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Diagnosis of Deep Vein Thrombosis, A New Gold Standard

Tori McCormick

Department of Nursing, Youngstown State University

NURS 6901: Theoretical Foundations

Dr. Valerie O’Dell

July 18, 2020

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Abstract

A well-built clinical foreground question allows healthcare professionals to identify a topic with

issues and formulate a plan based on research to improve the problems in a specific timeframe.

The d-dimer as the gold standard for diagnosis of deep vein thrombosis is changing due to health

care professionals uncovering alternatives comparable in accuracy and time-saving in the

emergency departments. With the evaluation of research including multiple single quantitative

studies, evidence has been built to answer the following question, in adult patients, how does

ultrasound as compared to a d-dimer affect the accuracy of ruling out deep vein thrombosis? The

importance of this question is apparent due to the d-dimer having an adequate sensitivity but

poor specificity leading to multiple other diagnostic tests ordered for individuals when many are

not warranted. Low specificity influences include numerous physiological and pathological

factors that may increase the result leading to a false positive. These factors include increased

age, pregnancy, trauma, cancer, and inflammation, to name a few. The ultrasound, in

comparison, is a straightforward diagnostic tool, not influenced by the same physiological and

pathological factors. The proposal from uncovering clinical evidence is to formulate a diagnostic

framework that places patients into areas of high and low probability so the plan of care that is

most cost and time effective along with the least invasive and least possible risk factors may be

completed.
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In adult patients, how does ultrasound as compared to a d-dimer affect the accuracy of

ruling out deep vein thrombosis?

Thorough research strategies stemming from EBSCOhost are implemented in this

research paper to bring quantitative studies related to this topic to the forefront. Through this

platform, academic libraries are available along with research databases. Specifically, Health

Source, Nursing Academic Edition, Medcom, Medline Complete, and CINALH Plus populated

the most valuable academic articles. With these databases, single quantitative research studies

are available that correlate with this topic. The search words used initially included deep vein

thrombosis diagnosis, ultrasound DVT, d-dimer DVT, and ultrasound d-dimer DVT. Many

studies proved that D-dimer arrays were the primary diagnosis strategy in regards to deep vein

thrombosis with these keywords. The articles discussing D-dimer arrays as the primary

diagnostic tool based on accuracy and efficiency are primarily from the 1990s to the early 2000s.

After trial and error, new search phrases were created that produced more recent studies with

comprehensive reviews of both ultrasounds and D-dimers. These search phrases included;

inaccuracy d-dimer, ultrasound accuracy DVT, venous thromboembolism testing, DVT

prognosis, and venous duplex ultrasound. Identifying flaws in the standard of medicine and

creating solutions based on research is the basis of what keeps the nursing practice progressing.

Uncovering the accuracy of ultrasound compared to a d-dimer may pave the way for safer, more

cost-effective practices in patients' future with the possibility of deep vein thrombosis.
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In adult patients, how does ultrasound as compared to a d-dimer affect the accuracy of

ruling out deep vein thrombosis?

Abbasi S, Bolverdi E, Zare MA, Hafezimoghadam P, Fathi M, Farsi D, Moghimi M.

Comparison of diagnostic value of conventional ultrasonography by emergency

physicians with Doppler ultrasonography by radiology physicians for diagnosis of deep

vein thrombosis. (2012). J Pak Med Assoc. 2012 May;62(5):461-5. PMID: 22755310.

Abstract

Objective: To determine sensitivity, specificity and other operating characteristics of bedside

three-point compression ultrasonography performed in emergency department by emergency

physicians in comparison with duplex ultrasonography.

Method: The cross-sectional study at Rasoul-e-Akram Hospital in Tehran, Iran, prospectively

evaluated 81 suspected patients of lower extremity deep vein thrombosis between March 2006

and March 2007. A trained second-year resident and one attending physician of emergency

medicine evaluated the veins of all the patients with through compression ultrasonography. Then,

a second-year resident of radiology assessed the patients with duplex ultrasonography. Finally,

data were compared and quantitative and categorical variables were worked out along with other

statistical analysis through SPSS version 16.

Results: The mean age of the patients was 47.2 +/- 18.6 years. When cases who lost the

compressibility of at least one of their femoral or popliteal veins were considered to be positive,
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there were 80.2% diagnosed by compression ultrasonography and 79% by the duplex variety.

Sensitivity, specificity and accuracy of the former in comparison with the latter were 85.9%,

41.2% and 84.6% respectively.

