Hemorrhagic Complications of Oral Anticoagulant Therapy

Hemorrhagic complications of oral anticoagulant therapy

Highly effective in preventing and treating thromboembolic conditions in acute and chronic settings, anticoagulant therapy is associated with a non-negligible risk of hemorrhagic complications with a considerable clinical impact. Advanced age and comorbidities further increase the risk of bleeding during heparinization, treatment with low-molecular-weight heparins or long-term oral warfarin anticoagulation. Multidetector computed tomography represents the mainstay diagnostic technique to image-suspected hemorrhages in anticoagulated patients, as it can quickly assess presence, site, and extent of hemorrhage, identify active bleeding, and possible underlying diseases. Cross-sectional imaging appearances of the wide spectrum of anticoagulant therapy–related bleeding complications are hereby presented, including peripheral and thoracic-abdominal wall muscular hematomas, intrathoracic, abdominal, retroperitoneal genitourinary, gastrointestinal, and brain hemorrhages. Prompt recognition and comprehensive diagnostic assessment with multidetector computed tomography allow clinicians to correctly choose treatment modification or withdrawal, surgery, or interventional procedures as needed, with the aim to reduce the associated morbidity and mortality.

Antithrombotic therapy represents the mainstay of treatment for prevention of recurrent ischemic events in patients with atherothrombotic disease processes. Although the benefits of antithrombotic pharmacotherapy in the elderly are well established, the elderly are generally more vulnerable to the adverse effects of antithrombotic drugs. Such higher vulnerability may be related to distinct pharmacokinetic and pharmacodynamic responses in the late age of life, during which drug–drug interactions due to polypharmacy further enhance the risk of adverse effects associated with the use of antithrombotic agents. Given that the prevalence of atherothrombotic disease, as well as diseases with thromboembolic potential, increases exponentially with age and that the elderly population is in continuous growth, understanding strategies of antithrombotic management in these patients is of key importance. The present paper provides an overview of the current available evidence on the use of antithrombotic therapy in elderly patients with the primary focus on treatment of coronary artery disease.

L’intérêt clinique des anti-vitamine K (AVK) a été largement démontré dans de nombreuses situations pathologiques. Leur prescription ne cesse d’augmenter chez les personnes âgées et la prévention des complications hémorragiques demeure un souci essentiel dans le suivi des patients âgés sous AVK.

Nous avons réalisé une étude prospective sur une période de 6 mois dans un service d’accueil d’un hôpital général : 291 patients âgés de 75 ans et plus traités par AVK ont été inclus. Nous avons comptabilisé les complications hémorragiques en 2 groupes : a) majeur et b) mineur ou non importants, selon la classification de Landefeld, et recherché les facteurs de risques indépendants en plus de l’âge élevé selon l’index de Beyth, c’est-à-dire l’antécédent de saignement gastro-intestinal, l’antécédent d’accident vasculaire cérébral et l’existence d’une co-morbidité (IDM récent, anémie sévère, diabète, insuffisance rénale).

Parmi les 291 patients entrants traités aux AVK, 44 ont présenté une complication hémorragique, soit 15 % de l’effectif. Le tractus gastro-intestinal a représenté le site le plus fréquent de saignement et les complications neurologiques ont été les plus graves. L’application de l’index de Beyth a permis d’affirmer que les patients ayant un index prédictif élevé (score 3-4) ont présenté plus de saignements hémorragiques majeurs (p < 0,01). Trois autres facteurs ont également été corrélés au risque hémorragique : le surdosage biologique de l’INR (ou International Normalized Ratio), les antécédents de saignement digestif et d’anémie sévère (p < 0,01).

Les patients âgés représentent les patients les plus susceptibles de bénéficier des AVK et ceux le plus à risque de développer une complication hémorragique. L’index de Beyth n’explique pas à lui seul la survenue de complications hémorragiques, mais la généralisation de son utilisation permettrait d’éviter un certain nombre de complications, tout en permettant aux patients de bénéficier des avantages d’un traitement par AVK.

