Thrombolyse bei tiefer Venenthrombose? [Thrombolytic therapy in deep venous thrombosis?]

Sie sehen eine 45-jährige Patientin mit einem bläulich-zyanotischen rechten Bein. Vor fünf Tagen habe ein Spannungsschmerz in der Wade begonnen und sich zunehmend in den Oberschenkel hochgezogen. Die rechte Wade misst im Umfang 4 cm mehr als die linke. Die Anamnese ergibt keine familiäre oder persönliche Vorgeschichte einer thromboembolischen Erkrankung. Die Patientin ist übergewichtig ( BMI 35 kg/m2) und nimmt seit einigen Jahren eine Östrogen-Progesteron-Kombination. Der Ultraschall zeigt eine Thrombose der tiefen Beinvenen, die bis in die äussere Beckenvene reicht.

Rate, type, and cost of adverse drug reactions in emergency department admissions.

Background: Adverse drug reactions (ADRs) are a threat to patients' health and quality of life, and can generate significant expenses. They are generally underreported, with different rates in different health care systems. Methods: We conducted a 6-month survey of all primary admissions to the medical emergency department of a university hospital and assessed the rate, characteristics, avoidability, and marginal costs of ADRs. Results: A total of 7% of all admissions were mainly caused by ADRs. The most frequent were gastrointestinal bleeding (22.3%) and febrile neutropenia (14.4%). Anticancer drugs were involved in 22.7% of the cases, and anticoagulants, analgesics, and non-steroidal anti-inflammatory drugs in 8% each. Physicians had prescribed 70% of these drugs. Patients were predominantly treated in intermediate care units and ordinary wards. The mean cost per case amounted to CHF 3586+/-342, or a total of CHF 821204 over the 6-month-period (1 CHF=0.56 US$=0.87 Euro). A total of 67% were considered definitely imputable to drug effects and 32% were retrospectively regarded as avoidable. Conclusions: Interventions aimed at reducing the incidence of ADRs should be directed towards both patient education and physician training. This could save hospitals admissions and money, and could be used as an indicator of prescription quality.

Hospitalized women experiencing an episode of excessive oral anticoagulation had a higher bleeding risk than men.

OBJECTIVE: Overanticoagulated medical inpatients may be particularly prone to bleeding complications. Among medical inpatients with excessive oral anticoagulation (AC), we sought to identify patient and treatment factors associated with bleeding. METHODS: We prospectively identified consecutive patients receiving oral AC admitted to the medical ward of a university hospital (February-July 2006) who had at least one international normalized ratio (INR) value >3.0 during the hospital stay. We recorded patient characteristics, AC-related factors, and concomitant treatments (e.g., platelet inhibitors) that increase the bleeding risk. The outcome was overall bleeding, defined as the occurrence of major or minor bleeding during the hospital stay. We used logistic regression to explore patient and treatment factors associated with bleeding. RESULTS: Overall, 145 inpatients with excessive oral AC comprised our study sample. Atrial fibrillation (59%) and venous thromboembolism (28%) were the most common indications for AC. Twelve patients (8.3%) experienced a bleeding event. Of these, 8 had major bleeding. Women had a somewhat higher risk of major bleeding than men (12.5% vs 4.1%, p = 0.08). Multivariable analysis demonstrated that female gender was independently associated with bleeding (odds ratio [OR] 4.3, 95% confidence interval [95% C1] 1.1-17.8). Age, history of major bleeding, value of the index INR, and concomitant treatment with platelet inhibitors were not independent predictors of bleeding. CONCLUSIONS: We found that hospitalized women experiencing an episode of excessive oral AC have a 4-fold increased risk of bleeding compared with men. Whether overanticoagulated women require more aggressive measures of AC reversal must be examined in further studies.

