Prueba de dímero D para embolia pulmonar

Temas relacionados
● Predicción clínica de la embolia pulmonar

● Embolia pulmonar (EP)

Descripción general
● El ensayo de dímero D no es lo suficientemente específico para confirmar el diagnóstico de embolia
pulmonar (EP)

● ensayos cuantitativos de dímero D que tienen una sensibilidad lo suficientemente alta como para que una
prueba negativa pueda descartar la EP
⚬ ensayos inmunoabsorbentes ligados a enzimas (ELISA)

– ELISA parece tener sensibilidad suficiente para descartar EP Nivel DynaMed 2

– ELISA tradicional para dímero D parece útil para descartar TEP si la probabilidad clínica es baja
Nivel DynaMed 2

⚬ ensayos turbidimétricos

– La prueba de dímero D turbidimétrica de látex puede tener una alta sensibilidad para diagnosticar la
EP Nivel DynaMed 2
– El inmunoensayo turbidimétrico mejorado con látex (HemosIL D-dimer HS 500) parece sensible para
la tromboembolia venosa Nivel DynaMed 2

● Las pruebas cualitativas de dímero D en el punto de atención pueden ser útiles para descartar
tromboembolismo venoso en pacientes de bajo riesgo Nivel DynaMed 2

● uso de ensayos de dímero D en algoritmos de diagnóstico

⚬ en pacientes con TEP prevista de riesgo bajo o intermedio, el punto de corte del dímero D ajustado por
edad es útil para descartar TEP
– en pacientes > 50 años, valor de corte ajustado por edad preferido = edad × 10 ng/mL

● El límite de dímero D ajustado por edad más una probabilidad clínica baja puede descartar la EP
en más pacientes que el límite de dímero D fijo de 500 mcg/L más una probabilidad clínica baja
Nivel DynaMed 1

● en pacientes > 50 años con probabilidad clínica no alta de tromboembolismo venoso, los valores
de corte de dímero D ajustados por edad parecen más específicos que los valores de corte de
dímero D convencionales Nivel DynaMed 2
– en pacientes ≤ 50 años, use el punto de corte de 500 ng/mL

● la sensibilidad del ensayo de dímero D para el tromboembolismo venoso agudo podría ser menor si se usa
> 6 días después del inicio de los síntomas Nivel DynaMed 2

● ver Predicción clínica de embolia pulmonar para seleccionar pacientes con baja probabilidad de EP para la
prueba de dímero D
⚬ las reglas de decisión clínica y la gestalt clínica pueden tener una sensibilidad de alrededor del 85 %
para la embolia pulmonar (EP) y pueden tener un valor predictivo negativo del 99 % cuando se
combinan con la prueba del dímero D Nivel DynaMed 2
 ⚬ La regla de Wells, la regla de Wells simplificada, la puntuación de Ginebra revisada y la puntuación de
Ginebra revisada simplificada tienen un rendimiento similar para descartar EP aguda en pacientes con
dímero D normal Nivel DynaMed 1

● consulte Embolia pulmonar (EP) para obtener información sobre otras pruebas de diagnóstico para PE

● después del curso de anticoagulación oral para el tromboembolismo venoso idiopático

⚬ Dímero D < 250 mg/dl predice un menor riesgo de recurrencia Nivel DynaMed 1

⚬ la anticoagulación > 3 meses puede reducir el riesgo de tromboembolismo venoso recurrente en

pacientes con niveles anormales de dímero D Nivel DynaMed 2

Tipos de ensayos de dímero D

● ensayos cualitativos de dímero D

⚬ aglutinación de sangre entera (SimpliRED)

⚬ aglutinación de látex (Minutex D-dimer)

● ensayos semicuantitativos de dímero D basados ​en inmunofiltración

⚬ Dímero D NycoCard
⚬ IA INSTANTÁNEO

● ensayos cuantitativos de dímero D

⚬ Los ensayos inmunoabsorbentes ligados a enzimas (ELISA) incluyen

– Dímero D VIDAS
– Dímero D de Asserachrom
– Enzygnost Dímero D Micro
– Fibrinostika FbDP

⚬ Los ensayos turbidimétricos de dímero D mejorados con látex incluyen

– Dímero D avanzado
– Dímero D LIATEST
– Prueba de IL Dímero D
– Dímero D de Tinaquant

● Referencia - Am J Clin Pathol 2003 Dec;120(6):930

Ensayos ELISA de dímero D

RESUMEN
● DEL ESTUDIO
Los ensayos inmunoabsorbentes ligados a enzimas parecen tener suficiente sensibilidad para descartar
la embolia pulmonar. Nivel DynaMed 2

REVISIÓN SISTEMÁTICA : Ann Intern Med 2004 20 de abril; 140 (8): 589

Detalles

⚬ basado en una revisión sistemática sin evaluación de la calidad del estudio

⚬ revisión sistemática de 78 estudios de diagnóstico prospectivos que evalúan ensayos de dímero D para
diagnosticar embolia pulmonar (EP) o trombosis venosa profunda (TVP)
⚬ Ensayos de dímero D incluidos
 – ensayo inmunoabsorbente ligado a enzimas (ELISA)
– ensayo ELISA rápido cuantitativo
– qualitative rapid ELISA assay
– semi-quantitative rapid ELISA assay
– quantitative latex agglutination assay, semi-quantitative latex agglutination assay, and whole-blood
agglutination assay
⚬ most studies evaluating D-dimer assays for PE diagnosis used ventilation perfusion lung scanning,
pulmonary angiography, or both as reference standard
⚬ most studies evaluating D-dimer assays for DVT diagnosis used venography or venography plus
ultrasonography as reference standard
⚬ pooled diagnostic performance of D-dimer assays for diagnosing PE (D-dimer cutoff 500 ng/mL)

– ELISA had sensitivity 95% (95% CI 88%-100%) and specificity 45% (95% CI 38%-53%)
– quantitative rapid ELISA had sensitivity 98% (95% CI 88%-100%) and specificity 40% (95% CI 29%-50%)
– qualitative rapid ELISA had sensitivity 92% (95% CI 71%-100%) and specificity 68% (95% CI 46%-90%)
– semi-quantitative rapid ELISA had sensitivity 94% (95% CI 81%-100%) and specificity 39% (95% CI
26%-52%)
– all agglutination assays had sensitivity ≤ 90%

⚬ pooled diagnostic performance of D-dimer assays for diagnosing DVT (D-dimer cutoff 500 ng/mL)

– ELISA had sensitivity 94% (95% CI 89%-98%) and specificity 43% (95% CI 36%-50%)
– quantitative rapid ELISA had sensitivity 97% (95% CI 92%-100%) and specificity 42% (95% CI 32%-52%)
– qualitative rapid ELISA had sensitivity 93% (95% CI 87%-99%) and specificity 53% (95% CI 43%-64%)
– semi-quantitative rapid ELISA had sensitivity 91% (95% CI 85%-98%) and specificity 43% (95% CI
34%-52%)
– all agglutination assays had sensitivity < 90%

⚬ Reference - Ann Intern Med 2004 Apr 20;140(8):589 , commentary can be found in J Fam Pract 2004
Sep;53(9):686 , commentary can be found in Ann Intern Med 2004 Sep 21;141(6):481 , commentary
can be found in ACP J Club 2004 Nov-Dec;141(3):77 , summary can be found in Am Fam Physician 2005
Feb 15;71(4):795

RESUMEN
● DEL ESTUDIO
El ensayo inmunoabsorbente ligado a enzimas (ELISA) tradicional para el dímero D parece útil para
descartar la embolia pulmonar (EP) si la probabilidad clínica es baja Nivel DynaMed 2

REVISIÓN SISTEMÁTICA : Ann Emerg Med 2002 Aug;40(2):133

Detalles

⚬ based on systematic review with wide confidence intervals

⚬ systematic review of 11 prospective cohort studies evaluating ELISA D-dimer testing for diagnosing PE in
2,126 adults presenting to emergency department with suspected PE
⚬ reference standards for positive diagnosis included positive angiogram, high-probability ventilation
perfusion lung scan, positive computed tomography (CT) scan, and positive lower extremity imaging
findings
⚬ acceptable reference standards for negative diagnosis included normal or low-probability ventilation
perfusion lung scan and clinical follow-up ≥ 3 months without thromboembolic events
⚬ PE prevalence ranged from 17% to 58%
 ⚬ pooled analysis of sensitivities for traditional ELISA D-dimer test included 2 high-quality studies with
confidence intervals including low-to-moderate values
⚬ pooled diagnostic performance of traditional ELISA D-dimer test (cutoff 500 ng/mL) for diagnosing PE in
analysis of 9 studies
– sensitivity 94% (95% CI 88%-97%)
– specificity 45% (95% CI 36%-55%)

⚬ sensitivity and specificity were lower in patients with symptom duration ≥ 4 days in 1 study
⚬ Reference - Ann Emerg Med 2002 Aug;40(2):133 , commentary can be found in J Fam Pract 2002
Nov;51(11):919 , Am Fam Physician 2002 Dec 15;66(12):2310 , ACP J Club 2003 Jan-Feb;138(1):24

RESUMEN
● DEL ESTUDIO
La prueba VIDAS ELISA D-dimer parece útil para descartar pero no para diagnosticar la EP
Nivel DynaMed 2

ESTUDIO DE COHORTE : J Am Coll Cardiol 2002 16 de octubre; 40 (8): 1475

Detalles

⚬ based on retrospective cohort study with reference test not applied to all patients
⚬ 1,106 emergency department patients with suspected acute PE had D-dimer levels measured using
VIDAS ELISA D-dimer test
⚬ reference standards included high-probability lung scan, positive chest computed tomography (CT) scan,
and positive pulmonary angiogram findings
⚬ PE excluded after 6 months without subsequent positive imaging results
⚬ only 482 patients had imaging results
⚬ 55 patients (5%) had PE
⚬ for diagnosing PE, VIDAS ELISA D-dimer test with cutoff 500 ng/mL had
– sensitivity 96.4%
– specificity 52%
– positive predictive value 9.5%
– negative predictive value 99.6%

⚬ Reference - J Am Coll Cardiol 2002 Oct 16;40(8):1475 , commentary can be found in Am Fam Physician
2003 Mar 15;67(6):1333 , commentary focuses on need to lower D-dimer normal limits to < 250 ng/mL
to have 100% sensitivity but this would increase the high false positive rate (J Fam Pract 2003
Feb;52(2):99 )

⚬
DynaMed Commentary

Other studies have suggested further evaluation in patients with normal D-dimers but high clinical
suspicion.

