Follow-up VTE

Beoordeeld: 23-09-2025

Uitgangsvraag

Hoe dienen patiënten met een VTE opgevolgd te worden?

Aanbeveling

Standaardiseer de follow-up van veneuze trombo-embolie om een goed en volledig beeld te krijgen van de aanwezigheid van de in deze module beschreven relevante complicaties van veneuze trombo-embolie die de kwaliteit van leven negatief beïnvloeden: Posttrombotisch syndroom (PTS, na DVT), CTEPH/CTEPD zonder PH (na longembolie) en psychosociale complicaties.

Een goede timing hiervoor is rond het drie maanden follow-up moment.
Geef ten minimale aandacht aan functionele beperkingen, benauwdheid en psychosociale impact, en - bij patiënten met een diep veneuze trombose – het post trombotisch syndroom.
Maak hiervoor bij voorkeur gebruik van PROMS en de Villalta score: daarmee worden deze symptomen reproduceerbaar en zo objectief mogelijk vastgelegd, en kan beloop ervan door de tijd en de effecten van behandeling goed worden gemonitord.

Patiënten met PTS

Behandel patiënten met aangetoonde PTS initieel met compressietherapie en bewegingstherapie.

Patiënten die aanhoudend benauwd zijn of inspanningsbeperking hebben

Voer aanvullende diagnostiek uit om chronische trombo-embolische pulmonale hypertensie/ziekte (CTEPH/CTEPD zonder PH) uit te sluiten en volg hierbij de volgende stappen, namelijk:

1. Verricht eerst een ECG en (NT-pro) BNP-bloedtest (en indien afwijkend, een echocardiografie) of primair een echocardiografie;

2. Indien er geen aanwijzingen zijn voor pulmonale hypertensie en er geen evidente andere verklaring is voor de klachten: voer een cardiopulmonale inspanningstest (CPET) uit.

3. Indien er aanwijzingen zijn voor CTEPH/CTEPD zonder PH bij echocardiografie of CPET of anderszins: beeldvorming van de pulmonale vaatboom/perfusie is geïndiceerd:

Verwijs patiënten met CTEPH/CTEPD zonder PH door naar een expertisecentrum.
Indien er geen sprake is van CTEPH/CTEPD zonder PH: overweeg om cardiopulmonale revalidatie in te zetten.

Patiënten met een vastgestelde relevante angststoornis of depressie

Zet een adequate behandeling in, bij voorkeur via de eerste lijn.

Overwegingen

Voor- en nadelen van de interventie en de kwaliteit van het bewijs

Voor deze module is er gekeken naar de impact van verschillende lange termijn complicaties van veneuze trombo-embolie (VTE) op kwaliteit van leven. De gegevens hierover zijn verzameld in observationeel onderzoek, voornamelijk uitgevoerd in Nederland, Canada en Scandinavië. Uit de narratieve review van in totaal tien studies (uit een selectie van de 106 studies uit de ICHOM-analyse (Gwodz, 2022), see Evidence Tables, Table ICHOM-studies that reported on the outcome quality of life) die keken naar chronische aandoeningen die kunnen ontstaan na een VTE, bleek dat het merendeel van deze aandoeningen consistent geassocieerd is met mindere kwaliteit van leven. De studies gaven niet genoeg informatie om te toetsen of dit verschil ook klinisch relevant is (Tabel 5).

In de uiteindelijke aanbeveling worden de gegevens uit de literatuuranalyse in een context geplaatst die aansluit op de dagelijkse praktijk. Het is ondoenlijk om voor alle mogelijke aanhoudende symptomen een aparte PICO te schrijven en tot een evidence based advies te komen over de te volgen strategie. Daarom is gekozen gebruik te maken van (inter)nationale consensus en recente internationale richtlijnen over het te voeren beleid (Delcroix, 2021; Humbert, 2022; Klok, 2022; Konstantinides, 2022).