Conclusion: Compression ultrasonography has relatively an acceptable sensitivity and accuracy

level, but has low specificity in the diagnosis of deep vein thrombosis in the hands of Iranian

emergency physicians. It is better to implement duplex ultrasonography whenever accessible.

Otherwise, compression ultrasonography results should be compared with the results of duplex

ultrasonography as soon as possible.

This study explains the accuracy of duplex ultrasonography in the diagnosis of deep vein

thrombosis. Identifying compression ultrasonography done at the bedside as an alternative

method for diagnosis also supports the proposal of diagnostic testing that decreases the length of

stays in emergency room settings. The bedside compression exam has an acceptable sensitivity

and accuracy, which only increases when completed in a controlled environment and interpreted

by an expert radiologist (Abbasi et al., 2012). The relevance of this article alludes to exposing

another accurate way to diagnose a deep vein thrombosis promptly that is cost-effective. This

article also explains that with either the bedside exam of a physician or an ultrasound, the length

of patient stay is considerably decreased compared to obtaining a D-dimer, with a significant

probability of being falsely positive. The increased wait for lab test results and possible

hemolysis requiring redraws increases the risk of complications such as progressing pulmonary

embolism, decreased patient satisfaction, and increased crowding in the emergency department,

causing exposure to diseases such as Covid-19, influenza A, and B, along with others.
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Der Sahakian, G., Claessens, Y. E., Allo, J. C., Kansao, J., Kierzek, G., & Pourriat, J. L. (2010).

Accuracy of D-Dimers to Rule Out Venous Thromboembolism Events across Age

Categories. Emergency Medicine International, 2010, 1–4.

https://doi.org/10.1155/2010/185453 

Abstract

Objective: As process of ageing is associated with altered concentrations of coagulation markers

including an increase in D-dimers levels, we investigated whether D-dimers could reliably rule

out VTE across age categories.

Method: We prospectively assessed the test performance in 1,004 patients visiting the emergency

department during the 6-month period with low or intermediate risk of VTE who also received

additional diagnostic procedures.

Results: 67 patients had VTE with D-dimers levels above the threshold, and 3 patients displayed

D-dimers levels below the threshold. We observed that specificity of D-dimers test decreased in

an age-dependent manner. However, sensitivity and negative predictive value remained at very

high level in each age category including older patients.

Conclusion: We conclude that, even though D-dimers level could provide numerous false

positive results in elderly patients, its high sensitivity could reliably help physicians to exclude

the diagnosis of VTE in every low- and intermediate-risk patient.

As stated in the introduction, D-dimers have many physiological and pathological factors

that may affect the result, and the primary factor in this quantitative study is age (Der Sahakian et
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al., 2010). Analysis of this article concludes that D-dimers are less accurate as the patient

foregoes the aging process. Because of the decreased accuracy, this diagnostic tool should be

used with caution in elderly patients. Specifically, an ultrasound does not produce as many false

positives as the D-dimer studies in this population (Der Sahakian et al., 2010). The quantitative

study taking place in this article showed that the D-dimer had a 57.4% specificity (Der Sahakian

et al., 2010). The inaccuracy mainly stems from the fact that 88% of patients 70 years of age or

above had elevated D-dimer tests while only 14% of the whole population in the study had deep

vein thrombosis (Der Sahakian et al., 2010). This study is beneficial in identifying significant

flaws of the D-dimer test and the inaccuracy relating to false positives and decreased specificity

percentage.

Kabrhel, C., Mark Courtney, D., Camargo, C. A., Plewa, M. C., Nordenholz, K. E., Moore, C.

L., Richman, P. B., Smithline, H. A., Beam, D. M., & Kline, J. A. (2010). Factors

Associated With Positive D-dimer Results in Patients Evaluated for Pulmonary

Embolism. Academic Emergency Medicine, 17(6), 589–597.

https://doi.org/10.1111/j.1553-2712.2010.00765.x 

Abstract

Objective: Available D-dimer assays have low specificity and may increase radiographic testing

for pulmonary embolism (PE). To help clinicians better target testing, this study sought to

quantify the effect of risk factors for a positive quantitative D-dimer in patients evaluated for PE.

Method: This was a prospective, multicenter, observational study. Emergency department (ED)

patients evaluated for PE with a quantitative D-dimer were eligible for inclusion. The main
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outcome of interest was a positive D-dimer. Odds ratio (ORs) and 95% confidence intervals

(CIs) were determined by multivariable logistic regression. Adjusted estimates of relative risk

were also calculated.