RESUMEN
● DEL ESTUDIO
El resultado negativo del dímero D de VIDAS parece descartar la EP en pacientes con antecedentes de
tromboembolismo venoso previo Nivel DynaMed 2

ESTUDIO DE COHORTE : Arch Intern Med 2006 23 de enero; 166 (2): 176

Detalles

⚬ based on pooled analysis of 2 prospective cohort studies with blinding not stated
⚬ 1,721 emergency department patients with clinically suspected PE had standard clinical evaluation and
D-dimer levels measured using VIDAS D-dimer assay
⚬ reference standard was positive findings on lower limb ultrasonography, helical CT, ventilation-perfusion
lung scan, or pulmonary angiogram
⚬ 415 patients (24%) had PE
⚬ negative D-dimer test (D-dimer level < 500 mcg/L) ruled out PE in 462 of 1,411 (33%) patients without
previous venous thromboembolism (VTE) and 49 of 308 (16%) patients with previous thromboembolism
⚬ no patient with negative D-dimer and previous thromboembolism had thromboembolism at 3 months
(95% CI for risk 0%-7.9%)
⚬ diagnostic performance of VIDAS D-dimer assay (cutoff 500 mcg/L) for diagnosing PE
– in patients with history of VTE

● sensitivity 100% (95% CI 97%-100%)

● specificity 27% (95% CI 21%-33%)

– in patients without history of VTE

● sensitivity 100% (95% CI 99%-100%)

● specificity 41% (95% CI 38%-44%)

⚬ Reference - Arch Intern Med 2006 Jan 23;166(2):176 , editorial can be found in Arch Intern Med 2006
Jan;166(2):147

RESUMEN
● DEL ESTUDIO
la combinación de probabilidad clínica baja y un ensayo de dímero D negativo puede descartar la EP
Nivel DynaMed 2

ESTUDIO DE COHORTE : Arch Intern Med 2002 22 de julio; 162 (14): 1631

Detalles

⚬ based on prospective cohort study

⚬ 234 patients with suspected PE had D-dimer testing and clinical probability assessment with clinical
decision rule
⚬ patients with low clinical probability based on clinical decision rule and D-dimer < 500 ng/mL had no
further work-up, others had ultrasound of legs followed by pulmonary angiography
⚬ 26% had low clinical probability and normal D-dimer level
⚬ 51 patients (22%) had confirmed PE
⚬ no patients in low-risk group died within 3 months, 3 patients had recurrent PE symptoms but PE
excluded by objective testing
⚬ in patients with low clinical probability and negative D-dimer assay, risk of PE at 3 months was 0% (95%
CI 0%-6%)
⚬ Reference - Arch Intern Med 2002 Jul 22;162(14):1631 , commentary can be found in Arch Intern Med
2003 Jan 27;163(2):243
Ensayos turbidimétricos de dímero D
Ensayos turbidimétricos de dímero D

RESUMEN
● DEL ESTUDIO
La prueba de dímero D turbidimétrica de látex puede tener una alta sensibilidad para diagnosticar la
embolia pulmonar Nivel DynaMed 2

REVISIÓN SISTEMÁTICA : Clin Chem 2003 Nov;49(11):1846

Detalles

⚬ based on systematic review with wide confidence intervals

⚬ systematic review of 9 prospective diagnostic studies evaluating latex turbidimetric D-dimer assays for
diagnosing pulmonary embolism (PE) in 1,901 patients presenting to emergency department with
suspected PE
⚬ reference standards included high-probability ventilation-perfusion scan, positive pulmonary computed
tomography (CT) scan, and positive lower extremity imaging findings
⚬ acceptable reference standards for negative diagnosis included negative angiogram, normal or very low
probability ventilation-perfusion scan, and absence of thrombolic events after 3 month clinical follow-up
⚬ mean PE prevalence was 26% (range 9%-62%)
⚬ most commonly used cutoff for positive D-dimer test was 500 mcg/L
⚬ pooled diagnostic performance of latex turbidimetric D-dimer assay for diagnosing PE in analysis of all
studies
– sensitivity 93% (95% CI 89%-96%)
– specificity 51% (95% CI 42%-59%)

⚬ Reference - Clin Chem 2003 Nov;49(11):1846

Ensayo de dímero D HemosIL

RESUMEN
● DEL ESTUDIO
El inmunoensayo turbidimétrico mejorado con látex (HemosIL D-dimer HS 500) parece sensible para la
tromboembolia venosa Nivel DynaMed 2

ESTUDIO DE COHORTE DE DIAGNÓSTICO : Thromb Res 2010 May;125(5):398

Detalles

⚬ based on diagnostic cohort study with same reference standard not applied to all patients
⚬ 747 consecutive outpatients > 16 years old with suspected proximal venous thromboembolism
(pulmonary embolism [PE] or deep vein thrombosis [DVT]) had D-dimer levels measured using HemosIL
D-dimer HS 500
– PE in 52 (15%) of 346 patients with suspected PE
– DVT in 90 (22.4%) of 401 patients with suspected DVT

⚬ positive test result defined as D-dimer > 500 ng/mL

⚬ only patients with elevated D-dimer levels and/or high pretest probability received further diagnostic
testing
⚬ for diagnosis of PE, D-dimer > 500 ng/mL had
 – sensitivity 100%
– specificity 48.3%
– negative predictive value 100%
– positive predictive value 25.5%

⚬ for diagnosis of DVT, D-dimer > 500 ng/mL had

– sensitivity 100%
– specificity 42.1%
– negative predictive value 100%
– positive predictive value 33.3%

⚬ Reference - Thromb Res 2010 May;125(5):398

Ensayo de dímero D Liatest

RESUMEN
● DEL ESTUDIO
El ensayo turbidimétrico del dímero D puede descartar la embolia pulmonar en pacientes con cáncer de
alto riesgo Nivel DynaMed 2

ESTUDIO DE COHORTE : Radiología 2008 Jun;247(3):854 | Texto completo

Detalles

⚬ based on cohort study with early termination due to slow recruitment

⚬ 214 patients with cancer and suspected pulmonary embolism (PE) had STA Liatest D-dimer assay and
computed tomography (CT) pulmonary angiography in urgent care setting
⚬ 13 patients excluded for not having D-dimer within 24 hours of CT pulmonary angiography
⚬ 44 (22)% patients had PE on CT pulmonary angiography
⚬ 171 (85%) patients had positive D-dimer result (≥ 210 ng/mL D-dimer units)
⚬ for diagnosing PE, STA Liatest D-dimer assay with cutoff 210 ng/mL had

– sensitivity 98% (95% CI 88%-100%)

– specificity 18% (95% CI 13%-25%)
– positive predictive value 25% (95% CI 19%-32%)
– negative predictive value 97% (95% CI 83%-100%)
– positive likelihood ratio 1.2 (95% CI 1.1-1.3)
– negative likelihood ratio 0.12 (95% CI 0.02-0.88)

⚬ diagnostic accuracy not significantly improved with addition of clinical symptoms to D-dimer result
⚬ Reference - Radiology 2008 Jun;247(3):854 full-text

Ensayo de dímero D de MDA

RESUMEN
● DEL ESTUDIO
El inmunoensayo de látex de dímero D de fibrina plasmática cuantitativa (ensayo de dímero D de MDA)
puede ayudar a descartar una embolia pulmonar aguda Nivel DynaMed 2

ESTUDIO DE COHORTE DE DIAGNÓSTICO : Mayo Clin Proc 2007 May;82(5):556

Detalles

⚬ based on diagnostic cohort study without validation

 ⚬ 1,355 patients with suspected acute pulmonary embolism (PE) had quantitative plasma fibrin D-dimer
latex immunoassay within 3 days of multidetector computed tomographic (CT) angiography
⚬ 208 patients (15%) had PE
⚬ for diagnosing PE, MDA D-dimer assay with cutoff 300 ng/mL had

– sensitivity 94% (95% CI 89%-97%)

– specificity 27% (95% CI 25%-30%)
– negative predictive value 96% (95% CI 93%-98%)

⚬ Reference - Mayo Clin Proc 2007 May;82(5):556

⚬
DynaMed Commentary

D-dimer assay used was MDA immunoturbidimetric assay from bioMerieux.

RESUMEN
● DEL ESTUDIO
La prueba cuantitativa de aglutinación de látex con dímero D puede ayudar a descartar una embolia
pulmonar Nivel DynaMed 2

ESTUDIO DE COHORTE DE DIAGNÓSTICO : J Thromb Haemost 2016 Mar;14(3):504

Detalles

⚬ based on diagnostic cohort study without blinding of results of D-dimer test

⚬ 808 patients (mean age 56 years, 70% women) with suspected pulmonary embolism (PE) were assessed
with quantitative latex agglutination (MDA D-dimer) testing
⚬ positive D-dimer test defined as ≥ 375 ng/mL D-dimer units (0.750 mcg/mL fibrinogen-equivalent units
[FEU])
⚬ reference standard was

– diagnostic imaging (computed tomographic pulmonary angiography or ventilation perfusion lung

scanning imaging) if D-dimer positive
– 3-month follow-up if D-dimer negative (or imaging negative after positive D-dimer)

⚬ 12.9% had venous thromboembolism (VTE) by reference standard (12.3% identified on imaging)
⚬ performance of MDA D-dimer with cutoff ≥ 375 ng/mL D-dimer units for detection of VTE

– sensitivity 99%
– specificity 59.5%
– positive predictive value 26.5%
– negative predictive value 99.8%

⚬ consistent results for sensitivity and specificity in subgroup analyses of patients with low, moderate, or
high clinical pretest probability based on Well's rule classification
⚬ Reference - J Thromb Haemost 2016 Mar;14(3):504

RESUMEN
● DEL ESTUDIO
El ensayo de aglutinación de látex (ensayo de dímero D de MDA) puede tener sensibilidad suficiente para
descartar tromboembolismo venoso Nivel DynaMed 2

ESTUDIO DE COHORTE DE DIAGNÓSTICO : Arch Intern Med 2001 12 de febrero; 161 (3): 447

Detalles

⚬ based on diagnostic cohort study without validation

⚬ 595 patients with suspected venous thromboembolism (VTE) had serum D-dimer testing using latex D-
dimer assay (MDA D-Dimer)
⚬ reference standard was objective VTE testing
⚬ 113 patients (19%) had VTE at 3 months (42.5% of whom had PE)
⚬ 35.9% had low pretest probability, 49.7% had moderate pretest probability, and 14.4% had high pretest
probability
⚬ overall diagnostic performance of MDA D-dimer assay for diagnosing VTE (cutoff 500 ng/mL)

– sensitivity 96%
– specificity 45%
– negative predictive value 98%
– negative likelihood ratio 0.09

⚬ similar results in patients with low or moderate clinical pretest probability

⚬ Reference - Arch Intern Med 2001 Feb 12;161(3):447

Ensayo de dímero D Tinaquant

RESUMEN
● DEL ESTUDIO
El ensayo de dímero D turbidimétrico (Tinaquant) puede tener una sensibilidad moderada pero poca
especificidad para diagnosticar la embolia pulmonar

