were hospitalized. The mean time between the start of anticoagulant treatment and the incLusion in the program was 48.9 +/- 71 months. For 95 patients (66.4%) the medication management at home required a caregiver who was present for sessions in 82 cases (57.3%). The questionnaires form and the organisation of the sessions were gradually improved between 2008 and the end of 2010. Thus, the impact of the EPP has been estimated from November 2010 to March 2013. The correct responses rates before and after the sessions were respectively: 47.8% vs 91.3% for knowledge of INR target values, 25.4% vs 91.3% for knowledge of hemorrhagic signs, 14.9% vs 87.0% for knowledge of the situations or the medications that may disturb the INR equilibrium. Furthermore, the mean number of correct responses, for the 23 patients participating in the entire program, is statistically different between the educational diagnostic and immediate evaluation (3.7/7 vs 5.4/7 p = 0.023) and no significant difference is observed between immediate and distant evaluation (5.4/7 vs 5.8/7 p = 0.720). CONCLUSION: An improvement of patient knowledge was observed with regard to the main educational objectives. Some improvements are proposed: to disseminate information to general practitioners, to add the follow up of INR values to assess an impact on anticoagulant treatment stability. Furthermore, this program is now adapted to the new oral anticoagulants. It is the role of hospital or community pharmacists to initiate and/or assess this type of EPP.

[Increase of serum procalcitonin levels during a neuroleptic malignant syndrome]. / Augmentation de la concentration sérique de la procalcitonine au cours d'un syndrome malin des neuroleptiques.

When fever occurs in a patient treated with a neuroleptic, the diagnosis of a neuroleptic malignant syndrome is difficult to differentiate to that of an infectious event. Among inflammation biomarkers of inflammation, serum procalcitonin levels increase both quickly and specifically during a bacterial infection. We report the first case of a neuroleptic malignant syndrome associated with a significant increase of serum procalcitonin levels, without concomitant septic syndrome. The neuroleptic malignant syndrome might be a non-infectious clinical situation associated with an increased serum procalcitonin concentration.

Bleeding risk of antiplatelet drugs compared with oral anticoagulants in older patients with atrial fibrillation: a systematic review and meta-analysis.

Essentials Hemorrhagic risk of antiplatelet drugs is generally thought to be lower than anticoagulants. We systematically reviewed trials comparing antiplatelet and anticoagulant drugs in older patients. Overall, the risk of major bleeding was similar with antiplatelet and with anticoagulant drugs. In elderly patients, risks and benefits of antiplatelet drugs should be carefully weighted. SUMMARY: Background The hemorrhagic risk of antiplatelet drugs in older patients could be higher than is usually assumed. Objective To compare the bleeding risk of antiplatelet drugs and oral anticoagulants in elderly patients. Methods We carried out a systematic review and meta-analysis. We searched PubMed, EMBASE and the Cochrane Library up to January 2016 for randomized and non-randomized controlled trials (RCTs) and parallel cohorts comparing antiplatelet drugs and oral anticoagulants in patients aged 65 years or older. Two independent authors assessed studies for inclusion. The pooled relative risk (RR) of major bleeding was estimated using a random model. Results Seven RCTs (4550 patients) and four cohort studies (38 649 patients) met the inclusion criteria. The risk of major bleeding when on aspirin or clopidogrel was equal to that when on warfarin in RCTs (RR, 1.01; 95% confidence interval (95% CI), 0.69-1.48; moderate-quality evidence), lower than when on warfarin in non-randomized cohort studies (RR, 0.87; 95% CI, 0.77-0.99; low-quality evidence) and not different when all studies were combined (RR, 0.86; 95% CI, 0.73-1.01). Bleeding of any severity (RR, 0.70; 95% CI, 0.57-0.86) and intracranial bleeding (RR, 0.46; 95% CI, 0.30-0.73) were less frequent with antiplatelet drugs than with warfarin. All-cause mortality was similar (RR, 0.99). Subgroup analysis suggested that major bleeding might be higher with warfarin than with aspirin in patients over 80 years old. Conclusion Elderly patients treated with aspirin or clopidogrel suffer less any-severity bleeding but have a risk of major bleeding similar to that of oral anticoagulants, with the exception of intracranial bleeding.

