Deep Vein Thrombosis and Pulmonary Embolism, Part 2

This issue of Seminars in Thrombosis and Hemostasis constitutes part 2 of a series on venous thrombosis and pulmonary embolism (PE).

In the first contribution, Pini and Spyropoulos discuss the prevention of venous thromboembolism (VTE). It is well recognized that many clinical conditions (such as surgery, trauma, acute medical conditions, and cancer) are associated with an increased risk for deep vein thrombosis (DVT) and PE. A considerable body of evidence supports these observations and the authors delineate these studies. Thromboprophylaxis with pharmacological agents and/or physical means has been shown to reduce the overall incidence of VTE in all patient groups. The authors review all options comprehensively and present a practical, concise outline of this important issue.

De Stefano and colleagues review prophylaxis and treatment of VTE in patients with inherited thrombophilia. There are considerable discussions and divided opinions in the literature on this topic, and the authors attempt to clarify the present thinking of experts in this field. The authors delineate who should be screened for thrombophilia and at what time, and who should receive thromboprophylaxis under which circumstances. Special emphasis is placed on pregnancy, puerperium, surgeries, and use of oral contraceptives and hormone replacement therapies. Follow-up management of these patients is also reviewed. This article provides health care practitioners with a valuable tool to manage patients with inherited forms of thrombophilia.

Pengo expertly discusses the use of oral anticoagulants in managing patients with VTE. Initiation of therapy, optimal dosing, laboratory monitoring, and long-term treatment are reviewed. This practical outline should assist health care providers in caring for patients who need treatment with oral anticoagulants.

Prandoni and coworkers next discuss new strategies for treating acute VTE. Although unfractionated heparin (UFH) is still used, low molecular weight heparins (LMWHs) are increasingly replacing it. The authors describe comprehensively the present experiences with heparin derivatives, their safety profiles, and their optimal use. In addition, vitamin K antagonists are reviewed, and new anticoagulants, such as factor Xa inhibitors and thrombin antagonists, are described. These are in various stages of development and testing, and present promising alternatives for future management of patients with VTE.

Agnelli and Becattini discuss new anticoagulants that were developed in recent years. These compounds may ultimately replace heparins, especially UFH. New agents either target the activation of the clotting system (tissue factor pathway inhibitor, active site-blocked factor VII, or a polypeptide from the canine hookworm Ancylostoma caninum) or specifically targeting factor Xa or thrombin. Many of these new drugs have been tested or are being tested in several clinical conditions to assess their safety and efficacy. This review provides an excellent perspective of what can be anticipated in the near future in the management of VTE.

Girolami and Girolami provide a brief overview of heparin-induced thrombocytopenia (HIT). They describe the incidence of HIT, its pathogenesis, the clinical presentation, diagnosis, and management. The diagnosis is still based largely on clinical findings, and for treatment it is important to immediately withhold all heparin-containing medications, institute an alternative anticoagulant, and avoid the use of vitamin K antagonists.

Piccioli and colleagues summarize the existing evidence suggesting that anticoagulant use in cancer patients, regardless of the presence of VTE, prolongs the life expectancy. Although current studies are limited, data appear to indicate that the concomitant use of certain LMWHs is associated with improved survival of these patients. The data in the literature are somewhat controversial, probably due to the heterogeneity of the patients studied, different stages of cancer, and different anticoagulant regimens. The authors suggest that additional studies be performed under more controlled conditions.

Wentel and Neumann review the management of the postthrombotic syndrome. This is the most costly complication of venous thrombosis. The authors discuss the incidence, the clinical signs and symptoms, its pathophysiology, and its management. They describe the approach that is taken at their own institution, the Rotterdam model, and make valuable recommendations based on their own extensive experience with these patients. This article presents a clear guideline to the long-term and expensive problem.

Palla and coworkers review the diagnostic aspects of PE. PE is a frequently underdiagnosed complication due to its silent clinical presentation and difficulties of accurate diagnosis. The authors examine all aspects of the diagnosis, review the literature related to this subject, and propose an algorithm that should be helpful in overcoming some of the difficulties encountered.

Vigo and colleagues describe the results of a multicenter study on the use of four-detector row spiral computed tomography (CT) in diagnosing PE. Spiral CT is increasingly employed as a first-line diagnostic modality to identify patients with suspected PE. Although single-slice CT is not accurate enough as a stand-alone test, multislice CT is supposed to be of greater value. The authors applied four-slice CT to 702 consecutive patients with clinically suspected PE. About 70% of these patients were interpreted as not having PE, but about half of these had positive D-dimer tests. Of these, 20% had a documented PE. The authors conclude that four-slice CT alone is not accurate enough to rule out PE, but that the combination of a negative CT plus a negative D-dimer practically rules out a PE. It appears to be safe to withhold anticoagulation in patients with negative CT plus a negative D-dimer.

In the next contribution, Kucher and Goldhaber describe the risk stratification of patients with PE. Risk stratification is helpful in management decisions and long-term considerations. Present approaches focus on early detection of patients to potentially avoiding fatal outcomes. Clinical evaluation, electrocardiography, arterial blood gases, echocardiography, cardiac biomarkers, and chest computed tomography procedures are presently in use. The authors detail these tools expertly and make valuable recommendations on how to approach patients with suspected PE.

Piovella and associates discuss the pathogenesis, diagnosis, and management of patients with chronic thromboembolic pulmonary hypertension. This disorder is relatively rare, but is due to pulmonary emboli that compromise pulmonary blood flow and thus influence cardiac performance. The diagnosis is difficult because so many other conditions also lead to pulmonary hypertension. The only successful long-term management appears to be surgical thromboendarterectomy. This is a difficult procedure and is only performed at very few centers. The authors describe their own experience in Pavia, and stress the need for a multidisciplinary team to perform this procedure successfully.

In the last article, Sakuma and colleagues describe the interesting association between the incidence of PE and an earthquake in Niigata, Japan. They observed that persons close to the epicenter, who spent long periods of time after the earthquake and during the aftershocks in an automobile (3 to 5 days), had a higher PE rate than those who were in other shelters. It also appears that women were at greater risk than men. The findings are similar to those reported after long plane flights. It is reasonable to assume that sitting for a long period of time together with the stress due to the earthquake may have been contributing factors.

I thank all authors for their informative contributions and Professor Paolo Prandoni for assembling these two very informative issues of the journal.