Thrombosis in paroxysmal nocturnal hemoglobinuria at a glance: a clinical review.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired stem cell disorder, with its primary clinical manifestations being hemolytic anemia, marrow failure and thrombophilia. Chronic hemolysis, failures of the fibrinolytic system, increased leukocyte-derived tissue factor levels in plasma, procoagulant microparticles generated through complement-mediated damage of platelets and venous endothelium are related to the acquired hypercoagulable state. Visceral thrombosis (including hepatic veins and mesenteric veins), cerebrovascular events and pulmonary embolism predict a poor outcome. Thrombosis is also associated with significant morbidity during pregnancy. Depending on the sites of thrombosis, a score-based probability to predict outcome can be assigned. Abdominal vein thromboses account for the majority of morbidity and mortality related to thrombosis, and time-dependent trends suggest that mortality rates tend to decline, with the advent of evolution of therapeutic and diagnostic strategies. In contrast, mortality rates from cerebrovascular events display no significant decline. Prompt diagnosis requires both clinical suspicion and sophisticated imaging techniques, along with multidisciplinary therapeutic intervention. In the eculizumab era, a significant reduction of thrombotic events was observed during therapy, and long-term follow up is needed to establish any benefit in rates and pattern of this complication. However, up to now, only bone marrow transplantation permanently abolishes the coagulation defect.

Risk of falls and major bleeds in patients on oral anticoagulation therapy.

BACKGROUND: The risk of falls is the most commonly cited reason for not providing oral anticoagulation, although the risk of bleeding associated with falls on oral anticoagulants is still debated. We aimed to evaluate whether patients on oral anticoagulation with high falls risk have an increased risk of major bleeding. METHODS: We prospectively studied consecutive adult medical patients who were discharged on oral anticoagulants. The outcome was the time to a first major bleed within a 12-month follow-up period adjusted for age, sex, alcohol abuse, number of drugs, concomitant treatment with antiplatelet agents, and history of stroke or transient ischemic attack. RESULTS: Among the 515 enrolled patients, 35 patients had a first major bleed during follow-up (incidence rate: 7.5 per 100 patient-years). Overall, 308 patients (59.8%) were at high risk of falls, and these patients had a nonsignificantly higher crude incidence rate of major bleeding than patients at low risk of falls (8.0 vs 6.8 per 100 patient-years, P=.64). In multivariate analysis, a high falls risk was not statistically significantly associated with the risk of a major bleed (hazard ratio 1.09; 95% confidence interval, 0.54-2.21). Overall, only 3 major bleeds occurred directly after a fall (incidence rate: 0.6 per 100 patient-years). CONCLUSIONS: In this prospective cohort, patients on oral anticoagulants at high risk of falls did not have a significantly increased risk of major bleeds. These findings suggest that being at risk of falls is not a valid reason to avoid oral anticoagulants in medical patients.

Clinical characteristics and outcome of inpatients versus outpatients with venous thromboembolism: findings from the RIETE Registry.

BACKGROUND: Patients with venous thromboembolism (VTE) treated with anticoagulants are at risk of death from pulmonary embolism (PE) and/or bleeding. However, whether patients who develop VTE in hospital have a higher complication rate than those who develop VTE in an outpatient setting is unclear. PATIENTS AND METHODS: RIETE is an ongoing, prospective registry of consecutive patients with acute, objectively confirmed, symptomatic VTE. We compared the 3-month incidence of fatal PE and fatal bleeding in patients in whom the VTE had developed while in hospital for another medical condition (inpatients) with those who presented to the emergency ward because of VTE (outpatients). RESULTS: Up to April 2008, 22,133 patients with acute VTE were enrolled: 10,461 (47%) presented with PE, 11,672 with deep vein thrombosis. Overall, 6445 (29%) were inpatients. During the study period, those who developed VTE as inpatients had a significantly higher incidence of fatal PE (2.1% vs. 1.5%; odds ratio: 1.4; 95% CI: 1.1-1.7), overall death (7.0% vs. 5.4%; odds ratio: 1.3; 95% CI: 1.2-1.5), and major bleeding (2.9% vs. 2.1%; odds ratio: 1.4; 95% CI: 1.1-1.6) than outpatients. The incidence of fatal bleeding was not significantly increased (0.7% vs. 0.5%; odds ratio: 1.2; 95% CI: 0.9-1.8). In multivariable analysis, inpatient status was significantly associated with a higher risk for fatal PE (odds ratio: 1.3; 95% CI: 1.1-1.7). CONCLUSIONS: VTE occurring in hospitalized patients carries a significantly higher risk for death of PE than in outpatients, underscoring the importance of VTE prevention strategies in the hospital setting.