Results: A total of 4,346 patients had D-dimer testing, of whom 2,930 (67%) were women. A

total of 2,500 (57%) were white, 1,474 (34%) were black or African American, 238 (6%) were

Hispanic, and 144 (3%) were of other race or ethnicity. The mean (±SD) age was 48 (±17) years.

Overall, 1,903 (44%) D-dimers were positive. Model fit was adequate (c-statistic = 0.739,

Hosmer and Lemeshow p-value = 0.13). Significant positive predictors of D-dimer positive

included female sex; increasing age; black (vs. white) race; cocaine use; general, limb, or

neurologic immobility; hemoptysis; hemodialysis; active malignancy; rheumatoid arthritis;

lupus; sickle cell disease; prior venous thromboembolism (VTE; not under treatment); pregnancy

and postpartum state; and abdominal, chest, orthopedic, or other surgery. Warfarin use was

protective. In contrast, several variables known to be associated with PE were not associated

with positive D-dimer results: body mass index (BMI), estrogen use, family history of PE,

(inactive) malignancy, thrombophilia, trauma within 4 weeks, travel, and prior VTE (under

treatment).

Conclusions: Many factors are associated with a positive D-dimer test. The effect of these factors

on the usefulness of the test should be considered prior to ordering a D-dimer.

This data analysis is focusing on comparing ultrasound and D-dimer accuracy concerning

deep vein thrombosis. This study takes the evaluation a step further by looking at pulmonary

embolism diagnosis. Results from this quantitative research are valuable because it identifies that

the false-positive D-dimer arrays are calling for computed tomography scans of the chest to rule
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out pulmonary embolisms, with a meager percent being positive (Kabrhel et al., 2010).

Clinically, if a D-dimer comes back as positive, the patient will need the CTA to rule out any

embolism; however, the patient is jeopardized by the exposure to radiation, increased length of

stay, and risk for reaction to contrast dye. Causative agents for a false positive D-dimer include

immobility, malignancy, pregnancy, recent surgery, and increasing age and body mass index

(Kabrhel et al., 2010). The population of this study included approximately 7,940 patients. With

44% of patients in this study having a positive D-dimer and the diagnosed patients with

pulmonary embolism yielding significantly less, factors have been identified that increase the

value of the D-dimer result (Kabrhel et al., 2010). The interpretation of the results concluded not

only the previous causative agents for a false elevation of a d-dimer but also that patients of

African American race were more likely to have an elevation than the Caucasian race. However,

there were no other identified associations with other races (Kabrhel et al., 2010). There are

numerous influences that can affect the result of the D-dimer, and this diagnostic test should be

used with caution in those populations.

Larsen, T. B., Stoffersen, E., Christensen, C. S., & Laursen, B. (2002). Validity of D-dimer tests

in the diagnosis of deep vein thrombosis: a prospective comparative study of three

quantitative assays. Journal of Internal Medicine, 252(1), 36–40.

https://doi.org/10.1046/j.1365-2796.2002.00998.x 

Abstract

Objective: To assess the diagnostic reliability of a new quantitative D-dimer assay (VIDAS

New) and an established quick test (Nycocard D-dimer assay) in the diagnosis of deep vein

thrombosis (DVT) compared with ultrasonography. A third assay (Auto Dimer) became
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available during sample collection and has been included in the final assessment. The diagnostic

performance of the Auto Dimer assay was evaluated on three different coagulation analysers.

Method: A clinical prospective study of patients admitted to hospital for evaluation of DVT.

Setting. The admission ward at Aalborg Hospital. Subjects. A total of 113 outpatients with

suspected DVT. Main outcome measures. Compression ultrasonography was used as the

reference method for a diagnosis of DVT and compared with different D-dimer assays. The

results were expressed as sensitivity, specificity, positive predictive value and negative

predictive value (NPV).

Results: Deep vein thrombosis was established in 49 patients (43%). Two D-dimer assays

(VIDAS New and Auto Dimer) showed sensitivities of 90 and 88%, specificities of 42 and 44%,

and NPV's of 85 and 83%, respectively. The Nycocard D-dimer assay showed a sensitivity of

63%, specificity of 67% and NPV of 71%.

