ADJUST-PE Study: ALiEM-Annals of EM Journal Club

ADJUST-PE Study: ALiEM-Annals of EM Journal Club

2017-03-05T14:18:40+00:00

ALiEM-AnnalsEM-SquareWe are very excited this month to bring you our fourth ALiEM-Annals of EM Global Journal Club on the use of age-adjusted D-dimer levels to help exclude the diagnosis of pulmonary embolism (PE). We hope you will participate in an online discussion of the four posted questions below from now until August 29th. Respond by commenting below or tweeting (#ALiEMJC). Mark your calendars: On Thursday, August 28th at 16:30 CST (17:30 EST), we will be hosting a 30-minute live Google Hangout with Drs. Jeff Kline and Jonathan Kirschner, the authors of the Annals of Emergency Medicine Journal Club for the ADJUST-PE Trial, that is informed by the discussion. Later this year, a summary of this journal club will hopefully be published in Annals of EM.

Google Hangout With Drs. Kline and Kirschner

Timestamps

  • 00:00  Dr. Salim Rezaie launches the Google Hangout.
  • 00:29  Dr. Sam Shaikh briefly reviews the ADJUST-PE study.
  • 01:17  Dr. Shaikh presents question 1 about the older medan age (63 years old) of the ADJUST-PE study population.
  • 01:41  Dr. Jonathan Kirschner (Indiana University-Purdue University Indianapolis) discusses spectrum bias, based on differing prevalence values, and how that may affect the generalizability of the ADJUST-PE findings.
  • 03:18  Dr. Jeff Kline (Indiana University-Purdue University Indianapolis) talks about why he PE seems to behave differently in the U.S. compared to Europe.
  • 04:44  Dr. Anand Swaminathan presents question 2 about the lack of uniformity of different d-dimer assays.
  • 05:13  Dr. Kline gives his perspective and shares unpublished survey data on PE’s and d-dimer.
  • 06:29  Dr. Kirschner elaborates on this survey data – 80% of respondents did not know what d-dimer assay they use.
  • 07:32  Dr. Swaminathan identified that different d-dimer cutoffs are set by local pathologists based on whether looking at venous thromboembolism vs DIC, which adds to clinician confusion.
  • 08:35  Dr. Kirschner advocates for normalized d-dimer values to avoid confusion.
  • 09:07  Dr. Kline explains that hospitals run assays and set their own cutoffs, as mandated by CLIA. Advocates for a grass-roots efforts to create a normalized d-dimer, because the FDA doesn’t have the power to mandate this across diagnostic lab companies.
  • 10:25  Dr. Teresa Chan asks about whether can calculate normalized d-dimers already right now. Dr. Kline answers that this is possible right now with “a little bit of work”.
  • 11:45  Dr. Rezaie reviews that the prevalence of the ADJUST-PE study was 19% which is much higher than in the U.S. (5-10%). Why the discrepancy? What’s the importance? Dr. Kirschner and Dr. Kline address this question about discrepancy.
  • 14:23  Dr. Rezaie introduces Dr. Anton Helman’s point from the blog comments about Canada’s PE prevalence rate (9.5%) based on earlier Wells’ study.
  • 15:00  Dr. Kline notes that the prevalence rates of PE are declining worldwide. He provides his hypothesis, based on a declining rate of community-based care in Europe which typically screens out the really low risk patients.
  • 17:17  Dr. Kirschner also notes that it may be a difference in “value” leading to PE prevalence with U.S. providers seemingly striving for the impossible goal of a zero-miss rate for diseases.
  • 18:08  Dr. Swaminathan is also surprised that Canada’s prevalence is similar to that of the U.S.
  • 18:50  Dr. Chan notes that “as the token Canadian, we LOVE our d-dimers”.
  • 21:20  Dr. Swaminathan asks question 4 — would you change your practice using the age-adjusted d-dimer cutoffs?
  • 21:48  Dr. Kirschner clarifies that age-adjusted d-dimer cutoffs are reasonable to use based on both this prospective ADJUST-PE and other retrospective studies.
  • 23:08  Dr. Chan and Dr. Kirschner note some pitfalls in the study methodology regarding the actual sample size (is it 3000’s or 300’s?) and the low event rate. “Clinical gestalt is still king” in the workup in PE.
  • 25:40  Dr. Rezaie and Dr. Kline talk about the fact that some deaths did not undergo an autopsy to definitive diagnose PE.
  • 26:54  Pneumonia is the most emergent diagnosis seen on CT pulmonary angiogram (about 10%). Dr. Kline suggests that older patients likely will undergo CT to assess for the chest symptoms regardless of d-dimer.
  • 27:55  Dr. Kline gives us an early peek at his proposed algorithm for the diagnosis of PE, which does include the age-adjusted d-dimer cutoff.
  • 29:54  Tweets from the audience:  Dr. Swaminathan brings in some live tweets including Dr. Rick Brody‘s point also advocating for a standardized, normalized d-dimer value across assays. Dr. Minh Le Cong‘s tweet asks about whether higher d-dimer confers higher mortality.