Algemene opmerking over subgroepen

Deze module is geschreven zonder rekening te houden met specifieke subgroepen, zoals de oudere en/of kwetsbare patiënt of de patiënt met levensbeperkende comorbiditeit. Bewijs voor de beste aanpak in deze en andere subgroepen ontbreekt. Derhalve moeten de omstandigheden van de individuele patiënt en de proportionaliteit van het inzetten van aanvullend onderzoek of behandelingen altijd worden meegewogen.

Post trombotisch syndroom (PTS)

Ongeveer 10 tot 50% van de patiënten die een DVT heeft doorgemaakt zal een PTS ontwikkelen (ten Cate-Hoek, 2018). Hierbij is de incidentie één jaar na DVT ongeveer 10% en dit neemt toe tot 50% in de periode van vijf tot acht jaar na DVT. De incidentie van ernstige PTS (veneus ulcus) is 1-2%. Het klinisch beeld van PTS is variabel. Patiënten kunnen pijn, een zwaar gevoel, zwelling, kramp, paresthesiën en of jeuk ervaren. De symptomen kunnen continu of intermitterend zijn en verbeteren in rust en bij omhoog leggen van het been. Ook kan er sprake zijn van veneuze claudicatio. De patiënt ervaart dit typisch bij sneller lopen, traplopen of bergop lopen. De diagnose PTS wordt gesteld met behulp van de Villalta score, die tenminste zes maanden na de oorspronkelijke diagnose vijf punten of meer moet zijn. Een deel van de score betreft zelf-gerapporteerde symptomen. Het is aan te bevelen in ieder geval na een periode van drie maanden de Villalta-score samen met patiënt te berekenen. De initiële behandeling van PTS bestaat uit compressietherapie en bewegingsadviezen. Zie verder ook de richtlijn van de European Society for Vascular Surgery (ESVS). Patiënten met een hoge ziektelast die veel beperkingen ervaren kunnen worden verwezen naar een expertisecentrum.

CTEPD/CTEPH en aanhoudende klachten van benauwdheid

Voor CTEPH/CTEPD zonder pulmonale hypertensie (PH) kon de prevalentie niet uit de besproken studies gehaald worden, maar een recente publicatie heeft aangetoond dat de prevalentie van CTEPH 2-3% is, net als dat van CTEPD zonder PH (Held, 2023; Luijten, 2023). CTEPH en CTEPD zonder PH worden gedefinieerd als de aanwezigheid van reststolsels in de pulmonaal arteriën ondanks ten minste drie maanden antistolling (met morfologie van een chronisch stolsel, zoals een zogenaamd webje) met perfusie defecten en pulmonale hypertensie (CTEPH), ofwel gepaard gaande met symptomen van benauwdheid of inspanningsbeperking én meetbare fysiologische afwijkingen zoals dode-ruimte ventilatie of pulmonale hypertensie bij inspanning (CTEPD zonder PH) (Humbert, 2022). Het is aangetoond dat een vroege diagnose van CTEPH (binnen maanden na de longembolie) resulteert in snellere behandeling en een betere overleving (Klok, 2017). Het blijkt echter dat door gebrek aan gestandaardiseerde follow-up van patiënten met een longembolie en een gebrek aan gedetailleerde kennis van dit ziektebeeld bij behandelaren de diagnostische vertraging in Nederland gemiddeld twee jaar is (Ende-verhaar, 2018). Verschillende studies laten zien dat het implementeren van een algoritme gericht op CTEPH inderdaad resulteert in een duidelijke verkorting van de diagnostische vertraging (Boon, 2021; Valerio, 2022). Zo’n algoritme begint met het op een gestandaardiseerde manier vaststellen van aanhoudende klachten, bijvoorbeeld met een PROM (Konstantinides, 2020, Klok, 2022). Een goed voorbeelden daarvan is de modified Medical Research Council Dyspnoe vragenlijst (mMRC). Patiënten met klachten verdienen aanvullend onderzoek. Het onderzoek van keuze bij verdenking op pulmonale hypertensie is een echocardiografie. Het is gebleken dat een normale ECG en (NT-pro) BNP-bloedtest de aanwezigheid van pulmonale hypertensie zeer onwaarschijnlijk maakt (Boon, 2021; Humbert, 2022). Met deze tussenstap kan het aantal verwijzingen voor een echocardiografie beperkt worden. Bij aanhoudende benauwdheid maar geen pulmonale hypertensie is een CPET de diagnostische test van keus. Hiermee kan onderscheid gemaakt worden tussen verschillende oorzaken van benauwdheid, en tevens aanwijzingen voor CTEPD zonder PH worden gevonden, bijvoorbeeld als er sprake is van dode ruimte ventilatie. Zowel patiënten met echografische verdenking op pulmonale hypertensie als verdenking op CTEPD zonder PH op basis van de CPET hebben een indicatie voor nieuwe beeldvorming van de pulmonaal vaten en perfusie (Humbert, 2022; Konstantinides, 2020). Dat kan met een CT-scan of nucleaire scan. Indien op basis van deze beeldvorming de verdenking op CTEPH of CTEPD zonder PH blijft bestaan, horen patiënten doorverwezen te worden naar een CTEPH-expertisecentrum. Adequate behandeling resulteert gemiddeld in een sterke verbetering van de kwaliteit van leven.