ESTUDIO DE COHORTE : Am J Respir Crit Care Med 2002 1 de febrero; 165 (3): 345

Detalles

⚬ based on cohort study

⚬ 314 consecutive patients > 18 years old with suspected pulmonary embolism (PE) had plasma D-dimer
levels measured using Tinaquant assay
⚬ all patients also had lung perfusion scintigraphy and extensive bilateral B-mode compression
ultrasonography of leg veins
⚬ PE diagnosis was confirmed by high-probability ventilation-perfusion scan with concurrent abnormal
spiral computed tomography (CT) scan or by abnormal pulmonary angiogram
⚬ 100 patients (32%) had PE
⚬ patients were then categorized by largest involved pulmonary artery branch

– central artery (main pulmonary trunk, left or right pulmonary artery, lobar artery)
– segmental artery
– subsegmental artery

⚬ for diagnosing PE, Tinaquant assay with cutoff 500 ng/mL had overall sensitivity 81% and specificity 63%
⚬ sensitivities by largest involved pulmonary artery branch

– segmental and larger 93% (95% CI 90%-96%)

– subsegmental 50% (95% CI 44%-56%)
 ⚬ Reference - Am J Respir Crit Care Med 2002 Feb 1;165(3):345

Otros ensayos de dímero D

Ensayos cualitativos de dímero D

RESUMEN
● DEL ESTUDIO
Las pruebas cualitativas de dímero D en el punto de atención pueden ser útiles para descartar
tromboembolismo venoso en pacientes de bajo riesgo Nivel DynaMed 2

REVISIÓN SISTEMÁTICA : BMJ 2009 14 de agosto; 339: b2990 | Texto completo

Detalles

⚬ based on systematic review of studies with methodologic limitations

⚬ systematic review of 23 studies of diagnostic accuracy of point of care D-dimer tests in 13,959
outpatients (aged 38-65 years)
⚬ venous thromboembolism in 4%-51%
⚬ methodologic limitations included

– differential verification in 30%

– incorporation bias in 31%
– blinding of index and reference test results, and presence of uninterpretable test results were poorly
reported
⚬ studies reported 2 qualitative point of care D-dimer tests (SimpliRED D-dimer and Clearview Simplify D-
dimer) and 2 quantitative point of care D-dimer tests (Cardiac D-dimer and Triage D-dimer)

Table 1. Results of D-Dimer Tests

Test Pooled Pooled Likelihood Post-Test

Sensitivity Specificity Ratio of Probability
Negative of Negative
Test Test in Low-
Risk
Patients*

SimpliRED 85% 74% 0.21 (95% CI 1.1%

0.15-0.29)

Clearview 87% 62% 0.22 (95% CI 1.1%

Simplify 0.17-0.28)

Cardiac D- 96% 57% 0.07 (95% CI 0.4%

dimer 0.04-0.16)
 Test Pooled Pooled Likelihood Post-Test
Sensitivity Specificity Ratio of Probability
Negative of Negative
Test Test in Low-
Risk
Patients*

Triage D- 93% 48% 0.18 (95% CI 0.9%

dimer** 0.08-0.43)

* Low risk = 5%

** Pooled sensitivity and specificity

                                                  could not be calculated due to small sample size;

                                                  traditional sample size weighted approach used

                                                  

⚬ Reference - BMJ 2009 Aug 14;339:b2990 full-text , commentary can be found in BMJ 2009 Aug
19;339:b2799

Ensayo de dímero D SimpliRED

RESUMEN
● DEL ESTUDIO
El ensayo de dímero D SimpliRED negativo no es suficiente para descartar tromboembolismo venoso en
pacientes con sospecha clínica

ESTUDIO DE COHORTE : Ann Emerg Med 2000 Feb;35(2):121

Detalles

⚬ based on prospective cohort study

⚬ 198 consecutive adult emergency department patients with suspected venous thromboembolism (deep
vein thrombosis [DVT] or pulmonary embolism [PE]) had plasma D-dimer levels measured with
SimpliRED D-dimer assay
– DVT was diagnosed by compression ultrasonography
– PE was diagnosed by ventilation-perfusion scintigraphy followed by pulmonary angiogram with or
without lower-extremity ultrasound scan
⚬ SimpliRED assay uses antibody specific for both D-dimers and red blood cells
⚬ positive test result defined as any amount of agglutination
⚬ threshold for clinical utility set at negative predictive value of 97.5% with 95% confidence interval lower
boundary of 95%
⚬ 173 patients included in analysis
⚬ 57 patients (33%) had VTE
⚬ for diagnosing VTE, SimpliRED D-dimer assay had

– sensitivity 65% (95% CI 53%-77%)

 – negative predictive value 81% (95% CI 74%-89%)
– negative likelihood ratio 0.47 (95% CI 0.32-0.68)

⚬ Reference - Ann Emerg Med 2000 Feb;35(2):121

RESUMEN
● DEL ESTUDIO
Ensayo de dímero D SimpliRED negativo asociado con bajo riesgo de tromboembolismo venoso
sintomático en pacientes con sospecha de EP y baja sospecha clínica Nivel DynaMed 2

ENSAYO ALEATORIZADO : Ann Intern Med 2006 Jun 6;144(11):812

Detalles

⚬ based on randomized trial with wide confidence intervals

⚬ 456 patients with suspected pulmonary embolism (PE) and negative SimpliRED results received clinical
assessment using Wells 7-item prediction rule and were randomized to no additional testing vs.
additional testing
⚬ patients were assigned to 1 of 2 probability categories (low probability or moderate to high probability)
at baseline and then randomized (within these categories) to no additional diagnostic testing vs.
additional diagnostic testing
⚬ additional diagnostic testing for patients with

– low pretest probability included ventilation-perfusion lung scan followed by ultrasonography of

proximal deep veins of legs on same day, and repeat ultrasound at 7 and 14 days for nondiagnostic
lung scan
– moderate to high pretest probability included ultrasonography of proximal deep veins of legs after 7
and 14 days
⚬ rate of venous thromboembolism at 6 months

– in patients with low pretest probability (373 patients)

● 0% in no additional testing group

● 0.5% in additional testing group (mean difference [MD] -0.5%, 95% CI -3% to 1.6%)

– in patients with moderate to high pretest probability (82 patients)

● 2.4% in no additional testing group

● 0% in additional testing group (MD 2.4%, 95% CI -6.4% to 12.6%)

⚬ Reference - Ann Intern Med 2006 Jun 6;144(11):812

⚬
DynaMed Commentary

Although this trial suggests SimpliRED assay has high negative predictive value, even in 82 patients
with moderate to high clinical probability, other studies suggested lower negative predictive value
for SimpliRED assay.

RESUMEN
● DEL ESTUDIO
la combinación de una baja probabilidad previa a la prueba y un ensayo de dímero D SimpliRED negativo
puede ayudar a descartar la EP Nivel DynaMed 2

ESTUDIO DE COHORTE : Ann Intern Med 2001 17 de julio; 135 (2): 98

Detalles

⚬ based on prospective cohort study with same reference standard not applied to all patients
⚬ 946 consecutive emergency department patients with suspected pulmonary embolism (PE) and
symptoms for < 30 days had clinical assessment and D-dimer levels measured using SimpliRED whole-
blood agglutination assay
⚬ simple clinical model for assessing clinical probability of PE (total score 0-12.5 points)

– 3 points for clinical signs and symptoms of deep venous thrombosis (DVT)
– 1.5 points for heart rate > 100 beats/minute
– 1.5 points for immobilization (bed rest for ≥ 3 consecutive days) or surgery in previous 4 weeks
– 1.5 points for previous objectively diagnosed DVT or PE
– 1 point for hemoptysis
– 1 point for malignancy (patients with cancer receiving treatment, patients who stopped treatment
within past 6 months, or patients receiving palliative care)
– 3 points for likelihood of PE diagnosis being similar or higher than alternative diagnosis

⚬ low pretest probability defined as score < 2 points, high pretest probability defined as score > 6 points
⚬ patients with low pretest probability and negative D-dimer result received no further testing
⚬ all other patients received ventilation-perfusion scan
⚬ 930 patients (98%) included in analysis
⚬ prevalence of PE was 9.5%
⚬ overall negative predictive value of SimpliRED assay 97.3% (95% CI 95.8%-98.4%)
⚬ negative predictive value by clinical pre-test probability

– low pre-test probability 99.5% (95% CI 98.4%-98.4%)

– moderate pre-test probability 93.9% (95% CI 89.8%-96.7%)
– high pre-test probability 88.5% (95% CI 69.9%-97.6%)

⚬ Reference - Ann Intern Med 2001 Jul 17;135(2):98

Simplifique el ensayo de dímero D

RESUMEN
● DEL ESTUDIO
Ensayo simplificado de dímero D negativo asociado con una tasa de EP de 0.7-1.2 % entre pacientes de
bajo riesgo

ESTUDIO DE COHORTE : Chest 2006 Jun;129(6):1417 | Texto completo

Detalles

⚬ based on cohort study

⚬ 2,302 emergency department patients with suspected pulmonary embolism (PE) had clinical assessment
and D-dimer levels measured using Simplify D-dimer assay
⚬ all patients with positive D-dimer result had standard imaging workup, patients with negative D-dimer
result had imaging at physician discretion
⚬ 108 patients (4.7%) had PE at 3 months
 ⚬ for diagnosis of PE in overall cohort, Simplify D-dimer assay had

– sensitivity 80.6% (95% CI 71.8%-87.5%)

– specificity 72.5% (95% CI 70.6%-74.4%)
– negative predictive value 98.7% (95% CI 98%-99.1%)

⚬ pretest probability was determined using 3 different assessment methods (3-tiered unstructured
clinician estimate, Canadian score, and Charlotte Rule), and negative predictive values were calculated
for patients with low pretest probability
⚬ negative predictive values for Simplify D-dimer in patients with low pretest probability

– 99.3% with 3-tiered unstructured clinician estimate < 15%

– 98.8% with Canadian Score < 2
– 98.9% with Charlotte Rule Negative

⚬ Reference - Chest 2006 Jun;129(6):1417 full-text

Ensayos semicuantitativos de dímero D

RESUMEN
● DEL ESTUDIO
El ensayo de dímero D de fibrina plasmática de aglutinación de látex semicuantitativa puede tener una
sensibilidad moderada y una especificidad baja para diagnosticar la embolia pulmonar aguda

ESTUDIO DE COHORTE : Mayo Clin Proc 2004 Feb;79(2):164

Detalles

⚬ based on retrospective cohort study

⚬ 946 inpatients or outpatients with suspected acute pulmonary embolism (PE) had semiquantitative latex
agglutination plasma fibrin D-dimer assay within 4 days of computed tomography (CT) angiography
⚬ 172 patients (18%) had PE based on CT angiography
⚬ for diagnosing PE, D-dimer with cutoff > 250 ng/mL had

– sensitivity 83% (95% CI 76%-88%)

– specificity 39% (95% CI 36%-43%)
– negative predictive value 91% (95% CI 87%-94%)