[Prescribing guidance pocket chart on the initiation of warfarin therapy in a geriatric hospital: a useful but challenging tool]. / Diffusion d'une fiche d'aide à la prescription pour l'initiation d'un traitement par warfarine dans un hôpital gériatrique: intérêt et difficultés de mise en place.

Elderly patients are at high risk of over-anticoagulation and of haemorrhagic risk when on warfarin, especially during treatment induction. In Charles Foix Hospital, a 800-bed geriatric hospital, we specifically developed for in-patients older than 70 years (target INR 2.5) a simple low-dose warfarin induction regimen. The dosing recommendations were summarized on a prescribing guidance pocket chart. Eighteen months after the distribution of the chart, we conducted a one-year observational study in order to evaluate: i/ the time needed to achieve the warfarin maintenance dose; ii/ the prescriber'adherence to the recommendations; iii/ the benefit for elderly patients receiving warfarin therapy. The mean time needed to achieve the warfarin maintenance dose was 12.3 +/- 7.0 days for the 89 patients included in the study: 10.6 +/- 5.9 days for the 30 patients whose prescribers followed the recommendations versus 13.5 +/- 7.6 days for the 59 patients whose prescribers did not follow the recommendations. There is a trend to a more frequent over-anticoagulation in patients whose prescribers did not follow the recommendations. The duration of the heparin-warfarin overlap was significantly shorter when the recommendations were followed. Finally, the reasons for non-adherence to the recommendations were analyzed. This study illustrates an assessment of practice in an health care institution.

[Relationship between maintenance dosages of fluindione (Préviscan) and warfarin (Coumadin) for patients 70 years and older]. / Nomogramme d'équivalence entre les posologies de fluindione (Préviscan) et de warfarine (Coumadine) pour des patients de 70 ans et plus.

INTRODUCTION: Switching from fluindione, an indanedione vitamin K antagonist derivative, to warfarin, a coumarin one, or vice versa, requires to know the relationships between dosages of these two molecules. METHODS: We conducted a prospective study in 288 consecutive patients aged 70 years and over, converted from fluindione to warfarin. Patients who were retained for the analysis were those for whom maintenance dosages were obtained for both vitamin K antagonists. RESULTS: Eighty-two patients, mean aged 83 ± 6 years, were analysed. The average daily maintenance dosages were 13.8 ± 6.7 mg (range 5-35) and 3.7 ± 1.7 mg (range 1-8) for fluindione and warfarin, respectively. Using a linear regression model, we built a transition algorithm for the maintenance dosages of warfarin and fluindione. CONCLUSION: This is the first study to propose a conversion algorithm to help prescribers to estimate the maintenance dosage when it is necessary for a patient to switch from fluindione to warfarin or conversely.

Elderly patients treated with tinzaparin (Innohep) administered once daily (175 anti-Xa IU/kg): anti-Xa and anti-IIa activities over 10 days.

Since low molecular weight heparins (LMWH) are partly eliminated by renal excretion, their pharmacodynamic profile may be modified in very elderly patients with age-related renal impairment. The aim of this prospective study was to determine whether tinzaparin (Innohep) 175 anti-Xa IU/kg administered subcutaneously once daily over 10 days does accumulate in hospital patients greater than 70 years of age. Plasma anti-Xa and anti-IIa amidolytic levels and APTT were determined prior to the first injection (day 0), and then, at peak level i.e. 5 h after the second injection (day 2) and subsequently on days 5, 7 and 10. Thirty consecutive inpatients (6 men, 24 women) requiring LMWHs at a curative dose for acute thromboembolic disease were included. Patients' characteristics (mean +/- SD) were: age 87.0+/-5.9 years (range 71-96), body weight 62.7+/-14.6 kg (range 38-90) and creatinine clearance 40.6+/-15.3 mL/min (range 20-72). The mean actual dose of tinzaparin delivered was 174.8 anti-Xa IU/kg. Since no patient had an anti-Xa activity above 1.5 IU/mL, the dose of tinzaparin remained fixed over 10 days. Anti-Xa and anti-IIa peak levels measured on day 2 were 0.66+/-0.20 IU/mL (range 0.26-1.04) and 0.33+/-0.10 IU/mL (range 0.18-0.55), respectively. Ex vivo anti-Xa/anti-IIa ratios were close to 2.1. APTT ratios (patient/control) were strongly correlated with anti-IIa activity (p <0.01). There was no progressive increase of the anti-Xa and anti-IIa activities after repeated administration of tinzaparin over the 10 day treatment period. No correlation was found between anti-Xa and anti-IIa activities and age, weight, or creatinine clearance. No major bleeding occurred during the study and only one minor haematoma at the injection site was reported. No thrombo-embolic complication or death occurred. Tinzaparin may thus be administered safely at a treatment dose (175 anti-Xa IU/kg) in older patients with age-related renal impairment. Neither dose adjustment, nor serial anti-Xa activity monitoring seems to be required in patients with creatinine clearance above 20 mL/min during the first ten day treatment.