Home versus in-hospital treatment of outpatients with acute deep venous thrombosis of the lower limbs.

BACKGROUND: Some physicians are still concerned about the safety of treatment at home of patients with acute deep venous thrombosis (DVT). METHODS: We used data from the RIETE (Registro Informatizado de la Enfermedad TromboEmbólica) registry to compare the outcomes in consecutive outpatients with acute lower limb DVT according to initial treatment at home or in the hospital. A propensity score-matching analysis was carried out with a logistic regression model. RESULTS: As of December 2012, 13,493 patients had been enrolled. Of these, 4456 (31%) were treated at home. Patients treated at home were more likely to be male and younger and to weigh more; they were less likely than those treated in the hospital to have chronic heart failure, lung disease, renal insufficiency, anemia, recent bleeding, immobilization, or cancer. During the first week of anticoagulation, 27 patients (0.20%) suffered pulmonary embolism (PE), 12 (0.09%) recurrent DVT, and 51 (0.38%) major bleeding; 80 (0.59%) died. When only patients treated at home were considered, 12 (0.27%) had PE, 4 (0.09%) had recurrent DVT, 6 (0.13%) bled, and 4 (0.09%) died (no fatal PE, 3 fatal bleeds). After propensity analysis, patients treated at home had a similar rate of venous thromboembolism recurrences and a lower rate of major bleeding (odds ratio, 0.4; 95% confidence interval, 0.1-1.0) or death (odds ratio, 0.2; 95% confidence interval, 0.1-0.7) within the first week compared with those treated in the hospital. CONCLUSIONS: In outpatients with DVT, home treatment was associated with a better outcome than treatment in the hospital. These data may help safely treat more DVT patients at home.

Gewisse Patienten profitieren von einem Selfmanagement der oralen Antikoagulation.

Cet article présente les résultats de la revue systématique: Garcia-Alamino JM, Ward AM, Alonso-Coello P, et al. Self-monitoring and self-management of oral anticoagulation. Cochrane Database of SystematicReviews 2010 Apr 14;(4):CD003839. doi:10.1002/14651858.CD003839.pub2.. PMID: 20393937.

prophylaxis of experimental endocarditis with antiplatelet and antithrombin agents : a role for long-term prevention of infective endocarditis in humans?

BACKGROUND: Infective endocarditis (IE) mostly occurs after spontaneous low-grade bacteremia. Thus, IE cannot be prevented by circumstantial antibiotic prophylaxis. Platelet activation following bacterial-fibrinogen interaction or thrombin-mediated fibrinogen-fibrin polymerization is a critical step in vegetation formation. We tested the efficacy of antiplatelet and antithrombin to prevent experimental IE. METHODS: A rat model of experimental IE following prolonged low-grade bacteremia mimicking smoldering bacteremia in humans was used. Prophylaxis with antiplatelets (aspirin, ticlopidine [alone or in combination], eptifibatide, or abciximab) or anticoagulants (antithrombin dabigatran etexilate or anti-vitamin K acenocoumarol) was started 2 days before inoculation with Streptococcus gordonii or Staphylococcus aureus. Valve infection was assessed 24 hours later. RESULTS: Aspirin plus ticlopidine, as well as abciximab, protected 45%-88% of animals against S. gordonii and S. aureus IE (P < .05). Dabigatran etexilate protected 75% of rats against IE due to S. aureus (P < .005) but failed to protect against S. gordonii (<30% protection). Acenocoumarol was ineffective. CONCLUSIONS: Antiplatelet and direct antithrombin agents may be useful in the prophylaxis of IE in humans. In particular, the potential dual benefit of dabigatran etexilate might be reconsidered for patients with prosthetic valves, who require life-long anticoagulation and in whom S. aureus IE is associated with high mortality.