 

NEW! Journal Jam with EM Cases

EM Cases now hosts Journal Jam, featuring the ALiEM-Annals Global EM Journal Club! Listen to the terrific re-mixed podcast version of this Google Hangout on Air with great additional commentaries by Dr. Anton Helman and Dr. Teresa Chan.

EM_Cases_JournalJam_Sidebar_ORIGINAL

Click here to go directly to the Journal Jam episode!

ADJUST-PE Study and Annals of EM Journal Club Citations

Righini M et al. Age-Adjusted D-Dimer Cutoff Levels to Rule Out Pulmonary Embolism: The ADJUST-PE Study. JAMA. Mar 2014; 311(11):1117-24. PMID: 24643601

Kirschner JM, Kline JA. Is it time to raise the bar? Age-adjusted D-dimer cutoff levels to exclude pulmonary embolism. Ann Emerg Med. 2014 Jul;64(1):86-7. PMID: 24951413.

ADJUST-PE Abstract

Importance: D-dimer measurement is an important step in the diagnostic strategy of clinically suspected acute pulmonary embolism (PE), but its clinical usefulness is limited in elderly patients.

Objective: To prospectively validate whether an age-adjusted D-dimer cutoff, defined as age x 10 in patients 50 years or older, is associated with an increased diagnostic yield of D-dimer in elderly patients with suspected PE.

Design, Settings, and Patients: A multicenter, multinational, prospective management outcome study in 19 centers in Belgium, France, the Netherlands, and Switzerland between January 1, 2010, and February 28, 2013.

Interventions: All consecutive outpatients who presented to the emergency department with clinically suspected PE were assessed by a sequential diagnostic strategy based on the clinical probability assessed using either the simplified, revised Geneva score or the 2-level Wells score for PE; highly sensitive D-dimer measurement; and computed tomography pulmonary angiography (CTPA). Patients with a D-dimer value between the conventional cutoff of 500 μg/L and their age-adjusted cutoff did not undergo CTPA and were left untreated and formally followed-up for a 3-month period.

Results: Of the 3346 patients with suspected PE included, the prevalence of PE was 19%. Among the 2898 patients with a non-high or an unlikely clinical probability, 817 patients (28.2%) had a D-dimer level lower than 500 μg/L (95%CI, 26.6%-29.9%) and 337 patients (11.6%) had a D-dimer between 500 μg/L and their age-adjusted cutoff (95%CI, 10.5%-12.9%). The 3-month failure rate in patients with a D-dimer level higher than 500 μg/L but below the age-adjusted cutoff was 1 of 331 patients (0.3%[95%CI,0.1%-1.7%]).Among the 766 patients 75 years or older, of whom 673 had a non-high clinical probability, using the age-adjusted cutoff instead of the 500 μg/L cutoff increased the proportion of patients in whom PE could be excluded on the basis of D-dimer from 43 of 673 patients (6.4%[95%CI, 4.8%-8.5%) to 200 of 673 patients (29.7% [95%CI, 26.4%-33.3%), without any additional false-negative findings.

Conclusions and Relevance: Compared with a fixed D-dimer cutoff of 500 μg/L, the combination of pretest clinical probability assessment with age-adjusted D-dimer cutoff was associated with a larger number of patients in whom PE could be considered ruled out with a low likelihood of subsequent clinical venous thromboembolism.

FOAM Discussion to Date on Age-Adjusted D-Dimer Testing

Website Title Author Type Country Date
Boring EM ADJUST-PE: Should We Adjust the D-Dimer Cut-Off for Age? Brent Thoma Blog Canada July 28th, 2014
REBEL EM Update on Age-Adjusted D-Dimer Salim R. Rezaie Blog United States July 11, 2014
REBEL EM Age-Adjusted D-Dimer Testing Salim R. Rezaie Blog United States April 28, 2014
EM Literature of Note Go Ahead, Age-Adjust the D-Dimer Ryan Radecki Blog United States April 16, 2014
Emergency Medicine Ireland Age Adjusted D-dimer Cut Offs Andy Neill Blog Ireland April 7, 2014
EM Nerd The Adventure of the Golden Standard Rory Spiegel Blog United States July 1, 2014

magnify_question_mark_400_clr_4858

Featured Questions

Q1: The median age of this European study population was 63 years, which is older than most American populations tested for PE. What effect might the older population studied have on the diagnostic accuracy of the D-dimer assay? What effect might older age have on the overall findings of this study?

