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ABSTRACT: Anemia, the most common hematological disorder in the elderly, increases the risk of mortality and morbidity and adversely affects quality of life. However, few studies focused specifically on anemia in the elderly, especially regarding the underlying causes. The main objective of this prospective study was to evaluate the causes of anemia in non-institutionalized elderly patients. We included 190 consecutive patients ≥70 years, admitted to a geriatric short-stay unit over a 1-year period. When the hemoglobin level was <120 g/L, the following serum assays were performed routinely: iron, ferritin, transferrin saturation, folate, vitamin B12, C-reactive protein, TSH, albumin, and haptoglobin. When these tests were normal, bone marrow aspiration was performed to look for myelodysplastic syndrome. Hemoglobin was <120 g/L in 83 (43.7%) of 190 included patients. Patients with anemia had a mean hemoglobin level of 105±11 g/L. The most common potential causes of anemia were inflammation, severe renal impairment, severe malnutrition, and iron deficiency; each of these causes was found in at least one-third of patients with anemia. Myelodysplastic syndrome was found in all anemic patients with a normal serum screen (12/83, 14.5%). Anemia was multifactorial in most patients: the mean number of potential causes per patient was 1.85±1, and 65.4% of the patients had two to four concomitant causes. The serum screen used in our study is easy to perform in ambulatory patients and identifies potential causes of anemia for which safe and effective treatments are available. Second-line bone marrow aspiration adds to the diagnostic yield.
Annales de biologie clinique. 12/2012; 70(6):643-7.
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ABSTRACT: The indications for digoxin are currently limited to rare cases of heart failure and/or atrial fibrillation. Its use should be even more rare in geriatrics its pharmacological characteristics, associated with age-related changes and comorbidities, particularly increase the risk of digoxin poisoning in the elderly. However, at least a third of aged patients suffering from heart failure and/or atrial fibrillation is treated by digitalis. Digoxin intoxication can provoke gastrointestinal troubles, neurological disturbances and, above all, cardiac conduction impairment and dysrythmias, which explain its severity and high mortality rate. Presently, first-line therapy is the administration of digoxin specific antibodies. Poor prognosis factors, frequently found in digoxin intoxications in the elderly, have been established for guiding the prescription of antibodies and their dosage. It is important for geriatricians to be able to recognize poisoning signs and the conditions in which an antidote treatment is necessary. This will permit a more effective management of the case, with the support of a poison control center and possible referral of the patient to an intensive care unit.
Geriatrie et psychologie neuropsychiatrie du vieillissement 12/2012; 10(4):355-363.
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ABSTRACT: Reversal of overanticoagulation to minimize the bleeding risk is important in elderly inpatients receiving vitamin K antagonist therapy. However, no study has specifically focused on this population. The objective of this study is to evaluate whether guidelines based on American College of Chest Physicians recommendations for the management of overanticoagulation (international normalized ratio [INR] ≥5.0) can apply to elderly inpatients, and notably allow 24-hour INRs to return to the 1.8-3.2 range in this population. The influence of different factors on the vitamin K response also was evaluated.
Inpatients aged ≥75 years with INR ≥5.0 were included in this observational study. INRs were assessed on the day of the overdosage (Day 0) and on the following day (Day 1).
Of 385 Day 0 INRs ≥5.0 (239 patients; 86±6 years), 217 were managed according to recommendations, with a mean INR decreasing from 6.8±2.4 (range: 5.0-20.0) on Day 0 to 2.7±1.3 (range: 1.1-10.1) on Day 1 (P<.0001); 55% of INRs were within the 1.8-3.2 range, 20% <1.8, and 25% >3.2. In the subset of Day 0 INRs between 5.0 and 6.0, mean INR decreased from 5.5±0.3 to 2.7±1.0 (P<.0001) on Day 1 after oral administration of 1 mg vitamin K1 (n=121) and from 5.3±0.3 to 5.0±1.6 (P=.149) without vitamin K1 administration (n=48). Among covariates entered in the multivariate analysis, including co-medications, only the vitamin K1 dose influenced Day 1 INRs, with higher doses of vitamin K1 associated with Day 1 INRs <1.8 (P<.0001).
In elderly inpatients with INR ≥5.0, both vitamin K antagonist dose omission and vitamin K1 administration according to recommendations were effective in reversing overanticoagulation, allowing most INRs to return to the 1.8-3.2 range without excessive overcorrection. Therefore, American College of Chest Physicians recommendations may be applied to elderly inpatients.