Conclusions: The diagnostic performance of VIDAS New and the Auto Dimer D-dimer assays is

almost identical, but this study suggests that neither of the D-dimer assays is suitable as the only

screening method for DVT, in a situation with a high pretest probability of DVT. This call for a

differential strategy that distinguishes between cases of low and high clinical probability using

either a D-dimer test or ultrasonography. Abbreviations DVT, deep venous thrombosis, NPV,

negative predictive value, PPV, positive predictive value.

This study exemplifies that the D-dimer is not suitable for the only screening method for

deep vein thrombosis, specifically in a patient with an elevated pretest probability of DVT. The

diagnostic strategy that differentiates between cases of high and low clinical pretest probability is
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ultrasonography. With the associated testing called for from a falsely elevated d-dimer, the new

gold standard is ultrasonography. Ultrasonography has high sensitivity and specificity for

proximal DVT and is only slightly lower for calf vein thrombosis. Specifically, through this

quantitative research study, the analysis proved a 43% probability of a false negative result when

the only parameter in excluding a DVT is a D-dimer (Larsen et al., 2002). Ultrasound is superior

to the D-dimer in patients with a high pretest probability of deep vein thrombosis. The D-dimer

test should be omitted in patients with a high pretest probability; this study indicates that a

differential strategy should be formulated to distinguish high and low-risk patients consistent

with this research thesis.

Mousa, A. Y., Broce, M., Gill, G., Kali, M., Yacoub, M., & AbuRahma, A. F. (2015).

Appropriate Use of d-Dimer Testing Can Minimize Over-Utilization of Venous Duplex

Ultrasound in a Contemporary High-Volume Hospital. Annals of Vascular

Surgery, 29(2), 311–317. https://doi.org/10.1016/j.avsg.2014.07.032 

Abstract

Background: The sensitivity of D-dimer (DD) in detecting deep venous thrombosis (DVT) is

remarkably high, however many institutions send patients immediately for a venous duplex

ultrasound (VDU). This study was designed to examine the appropriate utilization of DD and

VDU in a high volume hospital.

Method: A retrospective study was conducted on consecutive patients who presented to a high

volume emergency department (ED) with lower extremity limb swelling/pain over a 30-day

period, who were sent for VDU during an evaluation for DVT. VDU data were merged with
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electronic DD lab results. The enzyme-linked immunosorbent assay (ELISA) method was used

to provide DD values and thresholds. Values above 0.60 mg/SEU were considered abnormal.

Results: We reviewed the medical records of 517 ED patients in the month of June, 2013. After

applying the Wells criteria, 157 patients (30.4%) were excluded due to a history of DVT or PE,

having been screened for shortness of breath, or sent for surveillance; leaving 360 for analysis.

The average age was 59.3±16.5 years with more females (210, 58.3%), and the majority reported

limb pain or swelling (73.9%). DD was performed on 51 patients with an average value of

3.6±5.4 mg/SEU, of which 43 (84.3%) were positive. DD identified all positive and negative

DVT patients (100% sensitivity and negative predictive value), but also included 40 false

positives (16.7% specificity). On the other hand, 309 patients were sent directly to VDU without

DD; of those, 43 (13.9%) were positive for DVT. However, 266 (86.1%) patients were negative

for DVT by VDU.

False-positive D-dimers are the priority of this research paper because of the unnecessary

harm they put on patients. This harm including radiation exposure, risk of infection from an

invasive procedure, the risk for allergic reaction to contrast dye, increased length of stay in the

hospital, causing exposure to multiple diseases. Data analyzed from this case study concludes

there is a 16.7% false-positive rate of elevated d-dimers subjecting patients to further diagnostic

testing they do not need (Mousa et al., 2015). The statistics on the accuracy in sensitivity and

specificity of ultrasound in diagnosing proximal deep vein thrombosis conclude to be 97% and

94% respectively (Mousa et al., 2015). The ultrasound is an excellent alternative method for

diagnosing DVT, with high accuracy rates and no false-positive results per this case study

presented (Mousa et al., 2015).

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Rahiminejad, M., Rastogi, A., Prabhudesai, S., Mcclinton, D., MacCallum, P., Platton, S., &

Friedman, E. (2014). Evaluating the Use of a Negative D-Dimer and Modified Low Wells

Score in Excluding above Knee Deep Venous Thrombosis in an Outpatient Population,

Assessing Need for Diagnostic Ultrasound. ISRN Radiology, 2014, 1–5.

https://doi.org/10.1155/2014/519875 

Abstract

Objective: Colour doppler ultrasonography (CDUS) is widely used in the diagnosis of deep

venous thrombosis (DVT); however, the number of scans positive for above knee DVT is low.