Features of polymyositis and dermatomyositis in the elderly: a case-control study.

OBJECTIVE: Polymyositis (PM) and dermatomyositis (DM) are uncommon idiopathic inflammatory myopathies (IIM). Little is known about these diseases in the elderly. We attempted to define the characteristics of PM/DM in the elderly by a case-control study involving the retrospective review of medical files of PM/DM patients. METHODS: We drew from among 200 PM/DM patients being followed in our Internal Medicine Department 21 patients (14 F/7 M), aged > or = 65 years at the onset of myositis (17 PM/4 DM) (mean: 69.9 +/- 4.8 yrs.). They were compared with 21 (15 F/6 M) randomly selected younger patients with IIM: PM (14) and DM (7) (mean: 46.4 +/- 12.4 yrs). Clinical, biological, electrophysiological and pathologic features, treatment regimens and side-effects in the 2 groups were collected. RESULTS: Clinical features were similar for the 2 groups. Elderly patients tended to have a higher frequency of cancer (24% vs 9.5%, p = 0.06), particularly of rectal adenocarcinoma. The time from disease onset to diagnosis was significantly longer in older patients (26 +/- 37 months vs 9 +/- 15 months; p = 0.02), normal CK levels were more frequent (40% vs 5%; p = 0.02) and serum CK levels were lower than for the population as the whole (11.5 N vs 22 N, p < 0.03). Electromyography features were more frequently suggestive of a chronic form of the disease in elderly patients. Treatment regimens and short-term side-effects were similar for the 2 groups. CONCLUSION: PM and DM are often diagnosed late in the elderly. Biological data and electromyography features argue for a chronic form of the disease in this age group. Clinical and endoscopic rectal examinations should be carried out in elderly patients with PM/DM.

[Myelodisplasic syndromes diagnosed in a geriatric hospital: morphological profile in 100 patients]. / Syndromes myélodysplasiques diagnostiqués dans un hôpital gériatrique: profil cytologique de 100 patients.

Myelodysplastic syndrome (MDS) is particularly common in geriatric practice. As few data are available in very elderly patients, we conducted a 54-month retrospective study in patients over 70 years with MDS diagnosed at Hôpital Charles Foix. Patients with cobalamine, folate or iron deficiency were excluded. Regarding biological and morphologic approaches, MDS patients were classified according to the FAB criteria. We then tempted to reclassify the patients according to the WHO criteria. The Bournemouth scoring system was used as a prognostic tool. During the study period, 100 patients were included, 29 males and 71 females, median age 86 +/- 7 years (70-103). At the time of bone marrow sampling, a peripheral blood cytopenia was documented in 64 patients, a bicytopenia in 27 patients and a pancytopenia in 9 patients. Isolated anaemia (Hb < 12 g/dL) was found in 60 patients and isolated thrombocytopenia (< 150 x 10(9)/L) in 4. Macrocytosis (MCV > 100 fL) was observed in 21 % of the cases. According to the FAB criteria, the 100 patients were classified as follows: refractory anaemia (RA): 79%; RA with ringed sideroblasts (RARS): 8%; RA with excess of blasts (RAEB): 8%; RAEB in transformation: 1%; chronic myelomonocytic leukaemia: 4%. According to the WHO classification, the patients were reclassified as follows: RA (unilineage) (with or without ringed sideroblasts): 10%; refractory cytopenia with multilineage dysplasia with or without ringed sideroblasts (RCMD): 73%; RAEB: 7% (RAEB-1 6%, RAEB-21%); MDS/Myeloproliferative disorder: 4%; unclassified (hypocellularity): 5%; acute leukaemia: 1%. In order to estimate prognosis at the time of the bone marrow aspirate, we calculated the Bournemouth'score: 8 patients scored 0,57 scored 1,25 scored 2,8 scored 3 and 2 scored 4. In this geriatric population, 83% cases of MDS are RA or RCMD (with or without sideroblasts); MDS with excess of blasts are uncommon. Thus, elderly patients under study with MDS were diagnosed at an earlier stage of the disease than younger ones from series published in the literature. Due to frequent comorbidities, geriatric patients may be symptomatic for a slight decrease of haemoglobin level. Therefore, elderly patients are investigated as soon as they present with moderate anaemia that may explain the early MDS diagnosis.

