Deep Vein Thrombosis and Pulmonary Embolism, Part 1

This issue (part 1) and the following issue of Seminars in Thrombosis and Hemostasis review venous thromboembolism (VTE) comprehensively. The aspects of clinical presentation, diagnosis, and management are the focus of the two issues.

In the first contribution Ageno and coworkers present the epidemiology and risk factors of VTE. Due to the often clinically silent nature of VTE, its true incidence in the general population is difficult to assess, but an increasing tendency with advancing age is well recognized. In addition, differences related to ethnicity are known. Risk factors that predispose to VTE can be intrinsic (i.e., related to age, obesity, or previous history of VTE and thrombophilia [inherited or acquired]) or disease related. In the latter case, cancer, surgeries, cardiac failure, or respiratory failure are typical examples. Identification of risk factors influences thromboprophylaxis as well as treatment options.

Palareti and associates review the diagnosis of deep vein thrombosis (DVT). Before invasive diagnostic procedures are used, many patients can be identified as probably having a DVT. This is based on patient history and clinical findings. Imaging techniques are usually needed to confirm the diagnosis, and the advantages, limitations, and potential side effects of venography, ultrasonography, impedence plethysmography, spiral computerized tomography (CT), and magnetic resonance imaging (MRI) are reviewed extensively. The authors elaborate on diagnostic strategies for various patient groups and finalize their contribution with areas of uncertainty that pertain to the diagnosis of DVT.

Oudega and coworkers examine the value of D-dimer assays for diagnosing DVT and pulmonary embolism (PE) in a primary care setting. D-dimer assays are widely available and can be useful in selecting those patients who should be referred to tertiary facilities for imaging studies and management. The authors reviewed 1295 patients who presented with suspected DVT. Together with other diagnostic indicators such as gender, use of oral contraceptives, presence of trauma or malignancies, and clinical findings, the D-dimer assays reduced the number of referrals to specialized centers by 23%. A strategy for diagnosing DVT in a primary care setting is presented that should be tested in a multicenter study.

Michiels and colleagues review the different techniques presently used for D-dimer assays and highlight the differences that exist in confirming or ruling out DVT and PE. D-dimer assays should never be used as the sole diagnostic tool. Additional means, such as clinical scoring systems and imaging techniques, must be employed ultimately for the correct diagnosis. It is important, however, to consider the different sensitivities of the various D-dimer assays because not all are equal. In the correct setting, however, and together with other diagnostic modalities, D-dimer assays can be useful, especially in ruling out DVT and PE. This article provides a valuable assessment of all issues related to D-dimer testing.

Piccioli and coworkers stress the important relationship between cancer and VTE. Cancer patients are not only at high risk of developing VTE, but often VTE is the first clinical symptom of an as-yet unidentified malignancy. Understanding this relationship and appreciating the risk factors that lead to VTE improves thrombosis prophylaxis, thus reducing the potential risk of VTE in these patients. Evidence is presented that suggests that anticoagulant therapy with the proper compound improves cancer patient survival.

Simioni and associates review the relationship between inherited thrombophilia and VTE. The problems are reviewed expertly by the authors, including the determination of which congenital defects are most commonly associated with VTE, which additional risk factors play a role, who should not be tested for defects and which tests should be ordered first, and how these patients should be managed. This article represents a comprehensive overview of the role of inherited thrombophilic conditions and VTE.

Martinelli next examines thromboembolic diseases in women. VTE is not only age related and dependent on multiple acquired and congenital defects in the hemostasis system, but is of special importance in women. Use of oral contraceptives, hormonal replacement therapy, pregnancy, and puerperium all expose women to a higher risk for VTE. In addition, several obstetric complications, such as an impaired placental circulation, can be related to thromboembolic events.

Cattaneo examines the relationship between hyperhomocysteinemia and VTE. This issue is controversial and opinions on this association vary. The author presents comprehensive evidence for such an association, based on an extensive search of the literature. As is well recognized for other risk factors, it appears that defects in the homocysteine metabolism are also exacerbated by the concomitant existence of additional risk factors, and that a combination with one or more risk factors can cause VTE in these patients. This review sheds considerable light on hyperhomocysteinemia and VTE.

Tormene and coworkers review thromboembolism in children. In comparison with adults, children have far fewer VTE events, but these can be encountered under special circumstances. Venous and arterial catheters are likely the most common cause of VTE in children, but inherited or acquired thrombophilia can also contribute. The authors discuss thrombosis prophylaxis for children, but point out that there are no large prospective, randomized trials that could help establish firm guidelines for management of VTE in children.

The article by Bernardi et al discusses DVT in the upper limbs. In comparison to lower leg thromboses, upper extremity thromboses are rare, but up to 10% of DVT can involve the arms. Indwelling catheters and lines are the most common cause, but patients with cancer and thrombophilic states may also present with thromboses in the upper extremities. The authors review the diagnostic aspects, means of prevention, and treatment modalities for these patients. Upper limb thromboses are not benign, as has been claimed; they can lead to PE, postphlebitic syndrome, and other complications of VTE.

The risk factors, diagnosis, and treatment of superficial vein thrombosis (SVT) are described by Marchiori and coworkers. SVT is a common clinical finding, but the overall incidence has never been determined properly. In addition, this disease is viewed by many as benign and trivial. The authors point out, however, that SVT is often associated with DVT and all of its sequelae. Varicose veins are the most common underlying problem, but malignancies, autoimmune disorders, and thrombophilia may lead to SVT. Many medical and surgical treatment modalities have been proposed. However, optimal treatment strategies await multicenter studies. Short of these, no firm recommendations can be made about how these patients should be managed.

In the last article of this issue, Pesavento and colleagues give an overview of the postthrombotic or postphlebitic syndrome. This problem develops in one of every three patients with DVT and the sequelae are considerable. Many factors contribute to the development of the syndrome and several diagnostic modalities exist to assist with proper diagnosis of the syndrome. Adequate elastic compression stockings appear to be the best preventive measure because treatment is difficult and often frustrating for patients and health care providers. This article provides an excellent overview of this not uncommon complication of DVT.

I thank all of the authors for their excellent contributions, and also thank Professor Paolo Prandoni for assembling this important and very useful issue. This and the next issue of the journal contain a wealth of information on DVT and PE that is written in a comprehensive and practical manner by experts in the field.