Q2: Although all of the D-dimer assays used in this study had the same 500 μg/L cutoff for an abnormal value, many other quantitative D-dimer assays have different cutoffs for abnormal. What is the basis of the differences in cutoffs? Can the results of this study be translated to D-dimers with different cutoffs?

Q3: In diagnostic test accuracy studies, the prevalence of disease in the study population will directly affect the derived positive and negative predictive values—so-called posttest probabilities. The prevalence of PE in this study was 19%. How does that number compare with the prevalence of PE in studies performed in other countries? How does prevalence of disease in the study population affect the sensitivity and specificity of the diagnostic strategy?

Q4: Based on this study, would you change your practice, assuming that you have one of the 6 studied D-dimer assays? For instance, you see a 60 year-old woman with a non-high pretest probability for a PE. Your D-dimer result is 590 μg/L. Would you perform a CTPA?

Please participate in the journal club by answering either on the ALiEM blog comments below or by tweeting us using the hashtag #ALiEMJC. Please denote the question you are responding to by starting your reply with Q1, Q2, Q3, or Q4.

Best Blog and Tweet

NEW! Contest for Best Blog Comment and Tweet

We are implementing a contest for the Best Blog Quote and Best Tweet. What, emergency physicians – competitive? No… The winners will be announced in our Annals of EM publication curating this discussion.

Disclaimer: We reserve the right to use any and all tweets to #ALiEMJC and comments below in a commentary piece for an Annals of EM publication as curated conclusion piece for this global journal club.  Your comments will be attributed, and we thank you in advance for your contributions.


Salim Rezaie, MD

Salim Rezaie, MD

ALiEM Associate Editor
Clinical Assistant Professor of EM and IM
University of Texas Health Science Center at San Antonio
Founder, Editor, Author of R.E.B.E.L. EM and REBEL Reviews
  • Anton Helman

    Q3. The prevalence of PE in Canada is unknown, however, in Well’s landmark study ‘Excluding Pulmonary Embolism at the Bedside without Diagnostic Imaging: Management of Patient with suspected Pulmonary Embolism Presenting to the Emergency Department by Using a Simple Clinical Model and D-Dimer’ (the Well’s Score Study), was done in 4 Canadian EDs, with data from 1998-1999 (yes, this is old, so prevalence may now be higher), using the SimpliRed Assay and in 930 patients (mean age 50.%) the prevalence was only 9.5%. They warn not to apply the algorithm to patient populations with higher prevalence.

    • Salim R. Rezaie

      Hello Anton,
      Appreciate you making the first comment on the #ALiEMJC. Interesting about the 9.5% prevalence in Canada. Depending on which studies you read the prevalence of PE varies….for example:

      In the US:

      5.1% in the Penazola et al study in 2012
      10.6% in the Woller et al study 2014

      Which would put Canada near the US for prevalence.

      In the European studies it appears the prevalence of PE is much higher:

      24 – 31% in the Douma et al 2010 study, Jaffrelot et al 2012 study, and the van Es et al 2012 studies

      The prevalence of PE in this study was closer to the aforementioned European studies near 19%.

      Salim

      • Hi Anton and Salim: I think both of you make good points – population prevalence is still the best we currently have for determining whether to apply tests and decision tools. Until he advent of more personalized medicine, we will need to know local disease prevalence to estimate pretest probability when thinking about our diagnostic approaches.

        This is a very important idea to truly understand, since the idea so whether a test can get you closer to a probability that is acceptable is important.

        The toughest part of all of this, of course, is then to figure out a great way to have a decently cogent-but-simple explanation of all these concepts and guide our patients through the decision making with us.