[Myelodysplastic syndromes]. / Les syndromes myélodysplasiques.

Myelodysplastic syndromes (MDS) are clonal disorders of pluripotent hematopoietic stem cells. MDS occur predominantly over the age of 60 years. The diagnosis of MDS is based on the examination of both blood films and bone marrow aspirate. Diseases such as vitamin B12 and/or folate deficiency, or cytotoxic therapy leading to a marrow dysplasia should be ruled out. Five subtypes are described in the FAB classification : refractory anaemia or refractory cytopenia, refractory sideroblastic anaemia, refractory anaemia with excess of blasts, refractory anaemia with excess of blasts in transformation, chronic myelomonocytic leukaemia. This FAB classification is based on a small number of parameters: percentage of blood and marrow blasts, percentage of ringed sideroblasts and blood monocytes. The anaemia is typically normo- or macrocytic, non regenerative, and in half cases is associated with neutropenia and/or thrombocytopenia. During blood film examination, cell abnormalities have to be notified, i.e. anisocytosis, poikilocytosis of red cells, morphological abnormalities of neutrophils including hypogranulation, hypolobulation, abnormal large platelets. The prognostic and the treatment of MDS depend on the subtype of the FAB classification, the patient's age, the percentage of marrow blasts, the importance of cytopenia, the presence or not of cytogenetic abnormalities and the existence or not of HLA-identical donor.

[Oral anticoagulants in the elderly]. / Anticoagulation orale en pratique gériatrique.

PURPOSE: Atrial fibrillation and venous thromboembolism are particularly frequent in the elderly. Whether or not prescribe oral anticoagulant treatment in the elderly is therefore a common question for the physician. Despite the benefits of anticoagulation demonstrated in clinical trials, oral anticoagulant therapy is underused in the elderly. CURRENT KNOWLEDGE AND KEY POINTS: Indications for oral anticoagulation are discussed specifically in the elderly with a literature review. Only the length of anticoagulation treatment after a venous thromboembolism remained a purpose of discussion regarding the severity of the pathology. The frequency of systemic thromboembolism in nonvalvular atrial fibrillation is increasing with age. Oral anticoagulation reduces this risk. This benefice is to compare with the increasing rate of major bleeding complications in the elderly and in patient who had stroke, hyper-tension, diabetes mellitus or gastrointestinal bleeding. The objective of this article is to focus on the mode to measure oral anticoagulant benefice/risk ratio in the elderly and to propose several ways to minimize the risk for bleeding. FUTURE PROSPECTS AND PROJECTS: The potential drug side effect severity of oral anticoagulation must lead to find the "reasonable" clinical indications in term of benefice/risk ratio and what measures should be take to increase the safety of oral anticoagulation in the elderly. The comprehensive geriatric evaluation should be considered as a decision-aid tool in long-term oral anticoagulation in the frail elderly. Anticoagulation clinics, informatics'-prescription coupled with dose-adaptation decision-aid adapted to the elderly should be helpful in this research of quality. Finally, prescribers education supports must insist on the early course of therapy that is at higher risk of bleeding.

[Cytochrome P450 2C9 polymorphisms (CYP2C9) and warfarin maintenance dose in elderly patients]. / Polymorphismes du cytochrome P450 2C9 (CYP2C9) et posologie à l'équilibre pour des patients âgés traités par warfarine.