The American journal of medicine 06/2011; 124(6):527-33. · 4.47 Impact Factor
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ABSTRACT: Vitamin K antagonist tablets are often split to fractionate the dose by elderly patients. We performed a study in order to assess the divisibility of one dosage strength of score-lined warfarin and of score-lined fluindione.
Due to a recent change in the pharmaceutical form of fluindione in order to improve the divisibility, the study was performed over 2 different periods (with the « old » and with the « new » pharmaceutical form). In each period, 10 patients mean aged 82 years, 10 relatives, 10 nurses, 10 medical doctors) were asked to split in half warfarin tablets (W2 1(st) period et W2 2(d) period) and fluindione tablets (F2 et F'2), and to split fluindione tablets into 4 fragments (F4 et F'4). The first end-point was the accuracy of splitting estimated by the difference between the real and the expected weight of fragmented tablets. The statistical analysis was performed using an ANOVA test with 2 variables, subject and drug. The difference between the 2 periods were analyzed using an ANOVA test with 2 variables, subject and period.
Over the 2 periods, the differences between real and expected weight were of 4.65% for W2 1(st) phase, 9.48% for F2, 15.35% for F4, 5.56% for W2 2(d )period, 4.30% for F'2, and 6.98% for F'4. The quality of splitting was statistically poorer in the elderly patient group compared to other subjects.
This study was not design to assess the clinical relevance (bleeding or thromboembolism) or the anticoagulation control of the variations in drug mass due to inappropriate splitting of tablets. However, split form of drugs should be prescribe with caution to elderly patients.
Geriatrie et psychologie neuropsychiatrie du vieillissement 05/2011; 9(2):171-7.
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ABSTRACT: Aging is generally associated with an increased predisposition to infectious diseases and cancers, related in part to the development of immune senescence, a process that affects all cell compartments of the immune system. Although many studies have investigated the effects of age on natural killer (NK) cells, their conclusions remain controversial because the diverse health status of study subjects resulted in discordant findings. To clarify this situation, we conducted the first extensive phenotypic and functional analysis of NK cells from healthy subjects, comparing NK cells derived from newborn (cord blood), middle-aged (18-60 years), old (60-80 years), and very old (80-100 years) subjects. We found that NK cells in cord blood displayed specific features associated with immaturity, including poor expression of KIR and LIR-1/ILT-2 and high expression of both NKG2A and IFN-gamma. NK cells from older subjects, on the other hand, preserved their major phenotypic and functional characteristics, but with their mature features accentuated. These include a profound decline of the CD56(bright) subset, a specific increase in LIR-1/ILT-2, and a perfect recovering of NK-cell function following IL2-activation in very old subjects. We conclude that the preservation of NK cell features until very advanced age may contribute to longevity and successful aging.
Aging cell 08/2010; 9(4):527-35. · 7.55 Impact Factor
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ABSTRACT: To determine the effect of patient characteristics and of specific guidelines that were developed for managing warfarin therapy in older adults and included in an in-house computer program on anticoagulation quality.
Thirteen-month observational study.
Acute care, extended care, and rehabilitation geriatric wards of a teaching hospital in Paris, France.
Hospitalized patients (N=307, mean age 86.1 +/- 6.1) treated with warfarin with a therapeutic international normalized ratio range of 2.0 to 3.0.
Patients were assigned according to care unit to the computer-generated dosing group (CGD) or the standard management group (SM; usual physician-based care).
Relationships between anticoagulation quality criteria and covariates (age, sex, warfarin indication, treatment phase, follow-up duration, model of care).
According to multivariate analysis, only model of care and follow-up duration independently influenced anticoagulation control; the proportion of time within therapeutic INR range 2.0 to 3.0 was significantly greater in the CGD group than in the SM group (59% vs 48%, P=.004). When a wider INR range was analyzed (1.8-3.2), the proportion of time within range was 73% versus 64% (P=.006). Use of the computer was associated with fewer days with INRs greater than 3, a smaller percentage of INRs of 4 or greater, a longer time to the first INR of 4.0 or greater, and a smaller mean number of INRs per month than SM (all P<.01).
Initiation regimen and long-term rules that have specifically been developed and included in a computerized dosage program improve quality of anticoagulation in elderly inpatients, allowing them to benefit from a quality of care as high as that of younger ambulatory patients.