⚬ Reference - Mayo Clin Proc 2004 Feb;79(2):164

Uso de ensayos de dímero D en algoritmos de diagnóstico

Algoritmos de diagnóstico

Recomendaciones

● Guía del American College of Physicians (ACP) para la evaluación de pacientes con sospecha de embolia
pulmonar aguda
⚬ para pacientes > 50 años, los umbrales de dímero D ajustados por edad (edad x 10 ng/mL) son
preferibles al límite habitual < 500 ng/mL en pacientes con baja probabilidad de embolia pulmonar (EP)
previa a la prueba que no cumplen con todos criterios PERC y en pacientes con probabilidad pretest
intermedia (los niveles de dímero D no deben obtenerse en pacientes con probabilidad pretest alta)
⚬ en pacientes con probabilidad previa a la prueba baja o intermedia de EP con un nivel de dímero D por
debajo del límite ajustado por edad, se puede descartar la EP y no se deben obtener estudios por
 imágenes (consulte Embolia pulmonar para obtener más información)
⚬ Referencia - Ann Intern Med 2015 Nov 3;163(9):701 , el resumen para pacientes se puede encontrar
en Ann Intern Med 2015 Nov 3;163(9)

● Guía de práctica clínica de la Academia Estadounidense de Médicos de Familia/Colegio Estadounidense de

Médicos (AAFP/ACP) sobre el diagnóstico actual de tromboembolismo venoso (TEV) en la atención primaria
⚬ Se recomienda el dímero D de alta sensibilidad como opción razonable en pacientes adecuadamente
seleccionados con baja probabilidad previa a la prueba de TVP o EP
⚬ prueba negativa indica baja probabilidad de tromboembolismo venoso
⚬ Referencia - Ann Fam Med 2007 Ene-Feb;5(1):57 el texto completo que respalda la revisión
sistemática se puede encontrar en Ann Fam Med 2007 Jan-Feb;5(1):63 texto completo , el
comentario se puede encontrar en J Fam Pract 2007 May;56(5):350 , el editorial se puede encontrar
en Am Fam Physician 2007 Oct 15;76(8):1116 texto completo , el comentario se puede encontrar
en Am Fam Physician 2007 Dec 1;76(11):1712

Algoritmos de diagnóstico para EP

● Evidencia • Actualizado El 5 De Enero De 2022

RESUMEN DEL ESTUDIO

las reglas de decisión clínica con puntos de corte de dímero D que dependen de la probabilidad de EP
antes de la prueba pueden evitar la obtención de imágenes en el 41%-47% de los pacientes, pero pueden
estar asociadas con un riesgo de TEV a los 3 meses del 1,8%-2,8% en pacientes a los que se les descartó
la EP por clínica. regla de decisión sola, pero en pacientes con cáncer activo, las imágenes pueden
evitarse en 17%-26% y el riesgo de TEV a los 3 meses puede ser de 3,4%-3,9% Nivel DynaMed 2

METANÁLISIS : Ann Intern Med 2021 14 de diciembre temprano en línea

Detalles

⚬ based on individual patient data meta-analysis of diagnostic cohort studies without imaging of all
patients at baseline
⚬ systematic review and individual patient data meta-analysis of 16 diagnostic cohort studies evaluating
clinical decision rules with quantitative D-dimer testing for ruling out PE in 20,553 patients
⚬ studies including only patients with low clinical pretest probability were excluded
⚬ clinical decision rules were

– Wells score plus D-dimer test with fixed (< 500 mcg/L), age-adjusted (age multiplied by 10 mcg/L in
patients > 50 years old), or clinical pretest probability-dependent threshold
– revised Geneva score plus D-dimer test with fixed, age-adjusted, or clinical pretest probability-
dependent threshold as for Wells score
– YEARS algorithm (includes D-dimer threshold dependent on clinical pretest probability)

⚬ reference standard was clinical follow-up in patients in whom PE was ruled out by clinical decision rule
or imaging
⚬ missing values were imputed
⚬ efficiency defined as number of patients who had PE ruled out by clinical decision rule alone divided by
total number of patients (likelihood of avoiding use of imaging)
⚬ failure rate defined as number of patients with confirmed VTE at baseline or follow-up divided by total
number of patients who had PE ruled out at baseline by clinical decision rule alone (3-month risk of VTE)
⚬ percent of patients with VTE at baseline or during follow-up ranged from 7.4% to 41%
⚬ likelihood of avoiding use of imaging by clinical decision rule

Table 2. Likelihood of Avoiding Use of Imaging in Overall and Subgroup Populations

Group Wells Wells Wells Revise Revise Revise YEARS

Score Score Score d d d Algori
at with with Genev Genev Genev thm
Cutoff Age- Pretes a a a
D- adjust t Score Score Score
dimer ed D- Proba with with with
500 dimer bility- Cutoff Age- Pretes
mcg/L Cutoff depen D- adjust t
dent dimer ed D- Proba
D- 500 dimer bility-
dimer mcg/L Cutoff depen
Cutoff dent
D-
dimer
Cutoff

20,553 26% 32% 47% 30% 37% 44% 41%

patient
s
(overal
l)

8,391 26% 31% 45% 30% 36% 42% 40%

male
patient
s

12,162 27% 32% 48% 31% 37% 46% 42%

female
patient
s
 2,219 9.6% 15% 26% 12% 18% 17% 21%
patient
s with
active
cancer

18,334 28% 34% 50% 33% 39% 48% 44%

patient
s
withou
t active
cancer

2,942 12% 15% 31% 21% 27% 26% 32%

patient
s with
history
of VTE

17,611 30% 36% 51% 33% 39% 48% 44%

patient
s
withou
t
history
of VTE

Abbreviation: VTE, venous thromboembolism.

⚬ 3-month risk of VTE in patients who had PE ruled out by clinical decision rule alone

Table 3. 3-month Risk of VTE in Patients Who had PE Ruled Out by Clinical Decision
Rule Alone in Overall and Subgroup Populations
Group Wells Wells Wells Revise Revise Revise YEARS
Score Score Score d d d Algori
at with with Genev Genev Genev thm
Cutoff Age- Pretes a a a
D- adjust t Score Score Score
dimer ed D- Proba at with with
500 dimer bility- Cutoff Age- Pretes
mcg/L Cutoff depen D- adjust t
dent dimer ed D- Proba
D- 500 dimer bility-
dimer mcg/L Cutoff depen
Cutoff dent
D-
dimer
Cutoff

20,553 0.36% 0.76% 2.8% 0.58% 1.1% 2.8% 1.8%

patient
s
(overal
l)

8,391 0.34% 0.57% 3.4% 0.6% 1% 3.4% 2.2%

male
patient
s

12,162 0.36% 0.89% 2.4% 0.56% 1.2% 2.4% 1.6%

female
patient
s

2,219 no 1.1% 3.9% 1.3% 2.5% 3.5% 3.4%

patient failure
s with s
active occurr
cancer ed
 18,334 0.36% 0.74% 2.7% 0.55% 1% 2.8% 1.7%
patient
s
withou
t active
cancer

2,942 0.48% 1% 3.4% 1.2% 2.5% 2.8% 3.5%

patient
s with
history
of VTE

17,611 0.33% 0.7% 2.6% 0.48% 0.87% 2.7% 1.5%

patient
s
withou
t
history
of VTE

Abbreviation: VTE, venous thromboembolism.

⚬ Reference - Ann Intern Med 2021 Dec 14 early online , editorial can be found in Ann Intern Med 2021
Dec 14 early online

RESUMEN
● DEL ESTUDIO
La prueba de dímero D sola con un límite no ajustado por edad de ≥ 750 mcg/L puede no descartar la EP
Nivel DynaMed 2

ESTUDIO DE COHORTE DE DIAGNÓSTICO : J Thromb Haemost 2017 Feb;15(2):323 | Texto completo

Detalles

⚬ based on pooled analysis of 6 diagnostic cohort studies with D-dimer testing and imaging not performed
in all patients
⚬ 7,268 hemodynamically stable patients (mean age 56 years, 58% female) with suspected acute PE were
assessed by quantitative D-dimer testing
– D-dimer testing with quantitative latex-based assay or an enzyme-linked immunosorbent assay
– abnormal D-dimer test originally defined as > 500 mcg/L using conventional threshold in 5 studies
and age-adjusted threshold in 1 study, but were post hoc reclassified according to a D-dimer cutoff ≥
750 mcg/L
 – patients with Wells score ≤ 4 and with normal D-dimer test were managed without imaging, were not
given anticoagulants, and followed for 3 months
⚬ 23% had PE by imaging or symptomatic VTE during 3-month follow-up (reference standard)
⚬ 14% had missing D-dimer values, but all patients included in overall analysis
⚬ performance of D-dimer testing with cutoff ≥ 750 mcg/L for diagnosis of PE in analysis of all patient

– sensitivity 94.5% (95% CI 91.5%-96.4%)

– specificity 55.8% (95% CI 47.6%-63.7%)
– negative predictive value 97.2% (95% CI 94.9%-98.5%)

⚬ consistent results in analysis of patients without missing D-dimer values

⚬ negative predictive values of D-dimer testing with cutoff ≥ 750 mcg/L in subgroup analyses of patients
according to Wells score
– 99.2% (95% CI 98.6%-99.5%) in patients with Wells score < 2 points (low risk)
– 95.5% (95% CI 92%-97.5%) in patients with Wells score 2-6 points (moderate risk)
– 79.3% (95% CI 53%-92.8%) in patients with Wells score > 6 points (high risk)

⚬ Reference - J Thromb Haemost 2017 Feb;15(2):323 full-text

⚬
DynaMed Commentary

This pooled analysis is meant to validate a diagnostic study suggesting quantitative latex
agglutination D-dimer test alone may rule out PE. However, the original study was performed using
quantitative latex agglutination (MDA D-dimer) testing and the studies in the current analysis used 5
different D-dimer tests. The differences in types of D-dimer tests used may make this an
inadequate validation.

RESUMEN
● DEL ESTUDIO
las reglas de decisión clínica y la gestalt clínica pueden tener una sensibilidad de alrededor del 85 % para
la embolia pulmonar y pueden tener un valor predictivo negativo del 99 % cuando se combinan con la
prueba del dímero D Nivel DynaMed 2

REVISIÓN SISTEMÁTICA : Ann Intern Med 2011 4 de octubre; 155 (7): 448

Detalles

⚬ based on systematic review limited by heterogeneity

⚬ systematic review of 52 diagnostic cohort studies evaluating clinical decision rules and clinical gestalt
with and without D-dimer testing for diagnosis of pulmonary embolism (PE) in 55,268 patients
⚬ pooled sensitivity of clinical decision rules and clinical gestalt for PE

Rule Pooled Sensitivity (95% Number of Studies

CI)* Analyzed
 Rule Pooled Sensitivity (95% Number of Studies
CI)* Analyzed

Wells, cutoff < 2 84% (78%-89%) 19

Geneva 84% (81%-87%) 5

Revised Geneva 91% (73%-98%) 4

Gestalt 85% (78%-90%) 15

* Results limited by significant heterogeneity.