      • Q3. Hey folks: Thanks for pulling up the stats from Canada and the United States. Wow, these numbers of 5-10% make the Righini study prevalence of 19% really stand out as an outlier. I’m not a statistician and always have to look this up…

        Sensitivity/specificity numbers are set. They report a fixed property of a diagnostic test property. Predictive values (which is what we really want to know clinically) are dependent on prevalence. I always have to review this. Here’s a great explanation from the Univ of Ottawa with an illustrative table:

        http://www.med.uottawa.ca/sim/data/Sensitivity_and_Prevalence_e.htm

        • Anton Helman

          Q3. To add to that great link about predictive values, I’m reading a fantastic book that has an excellent explanation of the effect of prevalence on PVs, EBM and CDRs – by Chris Carpenter and others (http://tinyurl.com/qahgfxm), in preparation for an interview with Ian Steill. It dissects all the most relevant CDRs to 2013. I’ve learned so much!
          I imagine that applying this D-dimer study (prevalence 19%) to the lower prevalence population in Canada (prevalence say about 10%) would result in less of a decrease in imaging utilization than the study claims. Currently my practice is to almost never order D-dimers in the older patient as the specificity is likely too low. Would this study INCREASE our imaging utilization with False Positives the way the Well’s score inadvertently did?

        • Anand Swaminathan

          The prevalence numbers are interesting. I assume that human beings aren’t that different in Europe vs. Canada/America and population risks are probably similar in developed countries. The difference here is in who is being studied. We’ve lowered the prevalence by over-investigating. I’m surprised that the Canadian numbers are so close to the US ones as I thought they would more mimic the European side.
          I think the bottom line is that we (US/Canada) are investigating tons of patients with virtually no risk for VTE.

          • I agree Anand. Canada seems to have followed suite to it’s big brother when it comes to over-investigating low risk patients for PE. Anecdotally, it appears that most of this over-investigation is in YOUNG patients, where the radiation effects are most important. The ADJUST trial does not help this state of affairs, and my guess is that we may be investigating older patients appropriately because we don’t rely on D-dimer in these patients as much. If we start to use age-adjusted D-dimer on older patients, we may slide down the slippery slope of over-investigation for them too, as history has shown for the young patients!

  • Minh Le Cong

    hi folks
    this article is reassuring and helps us in ED , rationalise our approach to the patient with suspected PE.
    Q4 = yes I would change my practice and use the age adjusted cutoff

    I think this study helps to bring the disparate assays for D Dimer back to a minimum standard and use a cut off thats sensible and individualised to a degree.

  • Anand Swaminathan

    Q2 is the most interesting/controversial to me although I think there should be no controversy.
    At many of my hospitals, the “normal” d-dimer cutoff is lower than 500 (closer to 230-250). However, it’s my understanding that all of the newer generation d-dimer assays should have the same cutoff for d-dimer for VTE and that number is 500. This was mentioned last month on EMRAP. The lower cutoffs are either set looking for other diseases (i.e. DIC) and not for VTE. However, I’m still seeking confirmation/clarification on this point. Would be interested to hear if others have heard/seen similar things.

  • Brent Thoma

    I found this study very interesting. To address question #4 specifically:

    I think the age-adjusted D-Dimer is probably a good idea and is likely to be useful in our future practice. Based on this study I think we can begin having conversations with our patients that are below the age-adjusted cut-off. However, I don’t think this study conclusively proves that it is a safe strategy to rule out for a few reasons:

    First, this study was not nearly as big as it claimed. You’ll note that the population of interest (those who had PE ruled out using the age-adjusted D-Dimer) was quite small (only 331 patients). This is a big change of practice to consider based on such a relatively small validation cohort (I know there have been other meta-analyses on this rule, but they have some methodological problems that I outlined in a previous post on BoringEM here: http://boringem.org/2013/07/17/d-dimer-should-we-adjust-the-cut-off-value-for-age/). This would be okay if it had very tight confidence intervals around a miss rate 500 but below the age-adjusted threshold (in most locations this would be standard of care). This would have allowed us to calculate + and – LR’s for the age-adjusted cut-offs (something we can’t do due to their odd methodology) and provided better evidence of the age-adjusted D-Dimer’s worth to rule-out PE in elderly patients. Instead, we got half of a study on ruling out PE with the age-adjusted D-Dimer and half of a study assessing the D-Dimer’s 3-month prognostic value for future PE’s, something I think this is a different question altogether.

    Despite all of this, my bottom line on this study (and the other data on D-Dimers) is that age-adjusted D-Dimer’s are probably a good idea and we should discuss the low likelihood of a PE or adverse outcome with patients that score in this range. However, I do not think the ADJUST-PE study proved this strategy’s safety beyond a questionable doubt. I wanted to love this study (and its conclusions), but I can’t.