Characteristics and early and long-term outcome in patients with acute ischemic stroke and low ejection fraction.

OBJECTIVES: We assessed the clinical characteristics of patients with acute ischemic stroke (AIS) with left ventricular ejection fraction (EF) ≤ 35% and investigated the association of low EF with early and long-term outcome. METHODS: A total of 2439 patients of the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) were selected. Demographics, risk factors, pre-stroke treatment, and clinical, radiological and metabolic variables in patients with and without low EF were compared. Functional independence (modified Rankin Score ≤ 2) and mortality were recorded 1 week up to 12 months from admission. RESULTS: Low EF patients (n=119) were more commonly men, older, had higher rates of coronary artery disease and atrial fibrillation (AF), and more frequent pretreatment with anticoagulants, antiplatelets and antihypertensive agents. On admission, they presented with higher stroke severity and had lower values of systolic blood pressure, higher heart rate, and worse estimated glomerular filtration rate. Stroke-related disability and death rates were higher in low EF patients during follow-up (19.5% vs. 7.8% at 1 week, and 36.1% vs. 16.5% at 12 months). Increasing age, stroke severity, and AF were independent predictors of one-year mortality in these patients while prior use of statins had a favorable effect on early mortality. CONCLUSIONS: AIS in patients with low EF is associated with older age, cardiac comorbidities, and more severe clinical presentation. Low EF can identify a subset of AIS patients at high risk of early and long-term functional disability and mortality.

Traitement médicamenteux de l'artériopathie périphérique [Medical therapy in peripheral arterial occlusive disease]

Atherosclerotic peripheral arterial disease (PAD) is often asymptomatic. If symptomatic, patients present intermittent claudication, ischemic rest pain or tissue necrosis. The prevalence of PAD increases with age and affects about 2% of patients at 60 years. Patients with PAD have an increased risk of coronary or cerebro-vascular events. Measure of the ankle-brachial index (ABI) allows early detection of asymptomatic patients, and allows early preventive interventions, in order to reduce their cardio-vascular risk. The most important interventions are smoking cessation, normalisation of blood pressure and lipid levels, and introduction of an antiplatelet agent, such as aspirin 75 to 160 mg/d.

Cirugía bucal y anticoagulantes orales: una propuesta de actuación

El tratamiento con anticoagulantes orales, fundamentalmente acenocumarol (Sintrom), es cada vez más frecuente en nuestro país. Se ha revisado la literatura médica y odontológica, sobre las pautas terapéuticas empleadas en cirugía bucal en pacientes anticoagulados por vía oral. Se propone un protocolo de actuación basado en que el mantenimiento del régimen anticoagulante oral y el uso local de antifibrinolíticos (ácido tranexámico al 4,8%) como enjuagues, después de la cirugía bucal, disminuye el riesgo tromboembólico y la posibilidad de complicaciones hemorrágicas es comparable a aquellos pacientes que disminuyen el acenocumarol antes de la cirugía bucal.

Pautas de conducta frente a los pacientes bajo tratamiento anticoagulante en la clínica dental.

Nuestro trabajo pretende dar unas ideas básicas para el manejo de pacientes sometidos a tratamiento anticoagulante dando a conocer las posibles pautas a seguir respecto a su medicación: mantener intacta la terapia anticoagulante, modificar la terapia anticoagulante o realizar tratamiento combinado de heparina con anticoagulantes orales. La decisión deberá tomarse conjuntamente con el hematólogo responsable del paciente valorando cada caso según la morbilidad intrínseca de la intervención, el riesgo de tromboembolismo en función de la patología de base que presente el paciente y el grado de coagulación determinado mediante estudios de laboratorio (tiempo de protrombina e índice de trombotest).