Patiënten met aanhoudende benauwdheid en/of inspanningsbeperking waarbij CTEPH/CTEPD zonder PH is uitgesloten, hebben baat bij hart/long revalidatie (Boon/Janssen, 2021; Klok, 2022 and Jervan, 2023): de ervaringen beperkingen in het dagelijks leven nemen gemiddeld af en de kwaliteit van leven neemt toe.

Psychosociale complicaties

Erickson (2019) en Keller (2019) definieerden psychosociale complicaties als angst en depressie, en concluderen dat deze toestand kan leiden tot een relevante daling van de kwaliteit van leven. Ook voor angst en depressie bestaan bruikbare en gevalideerde PROMs. Een voorbeeld hiervan is de Vierdimensionale Klachtenlijst (4DKL). De 4DKL is een vragenlijst bestaande uit 50 items, gericht op psychosociale klachten. De lijst is ontwikkeld in de huisartsenpraktijk en maakt onderscheid tussen aspecifieke 'distress'-klachten, depressie, angst, en somatisatie. Deze vier symptoomdimensies vormen tevens de vier verschillende categorieën. De antwoordmogelijkheden van de lijst zijn ordinaal opgebouwd en hoe hoger een patiënt scoort op de vragenlijst, des te meer psychosociale klachten ondervindt hij in zijn dagelijkse handelingen. Met de 4DKL kunnen problemen in de genoemde dimensies worden opgespoord en het geeft handvatten voor de noodzaak tot nadere diagnostiek. Een alternatieve PROM is de “Hospital Anxiety and Depression Scale” HADS. De HADS meet kernklachten van angst en depressie zonder daarbij lichamelijke klachten te betrekken. Het is een korte vragenlijst, die gemakkelijk te gebruiken is. De schaal gaat in op gevoelens in de afgelopen vier weken en bestaat uit een angstschaal en een depressieschaal met beide zeven items. Hoe hoger een patiënt scoort op deze vragenlijst des te meer klachten hij/zij ervaart.