⚬ failure rate of clinical decision rules and gestalt when combined with D-dimer testing

D-dimer Test Failure Rate Prevalence of PE Number of

(95% CI) Studies Analyzed

Overall 0.7% (0.5%-1%) 14% 23

Quantitative D- 0.4% (0.2%-0.7%) 21.1% 12

dimer

Qualitative D- 1% (0.8%-1.3%) 8.3% 11

dimer

⚬ Reference - Ann Intern Med 2011 Oct 4;155(7):448

RESUMEN
● DEL ESTUDIO
los algoritmos de diagnóstico que utilizan la regla de predicción clínica más la prueba del dímero D
parecen descartar la EP en pacientes con tromboembolismo venoso previo Nivel DynaMed 2

REVISIÓN SISTEMÁTICA : Thromb Haemost 2015 Feb;113(2):406

Detalles

⚬ based on systematic review of diagnostic studies with inadequate quality assessment

⚬ systematic review of 4 studies evaluating a standard diagnostic algorithm for diagnosing PE in 1,286
patients with history of venous thromboembolism
⚬ quality assessment included patient enrollment, loss to follow-up, and funding source but not other
expected criteria
⚬ standard diagnostic algorithm steps included

– clinical prediction rule (Wells rule in 3 studies and Geneva rule in 1 study)
 – high-sensitivity quantitative D-dimer test if unlikely clinical probability of PE by rule
– CT pulmonary angiography if likely clinical probability by prediction rule or D-dimer level ≥ 0.5
mcg/mL
⚬ pooled incidence of pulmonary embolism 36% within 3 months by clinical follow-up (reference standard)
⚬ pooled performance of clinical prediction rule plus D-dimer test for diagnosis of pulmonary embolism

– sensitivity 100% (95% CI 99%-100%)

– specificity 25% (95% CI 20%-30%)

⚬ 810 patients from 3 studies had CT pulmonary angiography due to likely clinical probability of PE by
prediction rule or elevated D-dimer level
⚬ for ruling out PE, CT pulmonary angiography had sensitivity range of 96%-100% and negative predictive
value range of 97%-100%
⚬ Reference - Thromb Haemost 2015 Feb;113(2):406

RESUMEN
● DEL ESTUDIO
El algoritmo PEGed puede ayudar a descartar de forma segura la EP y reducir el uso de imágenes de
tórax en comparación con el algoritmo que descarta la EP en pacientes con baja probabilidad clínica
previa a la prueba y dímero D < 500 ng/mL en pacientes adultos ambulatorios con sospecha de EP
Nivel DynaMed 2

ESTUDIO DE COHORTE DE DIAGNÓSTICO : N Engl J Med 2019 28 de noviembre; 381 (22): 2125

Detalles

⚬ based on diagnostic cohort study with limited data to evaluate patients with moderate clinical pretest
probability and negative D-dimer testing
⚬ 2,017 adult outpatients (mean age 52 years, 66% women) with suspected PE had clinical pretest
probability assessed by 7-item Wells clinical prediction rule and were managed using PEGed algorithm
⚬ PEGed algorithm

– patients with low (Wells score ≤ 4) or moderate (Wells score 2.5-6) clinical pretest probability had D-
dimer test
● no further diagnostic testing and no anticoagulant therapy in patients with Wells score ≤ 4 and D-
dimer < 1,000 ng/mL
● no further diagnostic testing and no anticoagulant therapy in patients with Wells score 2.5-6 and
D-dimer < 500 ng/mL
– all other patients evaluated by chest imaging (computer tomography pulmonary angiography or
ventilation-perfusion lung scanning) and if chest imaging positive for PE, patients were given
anticoagulant therapy
⚬ symptomatic and objectively confirmed venous thromboembolism (PE or deep-vein thrombosis) was
assessed at 90 days by telephone or in clinic
⚬ 0.9% without PE at initial diagnostic testing started anticoagulant therapy for reasons other than venous
thromboembolism, 0.6% were lost to follow-up
⚬ rates of venous thromboembolism stratified by risk category using PEGed algorithm
 Clinical D-dimer Test Number of Venous Venous
Pretest Patients Thromboem Thromboem
Probability bolism bolism
Diagnosed Diagnosed
at Initial During 90-
Testing day Follow-
up

Low Negative 1,285 0% 0%

Low Positive 467 18.6% 0.4%

Moderate Negative 40 0% 0%

Moderate Positive 178 24.1% 0%

High Not 47 40% 0%

applicable

⚬ chest imaging in 34.3% with PEGed diagnostic algorithm vs. 51.9% with standard testing (PE ruled out if
low clinical pretest probability and D-dimer < 500 ng/mL) (p < 0.05)
⚬ Reference - N Engl J Med 2019 Nov 28;381(22):2125

RESUMEN
● DEL ESTUDIO
La regla de Wells, la regla de Wells simplificada, la puntuación de Ginebra revisada y la puntuación de
Ginebra revisada simplificada tienen un rendimiento similar para descartar EP aguda en pacientes con
dímero D normal Nivel DynaMed 1

ESTUDIO DE COHORTE DE DIAGNÓSTICO : Ann Intern Med 2011 7 de junio; 154 (11): 709

Detalles

⚬ based on diagnostic cohort study

⚬ 807 consecutive patients with suspected acute PE were assessed by 4 clinical decision rules for
probability of PE
– Wells rule
– simplified Wells rule
– revised Geneva score
– simplified revised Geneva score

⚬ if all rules classified patient as PE unlikely, patient had D-dimer test

– if D-dimer normal, then PE excluded

● no treatment given
● follow-up at 3 months
 – if D-dimer abnormal, then computed tomography (CT) performed

● if PE excluded on CT, then no treatment given, patient had follow-up at 3 months

● if PE diagnosed on CT, then patient treated for PE with anticoagulant
● if CT inconclusive, then more testing

⚬ if ≥ 1 rule indicated PE likely, then CT performed

– if PE excluded on CT, then no treatment given, patient had follow-up at 3 months

– if PE diagnosed on CT, then patient treated for PE
– if CT inconclusive, then more testing

⚬ 185 patients (23%) diagnosed with PE by CT

⚬ predictive performance for prediction rules (in combination with normal D-dimer test)

– sensitivity for each rule was 99.5%

– specificity was 30% for Wells rule, 29% for modified Wells rule, 30% for revised Geneva score, 31% for
simplified revised Geneva score
– negative predictive value was 99.4%-99.5% for each rule

⚬ Reference - Ann Intern Med 2011 Jun 7;154(11):709

RESUMEN
● DEL ESTUDIO
El algoritmo YEARS descarta con seguridad la EP con una tasa de falsos negativos < 1 % y parece reducir
la necesidad de angiografía pulmonar por TC en comparación con la regla de Wells más dímero D en
pacientes con sospecha de EP Nivel DynaMed 2

ESTUDIO DE COHORTE : Lancet 2017 15 de julio; 390 (10091): 289

Detalles

⚬ based on validation cohort study with indirect comparison to performance of Wells rule
⚬ 3,465 adults with suspected pulmonary embolism were managed based on YEARS algorithm and
followed for 3 months
⚬ reference standard was predefined clinical criteria including CT pulmonary angiography for PE,
compression ultrasonography for deep vein thromboembolism (DVT), and confirmation of PE or DVT by
autopsy in case of death
⚬ YEARS algorithm uses 3 factors from Wells rule (clinical signs of DVT, hemoptysis, and pulmonary
embolism as most likely diagnosis) plus D-dimer concentrations
– if 0 YEARS factors present and

● D-dimer < 1,000 ng/mL, then pulmonary embolism excluded

● D-dimer ≥ 1,000 ng/mL, then perform CT pulmonary angiography

– if ≥ 1 YEARS factor present and

● D-dimer < 500 ng/mL, then pulmonary embolism excluded

● D-dimer ≥ 500 ng/mL, then perform CT pulmonary angiography

⚬ 85% had PE ruled out (39% after CT pulmonary angiography) and were left untreated

– 18 patients (0.61% of patients with PE ruled out, 95% CI 0.36%-0.96%) had symptomatic venous
thromboembolism (VTE) during 3-month follow-up
– 6 of these patients had fatal PE

⚬ CT pulmonary angiography not indicated in 48% using YEARS algorithm vs. 34% if patients had been
managed by standard Wells rule plus fixed D-dimer threshold of < 500 ng/mL (difference 14%, 95% CI
 12%-16%)
⚬ Reference - YEARS study (Lancet 2017 Jul 15;390(10091):289 )
⚬ derivation of YEARS rule can be found in J Thromb Haemost 2015 Aug;13(8):1428

● La puntuación de la regla de Wells ≤ 4 más la prueba cualitativa del dímero D negativa ayuda a descartar la
EP en la mayoría de los pacientes de atención primaria, pero la tasa de falsos negativos es de alrededor del
6 % en pacientes ≥ 60 años Nivel DynaMed 1

RESUMEN
⚬ DEL ESTUDIO
La puntuación de la regla de Wells ≤ 4 más la prueba cualitativa del dímero D negativa ayuda a
descartar la EP en pacientes de atención primaria Nivel DynaMed 1

ESTUDIO DE COHORTE : BMJ 2012 Oct 4;345:e6564 | Texto completo

Detalles

– based on validation cohort study

– 598 patients (mean age 48 years, range 18-91 years) with suspected pulmonary embolism (PE) in
primary care were assessed using Wells rule and had qualitative point of care D-dimer test and
followed for 3 months
– reference standard was spiral computed tomography, ventilation-perfusion scanning, pulmonary
angiography, leg ultrasonography, or clinical probability assessment as done in secondary care (with
or without D-dimer testing)
– 73 patients (12.2%) had PE
– diagnostic performance of Wells score ≤ 4 combined with negative (normal) qualitative D-dimer test
for PE
● sensitivity 94.5% (95% CI 86.6%-98.5%)
● specificity 51% (95% CI 46.7%-55.4%)
● positive predictive value 21.2% (95% CI 16.9%-26%)
● negative predictive value 98.5% (95% CI 96.3%-99.6%)
● false negative rate 1.5% (95% CI 0.4%-3.7%)

– Reference - BMJ 2012 Oct 4;345:e6564 full-text

RESUMEN
⚬ DEL ESTUDIO
La regla de Wells ≤ 4 más una prueba de dímero D negativa no descarta con seguridad la EP en
pacientes ≥ 60 años con sospecha de EP Nivel DynaMed 1

ESTUDIO DE COHORTE : J Am Geriatr Soc 2014 Nov;62(11):2136

Detalles

– based on validation cohort study

– 294 unhospitalized patients ≥ 60 years old (mean age 76 years, 44% nursing home residents) with
clinically suspected PE were assessed by Wells rule and qualitative point-of-care D-dimer test
– 28.2% had PE by computed tomography and 3-month follow-up (reference standard)
– unlikely PE defined as Wells score ≤ 4 combined with negative (normal) D-dimer test
– 5.9% of 85 patients classified as unlikely had PE (negative predictive value 94.1%)
 – lowering Wells rule cutoff to > 2 points for likely PE reduced false negative rate in patients with
normal D-dimer from 5.9% to 2.9%
– Reference - J Am Geriatr Soc 2014 Nov;62(11):2136