The contribution of oral anticoagulants is widely known in various clinical settings. With increasing use in the elderly, the prevention of hemorrhagic complications remains an essential concern.

We carried out an exploratory study over a 6-month period in the emergency ward of a general hospital. Two hundred and ninety-one patients, aged 75 years or more, treated with oral anticoagulants, were included. The hemorrhagic complications were classified, according to Landefeld, into two groups: (i) major and (ii) minor or not important. Other risk factors than age were recorded in order to calculate the Beyth index, including history of gastrointestinal bleeding, history of stroke, and one or more of four specific comorbid conditions (recent heart attack, severe anemia, diabetes mellitus, kidney deficiency).

Among the 291 included patients, 44 (15%) presented a hemorrhagic complication. The gastrointestinal tract represented the most frequent site of bleeding and the neurological complications were the most serious ones. Patients with a high Beyth index (3-4) were shown to exhibit a higher risk of severe bleeding (p < 0.01). Three other factors were associated with risk of hemorrhage: overdose (INR, International Normalized Ratio), history of digestive bleeding and severe anemia (p < 0.01).

Elderly patients are both the most likely to benefit from oral anticoagulant therapy and the most likely to develop a hemorrhagic complication. Widespread use of the Beyth index could help to prevent some severe bleeding complications, while allowing most patients to benefit from the advantages of anticoagulant therapy.

Recent years have seen the introduction of a number of new anticoagulant agents, each offering a unique profile of benefits and potential drawbacks. Anticoagulants are now available or in development that target platelet recruitment, aggregation, and adhesion, in addition to a growing number of direct or indirect thrombin inhibitors. However, the potential for anticoagulant-induced hemorrhage and the need for effective antidotes that can reverse this adverse effect remain major considerations when prescribing any anticoagulant therapy. The expanding range of anticoagulants brings with it a renewed challenge of identifying suitable treatments to reverse anticoagulant-induced hemorrhage. This paper reviews different mechanisms of anticoagulant action and the theoretical role of recombinant factor VIIa (rFVIIa) and other agents currently in development to reverse bleeding complications associated with both traditional and novel anticoagulant therapies.

Introduction. – Il n’existe pas de méthode validée permettant de prédire en début de traitement anticoagulant oral, la dose quotidienne d’équilibre de fluindione chez les patients âgés.

Malades et méthodes. – Nous avons recherché de manière prospective chez 30 patients âgés en moyenne de 86,8 ans, une relation entre l’INR dosé après deux prises d’une dose fixe de fluindione et la dose quotidienne de fluindione nécessaire pour obtenir un INR entre 2 et 3. Dix milligrammes de fluindione étaient administrés le soir des deux premiers jours. L’INR était dosé le matin du troisième jour.

Résultats. – À partir de la valeur de l'INR, la dose de fluindione nécessaire pour maintenir un INR entre 2 et 3 pouvait être déterminée à 5 mg près.

Conclusion. – Chez ces patients très âgés, nous avons mis en évidence une relation entre l’INR à deux jours du début d’un traitement par fluindione à dose fixe et la dose d’équilibre nécessaire pour obtenir un INR compris entre 2 et 3.

Introduction. – There is no validated method to predict the daily maintenance dosage of oral anticoagulation treatment by fluindione in the elderly patients. The aim of our prospective study was to look for a relation between INR at day 2 after a fixed dosage of fluindione and the daily maintenance dosage of fluindione necessary to obtain an INR value between 2 and 3.

Patients and methods. – Ten milligrams of fluindione were administered on first and second day of treatment. INR was determined the third day.

Results. – From this value, we were able to determine the daily dosage of fluindione (± 5mg) that maintained a steady state INR value between 2 and 3.

Conclusion. – In these very elderly patients, there was a relation between INR at the third day after a fixed dosage of fluindione and the daily maintenance dosage of fluindione necessary to obtain an INR value between 2 and 3.