Journal of the American Geriatrics Society 02/2010; 58(2):242-7. · 3.74 Impact Factor
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ABSTRACT: Low-molecular-weight heparins (LMWHs) have been widely studied in pivotal clinical trials or in several meta-analyses. However, the safety and optimal use of LMWHs in high-risk patients such as the very elderly remains uncertain since these patients are usually excluded from clinical trials. In terms of LMWHs in the elderly, the main concerns are renal failure and the risk of accumulation. A clinical approach consisting of a LMWH dose reduction in the elderly should be considered with great caution in terms of efficacy, since it has been tested neither in the treatment of VTE nor in VTE prophylaxis. If monitoring is considered in patients receiving therapeutic dose LMWHs, appropriate target ranges for peak anti-Xa activity levels should be used and so far, no anti-Xa activity-based guidelines have been issued. Moreover, no data support any laboratory monitoring in elderly patients treated with prophylactic dose LMWHs.
Clinical Interventions in Aging 01/2010; 5:119-21. · 2.08 Impact Factor
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Eric Pautas
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ABSTRACT: VKA are underused in elderly patients with thrombo-embolic disease, mainly because of their increased risk of bleeding. However, in most cases, evaluation of this risk versus the efficacy in prevention of thrombo-embolic events, should not lead to a therapeutic abstention. The use of VKA in frail elderly patients requires a specific clinical assessment before and during treatment. Moreover, initiation and management of VKA therapy offers some specificities in older patients.
La Revue du praticien 12/2009; 59(10):1377-81.
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Anne Forest, Eric Pautas,
Patrick Ray,
Dominique Bonnet,
Marc Verny,
Nicolas Amabile,
Chantal Boulanger,
Bruno Riou,
Alain Tedgui,
Ziad Mallat,
Jacques Boddaert
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ABSTRACT: Microparticles (MP) are shed membrane vesicles released from activation or apoptosis of several cell types and carry a procoagulant activity. Age is associated with a procoagulant state, but the role of MP in this setting is unknown, as the relationship of MP to aging in humans. We tested the hypotheses that elderly persons compared with young persons may have different patterns of expression of MP and procoagulant activity in stable or septic conditions.
Patients from Emergency and Geriatric Departments were divided into four groups according to their age (< 50 or > or = 75 years old) and the presence of systemic infection (yes or no). The diagnosis of infection was reached when it was classified as certain or possible by an expert panel. Circulating MP were isolated from venous citrated blood. Cytofluorometry using specific antibodies was performed to determine the origins of MP (endothelial microparticles [EMP], red blood cell microparticles, or platelet microparticles). Procoagulant activity was determined using annexin V (prothrombinase activity) and tissue factor (TF) assays.
One hundred and eleven patients were included. Elderly patients expressed a decrease in EMP in stable conditions, associated with a decrease in procoagulant annexin V MP in septic conditions (p < .05), and higher EMP levels were found in elderly infected patients who died during hospital stay than in survivors (p = .04). Compared with young patients, response to sepsis was altered in elders concerning EMP, annexin V MP, and TF-bearing MP.
Elderly patients expressed a different pattern of MP in stable conditions, with a different response to sepsis in procoagulant activity modification.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences 11/2009; 65(4):414-20. · 4.60 Impact Factor
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Annals of internal medicine 05/2008; 148(8):633-5. · 16.73 Impact Factor
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ABSTRACT: Although the role of inflammation has been studied in specific diseases or in community living elderly, data in hospitalized acute care elderly patients are scarce. The present study was designed to determine the predictive value of sociodemographic, clinical and biological factors for mortality in acute care geriatric wards. Retrospective study was conducted in two acute care wards in a university-based geriatric hospital with elderly patients (n=224) consecutively admitted to acute care wards with available medical files. Sociodemographic variables, primary medical diagnosis and number of associated conditions, dementia, depression, pressure sores, functional status (measure by the activities of daily living=ADL scale), weight, and plasma levels of albumin, transthyretin, C-reactive protein (CRP) and orosomucoid were recorded at admission. Patients who died in the acute care wards were compared to those who survived. The mean length of stay was 16+/-13 days; mortality was 12%. Univariate analysis revealed that disability, no anti-depressant drug, pressure ulcers, a higher number of associated conditions, living with another person, and biological markers of malnutrition (albumin <35g/l, transthyretin <200mg/l) and inflammation (CRP < or =30mg/l, orosomucoid > or =1.25g/l) were significantly associated with an increase in the risk of death. The logistic regression model retained CRP > or =30mg/l (odds ratio (OR)=3.72, 95% confidence interval (CI)=1.34-10.31; p=0.009) and disability for at least one ADL item (OR=2.16, 95% CI=1.55-2.99; p<0.001) as independent risk factors for death. We conclude that CRP and disability are strong independent risk factors for death in this population, and special attention should be paid to these patients in an integrated therapeutic approach to geriatric care.