The present study evaluates the reliability of the D-dimer test combined with a clinical

probability score (Wells score) in ruling out an above knee DVT and identifying patients who do

not need a CDUS.

Method: This study is a retrospective audit and reaudit of a total of 816 outpatients presenting

with suspected lower limb DVT from March 2009 to March 2010 and from September 2011 to

February 2012. Following the initial audit, a revised clinical diagnostic pathway was

implemented.

Results: In our initial audit, seven patients (4.9%) with a negative D-dimer and a low Wells score

had a DVT. On review, all seven had a risk factor identified that was not included in the Wells

score. No patient with negative D-dimer and low Wells score with no extra clinical risk factor

had a DVT on CDUS (negative predictive value 100%). A reaudit confirmed adherence to our

revised clinical diagnostic pathway.

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Conclusions: A negative D-dimer together with a low Wells score and no risk factors effectively

excludes a lower limb DVT and an ultrasound is unnecessary in these patients.

This quantitative case study was included in the item analysis to prove further that D-

dimers are not the most accurate testing tool to diagnose patients with deep vein thrombosis.

False-positive elevation has been noted in many previous studies; however, this analysis explains

how false negatives are also present with the diagnostic tool. Per this study, the d-dimer had a

false negative result in approximately 5% of the population tested (Rahiminejad et al., 2014).

The Well's scoring criteria is also evaluated in this analysis which proved some errors in the

placement of patients into low and high-risk pretesting categories (Rahiminejad et al., 2014).

This research paper will propose a higher-level diagnostic framework tool to identify low and

high-risk patients based on the trial and errors of Well's clinical probability scoring test. The

ultrasound is the superior diagnostic tool regarding deep vein thrombosis for both low and high-

risk patients.
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References

Abbasi S, Bolverdi E, Zare MA, Hafezimoghadam P, Fathi M, Farsi D, Moghimi M.

Comparison of diagnostic value of conventional ultrasonography by emergency

physicians with Doppler ultrasonography by radiology physicians for diagnosis of deep

vein thrombosis. (2012). J Pak Med Assoc. 2012 May;62(5):461-5. PMID: 22755310.

Der Sahakian, G., Claessens, Y. E., Allo, J. C., Kansao, J., Kierzek, G., & Pourriat, J. L. (2010).

Accuracy of D-Dimers to Rule Out Venous Thromboembolism Events across Age

Categories. Emergency Medicine International, 2010, 1–4.

https://doi.org/10.1155/2010/185453 

Kabrhel, C., Mark Courtney, D., Camargo, C. A., Plewa, M. C., Nordenholz, K. E., Moore, C.

L., Richman, P. B., Smithline, H. A., Beam, D. M., & Kline, J. A. (2010). Factors

Associated With Positive D-dimer Results in Patients Evaluated for Pulmonary

Embolism. Academic Emergency Medicine, 17(6), 589–597.

https://doi.org/10.1111/j.1553-2712.2010.00765.x 

Larsen, T. B., Stoffersen, E., Christensen, C. S., & Laursen, B. (2002). Validity of D-dimer tests

in the diagnosis of deep vein thrombosis: a prospective comparative study of three

quantitative assays. Journal of Internal Medicine, 252(1), 36–40.

https://doi.org/10.1046/j.1365-2796.2002.00998.x 

Mousa, A. Y., Broce, M., Gill, G., Kali, M., Yacoub, M., & AbuRahma, A. F. (2015).

Appropriate Use of d-Dimer Testing Can Minimize Over-Utilization of Venous Duplex

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Ultrasound in a Contemporary High-Volume Hospital. Annals of Vascular Surgery, 29(2),

311–317. https://doi.org/10.1016/j.avsg.2014.07.032 

Rahiminejad, M., Rastogi, A., Prabhudesai, S., Mcclinton, D., MacCallum, P., Platton, S., &

Friedman, E. (2014). Evaluating the Use of a Negative D-Dimer and Modified Low Wells

Score in Excluding above Knee Deep Venous Thrombosis in an Outpatient Population,

Assessing Need for Diagnostic Ultrasound. ISRN Radiology, 2014, 1–5.

https://doi.org/10.1155/2014/519875