RESUMEN
● DEL ESTUDIO
La puntuación de la regla de Wells ≤ 4 más la prueba cuantitativa negativa del dímero D puede ayudar a
descartar la EP en la mayoría de los pacientes de atención primaria Nivel DynaMed 2

ESTUDIO DE COHORTE : J Thromb Haemost 2015 Jun;13(6):1004

Detalles

⚬ based on post hoc secondary analysis of validation cohort study

⚬ 401 patients had quantitative D-dimer test (582 patients had qualitative D-dimer test, results in study
above)
⚬ 73 patients (12.2%) of 582 total patients had PE
⚬ missing values imputed using multiple imputation techniques based on correlation between each
variable with missing values and all other variables as estimated from total subjects
⚬ diagnostic performance of Wells score ≤ 4 combined with negative (normal) quantitative D-dimer test for
PE
– sensitivity 98.6% (95% CI 92.6%-100%)
– specificity 47.2% (95% CI 43%-51.5%)
– positive predictive value 20.6% (95% CI 16.4%-24.9%)
– negative predictive value 99.6% (95% CI 97.8%-100%)
– false negative rate 0.4% (95% CI 0%-2.2%)

⚬ Reference - J Thromb Haemost 2015 Jun;13(6):1004

RESUMEN
● DEL ESTUDIO
La regla de Wells ≤ 4 más una prueba de dímero D cuantitativa negativa puede ayudar a descartar EP en
pacientes de cuidados agudos Nivel DynaMed 2

ESTUDIO DE COHORTE DE DIAGNÓSTICO : JAMA 2006 11 de enero; 295 (2): 172

Detalles

⚬ based on diagnostic cohort study without independent validation cohort

⚬ 3,306 adults (57% female) with clinically suspected PE (sudden onset dyspnea, sudden deterioration of
exisiting dyspnea, or sudden onset pleuritic chest pain without other apparent cause) were assessed
– patients presenting to emergency department and inpatients were included
– patients were excluded for unfractionated or low-molecular-weight heparin treatment with
therapeutic doses for > 24 hours, life expectancy < 3 months, allergy to IV contrast agents, renal
insufficiency, or hemodynamic instability
⚬ reference standard was CT angiography or 3-month follow-up
⚬ all patients were assessed with Wells clinical decision rule used to determine clinical probability of PE

– 3 points if clinical signs of DVT (leg swelling and pain with palpation of deep veins)
– 3 points if alternative diagnosis less likely than PE
– 1.5 points if heart rate > 100/minute
– 1.5 points if immobilization > 3 days or surgery in previous 4 weeks
 – 1.5 points if previous PE or DVT
– 1 point if hemoptysis
– 1 point if malignancy with treatment in last months

⚬ PE considered unlikely if total ≤ 4 points, likely if > 4 points

⚬ 2,206 patients with PE unlikely (Wells score ≤ 4) had D-dimer test

– PE excluded in 1,057 (32% of total population) with D-dimer ≤ 500 ng/mL

– 97.3% with PE excluded were followed for 3 months without anticoagulation, 5 (0.5%) had PE or DVT,
no PE deaths
⚬ 1,149 with PE unlikely (Wells score < 4), but abnormal D-dimer results and 1,100 patients with PE likely
(Wells score > 4) had CT pulmonary angiography
– 1,505 patients (45.5% of total population) had PE excluded on CT angiography
– 95.4% with PE excluded were followed for 3 months without anticoagulation, 18 patients (1.3%) had
thromboembolism including 7 fatal PEs, 11 nonfatal PEs, and 8 DVTs
– 674 patients (20.4% of total population) had PE on CT angiography
– 50 patients did not have CT angiography

⚬ 98.5% completed treatment algorithm

⚬ 97.9% had treatment decision based on algorithm
⚬ Reference - JAMA 2006 Jan 11;295(2):172 , editorial can be found in JAMA 2006 Jan 11;295(2):213 ,
commentary can be found in JAMA 2006 Jun 14;295(22):2603

RESUMEN
● DEL ESTUDIO
La estrategia diagnóstica que usa la prueba ELISA de dímero D más TC multidetector es más rentable y
funciona tan bien como la estrategia que usa ELISA dímero D más ultrasonido de compresión venosa
más TC multidetector para la tasa de detección de TEP y bajas tasas de eventos tromboembólicos
después de descartar TEP Nivel DynaMed 1

ENSAYO ALEATORIZADO : Lancet 2008 19 de abril; 371 (9621): 1343

Detalles

⚬ based on randomized trial

⚬ 1,819 consecutive outpatients with clinically suspected pulmonary embolism randomized to diagnostic
strategy using ELISA D-dimer test plus multidetector CT vs. diagnostic strategy using ELISA D-dimer test
plus venous compression ultrasound of legs plus multidetector CT
⚬ 1,693 patients who had complete follow-up and were not excluded for receiving anticoagulant
medication for other reason were included in per-protocol analysis
⚬ all patients had clinical probability assessment prior to randomization by revised Geneva score

– low to intermediate probability in 1,643 patients

– high probability in 50 patients

⚬ in D-dimer plus multidetector CT strategy (D-dimer/CT)

– if low to intermediate clinical probability of PE

● if negative D-dimer test, PE ruled out

● if D-dimer level > 500 ng/mL, then multidetector CT; anticoagulant treatment if positive for PE

– if high clinical probability of PE

● no D-dimer test
 ● CT and treatment if positive for PE
● if CT negative or inconclusive, then ventilation-perfusion scintigraphy or pulmonary angiography
or both
⚬ in D-dimer plus ultrasound plus multidetector CT strategy (D-dimer/US/CT)

– if low to intermediate clinical probability of PE

● if negative D-dimer test, PE ruled out

● if D-dimer concentration > 500 ng/mL, then venous compression ultrasound of both legs

⚬ if proximal DVT, then patient given anticoagulant drugs

⚬ if no proximal DVT then multidetector CT; anticoagulant treatment if positive for PE

– if high clinical probability of PE

● no D-dimer test
● ultrasound and treatment if positive for DVT
● CT if ultrasound negative and treatment if CT positive for PE
● if CT negative or inconclusive, then ventilation-perfusion scintigraphy or pulmonary angiography
or both
⚬ primary outcome was 3-month risk of thromboembolism in patients left untreated after exclusion of PE
by diagnostic strategy
⚬ comparing D-dimer/CT strategy vs. D-dimer/US/CT strategy

– prevalence of PE in intention-to-diagnose population 20.6% vs. 20.6% (not significant)

– patients excluded from primary per-protocol analysis for protocol violations or other criteria 7.2% vs.
6.7%
– prevalence of PE in per-protocol analysis 21.5% vs. 20.7% (not significant)
– 3-month risk of venous thromboembolism among 1,276 patients without PE and not treated with
anticoagulants 0.3% (2 cases) vs. 0.3% (2 cases) (not significant)
– all-cause mortality 2.7% vs. 4.5% in per-protocol analysis
– no differences in adverse events

⚬ proximal deep vein thrombosis on ultrasound detected only 53 (30%) of 177 patients with venous
thromboembolism in D-dimer/US/CT group
⚬ D-dimer/CT strategy cost 24% less in per-protocol analysis (p < 0.05), 21% less in intention-to-diagnose
analysis (p < 0.05)
⚬ Reference - Lancet 2008 Apr 19;371(9621):1343 , editorial can be found in Lancet 2008 Apr
19;371(9621):1312 , commentary can be found in Lancet 2008 Aug 9;372(9637):447 , ACP J Club
2008 Sep 16;149(3):13

Límite de dímero D ajustado por edad para la predicción de PE

RESUMEN
● DEL ESTUDIO
El límite de dímero D ajustado por edad para edad ≥ 50 años más una probabilidad clínica baja descarta
la embolia pulmonar en más pacientes que el límite de dímero D fijo de 500 mcg/L más una probabilidad
clínica baja Nivel DynaMed 1

ESTUDIO DE COHORTE DE DIAGNÓSTICO : JAMA 2014 19 de marzo; 311 (11): 1117

Detalles

⚬ based on diagnostic cohort

 ⚬ 3,346 patients presenting to emergency department with suspected pulmonary embolism were
evaluated by quantitative, high-sensitivity D-dimer assays (ELISA or latex-enhanced turbidimetric), and
clinical probability assessment and followed for 3 months
– in patients < 50 years old, D-dimer cutoff was 500 mcg/L
– in patients ≥ 50 years old, age-adjusted D-dimer cutoff was age multiplied by 10
– clinical probability assessment performed with simplified revised Geneva score or 2-level Wells score
for pulmonary embolism (nonhigh or unlikely clinical probability with score ≤ 4 on either assessment)
⚬ 87.2% of patients had nonhigh or unlikely clinical probability

– 28.2% had D-dimer level < 500 mcg/L

– 11.6% had D-dimer level > 500 mcg/L but < age-adjusted cutoff

⚬ 64.9% of patients with high or likely clinical probability or D-dimer levels > age-adjusted cutoff had
computed tomography pulmonary angiography
⚬ 19% had pulmonary embolism
⚬ failure rate defined as rate of adjudicated symptomatic thromboembolic events during 3-month follow-
up period among patients not treated with anticoagulants based on negative test results
⚬ failure rates at 3 months

– 0.1% of 810 patients with D-dimer levels < 500 mcg/L

– 0.3% of 331 patients with D-dimer level > 500 mcg/L but < age-adjusted cutoff
– 0% of 195 patients ≥ 75 years old with D-dimer level > 500 mcg/L but < age-adjusted cutoff
– 0.5% of 1,481 patients with negative computed tomography pulmonary angiography

⚬ Reference - ADJUST-PE study (JAMA 2014 Mar 19;311(11):1117 ), correction can be found in JAMA 2014
Apr 23-30;311(16):1694, correction can be found in JAMA. 2014 Apr 23-30;311(16):1694
⚬ derivation of age-adjusted D-dimer cutoff with 2 retrospective validation cohorts can be found in BMJ
2010 Mar 30;340:c1475 full-text , commentary can be found in Nat Rev Cardiol 2010 Jul;7(7):358

RESUMEN
● DEL ESTUDIO
Los valores de corte de dímero D ajustados por edad parecen más específicos que los valores de corte de
dímero D convencionales en pacientes > 50 años con probabilidad clínica no alta de tromboembolismo
venoso Nivel DynaMed 2

REVISIÓN SISTEMÁTICA : BMJ 2013 3 de mayo; 346: f2492 | Texto completo

Detalles

⚬ based on systematic review limited by clinical heterogeneity

⚬ systematic review of 5 diagnostic studies (including 7 cohorts with PE and 6 cohorts with DVT) comparing
D-dimer test using conventional vs. age-adjusted cutoff values in 6,969 patients > 50 years old with
suspected venous thromboembolism (VTE)
– conventional cutoff was D-dimer < 500 mcg/L
– age-adjusted cutoff was age in years multiplied by 10 mcg/L for patients > 50 years old