Archives of gerontology and geriatrics 05/2008; 48(3):406-10. · 1.36 Impact Factor
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ABSTRACT: Warfarin is difficult to use because of a marked inter- and intraindividual variability among patients in the required dosage. Recent advances in understanding the vitamin K cycle have been made. Besides well-known demographic or environmental factors (advanced age, vitamin K intake, concomitant drugs, comorbid conditions, and acute illnesses), genetic single nucleotide polymorphisms (SNPs) have been identified as strongly affecting the maintenance dosage and its variability. SNPs of vitamin K epoxide reductase complex subunit-1 (VKORC1) gene have been identified, affecting the enzyme shown as one of the target of vitamin K antagonist. SNPs of cytochrome P450 2C9 (CYP2C9) gene have been shown to decrease the catabolism of warfarin. The combined analysis of VKORC1, CYP2C9 SNPs, and age may account for more than 50% of the individual variability in the warfarin maintenance dosage. Predicting models of warfarin maintenance dosage taking into account these individual parameters are currently developed.
Vitamins & Hormones 02/2008; 78:247-64. · 2.19 Impact Factor
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ABSTRACT: Repeated administration of low-molecular-weight heparin (LMWH) to elderly patients with an impaired renal function may lead to an accumulation effect with an increased risk of bleeding. In this setting, Cockcroft-Gault (CG) is the most widely used formula for glomerular filtration rate (GFR) estimation. In hospitalized patients over the age of 70, the six-variable Modification of Diet in Renal Disease (MDRD) formula was compared with the CG formula to detect patients with renal impairment who are at higher risk of bleeding when treated with LMWH.
We combined retrospective data from 366 patients aged 86.2 +/- 6.6 years, treated with LMWHs. CG and MDRD GFR estimates were compared using the Bland-Altman method and the agreement between the two formulae by the kappa coefficient.
The mean CG and MDRD estimated GFR were 45.9 +/- 21.9 mL/min and 75.6 +/- 32.6 mL/min/1.73 m(2), respectively, with a mean bias of 29.6 mL/min. The concordance between the formulae to classify patients into stages of kidney disease was very poor (weighted kappa = 0.17): 21.8% patients had severe renal function impairment with the CG formula versus 1.3% with the MDRD formula. In our population, the MDRD thresholds that would correspond to CG estimates of 30 mL/min and 60 mL/min were found at 63 mL/min/1.73 m(2) and 80 mL/min/1.73 m(2), respectively.
In elderly patients, GFR estimates using MDRD and CG formulae differ widely and identify different numbers of individuals with kidney disease. Prospective comparative studies are needed to validate these formulae and their different thresholds to better detect elderly patients at higher risk of bleeding when treated with LMWH.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences 12/2007; 62(11):1300-5. · 4.60 Impact Factor
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ABSTRACT: As the population ages, the number of patients aged 75 years and over treated with vitamin K antagonists (VKAs) is steadily increasing. In this age group, the two main indications for oral anticoagulant therapy are the treatment of venous thromboembolic disease and the prevention of systemic embolism in patients with nonvalvular atrial fibrillation. In both indications, a target international normalized ratio of 2.5 (range: 2.0-3.0) is recommended. Although VKAs are beneficial in thromboembolic disorders, they are still underused. In this review, we will focus on two crucial topics in elderly patients, the specific management of VKAs in these patients and the hemorrhagic risk. Current recommendations concerning the management at the start of treatment, education and adequate monitoring may help to minimize the hemorrhagic risk in these frail patients.
Future Cardiology 05/2007; 3(3):321-30.
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ABSTRACT: The safety and optimal use of prophylactic treatment with low-molecular-weight heparins in elderly patients with impaired renal function remain undefined.
The primary aim of this study was to analyse, in 'real life', the influence of renal function, as assessed by creatinine clearance (CL(CR)), on the level of anti-Xa activity in medical hospitalised elderly patients receiving prophylactic dosages of enoxaparin. Consecutive hospitalised acutely ill medical patients aged >or=75 years receiving daily dosages of enoxaparin 4000 IU for up to 10 days were prospectively enrolled in two centres. Peak anti-Xa activity was measured at the beginning and during the course of therapy.