Internationale consensus

De 2019 ESC/ERS longembolie richtlijn suggereert gebruik te maken van PROMS om te bepalen bij welke patiënten aanvullend onderzoek naar CTEPH geïndiceerd is (Konstantinides, 2020). Het in 2022 gepubliceerde ESC/ERS consensus document over follow-up na acute longembolie is wat specifieker op dit onderwerp en adviseert naast een PROM voor dyspnoe ook een PROM voor het vaststellen van functionele beperkingen voor. Dit helpt bij het inschatten van de ernst van aanhoudende symptomen maar ook om de potentiële impact van een behandeling in te schatten. De Post-VTE Functionele Status (PVFS) schaal richt zich op relevante aspecten van het dagelijks leven in de eerste periode na een VTE-diagnose (Boon, 2020). Het is bedoeld om de zorgmedewerker en patiënt bewust te maken van goed of minder goed herstel van VTE en de gevolgen daarvan op het functioneren van de patiënt. Minder goed herstel kan wijzen op lange termijn complicaties die behandeling behoeven. De PVFS-schaal is ordinaal en heeft zes klassen die variëren van nul (geen symptomen) tot vijf (dood, D). De schaal bestrijkt het gehele spectrum aan functionele uitkomsten door zich te richten op zowel beperkingen in gebruikelijke taken/activiteiten in de thuissituatie, op het werk of de studie, als op veranderingen in levensstijl. De klassen van de PVFS-schaal zijn intuïtief en kunnen gemakkelijk worden beoordeeld en vervolgens worden geïnterpreteerd door artsen en patiënten.

Een internationale werkgroep van zorgmedewerkers en patiënten heeft zich gericht op het vaststellen van de kernuitkomsten van veneuze trombo-embolie die voor alle patiënten relevant zijn: ICHOM-VTE (Gwodz, 2022). Nadat de kernuitkomsten waren vastgesteld, werd er voor elke uitkomst een instrument bepaald, met als belangrijkste kenmerk dat deze zo mogelijk patiënt-gerapporteerd, gevalideerd, makkelijk (en gratis) in veel talen beschikbaar en toegankelijk is. In deze uitkomst set zitten PROMS voor kwaliteit van leven, pijn, benauwdheid, angst, depressie, functionele beperkingen, patiënttevredenheid en verandering van levensvisie. Om het aantal in te vullen vragen te beperken heeft de set enkele cascade opties ingebouwd.

De internationale vereniging voor trombose en hemostase (ISTH) heeft in recente publicaties de relevantie van het gebruik van PROMS bevestigd, en onderschrijft de relevantie van de ICHOM set (de Jong, 2023).

Waarden en voorkeuren van patiënten (en evt. hun verzorgers)

In deze module staat de kwaliteit van leven van de patiënt centraal. De ICHOM-set die wordt besproken, is ontwikkeld met en voor patiënten. Hierbij was ook een Nederlandse patiëntpartner betrokken. In de follow-up is het voor patiënten belangrijk dat er goede informatie gegeven wordt over de aandoening en ook (de inhoud van) het nazorgtraject. Ook dient duidelijk te zijn wie het aanspreekpunt is bij eventuele vragen vanuit de patiënt.

Kosten (middelenbeslag)

Er is nauwelijks tot geen onderzoek voor handen naar de kosteneffectiviteit van (PROMS gestuurde) symptoomgerichte follow-up na VTE. Wel is er een Nederlandse analyse die aantoont dat eerdere diagnose van CTEPH na longembolie kosteneffectief is (Boon/ Van den Hout, 2021). Het is mogelijk dat gestandaardiseerde nazorg van veneuze trombo-embolie overdiagnostiek voorkomt, en leidt tot gerichte verwijzingen. Het gebruik van PROMS is kosteloos, al moet er wel worden geïnvesteerd in patiënten motivatie/instructie en een (liefst digitale) manier om de PROMS-uitkomsten te verwerken en op te slaan. Een gestandaardiseerde en gestructureerde nazorg van VTE-patiënten is mogelijk doelmatig en voorkomt onnodige zorg (Ende-Verhaar, 2018).

Aanvaardbaarheid, haalbaarheid en implementatie

Het implementeren van PROMS kan lastig zijn. Niet alleen moeten de juiste PROMS worden gekozen, ook moeten er juiste instructie aan patiënten én zorgmedewerkers komen, en is een infrastructuur voor de invullen, opslaan en verwerken van de PROM-resultaten noodzakelijk. Het bespreken van PROM-uitslagen kost tijd, al kan het ook versnellend werken omdat een deel van de anamnese reeds ondervangen is. Er is een PROM-toolbox samengesteld door het Zorginstituut die houvast kan geven. De PROM-toolbox bestaat uit de PROM-wijzer en de PROM-cyclus. De PROM-wijzer gaat over de oriëntatie en voorbereiding op het gebruik van PROMs. De PROM-cyclus gaat over de selectie en toepassing van PROMs.