    • Sameed Shaikh

      Brent, you do a great job articulating many limitations in this studies methodology. As far as Q4 if I had a 60 year old with PE on the differential diagnosis & a d-dimer of 590 I think would be scanning her even if this study had bigger numbers and clearer methodology. If further data comes out affirming the age-adjusted cutoff, I may consider forgoing the CTPA in a 70 or 80 year old with d-dimer 590.

    • I’m with you Brent about the oddities of the study design. As a general rule, I’m always skeptical and never the first to implement any new sweeping changes with diagnostic tests. That being said, I will calculate the age-adjusted normal cutoff for patients age >50 and factor it in with caution– meaning that if I’m anywhere on the fence about it, I’ll err on the side obtaining a CTPA to r/o PE.

  • Brent Thoma

    Another note regarding Question #4:

    Salim, you mention having one of the 6 studied D-Dimer assays. I think it’s important to note that only 3/6 of the assays were used on >50 patients in the population of interest (D-Dimer >500 and <age-adjusted value). Without greater familiarity with the background research on D-Dimer assays, I'm not sure whether they are consistent enough to generalize the results so broadly. Notably, when this study was registered with ClinicalTrials.gov they only planned to use the VIDAS assay.

    -Brent

  • I’ll jump in for Q2!

    This study probably can not be translated to other dimer cutoffs: http://www.ncbi.nlm.nih.gov/pubmed/?term=24247319

    The above referenced study tried to “normalize” 5 dimer assays. STA-Liatest D-Dimer and HemosIL D-Dimer outperformed AxSYMD-Dimer, VIDAS D-Dimer, INNOVANCE D-Dimer in ruling out thromboembolism. Unfortunately, the study I referenced is a small study. It has tons of limitations. If your institute uses the same reagents as the ADJUST-PE study, great. If not, you’re kind of stuck to either hope that it is as accurate, do the age-adjusting study for your institute, or hope that the peer review process at your facility is forgiving.

    If you dont know the limitations of the dimer assay at your institute, adjust that dimer at your own peril. Or until Kline convinces the FDA to standardize the dimer assay (https://twitter.com/klinelab/status/467412141352316928).

    • Brent Thoma

      Awesome point!

      I’d say that this is actually a limitation of ADJUST-PE as well because, while it used 6 different D-Dimer assays, only 3 of them were used on >50 patients in the population of interest (those with D-Dimers >500 and < the age-adjusted cut-off). That makes it difficult to know whether some of the assays performed well at a 500 cutoff or just 'got lucky.'

      Notably, when it was registered on clinicaltrials.gov this study was planned to use only the VIDAS D-Dimer. Had it only used a single one we could just learn how our institutions' assays compare with it. By using 6 (and some of them for a very small number of patients) the waters are muddied.

      -Brent

      • Brent, I agree. The authors make a noble effort, but to me, a retrospective study looking at the last 3000 patients scanned (or the last 500 PEs) and their respective dimer values would hold more water to me. If, retrospectively, age adjusted dimer filtered out big PEs but may catch subsegmental PEs that dont cause increased morbidity/mortality, then great. The only way to find out is with imaging, no? I haven’t done the dirty work, but I imagine a pilot like this exists? The question is not just “what’s the missed PE rate” its “are you missing harmful PEs”?

        • update: http://bestbets.org/bets/bet.php?id=2612 The data isnt great, but perhaps these are the people with the minimally elevated dimer. subsegmental PEs that dont get treated and dont have recurrence. Curiousity (and its treatment) doesnt just kill the cat.