PURPOSE: Allelic variants of the gene coding for cytochrome P450 isoform 2C9 (CYP2C9), 2C9*2 and 2C9*3, were shown to increase sensitivity to warfarin in adults. In the elderly, the maintenance dose is influenced by acquired factors including comorbidities and polymedication. The aim of our purpose was to investigate whether a genetic factor, such as cyp2c9 genotype, does influence the warfarin maintenance dose in very elderly patients. METHODS: In-patients treated with warfarin were recruited with the following inclusion criteria: i/ 75 years-old or over; ii/ a stable INR within the therapeutic range (INR 2.0-3.0). Genotypes were coded as numbers of alleles for each of the three polymorphisms, namely 2C9*1 (wild-type), 2C9*2, and 2C9*3. RESULTS: CYP2C9 genotype was performed in 126 patients, mean age 87 +/-6 years (75-103), 29 males-97 females. The mean daily dose of warfarin was 3.0 +/-1.4 mg, with 3.1 mg in patients with the wild-type *1/*1 genotype (n =80), 2.7 mg in *1/*2 heterozygotes (n =20), 2.9 mg in *1/*3 heterozygotes (n =18), 1.2 mg in *2/*2 homozygotes (n =2), 2.3 mg in compound heterozygotes *2/*3 (n =6). The relationships between dose and potential factors were assessed using the correlation coefficient test for age and Fischer exact tests for the categorical variables. The only factors significantly linked to the dose were the numbers of 2C9*1 and 2C9*2 alleles. CONCLUSION: In elderly patients, a genetic influence on response to warfarin does exist as in younger patients.

[Monitoring of tinzaparin in a ten day treatment dose in elderly patients]. / Surveillance d'un traitement par la tinzaparine à dose curative pendant dix jours chez le sujet âgé.

PURPOSE: Renal impairment, which is frequently observed in elderly patients, raises the question of low molecular weight heparins treatment dose adjustment in this population. Thus, we conducted a prospective study to determine whether tinzaparin, administered subcutaneously at treatment dose (175 anti-Xa IU/kg) once daily for 10 days, does accumulate in patients older than 70 years of age. METHODS: Accumulation criteria were an increase of plasma anti-Xa and anti-IIa levels determined prior to the first injection and on days 2, 5, 7 and 10. The characteristics of the 30 consecutive included patients receiving tinzaparin at treatment dose (six men, 24 women) were: age 87.0 +/- 5.9 years (range: 71-96 years), body weight: 62.7 +/- 14.6 kg (range: 38-90 kg) and creatinine clearance 40.6 +/- 15.3 mL/min (range: 20-72 mL/min). RESULTS: None of the patients required a dose adjustment of tinzaparin over the 10-day treatment period. Anti-Xa and anti-IIa activity levels on day 2 were 0.66 +/- 0.20 IU/mL (range: 0.26-1.04 IU/mL) and 0.33 +/- 0.10 IU/mL (range: 0.18-0.55 IU/mL), respectively. These levels did not significantly change over the 10 days. These results favor the absence of the accumulation effect of tinzaparin. There was no correlation between anti-Xa and anti-IIa activities and age, weight, or creatinine clearance. Concerning the side-effects, only one minor hematoma at the injection site was reported. CONCLUSION: Tinzaparin may thus be administered in older patients with renal impairment, at a treatment dose (175 anti-Xa IU/kg/d) for a 10-day treatment period, without accumulation effect nor hemorrhagic side-effect in patients with creatinine clearance greater than 20 mL/min.

[Underestimation of medical activity measured by daily activity scores]. / Sous-estimation de l'activité de soins mesurée par les scores d'activité en pratique quotidienne.

OBJECTIVES: To assess the effectiveness of a scoring system (omega) for medical activity. METHODS: In 100 consecutive patients (phase A), the omega scores were calculated by the physician in charge and controlled by an independent physician. In 100 additional patients, the omega scores were controlled again while using corrective measures (phase B). RESULTS: Phase A: at least one item was forgotten in 54% of the stays. The amount of medical activity lost (MAL) was 14 +/- 13%. Phase B: there was no significant reduction in the number of stays with forgotten items (45%, p = 0.41 vs phase A) and the MAL was 17 +/- 16% (p = 0.19 vs 6 +/- 10 days, p = 0.002) and high omega II score (items recorded every time they are performed) (0.8 +/- 1.3 vs 0.4 +/- 0.7, p = 0.01) were associated with forgetting items. The MAL was negatively correlated with the length of stay (r = -0.69, p < 0.001) and omega score (r = -0.40, p = 0.001). CONCLUSION: In routine practice, scoring systems may underestimate medical activity.

[Vitamin B 12 deficiency in the aged]. / Carence en vitamine B12 chez le sujet âgé.

