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Validation of two age dependent D-dimer cut-off values for exclusion of deep vein thrombosis in suspected elderly patients in primary care: retrospective, cross sectional, diagnostic analysis

BMJ 2012; 344 doi: http://dx.doi.org/10.1136/bmj.e2985 (Published 6 June 2012)
Cite this as: BMJ 2012;344:e2985

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The need for an accurate understanding of the D Dimer assay by those requesting the test to improve interpretation of the result.

1 August 2012

We read with interest your recent article regarding validation of two age dependent D-dimer cut-off values for exclusion of deep vein thrombosis in suspected elderly patients in primary care.

In our institution, we carried out a prospective study of all D Dimer tests carried out over a one month period as we felt that the majority of the 'false positive' tests that were being obtained were due to inappropriate use of the test. 345 cases were reviewed. The average age of those tested was 58.91 years (Range 14-95). The vast majority of the tests were requested in the emergency department. The main reasons for requesting the test were dyspnoea, chest pain, the patient being generally unwell and limb swelling but it was requested for a wide variety of reasons, many of which were inappropriate. 193 patients had positive D dimer results – (D dimer>0.5) and 12 of these had a radiologically proven venous thrombo-embolism (VTE). 11 of the 193 patients who had positive D-Dimer test went on to have CT pulmonary-angiograms and one of these had a pulmonary embolus. 15 of the 193 patients who had positive D-Dimer tests went on to have Doppler ultrasound examinations and 9 of these had VTE. The remaining 2 patients with VTE had it diagnosed on CT Thorax-Abdomen-Pelvis. This low correlation between elevated D Dimer levels and VTE specific radiological procedures indicates that in our institution, physicians depend primarily on their clinical skills when diagnosing VTE.

We also surveyed the junior doctors in the hospital to ascertain their knowledge of the test, as they were the people primarily ordering the test. 31% responded to our survey. 60% recognized that the D Dimer test is useful to outrule VTE when there is a low suspicion and 92% felt that a risk assessment score e.g. Wells score was warrented. Most did not know how much the test cost, despite ordering it frequently.

While we welcome the validation of age dependent D-dimer cut-off values for exclusion of deep vein thrombosis in suspected elderly patients, as it raises the issue that the results obtained do not mean the same in every patient population, we feel that this is too narrow a focus and the most important issue is to raise doctors' awareness of the uses and limitations of this commonly ordered test.

There is a multitude of reasons for a positive D Dimer result including malignancy, inflammation, VTE and increasing age. Inappropriate use of the test may lead to inappropriate radiological procedures which are not without risk. There is also the issue of ordering tests that do not impact on patient care. This is becoming more of an issue of late, in these times of austerity when laboratory medicine services are being forced to make large budget cuts.

In summery, The limitations of the test must be fully understood by those ordering it to use it most effectively.

Competing interests: None declared

Maeve P Crowley, Haematology Specialist Registrar

Barry Kevane.

Mercy University Hospital, Grenville Place, Cork, Ireland

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D-dimer can be normal in cases of venous thromboembolism

9 June 2012

The study by Schouten and colleagues are very much welcome in the current environment of increasing investigations for diagnosing venous thromboembolism [1]. However, one of the messages from this study which needs to be stressed is the need for a thorough clinical evaluation first and then, the D-dimer. Reliability on the D-dimer in isolation can have problems especially since there is evidence in the literature for thromboembolic episodes occurring in the context of normal D-dimer [2,3].

There are several possible explanations for this rare combination. The levels of D-dimer increase in the circulation due to the breakdown of the fibrin-bound clots. Very often, individuals present with lower limb thrombosis many days after their initial symptoms (related to thrombosis) had commenced. The clot breakdown in these cases may have ceased by the time they arrive for medical attention and the result would be a normal D-dimer. Secondly, in the patients who receive anticoagulation treatment sometimes before the hospital assessment is undertaken (patients who have problems with transport, or from the hospice, started on anticoagulation empirically), inhibition of clot lysis can cause normal D-dimer. This phenomenon has been noted to occur within 24 hours after receiving heparin therapy [4]. It is also important to bear in mind that a normal cut-off of D-dimer is arbitrary and may not be applicable to every individual, since the fibrinolytic breakdown capacity varies between individuals. This is exemplified by the report in pregnancy of deep vein thrombosis and normal D-dimer [3]. In most cases of pregnancy, D-dimer levels are usually elevated. Lastly, there is the issue of wide variability between many different D-dimer assays [5]. Each hospital should take into consideration the appropriate cut-off suited for the assay and setting before they can attribute a level as suggested in the present study.

In summary, there is no alternative to good clinical assessment in the exclusion of venous thromboembolism and D-dimer level is only a useful adjunct.

1.Schouten HJ, Koek HL, Oudega R, Geersing GJ, Janssen KJ, van Delden JJ, Moons KG. Validation of two age dependent D-dimer cut-off values for exclusion of deep vein thrombosis in suspected elderly patients in primary care: retrospective, cross sectional, diagnostic analysis. BMJ. 2012;344:e2985.
2. Kutinsky I, Blakley S, Roche V. Normal D-dimer levels in patients with pulmonary embolism. Arch Intern Med. 1999;159(14):1569-72.
3. To MS, Hunt BJ, Nelson-Piercy C. A negative D-dimer does not exclude venous thromboembolism (VTE) in pregnancy. J Obstet Gynaecol. 2008;28(2):222-3.
4. Couturaud F, Kearon C, Bates SM, Ginsberg JS. Decrease in sensitivity of D-dimer for acute venous thromboembolism after starting anticoagulant therapy. Blood Coagul Fibrinolysis. 2002;13(3):241-6.
5. Goodacre S, Sampson FC, Sutton AJ, Mason S, Morris F.Variation in the diagnostic performance of D-dimer for suspected deep vein thrombosis.QJM. 2005;98(7):513-27.

Competing interests: None declared

Jecko Thachil, Consultant Haematologist

Manchester Royal Infirmary, Oxford road, Manchester, M13 9WL

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