  • Dr. Cenker EKEN

    Thanks for the global journal club.
    The questions arises from the present article are listed below:
    1. The only outcome that we can be sure with the telephone follow-up is death regardless of its cause except a post-mortem autopsy. There are 7 deaths in patients with a d-dimer level of higher than 500µg/lt and below age adjusted cutoff. I cannot be sure about the cause of these 7 deaths except the existence of an autopsy.
    2. One of the exclusion criteria of this study is life expectancy less than three months. This means that study patients with malignancy have a life expectancy of more than three months. One of the patients among seven deaths was stated to be related to malignancy. However, hypercoagulation is an important complication of malignancies. If this patients has a life expectancy of more than three months, we cannot exclude PE as the cause of the death. Also deaths of three patients were stated to be related to COPD. As the patients with malignancies, we cannot completely exclude PE as the cause death in these patients except a post-mortem autopsy.
    3. I think it may be mentioned a gold-standard problem in the present study. If you don’t have a definite and strict gold standard, accepting all the deaths or adverse events as an outcome of the study and determining the diagnostic performance by using the negative patients might be more reliable.
    4. Actually I would like to know the mean age of the patients with a d-dimer level of lower than 500µg/lt. We have to consider that there are patients over 50 years old with d-dimer levels of lower than than 500µg/lt. So, it would be better to compare the patients over 50 years old who have d-dimer levels of lower than 500µg/lt to patients with a d-dimer level of higher than 500µg/lt and below age adjusted cutoff. Because the number of adverse outcomes are higher in the targeted group despite the 331 patient and 880 in patients with a d-dimer level of lower than 500µg/lt. The higher rate of the adverse events in this group is related to age or higher d-dimer levels or sth else?
    5. A ROC analysis would be helpful that includes all the patients over 50 years old with a d-dimer level of lower than age adjusted cutoff (also including patients lower than 500µg/lt) for determining a new cutoff for elder patients with a proper sensitivity.
    Cenker EKEN, MD
    Associate Proffesor of Emergency Medicine
    Antalya/Turkey

  • Dr. Cenker EKEN

    Q3:although the prevalance of the disease affects the predictive values, there is no problem with calculating the sensitivity and spececifity, thus also no problem with + and – likelihood ratios and post test probability.

  • Anand Senthi

    Re Q4:
    I think when considering this question one should consider
    the broader context that this sits within: that there is no good evidence that
    the investigation of patients who are at low risk for PE provides them with a
    net benefit and there is some evidence they are probably exposed to net harm
    instead. Viewed within this framework we should be quite ready to accept
    age-adjusted d-dimer as it should start pushing the risk-benefit equation back
    towards the patient’s favour.

    At the very least, those with d-dimer levels between 500 and
    their age adjusted cut offs should be provided the information to decide for
    themselves within a shared decision making framework. Based on the ADJUST-PE study you could let the patients know that the current evidence estimates that their risk of a relevant
    fatal or non-fatal PE over the next 3 months is likely about 1% (or less).
    Given this risk is very low and considering the risks of CTPA (including
    contrast, radiation and the intermediate to long term anticoagulation of the substantial false positives) many/most patients would likely decline further investigation.

    Interestingly this approach has already been recently studied in a
    very similar situation and resulted in substantial deference of testing by the
    patients.
    Geyer BC, Xu M, Kabrhel C. Patient preferences for testing for pulmonary embolism in the ED using a shared decision-making model. Am J Emerg Med. 2013).

    • Anand Senthi

      I do however share Anton’s concern that excessive exuberance about age adjusted d-dimer and its improved specificity may result in clinician’s increasing their use of it in older patients, where they would have usually gone straight to CTPA where they may have been more selective in their decision to investigate.

    • Using Age Adjusted D-dimer may make us more likely to order D-dimer in low risk older patients and so may increase imaging inadvertently similar to the way the Wells Score did.

  • Anand Senthi

    I concur with the prevalence figures from the ED studies I’ve seen. US ED studies usually have PE prevalence in those investigated at around 5-10% while mainland europeans are around 20-30%. This is likely due to the difference in legal systems and litigation (the absence of tort law in mainland europe). Given the lower prevalence, the NPV of age-adjusted d-dimer should be even lower in US practice (i.e. even safer).

    • While Canadians generally seem to practice less defensively from a legal perspective than Americans, I think we share a culture if the desire for diagnostic certainty, which may account for the similar prevalence rates for PE.

      • Anand Senthi

        it may indeed, though I’m not sure we have enough Canadian studies to conclude that their prevalence rates are in fact the same as the US, though it is likely they are in the same ball park

  • David Todd Schwartz

    Q2 and online discussion with Dr. Kirschner and Dr. Kline.
    Regarding the different cut-off values for D-dimer assays among various manufacturers, the units are actually different.
    For the assays that have a cut-off of 500, the units are ng/mL in Fibrinogen Equivalent Units (FEU).
    For the Instrumentation Laboratories (IL) HemosIL D-Dimer HS, the cut off of 230 is in ng/mL in D-dimer Units (DDU).
    IL has a newer assay called HemosIL D-Dimer HS 500 with a cut-off value of 500 that uses ng/mL FEU and therefore corresponds with other manufacturers.
    Therefore, the affinity of the monoclonal antibody used in these assays may be equivalent, only the units used to quantify the D-dimer levels are different.
    The HS in the assay name refers to “High Specificity” meaning that there is less confounding with other molecules and substances that affect turbidity assessment in the assay.