A COMMON CONDITION: Vitamin B12 deficiency is common in the elderly. Search for deficiency should be undertaken whenever the clinical situation could lead to vitamin deficiency whether macrocytic anemia is present or not as its development may come late. PATHOPHYSIOLOGICAL IMPLICATIONS: The potential relationships between degenerative neuropsychiatric disorders and cerebrovascular or cardiovascular disease, mainly via hyperhomocysteinemia, emphasize the importance of searching for vitamin B12 deficiency in the elderly. SPECIFIC CAUSES: In the elderly, it is important to recognize specific causes of vitamin B12 deficiency, mainly resulting from vitamin malabsorption.

[Myelodysplastic syndromes. Diagnosis and care in patients over 70 years of age]. / Les syndromes myélodysplasiques. Diagnostic et prise en charge des patients de plus de 70 ans.

A FREQUENT CONDITION IN GERIATRICS: Myelodysplastic syndromes comprise a group of bone marrow disorders characterized by abnormal hematopoetic stem cell clones. They are generally observed after 60 years of age with a peak frequency in the 70-80 year age group. Prevalence is probably underestimated and diagnosis is commonly made in geriatric wards. DIAGNOSIS: Clinical presentations vary widely, making diagnosis a difficult task. Cytology studies play a predominant role. Recent progress in our understanding of myelodysplastic syndromes have been achieved with cytogenic and molecular biology techniques, although the diagnostic procedures and management of elderly subjects have changed little. DISEASE COURSE AND TREATMENT: Prognosis of myleodysplastic syndromes is highly variable and mainly depends on the type of syndrome according to the international FAB classification. Therapeutic management in patients over 70 is limited in most cases to symptomatic treatment, principally with transfusional support.

[Excess antivitamin K in elderly hospitalised patients aged over 70. A one-year prospective survey]. / Surdosages en antivitamine K dans une population de patients hospitalisés âgés de plus de 70 ans. Enquête prospective sur un an.

INTRODUCTION: Antivitamin K treatments (AVK) are related to increased morbidity and mortality, notably in elderly patients. The International Normalized Ratio (INR) should be well controlled and its stabilisation within the therapeutic range help to prevent the haemorrhagic complications. METHODS: A one-year prospective survey on all the cases of excess AVK was conducted in hospitalised patients aged over 70. RESULTS: During the study period, 225 hospitalised patients treated with AVK (mean age 84 years) were identified: 62% received warfarin, 19% fluindione, 8% acenocoumarol and 11% received several successive AVK. During this period, 1.904 INR measurements were recorded: 97 (5.1%) were > or =5.0 and 12 (0.63%) were > or =9.0. In all, 59 patients (23.1%) exhibited one or several episodes of excess AVK (INR > or =5.0) and 57 exhibited a target INR of 2.5. Three patients died of accidental haemorrhage--two of them due to intra-cerebral bleeding--among the 59 patients with excess AVK. In three cases, the INR was greater than 7.0 at the time of the accident. DISCUSSION: In half of the cases of excess, the episode occurred during the month following initiation of treatment with AVK. In nearly two thirds of cases, a change had been made in drug therapy in the 10 days preceding the excess, with the prescription of a drug enhancing the effect of the AVK: anti-infection agents (antibiotics and anti-fungals) and amiodarone were the drugs most frequently involved. Oral or intravenous vitamin K1 was administered in only 19% of cases. CONCLUSION: In very old patients treated with oral anticoagulants, certain risk factors must be identified: the initiation period of treatment, the occurrence of an intercurrent disease and the subsequent change in the drug therapy. INR monitoring should be intensified in order to detect any excess and, if detected, ensure the optimal management of the patient.

[Myasthenia in the aged: a case with unusually late onset]. / Myasthénie du sujet âgé. Un cas de révélation particulièrement tardive.

BACKGROUND: Myasthenia is an uncommon autoimmune condition that can occur at any age. Peak frequency is seen around the age of 65 years. We report a case with a particularly late onset and discuss the particular conditions of myasthenia in the elderly subject. CASE REPORT: A 97-year-old patient was hospitalized for dysphonia and dysphagia associated with exercise-induced dyspnea. The general picture suggested generalized myasthenia confirmed by the electromyography exploration and a positive anticholinesterase test. Treatment with acetylcholinesterase inhibitor was effective although cure was incomplete. Further improvement was obtained with immunosuppressor therapy using azathioprine. DISCUSSION: The clinical presentation of very late onset myasthenia differs little from that in younger subjects excepting the very high frequency of brain stem involvement in the initial presentation. Diagnosis may however be more difficult as other conditions are more easily taken to be the causal element. Thus, for the elderly patient, the real problem is to envisage the diagnosis of myasthenia. Positive diagnosis is based on the same criteria as in younger subjects. Clinicians should be aware of the possibility of myasthenia in the geriatric population as specific treatment can improve functional prognosis with satisfactory efficacy.