One hundred and twenty-five patients (31 men, 94 women), mean age 87.5 +/- 6.3 years, mean bodyweight 56.4 +/- 11.9 kg and mean CL(CR) 39.8 +/- 16.1 mL/min, were enrolled in the study. The mean maximum anti-Xa activity (day 1 to day 10) [anti-Xa(max1-10)] was 0.64 +/- 0.23 IU/mL (range 0.24-1.50 IU/mL). Weak negative correlations were found between CL(CR) and anti-Xa(max) and between bodyweight and anti-Xa(max). Mean anti-Xa(max) was slightly but significantly higher in patients with CL(CR) of 20-30 mL/min compared with patients with CL(CR) of 31-40, 41-50 or 51-80 mL/min (0.72 versus 0.61, 0.61 and 0.60 IU/mL, respectively), and in patients weighing <50 kg compared with patients weighing 50-60 kg or >60 kg (0.74 vs 0.64 and 0.52 IU/mL, respectively). Serious bleeding occurred in five patients, but anti-Xa(max) values in these patients were not different to those in patients without bleeding (p = 0.77). Individual anti-Xa(max) at the beginning or during the course of treatment was measured in the subgroup of 58 patients in whom anti-Xa activity was measured at least once during the study. The mean anti-Xa(max) value was slightly but significantly higher during the course of the therapy than at the beginning of the study (0.63 +/- 0.26 IU/mL vs 0.56 +/- 0.23 IU/mL, p = 0.012).
Only CL(CR) <30 mL/min and bodyweight <50 kg were associated with significantly higher anti-Xa(max) values. The clinical relevance of these increases remains questionable. No conclusions about the safety of enoxaparin in elderly medical patients can be drawn from these findings.
Drugs & Aging 02/2007; 24(1):63-71. · 2.67 Impact Factor
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ABSTRACT: In patients >75 years of age, the two main indications for oral anticoagulant therapy with vitamin K antagonists (VKAs) are treatment of venous thromboembolic disease and prevention of systemic embolism in patients with nonvalvular atrial fibrillation. In both indications, a target International Normalized Ratio of 2.5 (range 2.0-3.0) is recommended. Bleeding is the adverse effect feared by physicians that most limits the use of VKAs in older frail patients. In this paper, we discuss (i) the risk of VKA-related bleeding with advancing age; (ii) the severity of bleeding complications and particularly the risk of intracranial haemorrhage in older patients; (iii) the risk factors for bleeding related to patient characteristics; and (iv) the risk factors or determinants for bleeding related to treatment variables (warfarin induction and maintenance administration, instability of anticoagulation, poor compliance and patient's education level, and concomitant use of drugs). Avoiding over-anticoagulation and/or reducing periods of overdosing in the course of oral anticoagulant treatment with tailored monitoring may help to minimise the risk of bleeding in older patients.
Drugs & Aging 02/2006; 23(1):13-25. · 2.67 Impact Factor
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Journal of the American Geriatrics Society 06/2005; 53(5):913-4. · 3.74 Impact Factor
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Virginie Siguret,
Isabelle Gouin,
Matthieu Debray,
Christine Perret-Guillaume,
Jacques Boddaert,
Isabelle Mahé,
Valérie Donval,
Marie-Laure Seux,
Marjolaine Romain-Pilotaz,
Mathilde Gisselbrecht,
Marc Verny, Eric Pautas
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ABSTRACT: Elderly patients are at high risk of over-anticoagulation when treated with warfarin, especially during treatment induction. We developed a simple low-dose regimen for starting warfarin therapy in elderly inpatients. The daily maintenance dosage is predicted from the international normalized ratio (INR) measured the day after the third daily intake of a 4-mg dose. We conducted a prospective multicenter study to evaluate the accuracy and safety of this regimen.
We studied 106 elderly (age >or=70 years) inpatients (mean [+/- SD] age, 85 +/- 6 years; range, 71 to 97 years) who had a target INR of 2.0 to 3.0. Accuracy in predicting the daily maintenance dose from INR value on day 3 was evaluated.
The predicted daily maintenance warfarin dose (3.1 +/- 1.6 mg/d) correlated closely with the actual maintenance dose (3.2 +/- 1.7 mg/d; R(2) = 0.84). The predicted dose was equal to the actual dose in 77 patients (73%; 95% confidence interval [CI]: 64% to 81%) and within 1 mg in 101 patients (95%; 95% CI: 91% to 99%). The mean time needed to achieve a therapeutic INR was 6.7 +/- 3.3 days (median, 6.0 days); the mean time needed to achieve the maintenance dose was 9.2 +/- 4.5 days (median, 7.0 days). None of the patients had an INR >4.0 during this period. One fatal bleeding event was recorded in a patient with an INR in the therapeutic range.
