Validating the HERDOO2 Rule to Guide Treatment Duration for Women With Unprovoked Venous Thrombosis: Multinational Prospective Cohort Management Study

Abstract

ObjeCtiveTo prospectively validate the HERDOO2 rule (Hyperpigmentation, Edema, or Redness in either leg; D-dimer level ≥250 μg/L; Obesity with body mass index ≥30; or Older age, ≥65 years), which states that women with none or one of the criteria can safely discontinue anticoagulants after short term treatment. DesignProspective cohort management study. setting 44 secondary or tertiary care centres in seven countries. PartiCiPantsOf 3155 consecutive eligible participants with a first unprovoked venous thromboembolism (VTE, proximal leg deep vein thrombosis or pulmonary embolism) who completed 5-12 months of short term anticoagulant treatment, 370 declined to participate, leaving 2785 enrolled participants. 2.3% were lost to follow-up.interventiOns Women with none or one of the HERDOO2 criteria were classified as at low risk of recurrent VTE and discontinued anticoagulants (intervention arm), whereas anticoagulant management for high risk women (≥2 HERDOO2 criteria) and men was left to the discretion of the clinicians and patients (observation arm). Main OutCOMe MeasureRecurrent symptomatic VTE (independently and blindly adjudicated) over one year of follow-up. resultsOf 1213 women, 631 (51.3%) were classified as low risk and 591 discontinued oral anticoagulant treatment. In the primary analysis, 17 low risk women who discontinued anticoagulants developed recurrent VTE during 564 patient years of follow-up (3.0% per patient year, 95% confidence interval 1.8% to 4.8%). In 323 high risk women and men who discontinued anticoagulants, 25 had VTE during 309 patient years of follow-up (8.1%, 5.2% to 11.9%), whereas in 1802 high risk women and men who continued anticoagulants 28 had recurrent VTE during 1758 patient years of follow-up (1.6%, 1.1% to 2.3%). COnClusiOnsWomen with a first unprovoked VTE event and none or one of the HERDOO2 criteria have a low risk of recurrent VTE and can safely discontinue anticoagulants after completing short term treatment.trial registratiOn clinicaltrials.gov NCT00967304.

External validation of the DASH prediction rule: a retrospective cohort study

“…Among possible study limitations, we have already mentioned the overrepresentation of low-risk subjects in our validation sample. Consequently, we observed an annualized recurrence rate (4.8%) that is lower than that reported for the original DASH cohort (6.0%) [29], or by other recent validation studies [30,31]. Overrepresentation of low-risk subjects does not, however, affect the study validity, as the aim of our study was to validate a predefined prognostic rule without any therapeutic or etiologic aim.…”

A randomised controlled trial of extended anticoagulation treatment versus standard treatment for the prevention of recurrent venous thromboembolism (VTE) and post‐thrombotic syndrome in patients being treated for a first episode of unprovoked VTE (the ExACT study)

“…It is possible that a lower D‐dimer cutoff threshold could be more informative for patients on anticoagulation. The HERDOO2 rule has been prospectively validated using a lower cutoff (250 mcg/l) and a different D‐dimer assay (VIDAS) (Rodger et al , ). However, other investigators have not used this cutoff (e.g.…”

What have we learned from coagulation laboratory participation in external quality programs?

“…Failure to communicate the D‐dimer unit type is common in published literature in this area, including in a recent proposed guideline update for diagnosis of periprosthetic joint infections that does not specify either the D‐dimer assay used by study sites or the D‐dimer unit type . The HERDOO2 clinical decision rule for anticoagulation duration in women with unprovoked venous thromboembolism was developed using a single D‐dimer assay . However, subsequent studies suggest that not every D‐dimer assay can be used in the HERDOO2 rule, a clinical consequence of the significant D‐dimer assay variability previously observed in EQA data …”

“…12 The HERDOO2 clinical decision rule for anticoagulation duration in women with unprovoked venous thromboembolism was developed using a single D-dimer assay. 13 However, subsequent studies suggest that not every D-dimer assay can be used in the HERDOO2 rule, a clinical consequence of the significant D-dimer assay variability previously observed in EQA data. 14…”