Deep Venous Thrombosis and Pulmonary Thromboembolism: Evolving Concepts and Controversies

Venous thromboembolism (VTE) continues to prove elusive, and acute pulmonary embolism (PE) is frequently fatal. All too commonly, the diagnosis is not made until after death. Clinical presentations are complicated by concomitant disease, and symptoms of acute PE may be blamed on pneumonia, congestive heart failure, or chronic obstructive pulmonary disease exacerbations; diseases that contribute to the risk of acute VTE. Treatment reduces mortality, and the use of prophylaxis in specific settings is clearly beneficial. In this issue of Seminars in Respiratory and Critical Care Medicine, a series of superb treatises on VTE are presented by an international group of experts and include discussions on diagnosis, management, and prevention of this common and potentially deadly entity, as well as complications involved with therapy.

In the diagnostic realm, Lisa Moores and Aaron Holley offer a very informative update on the use of chest computed tomography (CT), emphasizing its accuracy as well as its limitations. Multidetector scanners have replaced single-detector in most centers, raising further questions about accuracy and when smaller emboli are truly significant. We have learned that diagnostic algorithms generally differ across studies, so that PE prevalence and patient populations vary. It will be important to standardize and validate the evaluation of right heart function and pulmonary artery pressures by CT, which may lead to more accurate prognostication.

Bill Hargett, a pulmonologist from Duke University Medical Center, serves as the lead author of a very through review of how clinical prediction rules may help to clarify complex scenarios using simple to acquire and rapidly available information, and how D-dimer testing, combined with this approach, may minimize the necessary testing required to comfortably exclude VTE. The Geneva and Canadian scores have served as the classic clinical prediction rule models. Development and revision of these models and the evolution of others have advanced our knowledge in this area, and continued efforts should prove useful. Clinicians continue to abuse D-dimer testing. Use with a clinical prediction rule optimizes the potential of both.

Nicole Whitlatch and Tom Ortel from Duke University have presented an excellent overview of testing for thrombophilias, offering guidance on this subject utilizing a case-based approach. They address such questions as who should be tested for inherited and acquired thrombophilia risk factors, what the best strategy is for obtaining a hypercoagulable workup, and how the results of testing impact upon decisions concerning therapy.

The experience of David Garcia and Alex Spyropoulos from Albuquerque, New Mexico, has culminated in a superb review of current approaches to therapy for VTE. The approaches to both short-term and long-term anticoagulation are reviewed, emphasizing the potential benefits of low molecular weight heparins and outpatient therapy, which have become firmly entrenched in our armamentarium.

Treatment of acute venous thromboembolism must include the approach to massive pulmonary embolism. Thrombolytic therapy can clearly be life saving but also remains controversial. Stavros Konstantinides has conducted key clinical trials in thrombolytic therapy, and presents a superb overview of this topic. The routine use of thrombolytic therapy in submassive PE (i.e., in normotensive patients with right ventricular dysfunction by echocardiography, CT scan, or a positive biomarker test) remains controversial, with the largest clinical trial to date already under way.

Suresh Vedantham, an interventional radiologist from the Mallinckrodt Institute of Radiology in St. Louis, offers an in-depth look at the substantial advances in endovascular approaches to thromboembolism therapy. These techniques are used extensively at some centers for VTE, and minimally at others. Although we are in need of more randomized trial data, Dr. Vedantham's experience and review offer us one of the most comprehensive sources on this topic to date.

Complications of anticoagulation therapy cannot be ignored. Among the most devastating is heparin-induced thrombocytopenia (HIT). Lori-Ann Linkins and Ted Warkentin offer tremendous expertise and experience, providing an outstanding look at this entity, including how to suspect it, how to diagnose it, and when and how to institute therapy in this setting. The interesting and important phenomenon of HIT-associated thrombosis preceding thrombocytopenia is also addressed.

Prophylaxis of VTE is an important topic but also an approach that has proven to be underutilized. Experts from different institutions in London thoroughly discuss this topic. The acutely ill medical patient is at high risk for VTE and this group of patients in particular appears to be frequently ignored, as evidenced by recently published registries. Yshai Yavin and Ander Cohen offer a critical appraisal of the medically ill prophylaxis data and the important clinical trials from which our evidence base arises. We have learned a substantial amount from recent clinical trials presented in this manuscript, such as MEDENOX, PREVENT, and ARTEMIS.

The general surgery population is clearly at risk, and more data are available in this population than for the medically ill. Risk-stratification and appropriate prophylaxis are discussed in detail by Gloria Petralia and Ajay Kakkar. These experts emphasize evidenced-based strategies as well as appropriate use of published guidelines. They outline an approach to risk stratification together with suggested prophylaxis.

The future of anticoagulation appears very promising. A renowned group of scientists from the Hemostasis and Thrombosis Research Unit at Loyola University, including Debra Hoppensteadt, Walter Jeske, Jeanine Walenga, and Jawed Fareed, present a superlative overview of the evolution of anticoagulation and where we are headed. New agents, including orally bioavailable drugs, are being studied and appear to be nearing the clinical arena. In addition, new concerns are raised with the introduction of generic anticoagulants. Certain complex biologicals, such as low molecular weight heparins, cannot be guaranteed to be reproduced identically, and regulation is crucial. The clinical efficacy and safety of newer drugs require an objective validation.

Overall, this issue is a compilation of outstanding treatises that offer the reader an overview of a continuously evolving field. We thank these outstanding authors for their tremendous efforts. We hope that the tremendous expertise shared in this issue will stimulate additional thought and research.