Plasma DNA is not unique to pulmonary embolism but can occur transiently in various clinical circum­stances. In 1975 Steinman searched for DNA in the plasma and serum of normal human adults using four different assays with antiserum sensitive to 0.05 \Lg/ ml of native DNA. No plasma DNA was detected, but a mean serum DNA concentration of 1.9 |xg/ml was noted in 14 of 16 people. Later, Steinman found plasma DNA in patients with SLE with active vascu­litis or cerebritis and in patients undergoing hemodi­alysis. Hughes et al reported serum DNA in patients receiving high-dose corticosteroids and patients un­dergoing open heart surgery and extracorporeal oxy­genation of blood. In the current study as well as in our previous studies, we found plasma DNA in various additional clinical situations that involved tissue dam­age (see Table l).

The origin of the plasma DNA in patients with pulmonary embolism is not clear. Relatively few pul­monary emboli lead to pulmonary infarction, so it is doubtful that necrotic lung parenchyma explains the presence of plasma DNA in the large majority of our patients with pulmonary embolism. However, it is possible that subclinical pulmonary infarctions are occurring and leading to the release of DNA. Although clotting blood in vitro leads to DNA release from white blood cells, plasma DNA has not been detected in patients who have had in vivo clot formation such as in venous thrombi. Pulmonary emboli may evoke release of DNA from the pulmonary vascular endo­thelium, but there is no clinical or experimental evidence to support this. Riboldi and others analyzed the plasma DNA of six patients with pulmonary embolism: it was double-stranded, had low molecular weight, included approximately 400 base pairs, and appeared to circulate linked to plasma proteins that may have conferred protection from plasma nucleases; however, beyond these characteristics, the origin of the DNA remained obscure.

Before recommending the use of this test in routine clinical situations, several limitations of our study need to be mentioned. First, the assay depends on the availability of sensitive precipitating anti-dsDNA se­rum samples. We have relied on serum samples from patients with active lupus; such sources could obvi­ously not support widespread use of this test. Improved human monoclonal techniques may provide standard­ized precipitating anti-dsDNA antibody. Second, be­cause of the problems involved in clearly demonstrat­ing pulmonary emboli or absolutely excluding pulmonary emboli, it is difficult to maintain a satisfac­tory gold standard of diagnosis for all patients with which to compare the plasma DNA test. Although the likelihood of a positive test increased with the lung scan probability (Table ЗА), and the diagnosis uncertain group was clinically similar to the diagnosis established group, only a third of our patients had both a clearly established disease status and none of the exclusion criteria. Further studies are needed in which plasma DNA results are compared with pulmonary angiogram results in a consecutive series of patients with sus­pected pulmonary embolism. Finally, many of the conditions that are associated with detectable plasma DNA (eg, major trauma) are also high-risk settings for pulmonary embolism. The clinical utility of plasma DNA will thus suffer from lack of specificity in some of the more challenging diagnostic settings. cialis canadian pharmacy

While the diagnosis of pulmonary embolism cannot rest solely on the plasma DNA result, a DNA deter­mination may help physicians in deciding which step to take next when faced with abnormal but nondiag­nostic lung scan findings. Except in disease states where “false positives” are common, finding evidence of circulating DNA argues for the diagnosis of pulmo­nary embolism, especially in clinically suspicious settings with a low or intermediate probability scan reading. A negative plasma DNA result obtained within 48 hours of symptom onset, even in patients with diseases associated with increased levels of plasma DNA, would be evidence against pulmonary embolism. If the plasma is not obtained immediately, the patient may clear the DNA rapidly and thus have a false-negative test. Similarly, plasma DNA results could influence diagnostic decisions when high prob­ability scans are seen in clinically unlikely circum­stances. Since the lung scan frequently fails to confirm or exclude pulmonary embolism, detection of plasma DNA may prove very useful in helping physicians clarify the diagnosis.