Review of the Evidence on Diagnosis of Deep Venous Thrombosis and Pulmonary Embolism

The clinical practice guidelines reported in the Annals of Family Medicine (1, 2, 3) articulate practical clinical recommendations. Recent publications provide additional information which either strengthens or modifies the suggested clinical guidelines.

1. Spiral computed tomography.

The findings of recent level 1 studies which are not available in the guideline report mandate a revision for the practice guidelines for the diagnosis of pulmonary embolism. These level 1 studies provide a critical link for clinical practice guidelines for the use of helical (spiral) CT of the chest and lower extremity.

In brief, the clinical practice guideline authors concluded from the citations included in their report that the evidence for the use of helical CT (multidetector CT) is level 2. This conclusion can now be altered to level 1 on the basis of three very large rigorous studies published in 2005 and 2006 which further elicidate the role of multidetector CT.(4, 5, 6) In addition, important information concerning the role of computed tomographic venography is now cited.(6)

Perrier et al (4) report the findings of a large outcome study. They conclude that “our data indicate the potential clinical use of a diagnostic strategy for ruling out pulmonary embolism on the basis of D- dimer testing and multidetector-row CT without lower limb ultrasonography. A larger outcome study is needed before this approach can be adopted.” The findings by Perrier et al are supported by the findings of the Christopher Study,(5) also a large outcome study. The authors of the Christopher Study conclude appropriately “A diagnostic management strategy using a simple clinical decision rule, D-dimer testing, and CT is effective in the evaluation and management of patients with clinically suspected pulmonary embolism. Its use is associated with low risk for subsequent fatal and nonfatal VTE.”

Further critical evidence for the use of the spiral CT is reported by Stein et al,(6) who report the findings of PIOPED II, a large accuracy study evaluating spiral CT and computed tomographic venography (CTV). The results of PIOPED II demonstrate that “In patients with suspected pulmonary embolism, multidetector CTA–CTV has a higher diagnostic sensitivity than does CTA alone, with similar specificity. The predictive value of either CTA or CTA–CTV is high with a concordant clinical assessment, but additional testing is necessary when the clinical probability is inconsistent with the imaging results.”

Finally, based on these aggregate data, “The PIOPED II investigators (7) recommend stratification of all patients with suspected pulmonary embolism according to an objective clinical probability assessment. D- dimer should be measured by the quantitative rapid enzyme-linked immunosorbent assay (ELISA), and the combination of a negative D-dimer with a low or moderate clinical probability can safely exclude pulmonary embolism in many patients. If pulmonary embolism is not excluded, contrast -enhanced computed tomographic pulmonary angiography (CT angiography) in combination with venous phase imaging (CT venography), is recommended by most PIOPED II investigators, although CT angiography plus clinical assessment is an option. In pregnant women, ventilation/perfusion scans are recommended by many as the first imaging test following D-dimer and perhaps venous ultrasound. In patients with discordant findings of clinical assessment and CT angiograms or CT angiogram/CT venogram, further evaluation may be necessary. The sequence for diagnostic test in patients with suspected pulmonary embolism depends on the clinical circumstances.”

It is evident from these new findings that the practice guidelines for the use of spiral CT for the Annals of Family Medicine should be revised.

Finally, Roy et al (8) report the findings of a key study showing the importance of adhering to guidelines for the diagnosis of pulmonary embolism. Failure to adhere to guidelines is harmful in patients with suspected pulmonary embolism.

2. LMWH use instead of vitamin-k-antagonists

The authors recommendations for this practice guideline are strengthened by the finding of two recent randomized trials (9, 10) which support the practice guideline authors’ conclusions. Hull et al performed a randomized, multicentre study comparing long-term therapeutic low- molecular-weight heparin subcutaneously once daily with long-term vitamin- K-antagonist therapy for 3 months in a broad spectrum of patients and in patients with cancer. Hull and colleagues concluded “that LMWH is similar in effectiveness to the usual-care vitamin-K-antagonist treatment for preventing recurrent venous thromboembolism in a broad spectrum of patients. It causes less harm and enhances the clinicians’ therapeutic options for patients with proximal deep vein thrombosis. Our findings reported here suggest the possibility of a broader role for long-term LMWH in selected patients.” The findings in patients with cancer “confirm the limited but benchmark data in the literature that long-term low-molecular- weight heparin is more effective than vitamin-K-antagonist therapy for preventing recurrent venous thromboembolism in patients with cancer and proximal venous thrombosis.”

References:

1. Segal JB, Eng J, Tamariz LJ, Bass EB. Review of the Evidence on Diagnosis of Deep Venous Thrombosis and Pulmonary Embolism. Ann Fam Med 2007; 5: 63-73.

2. Snow V, Qaseem A, Hornbake ER, et al. Management of Venous Thromboembolism: A Clinical Practice Guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Fam Med 2007; 5: 74-80.

3. Qaseem A, Snow V, Barry P, et al. Current Diagnosis of Venous Thromboembolism in Primary Care: A Clinical Practice Guideline from the American Academy of Family Physicians and the American College of Physicians. Ann Fam Med 2007; 5: 57-62.

4. Perrier A, Roy P-M, Sanchez O, et al. Multidetector-Row Computed Tomography in Suspected Pulmonary Embolism. N Engl J Med 2005;352:1760-8.

5. Writing Group for the Christopher Study Investigators. Effectiveness of Managing Suspected Pulmonary Embolism Using an Algorithm Combining Clinical Probability, D-Dimer Testing, and Computed Tomography. JAMA. 2006;295:172-179.

6. Stein PD, Fowler SE, Goodman LR, et al, for the PIOPED II Investigators. Multidetector Computed Tomography for Acute Pulmonary Embolism. N Engl J Med 2006;354:2317-27.

7. Stein PD, Woodard PK, Weg JG, et al. Diagnostic Pathways in Acute Pulmonary Embolism: Recommendations of The PIOPED II Investigators. Am J Med 2006; 119, 1048-1055.

8. Roy P-M, Meyer G, Vielle B, et al for the EMDEPU Study Group. Appropriateness of Diagnostic Management and Outcomes of Suspected Pulmonary Embolism. Ann Intern Med 2006; 144: 157-164.

9. Hull RD, Pineo GF, Brant RF, et al for the LITE Trial Investigators. Long-term Low-Molecular-Weight Heparin versus Usual Care in Proximal-Vein Thrombosis Patients with Cancer. Am J Med 2006 119, 1062 -1072.

10. Hull RD, Pineo GF, Brant RF, et al for the LITE Trial Investigators. Self-Managed Long-Term Low-Molecular-Weight Heparin Therapy: The Balance of Benefits and Harms. Am J Med 2007 120, 72-82.

Competing interests:   None declared