⚬ non-high clinical probability of VTE defined as

– Wells score ≤ 4 or Geneva score ≤ 10 in studies with patients with suspected pulmonary embolism
– Wells score ≤ 2 or ≤ 1 in studies with patients with suspected DVT

⚬ reference tests to rule out VTE and D-dimer assay methodology varied across studies
⚬ median VTE prevalence range 12.3%-21.5%
 ⚬ pooled specificity of D-dimer comparing age-adjusted cutoff vs. conventional cutoff

– 35.2% vs. 14.7% in patients ≥ 80 years old (p < 0.001)

– 44.2% vs. 24.5% in patients aged 71-80 years (p < 0.001)
– 49.5% vs. 39.4% in patients aged 61-70 years (p < 0.001)
– 62.3% vs. 57.6% in patients aged 51-60 years (p = 0.005)

⚬ sensitivities ranged from 97%-99.4% with age-adjusted cutoffs and 98.7%-100% with conventional
cutoffs (no significant differences)
⚬ Reference - BMJ 2013 May 3;346:f2492 full-text

RESUMEN
● DEL ESTUDIO
el valor de corte del dímero D ajustado por edad puede descartar la EP en más pacientes que el valor de
corte del dímero D fijo sin aumentar la tasa de falsos negativos en pacientes con baja probabilidad
clínica de EP Nivel DynaMed 2

REVISIÓN SISTEMÁTICA : Ann Intern Med 2016 16 de agosto; 165 (4): 253

Detalles

⚬ based on systematic review of diagnostic studies with wide confidence intervals

⚬ systematic review with individual patient data meta-analysis of 6 studies evaluating Wells rule plus age-
adjusted vs. fixed D-dimer cutoff for ruling out PE in 7,268 patients with suspected PE (63% > 50 years
old)
– age-adjusted D-dimer threshold was age × 10 mcg/L in patients > 50 years old
– D-dimer fixed threshold was < 500 mcg/L
– D-dimer assays included both ELISA and latex-based assays

⚬ mean prevalence of PE 22% across studies by CT pulmonary angiography or ventilation-perfusion scan

⚬ patients with low clinical probability of PE (Wells score ≤ 4) and negative D-dimer results were followed
for 3 months without imaging or anticoagulant therapy
⚬ outcome definitions

– efficiency defined as proportion of patients with low clinical probability of PE plus negative D-dimer
(PE ruled out)
– false-negative defined as symptomatic VTE or nonfatal or fatal PE in 3-month follow-up, or PE
confirmed at baseline in patients with low clinical probability of PE plus negative D-dimer, with false-
negative rate < 3% at limit of 95% CI considered safe
⚬ efficiency comparing age-adjusted D-dimer cutoff vs. fixed D-dimer cutoff

– 32.6% (95% CI 25%-42%) vs. 28% (95% CI 21%-37%) overall

– 28% vs. 22.4% in subgroup of 3,398 patients aged 51-74 years (p < 0.05)
– 20.3% vs. 8.4% in subgroup of 1,200 patients ≥ 75 years old (p < 0.05)

⚬ age-adjusted D-dimer cutoff also associated with significantly increased efficiency in subgroups of
patients with and without active cancer, with and without COPD, and with and without previous VTE
⚬ overall false-negative rate was 0.94% (95% CI 0.6%-1.5%) with age-adjusted D-dimer cutoff vs. 0.65%
(95% CI 0.4%-1.1%) with fixed D-dimer cutoff (not significant), but statistical power limited due to low
event rates
⚬ Reference - Ann Intern Med 2016 Aug 16;165(4):253
● las preocupaciones en torno a la estandarización de las pruebas de dímero D ajustadas por edad se
pueden encontrar en Ann Intern Med 2017 Mar 7;166(5):361

Información adicional

RESUMEN
● DEL ESTUDIO
la sensibilidad del ensayo de dímero D para el tromboembolismo venoso agudo podría ser menor si se
usa > 6 días después del inicio de los síntomas Nivel DynaMed 2

ESTUDIO DE COHORTE : J Thromb Thrombolysis 2011 Jan;31(1):1

Detalles

⚬ based on retrospective cohort study without direct reporting of test sensitivity

⚬ 734 patients with single quantitative turbidimetric D-dimer assay (D-dimer Plus) result done in
emergency department for evaluation of suspected acute venous thromboembolism and results on
objective imaging were evaluated
⚬ 197 patients (27%) had acute venous thromboembolism on Doppler ultrasound, lung scan, or
computerized tomography angiography
⚬ among patients with venous thromboembolism, mean D-dimer levels were

– 785-789 mcg/L at 2-4 days after symptom onset

– 427-438 mcg/L at 5-12 days after symptom onset
– 383 mcg/L at > 12 days after symptom onset

⚬ among patients without venous thromboembolism, mean D-dimer levels were 183-198 mcg/L at 2-6
days after symptom onset and 237-248 mcg/L at ≥ 7 days after symptom onset
⚬ receiver operating curve statistics (which measures overall diagnostic accuracy and not test sensitivity
alone) was lower for D-dimer assay > 6 days after symptom onset
⚬ Reference - J Thromb Thrombolysis 2011 Jan;31(1):1

⚬
DynaMed Commentary

The authors do not report the test sensitivity. They only compare average levels of D-dimer at
different times from symptom onset. What is more clinically important would be to know how
many patients, if any, would have been missed (false negatives) at the different time periods.
Another article suggests cutoffs for D-dimer Plus of either 130 mcg/L or 79 mcg/L (Br J Haematol
2005 Mar;128(6):842 ).

● una revisión que evalúa el rendimiento de las pruebas de dímero D para diagnosticar la embolia pulmonar
en pacientes mayores se puede encontrar en J Am Geriatr Soc 2005 Jun;53(6):1039

Factores asociados con el aumento de los niveles de dímero D

RESUMEN
● DEL ESTUDIO
múltiples factores asociados con resultados falsos positivos de dímero D en pacientes evaluados por
sospecha de embolia pulmonar

ESTUDIO DE COHORTE : Acad Emerg Med 2010 Jun;17(6):589 | Texto completo

Detalles

⚬ based on prospective cohort study

⚬ 4,346 patients (mean age 48 years) were evaluated for pulmonary embolism with D-dimer testing
⚬ factors significantly associated with false positive results included

– age ≥ 60 years
– female sex
– black or African American race
– cocaine use
– immobility
– coronary artery disease
– rheumatoid arthritis
– systemic lupus
– hemodialysis
– active malignancy
– sickle cell disease or trait
– pregnancy
– recent surgery
– venous thromboembolism not currently being treated

⚬ Reference - Acad Emerg Med 2010 Jun;17(6):589 full-text

● factores asociados con el aumento de los niveles de dímero D

⚬ condiciones patológicas

– malignidad
– trauma
– preeclampsia
– coagulación intravascular diseminada (CID)
– anemia drepanocítica
– tromboembolismo arterial
– Tromboembolismo venoso
– fibrilación auricular
– El síndrome coronario agudo
– carrera
– hemorragia digestiva alta aguda

⚬ otros factores

– mayor edad
– movilidad limitada
– el embarazo
– estado postoperatorio
– fumar cigarrillos
– raza negra
 ⚬ Referencia - Emerg Med J 2003 Jul;20(4):319 PDF

Niveles de dímero D para el pronóstico

RESUMEN
● DEL ESTUDIO
El dímero D < 250 mg/dL después del curso de anticoagulación oral para el tromboembolismo venoso
idiopático predice un menor riesgo de recurrencia Nivel DynaMed 1

ESTUDIO DE COHORTE : JAMA 2003 27 de agosto; 290 (8): 1071

Detalles

⚬ based on prospective cohort study

⚬ 610 adults with first spontaneous venous thromboembolism (38.4% with PE) were treated with oral
anticoagulants for at least 3 months, then had D-dimer levels measured shortly after anticoagulant
discontinuation
⚬ mean follow-up 38 months
⚬ risk of recurrent venous thromboembolism at 2 years was 3.7% among 209 patients with D-dimer < 250
mg/dL and 11.5% among patients with D-dimer > 250 mg/dL
⚬ risk of recurrent thromboembolism during the study was 7.7% among patients with D-dimer < 250
mg/dL and 14.3-18.6% among patients with D-dimer > 250 mg/dL
⚬ Reference - JAMA 2003 Aug 27;290(8):1071 , commentary can be found in JAMA 2003 Dec
24;290(24):3192 , J Fam Pract 2004 Jan;53(1):20 , ACP J Club 2004 Mar-Apr;140(2):50

RESUMEN
● DEL ESTUDIO
la anticoagulación > 3 meses puede reducir el riesgo de tromboembolismo venoso recurrente en
pacientes con niveles anormales de dímero D Nivel DynaMed 2

ENSAYO ALEATORIZADO : N Engl J Med 2006 Oct 26;355(17):1780 | Texto completo

Detalles

⚬ based on randomized trial without allocation concealment or blinding

⚬ 608 patients ages 18-85 years with first episodes of symptomatic, unprovoked venous
thromboembolism (DVT and/or PE) who completed at least 3 months of anticoagulation with oral
vitamin K antagonist (warfarin or acenocoumarol to target INR 2-3) underwent D-dimer testing 1 month
after stopping anticoagulant
⚬ mean follow-up 1.4 years, range 9-18 months
⚬ 223 patients (37%) with abnormal D-dimer assay were randomized to resume vs. discontinue
anticoagulation
⚬ comparing patients resuming anticoagulation vs. discontinuing anticoagulation

– recurrent thromboembolism in 1.9% vs. 15% (p = 0.02, NNT 9)

– episodes of major bleeding 1 vs. 0

⚬ Reference - PROLONG study (N Engl J Med 2006 Oct 26;355(17):1780 full-text ), correction can be
found in N Engl J Med 2006 Dec 28;355(26):2797, commentary can be found in N Engl J Med 2007 Jan
25;356(4):421 and in ACP J Club 2007 Mar-Apr;146(2):29
⚬ presence of comorbidities does not appear to increase risk of recurrent venous
thromboembolism (VTE) in analysis adjusted for abnormal D-dimer
 DynaMed Level 2

– based on extension of PROLONG study

– patients were assessed for comorbidities at time of vitamin K antagonist withdrawal including

● coronary heart disease, peripheral arterial disease, cerebrovascular disease

● chronic inflammatory bowel disease
● COPD
● autoimmune disease
● diabetes
● arterial hypertension
● dyslipidemia

– 51% had ≥ 1 comorbidity

– mean follow-up 2.6 years
– abnormal D-dimer test in 44% with comorbidities vs. 29% without comorbidities (p = 0.0003)
– comparing patients with vs. without comorbidities in analysis of 483 patients who did not resume
anticoagulation
● VTE recurrence in 24.6% vs. 21.3% in patients with abnormal D-dimer (not significant)
● VTE recurrence in 14.3% vs. 10.8 in patients with normal D-dimer (not significant)

