Dimerized plasmin fragment D: a reliable biomarker for diagnosing aortic dissection?

Abstract

Acute aortic dissection (AAD) is an important differential diagnosis in the early management of acute chest pain syndrome. Early recognition and treatment are crucial and will lead to a better survival. However, bedside evaluations including the symptoms, signs, or laboratory tests are all not sensitive [Arch Intern Med. 2000; 160(19):2977-2982]. Advanced diagnostic tools, such as contrast-enhanced computed tomography, transesophageal echocardiography, and magnetic resonance imaging, are usually time- and cost-consuming and not readily available in the emergency department [Arch Intern Med. 2006;166(13):1350-1356]. In recent years, the dimerized plasmin fragment D (d-dimer) test has been largely reported as a useful diagnostic biomarker with 100% sensitivity in AAD [J Am Coll Cardiol. 2004;44(4):804-809; Acad Emerg Med. 2004;11(4):397-400; Circulation. 2004;109(3):E24; Chest. 2003;123(5):1375-1378], and it was proposed to be a reliable tool in exclusion of AAD. However, its reliability in clinical practice remains inconclusive. Here, we present a case of type I acute aortic dissection without positive d-dimer test result. The d-dimer test can be a useful tool in initial evaluation of acute chest pain syndrome. However, the diagnosis of aortic dissection cannot be excluded by using only a negative d-dimer test result. A high clinical index of suspicion is still the key for accurate and timely diagnosis. Acute aortic dissection (AAD) is an important differential diagnosis in the early management of acute chest pain syndrome. Early recognition and treatment are crucial and will lead to a better survival. However, bedside evaluations including the symptoms, signs, or laboratory tests are all not sensitive [1]. Advanced diagnostic tools, such as contrast-enhanced computed tomography, transesophageal echocardiography, and magnetic resonance imaging, are usually time- and cost-consuming and not readily available in the emergency department [2]. In recent years, the dimerized plasmin fragment D (d-dimer) test has been largely reported as a useful diagnostic biomarker with 100% sensitivity in AAD [3-6], and it was proposed to be a reliable tool in exclusion of AAD. However, its reliability in clinical practice remains inconclusive. Here, we present a case of type I acute aortic dissection without positive d-dimer test result. A 44-year-old previously healthy man visited the emergency department with the chief complaint of acute resting-onset chest tightness for 30 minutes. The discomfort was not tearing in character. Neither cold sweating nor aggravating factors for the chest discomfort were found. He has no fever, with an initial pulse rate of 88/min and a respiratory rate of 22/min. Blood pressure was 172/113 mm Hg, without deficit or differential pulsation over 4 extremities. There was no audible cardiac murmur in the physical examination. The supine chest x-ray film (CXR) showed widening of the mediastinum at the supracardiac region (Fig. 1A). The electrocardiogram showed normal sinus rhythm and no ST-T segment deviation. Initial laboratory examinations revealed normal hemogram and serum cardiac markers (creatinine kinase, 110 U/L; creatinine kinase-MB, 13.7 U/L; troponin I, 0.005 ng/mL). The d-dimer test result was normal (1.35 μg/mL; normal, <2.09 μg/mL). Contrast-enhanced chest computed tomography showed DeBakey type I AAD with intimal flap in the ascending aorta extending to the aortic arch and no thrombus formation in the false lumen (Fig. 1B). The 4-hour d-dimer test before operation was also within normal limits (1.37 μg/mL). After consultation with the cardiovascular surgeon, emergent operation with ascending aortic grafting was performed. The patient was discharged smoothly after the operation. Acute aortic dissection has various presentations, typically with anterior chest pain, tearing sensation, radiation to back, and pulse deficits, but none of them were sensitive. Results of the CXR are abnormal in nearly all patients, but the typical mediastinum widening occurs in only 61.6% [7]. It is particularly of limited value while involving the ascending aorta [8]. Emergency ultrasonography may show specific signs of AAD, such as dilated thoracic diameter and intimal flap, but the sensitivity was only 67% to 80% [9,10]. Recently, the d-dimer test, an important biomarker widely used in the diagnosis of pulmonary embolism, has been reported to be reliable in the work-up of acute chest pain syndrome. It showed 100% sensitivity of acute aortic dissection in different studies. Weber et al [6] reported the first case series of 10 cases of AAD. All cases showed d-dimer values above the normal upper limit. Thus, the author suggested that a negative d-dimer test result makes acute aortic dissection unlikely. The largest retrospective study of 94 cases showed that the d-dimer test result was positive in 93 patients, except for 1 case with localized intramural hematoma (sensitivity, 99%; specificity, 34%) [11]. In our case, the d-dimer values were both within normal limits initially and 4 hours after presentation. However, the chest contrast-enhanced computed tomography showed DeBakey type I AAD. Thus, the reliability of the d-dimer test in excluding AAD is challenged. To the best of our knowledge, there is only 1 retrospective study of 113 cases of AAD showing inconsistency after reviewing the available literatures [9]. Hazui H. [13] conducted the study in Japan from 2001 to 2005, and it showed that sensitivity was only 93%. Younger patients (<70 years) with short dissection length and a thrombosed false lumen without ulcer-like projection are liable to have false-negative d-dimer test results. It is proposed that a complete thrombosed false lumen makes the coagulation factor unlikely to enter the blood stream. This may also explain the negative d-dimer value in intramural hematoma in the study. In our case, there was neither thrombosed false lumen nor intramural hematoma revealed in both image and surgery. The only possible factors of the negative d-dimer test result may be young age and short dissection length. However, in this group of patients, early operation carries the same importance. Besides, unlike pulmonary embolism, there is no well-established prerest probability test for the application of the d-dimer test in AAD. In addition, our patient had no known risk factors of AAD of the young age group (eg, congenital heart disease, connective tissue diseases, and cocaine use) [12]. With a negative d-dimer test result, we were still not able to exclude the diagnosis of AAD. In our opinion, the d-dimer test is a useful tool in initial evaluation of acute chest pain syndrome. However, the diagnosis of aortic dissection cannot be excluded by using only a negative d-dimer test result, especially in younger patients. We strongly suggest that high clinical index of suspicion is still the key for accurate and timely diagnosis. Currently, there is still a lack of evidence supporting the use of d-dimer as a screening tool for AAD. ? 2010 Elsevier Inc. All rights reserved.