No accumulation of the peak anti-factor Xa activity of tinzaparin in elderly patients with moderate-to-severe renal impairment: the IRIS substudy.

BACKGROUND: In the elderly, concerns have been raised regarding the risk of accumulation of low molecular weight heparins, owing to their renal elimination. Although data exist for tinzaparin, they are observational. OBJECTIVES: To assess whether: (i) there was an accumulation of anti-factor Xa activity; and (ii) there was any relationship between anti-FXa activity and age, weight, creatinine clearance or clinical outcomes in patients with moderate-to-severe renal impairment receiving tinzaparin (175 IU kg(-1) per 24 h) for acute venous thromboembolism. METHODS: In 38 centers participating in the Innohep in Renal Insufficiency Study (IRIS), peak plasma anti-FXa activity was measured on day 2/day 3 and on day 5 or at visit S (VS) (end of tinzaparin treatment). There was considered to be absence of accumulation if the 90% confidence interval (CI) of the (anti-FXa day 5/VS)/(anti-FXa day 2/3) ratio did not exceed the predefined limit of 1.25. RESULTS: Eighty-seven patients, with a mean age of 83 ± 5 years (range: 75-99 years) and a mean creatinine clearance (CrCl) of 40.8 mL min(-1) , 24.1% of whom had severe renal impairment, were included. The mean duration of tinzaparin treatment was 8.4 days. No significant accumulation was detected: the mean accumulation ratio was 1.06 (90% CI 1.01-1.11). There was no correlation between the accumulation ratio and age, weight, or CrCl. The mean anti-FXa activity did not differ significantly between the eight patients who experienced clinically relevant bleeding and those who did not. CONCLUSIONS: No accumulation of anti-FXa activity was observed in elderly patients with renal impairment receiving therapeutic doses of tinzaparin, suggesting that there is no need for systematic anti-FXa monitoring in these patients. The high proportion of high molecular weight moieties in tinzaparin may account for its reduced dependence on renal elimination.

Predicting the warfarin maintenance dose in elderly inpatients at treatment initiation: accuracy of dosing algorithms incorporating or not VKORC1/CYP2C9 genotypes.

BACKGROUND: Initiating warfarin is challenging in frail elderly patients because of low-dose requirements and interindividual variability. OBJECTIVES: We investigated whether incorporating VKORC1 and CYP2C9 genotype information in different models helped to predict the warfarin maintenance dose when added to clinical data and INR values at baseline (Day 0), and during warfarin induction. PATIENTS: We prospectively enrolled 187 elderly inpatients (mean age, 85.6 years), all starting on warfarin using the same 'geriatric dosing-algorithm' based on the INR value measured on the day after three 4-mg warfarin doses (INR(3)) and on INR(6 ± 1). RESULTS: On Day 0, the clinical model failed to accurately predict the maintenance dose (R(2) < 0.10). Adding the VKORC1 and CYP2C9 genotypes to the model increased R(2) to 0.31. On Day 3, the INR(3) value was the strongest predictor, completely embedding the VKORC1 genotype, whereas the CYP2C9 genotype remained a significant predictor (model- R(2) 0.55). On Day 6 ± 1, none of the genotypes predicted the maintenance dose. Finally, the simple 'geriatric dosing-algorithm' was the most accurate algorithm on Day 3 (R(2) 0.77) and Day 6 (R(2) 0.81), under-estimating (≥ 1 mg) and over-estimating the dose (≥ 1 mg) in fewer than 10% and 2% of patients, respectively. Clinical models and the 'geriatric dosing-algorithm' were validated on an independent sample. CONCLUSIONS: Before starting warfarin therapy, the VKORC1 genotype is the best predictor of the maintenance dose. Once treatment is started using induction doses tailored for elderly patients, the contribution of VKORC1 and CYP2C9 genotypes in dose refinement is negligible compared with two INR values measured during the first week of treatment.