– Reference - Thromb Haemost 2010 Jun;103(6):1152

RESUMEN
● DEL ESTUDIO
las pruebas repetidas de dímero D después de suspender la terapia anticoagulante pueden identificar a
los pacientes con riesgo de recurrencia

ESTUDIO DE COHORTE : Sangre 2010 21 de enero; 115 (3): 481

Detalles

⚬ based on prospective cohort study

⚬ 355 patients who had stopped anticoagulation therapy for unprovoked venous thromboembolism and
had normal D-dimer 1 month after stopping therapy had repeated D-dimer testing every 2 months for 1
year
⚬ patients with abnormal D-dimer levels at 3 months and thereafter were at increased risk for recurrence
vs. patients with normal D-dimer levels at 3 months and thereafter (p = 0.002)
⚬ Reference - Blood 2010 Jan 21;115(3):481

RESUMEN
● DEL ESTUDIO
la edad del paciente y el momento y el punto de corte del dímero D no parecen afectar el rendimiento del
dímero D para evaluar el riesgo de tromboembolismo venoso recurrente (TEV) después de la
interrupción de la anticoagulación

METANÁLISIS DE DATOS DE PACIENTES INDIVIDUALES : Ann Intern Med 2010 Oct 19;153(8):523

Detalles

⚬ based on pooled analysis of individual patient data

⚬ pooled analysis of 1,818 patients from 7 studies (2 randomized trials, 5 prospective cohorts)
 ⚬ mean follow-up 26.9 months after end of anticoagulation was stopped, and the median follow-up was
22.4 months (range, 0.9 to 115 months)
⚬ 826 patients (45.4%) had positive postanticoagulation D-dimer test
⚬ mean timing of D-dimer test was 38.5 days after end of anticoagulation
⚬ comparing annualized risk per 100 patient years of recurrent VTE for positive vs. negative d-dimer

– for end of coagulation

● within 3 weeks 8.2 vs. 2 in analysis of 220 patients

● 3-5 weeks 10.2 vs. 4.2 in analysis of 1,028 patients
● > 5 weeks 7.4 vs. 4.6 in analysis of 365 patients

– for patient age

● ≤ 65 years old 8.2 vs. 3.3 in analysis of 961 patients

● > 65 years old 9.4 vs. 4.9 in analysis of 652 patients

⚬ no significant differences in test performance for d-dimer cutpoints of 500 mcg/L vs. 250 mcg/L
⚬ Reference - Ann Intern Med 2010 Oct 19;153(8):523

RESUMEN
● DEL ESTUDIO
en pacientes con resultados negativos de dímero D después de 4 a 8 meses de terapia anticoagulante
(warfarina) para el primer tromboembolismo venoso (TEV) no provocado, se notificó TEV recurrente en
un 6,7 % por paciente-año en general, con mayor recurrencia en hombres Nivel DynaMed 3

ENSAYO NO CONTROLADO : Ann Intern Med 6 de enero de 2015; 162 (1): 27

Detalles

⚬ based on uncontrolled trial

⚬ 410 adults ≤ 75 years old with first unprovoked proximal deep venous thrombosis or pulmonary
embolism who had completed 3-7 months of anticoagulant therapy (warfarin) had repeat D-dimer test
after 1 month (while still receiving anticoagulant therapy)
– patients with a positive result continued anticoagulant therapy indefinitely
– patients with a negative result stopped therapy and had a second D-dimer test 1 month later; if the
second test result was positive anticoagulant therapy restarted, if negative, anticoagulation therapy
discontinued indefinitely
⚬ mean follow-up of 2.2 years
⚬ in 319 patients who had 2 negative D-dimer results and did not restart anticoagulant therapy, rate of
recurrent VTE per patient-year
– 6.7% overall (42 of 319 patients)
– 9.7% in men (33 of 180 men)
– 5.4% in women with VTE not associated with estrogen therapy (9 of 81 women)
– 0% in women with VTE associated with estrogen therapy (0 of 58 women)

⚬ Reference - Ann Intern Med 2015 Jan 6;162(1):27 , commentary can be found in Ann Intern Med 2015
May 5;162(9):670

RESUMEN
● DEL ESTUDIO
La puntuación de riesgo del dímero D, la edad, el sexo y la terapia hormonal (DASH) puede ayudar a
predecir la recurrencia en pacientes con tromboembolismo venoso (TEV) no provocado Nivel DynaMed 2
ESTUDIO DE COHORTE : J Thromb Haemost 2012 Jun;10(6):1019

Detalles

⚬ based on retrospective cohort study without external validation

⚬ derivation cohort included 1,818 patients (mean age 62 years) with first episode of unprovoked VTE
treated with vitamin K antagonists for ≥ 3 months and followed for median 22 months
⚬ VTE recurred in 13%
⚬ DASH prediction score based on 4 risk factors significantly associated with VTE recurrence with points
assigned to each (score range -2 to +4 points)
– +2 points for abnormal D-dimer (≥ 500 ng/mL fibrinogen equivalent units) after stopping
anticoagulation
– +1 point for age ≤ 50 years
– +1 point for male sex
– -2 points for woman receiving hormonal therapy at time of initial VTE

⚬ recurrence of VTE in

– 4.7% of 43 patients with -2 points

– 2.6% of 156 patients with -1 point
– 5.2% of 249 patients with 0 points
– 8.8% of 491 patients with 1 point
– 14.1% of 454 patients with 2 points
– 22.7% of 361 patients with 3 points
– 48% of 64 patients with 4 points

⚬ Reference - J Thromb Haemost 2012 Jun;10(6):1019

⚬ DASH score helps predict risk of recurrence in patients with first unprovoked VTE after withdrawal of
anticoagulant in patients ≤ 65 years old
DynaMed Level 1

– based on validation cohort study

– 827 patients (mean age 55 years, 100% White) with first episode of unprovoked VTE and
anticoagulant withdrawal after ≥ 3-month treatment with vitamin K antagonist or direct oral
anticoagulant were assessed by DASH risk score
● all included patients had D-dimer measured 20-40 days after anticoagulant withdrawal and were
followed for ≥ 3 months
● patients with VTE associated with hormonal therapy were included

– 12.1% had recurrent VTE recurrence during median 25.2 months of follow-up; annualized recurrence
rate 4.8%
– rate of recurrent VTE by DASH score

DASH Score Observed VTE Observed Number of

Rate at 2 Years Annualized VTE Patients
Rate

≤ -1 point 0.7% 0.5% 147

 DASH Score Observed VTE Observed Number of
Rate at 2 Years Annualized VTE Patients
Rate

0 points 5.9% 2.4% 111

1 point 8.4% 3.9% 290

2 points 11.1% 6.4% 186

3 points 15.2% 10.8% 83

4 points 31.4% 19.9% 10

Abbreviations: DASH, D-dimer, age, sex, hormonal therapy; VTE, venous thromboembolism.

– DASH score had lower discrimination in patients > 65 years old compared to patients ≤ 65 years old
(c-statistic 0.54 vs. 0.72)
– risk of recurrent VTE was < 5% in patients ≤ 65 years old with low risk (DASH score ≤ 1), but all DASH
scores had > 5% risk in patients > 65 years old
– Reference - J Thromb Haemost 2017 Oct;15(10):1963

–
DynaMed Commentary

Authors state that patients with DASH score ≤ 1 may be considered for suspension of
anticoagulation because of low annualized recurrence rate (3.5%, 95% CI 2.5-4.7). However,
further studies are needed to validate this approach.

Directrices y recursos
Pautas

● La guía de práctica clínica de la Academia Estadounidense de Médicos de Familia/Colegio Estadounidense

de Médicos (AAFP/ACP) sobre el diagnóstico actual de tromboembolismo venoso en la atención primaria se
puede encontrar en Ann Fam Med 2007 Jan-Feb;5(1):57 texto completo , también publicado en Ann
Intern Med 2007 Mar 20;146(6):454 , el resumen se puede encontrar en Am Fam Physician 2007 Oct
15;76(8):1225 , la revisión sistemática de apoyo se puede encontrar en Ann Fam Med 2007 Jan-
Feb;5(1):63 texto completo

Revisar articulos
● revisión de una prueba en contexto: el dímero D se puede encontrar en J Am Coll Cardiol 2017 Nov
7;70(19):2411

● se puede encontrar una revisión del uso clínico del ensayo de dímero D en Mayo Clin Proc 2003
Nov;78(11):1385

● una revisión del dímero D plasmático en el diagnóstico de tromboembolismo venoso se puede encontrar
en Arch Intern Med 2002 Apr 8;162(7):747 , el comentario se puede encontrar en Arch Intern Med 2003
Jan 27;163(2):246

Referencias
Proceso editorial de DynaMed

● Los temas de DynaMed son creados y mantenidos por el equipo editorial y el proceso de DynaMed .

● Todos los miembros del equipo editorial y los revisores han declarado que no tienen intereses financieros
ni de otro tipo relacionados con este tema, a menos que se indique lo contrario.

● El contenido de DynaMed incluye actualizaciones de cambio de práctica, con el apoyo de nuestros socios,
McMaster University y F1000.

Agradecimientos especiales

● Los temas de DynaMed se escriben y editan a través de los esfuerzos de colaboración de las personas
mencionadas anteriormente. Los editores adjuntos, los editores de sección y los editores de temas están
activos en la práctica médica clínica o académica. Los editores de recomendaciones participan activamente
en el desarrollo y/o evaluación de las guías.

● Definiciones de funciones del equipo editorial

Los editores de temas definen el alcance y el enfoque de cada tema formulando un

conjunto de preguntas clínicas y sugiriendo pautas importantes, ensayos clínicos y otros
datos que deben abordarse dentro de cada tema. Los editores de temas también sirven
como consultores para el equipo editorial interno de DynaMed durante el proceso de
redacción y edición, y revisan los borradores finales de los temas antes de su
publicación.

Los editores de sección tienen responsabilidades similares a las de los editores de temas,
pero tienen un rol más amplio que incluye la revisión de múltiples temas, la supervisión
de los editores de temas y la vigilancia sistemática de la literatura médica.

Los editores adjuntos son empleados de DynaMed y supervisan los grupos editoriales
internos de DynaMed. Cada uno es responsable de todo el contenido publicado dentro
de ese grupo, incluida la supervisión del desarrollo del tema en todas las etapas del
proceso de redacción y edición, la revisión final de todos los temas antes de la
publicación y la dirección de un equipo interno.
como citar

Biblioteca Nacional de Medicina, o "estilo Vancouver" (Comité Internacional de Editores de Revistas Médicas):

● Dyna Med [Internet]. Ipswich (MA): Servicios de información de EBSCO. 1995 - . registro n.º T114964 ,
prueba de dímero D para embolia pulmonar ; [actualizado el 30 de noviembre de 2018 , lugar citado
fecha citada aquí ]. Disponible en https://www.dynamed.com/topics/dmp~AN~ T114964 . Se requiere
registro e inicio de sesión.

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