Pulmonary embolism prophylaxis and treatment: What's right, what's wrong, and the future

Abstract

Recognition of the importance of effective pulmonary embolism treatment and prophylaxis has improved inpatient care in many settings. Recommended drug treatment and prophylaxis of acute pulmonary embolism have changed little over the past 10 years. However, new information has emerged, which when combined with early pharmacology studies of unfractionated heparin and low molecular weight heparin, clearly shows important deficits in current practice that, if remedied, could reduce risk and likely save lives. These involve ensuring improved bioavailability of low molecular weight heparin prophylaxis dosing by abandoning once-daily dosing, adopting weight- or weight-category based dosing, and dosing twice daily or by continuous infusion in critically ill patients. For pulmonary embolism treatment, failure to recognize that presenting patients often have subnormal perfusion resulting in unpredictable bioavailability of subcutaneous anticoagulant has meant undertreatment, and delay in reaching a therapeutic anticoagulant level, assuredly resulting in failure of timely improvement as well as recurrent thromboembolism. Intravenous anticoagulant should be rapidly adopted as first treatment for acute pulmonary embolism until normal hemodynamic values are restored and cutaneous perfusion returns. Treatments under development include clinical investigation of intensive care unit (ICU) patients receiving intravenous low molecular weight heparin prophylaxis, weight-based, targeting an anticoagulant level in anti-Xa units that is both effective and safe. The same would be useful for pulmonary embolism treatment, although return to initial anticoagulation with unfractionated heparin is more easily monitored by activated partial thromboplastin time (aPTT) and is an easy standard of care to adopt. Pulmonary embolism clot removal is being accomplished by suction thrombectomy and catheter-directed lysis, each with its own different procedural characteristics. Whether either confers benefit compared to conscientiously administered intravenous anticoagulation cannot be shown in ongoing studies using subcutaneous treatment in control patients with subnormal perfusion. Factor XI/XIa inhibition is another treatment approach being studied. Another approach to lytic therapy under study, administering an inhibitor of alpha-2-antiplasmin, may cause less bleeding than tissue plasminogen activators.