Our warfarin induction regimen was simple, safe, and accurate in predicting the daily maintenance warfarin dose in elderly hospitalized patients.
The American Journal of Medicine 02/2005; 118(2):137-42. · 5.43 Impact Factor
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ABSTRACT: Low-molecular weight heparins (LMWHs) have been shown to be as safe and effective as unfractionated heparin (UFH) for the treatment of acute venous thrombosis and non-life-threatening pulmonary embolism. Different reports have shown that LMWHs may also be used to treat patients with unstable angina or non-Q-wave infarction. The safety of LMWHs used at therapeutic dose has been widely studied in pivotal clinical trials and analysed in several meta-analyses. However, despite the wide development and use of LMWHs, several issues regarding the safety and optimal use of LMWHs remain unanswered. The main adverse effect of LMWHs is bleeding and it is uncertain whether a weight-adjusted dosage regimen without laboratory monitoring can be used in patients with a high risk of bleeding, such as patients with renal failure, elderly patients, obese patients or pregnant women. These patients are usually excluded from clinical trials and only a few studies, not sufficiently powered to estimate efficacy and safety, have been carried out in these special populations. Most of the available data comes from pharmacokinetic or population pharmacodynamic studies or clinical reports. Results in patients with renal impairment who are not undergoing haemodialysis suggest that a reduction in calculated creatinine clearance levels is associated with an increased risk of accumulation of anti-Xa activity, the extent of which differs depending on the individual LMWH and the extent to which the compound is cleared by the kidney. The limited data available regarding the use of therapeutic doses of LMWHs in obese patients suggest that there is no need to cap the dose at a maximal allowable dose. Long-term (3-month) treatment with LMWHs appears to be as effective and safe as oral anticoagulant therapy for the treatment of venous thromboembolism. It appears that each LMWH is a distinct compound with unique pharmacokinetic and pharmacodynamic profiles. Until more data are available regarding these special populations, periodic monitoring of anti-Xa activity levels may be recommended to detect accumulation and/or an overdose and minimise the bleeding risk. The non-haemorrhagic adverse effects of the LMWHs include heparin-induced thrombocytopenia (HIT) and osteoporosis. The incidence of HIT appears to be lower with LMWHs than with UFH; there is currently not enough data to compare the frequency of HIT between the various LMWHs. LMWHs also appear to carry a lower risk of causing osteoporosis than UFH. In conclusion, studies that include special population patients are required to make conclusive recommendations concerning the safety and monitoring of the different LMWHs.
Drug Safety 02/2005; 28(4):333-49. · 3.63 Impact Factor
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ABSTRACT: Low molecular weight heparin has become the treatment of choice for venous thromboembolism events and acute coronary syndromes. In contrast to unfractionated heparin, low molecular weight heparins are mainly excreted by the kidney. Thus, repeated administration of therapeutic doses of low molecular weight heparins may lead to overdosage and/or an accumulation effect in patients with renal impairment, such as the elderly. Moreover, older patients are often excluded from clinical trials. Little evidence is available to assess the risk/benefit ratio of low molecular weight heparins used at therapeutic dosages in elderly patients with or without renal insufficiency in normal clinical practice.
Pharmacovigilance data, case reports, and observational studies reporting major bleeding complications in the elderly highlight the potential risk of using low molecular weight heparins at therapeutic dosages in these patients. An evaluation of renal function is thus essential before therapy with low molecular weight heparins is begun. Moreover, multiple-dose pharmacokinetic studies in the elderly have shown that the pharmacokinetic response to impaired renal function, especially the risk of accumulation effect, may differ among preparations of low molecular weight heparins.
Three approaches to improve the safety of low molecular weight heparins in the elderly are discussed: (1) to replace low molecular weight heparin therapy with monitored unfractionated heparin therapy in cases of severe renal insufficiency, but comparative studies are necessary to clarify whether unfractionated heparin offers better safety in this setting; (2) to use initial reduced dosages in elderly patients with or without renal failure, but these regimens have to be validated for each low molecular weight heparin in terms of efficacy in controlled trials; and (3) to monitor anti-Xa activity to detect any overdosage and/or any accumulation effect of low molecular weight heparins.
Current opinion in pulmonary medicine 10/2004; 10(5):366-70. · 3.08 Impact Factor
