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Editor's Correspondence
January 27, 2003

Plasma D-Dimer Test Accuracy Can Be Affected by Heparin Administration—Reply

Arch Intern Med. 2003;163(2):247. doi:10.1001/archinte.163.2.246-a

In reply. We are most grateful to Dr Siragusa for highlighting the important issue of the potential for false-negative results when plasma D-ds are used as an exclusionary test for VTE in patients already receiving heparin. In the report by Couturaud et al,1 pooled data from 3 studies showed that D-d levels in patients with VTE decreased by 25% after 24 hours of anticoagulant therapy. Although the absolute levels at this stage were 10-fold higher than the reference limit, this still resulted in a small decrease in sensitivity that might be clinically significant. Furthermore, D-d assay may also be less sensitive in patients receiving ongoing oral anticoagulation who have a suspected new episode of VTE: in a retrospective study of 704 outpatients with suspected deep vein thrombosis (DVT), the overall sensitivity of the Minutex assay (Diapharma Group, Inc, West Chester, Ohio) was 99%, falling to 75% in 61 patients receiving oral anticoagulants.2

Four clinical management studies36 have validated the safety of withholding imaging and treatment in patients with suspected VTE, low pretest probability (PTP), and a negative D-d assay result (SimpliRED [AGEN Biomedical Ltd, Brisbane, Australia]35 or VIDAS [bioMérieux SA, Marcy-Étoile, France]6); 2 studies have validated the safety of obviating a second ultrasound test in patients with suspected DVT, an initial negative study finding, and negative D-d assay result7,8 (Instant IA [Diagnostica Stago, Inc, Parsippany, NJ] or SimpliRED); and 2 studies have shown that further imaging and treatment can safely be withheld in patients with suspected pulmonary embolism, non–high PTP, and indeterminate ventilation perfusion scans9,10 (Asserachrom D-d [American Bioproducts Co, Parsippany, NJ] or SimpliRED). Patients were excluded from 3 of these studies if they had received anticoagulants for more than 24 hours and from 2 of these studies if anticoagulants were given for more than 48 or more than 72 hours, and no restrictions were stated in the remainder. Outcomes were excellent in all of these studies, although the proportion of patients included who had received heparin prior to measurement of D-d level is unknown. One outcomes study has investigated the safety of using D-d assay (VIDAS) as a stand-alone exclusionary test in suspected pulmonary embolism, from which patients were excluded if they had received any anticoagulant therapy.

We fully concur with Dr Siragusa that the relationship between sensitivity and pretreatment with heparin use should be further investigated. However, in practice, data from these outcomes studies suggest that VTE can still be excluded in patients with negative D-d assay results who have received heparin for up to 24 hours in defined subgroups identified as having a low disease prevalence on the basis of the PTP and/or noninvasive testing. For example, patients with a low PTP already have a less than 5% prevalence,11 so a small reduction in sensitivity of the D-d assay used should be relatively unimportant. However, the same reduction in sensitivity becomes much more important if a highly sensitive assay such as VIDAS is to be used as a stand-alone test, an approach, in any case, probably requiring further validation before it gains widespread acceptance. Finally, as an assessment of PTP and D-d testing increasingly becomes accepted as the first step in the diagnostic evaluation of patients with suspected VTE, the proportion of patients pretreated with heparin is likely to diminish.

References
1.
Couturaud  FKearon  CBates  SMGinsberg  JS Decrease in sensitivity of D-dimer for acute venous thromboembolism after starting anticoagulant therapy. Blood Coagul Fibrinolysis. 2002;13241- 246Article
2.
Schutgens  REEsseboom  EUHaas  FJNieuwenhuis  HKBiesma  DH Usefulness of a semi-quantitative D-dimer test for the exclusion of deep venous thrombosis in outpatients. Am J Med. 2002;112617- 621Article
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Kearon  CGinsberg  JSDouketis  J  et al.  Management of suspected deep venous thrombosis in outpatients by using clinical assessment and D-dimer testing. Ann Intern Med. 2001;135108- 111Article
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Wells  PSAnderson  DRRodger  M  et al.  Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and D-dimer. Ann Intern Med. 2001;13598- 107Article
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Bernardi  EPrandoni  PLensing  AW  et al.  D-dimer testing as an adjunct to ultrasonography in patients with clinically suspected deep vein thrombosis: prospective cohort study. BMJ. 1998;3171037- 1040Article
8.
Kraaijenhagen  RAPiovella  FBernardi  E  et al.  Simplification of the diagnostic management of suspected deep vein thrombosis. Arch Intern Med. 2002;162907- 911Article
9.
de Groot  MRvan Marwijk Kooy  MPouwels  JGEngelage  AHKuipers  BFBuller  HR The use of a rapid D-dimer blood test in the diagnostic work up of pulmonary embolism. Thromb Haemost. 1999;821588- 1592
10.
Perrier  ADesmarais  SGoehring  C  et al.  D-dimer testing for suspected pulmonary embolism in outpatients. Am J Respir Crit Care Med. 1997;156492- 496Article
11.
Kelly  JRudd  ALewis  RRHunt  BJ Plasma D-dimers in the diagnosis of venous thromboembolism. Arch Intern Med. 2002;162747- 756Article
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