Rationale van de aanbeveling

Om richting te geven aan de optimale nazorg van patiënten met een VTE heeft de werkgroep vastgesteld welke complicaties de kwaliteit van leven na een VTE negatief beïnvloeden, namelijk PTS, CTEPH/CTEPD zonder PH en psychosociale complicaties. De werkgroep acht het van belang dat er in de nazorg voor de patiënten met een VTE aandacht wordt gegeven aan tenminste deze complicaties, bijvoorbeeld tijdens het drie maanden follow-up moment. Op basis van beschikbare literatuur en bestaande (recente) internationale richtlijnen zijn er aanbevelingen opgesteld hoe deze complicaties opgespoord kunnen worden en wat mogelijke vervolgstappen zijn.

Onderbouwing

Achtergrond

In the follow-up of patients with venous thromboembolism (VTE), most attention is paid to prevent recurrent disease and bleeding, and there is an important focus on the decision to stop or continue anticoagulation after 3 months. Recurrent disease and bleeding are indeed associated with mortality and morbidity, and lead to a decrease in quality of life. However, other disease-related complications also have an impact on the patient's recovery and the possibility of resuming life after diagnosis. Up to half of patients with VTE appear to have residual symptoms that hinder functional recovery months after diagnosis and adequate anticoagulation treatment, having post-thrombotic syndrome or post-pulmonary embolism syndrome. Since from the patient's perspective, functional recovery is an important if not the most important outcome of treatment of VTE, the follow-up pathway should be designed to detect and treat all relevant complications. However, studies on optimal follow-up of VTE are limited, and randomized studies are completely lacking. For this reason, there is great variation in the design of follow-up pathways for VTE, both within and between primary and secondary care. Diagnostic pathways to detect complications are limited in their focus and insufficient. In order to provide direction for optimal follow-up of VTE, this module focus on which complications have been proven to have a negative impact on quality of life. For all these complications, a proposal is then made for the best way to detect them, based on available literature and existing international recommendations.

Conclusies / Summary of Findings

Post thrombotic syndrome (PTS)

GRADE

PTS may result in a relevant decrease in quality of life as compared to VTE patients without PTS.

Sources: Kahn, 2008; Haig, 2016 and Ljungqvist, 2018

Chronic thromboembolic pulmonary disease (CTEPD) without PH/chronic thromboembolic pulmonary hypertension (CTEPH)

GRADE

CTEPD without PH or CTEPH may result in a relevant decrease in quality of life as compared to VTE patients without CTEPD without PH or CTEPH.

Sources: Roman, 2013 and Taboada, 2014

Residual complaints

GRADE

Residual complaints may result in a relevant decrease in quality of life as compared to VTE patients without residual complaints.

Sources: Kahn, 2017; Keller, 2019; Tavoli, 2018 and Valerio, 2022

Psychosocial unwellness

GRADE

Psychosocial unwellness may result in a relevant decrease in quality of life as compared to VTE patients without psychosocial unwellness, but the evidence

is uncertain.

Sources: Erickson, 2019 and Keller, 2019

Samenvatting literatuur

The ICHOM-search query with accompanying PICO was drawn up more broadly than the PICO as defined by the working group. The ‘ICHOM-PICO’ included other outcomes in addition to the outcome quality of life. In total, 106 studies reported on the outcome quality of life (see Evidence Tables, Table ICHOM-studies that reported on the outcome quality of life). Since all those studies were considered to fit (at least part of) the PICO, and while there were no resources to systematically review all these studies in this guideline module, it was decided by the working group to select the studies that were deemed most relevant for this module.

In addition one study (i.e., the first study, published in 2008) that reported on quality of life in patients with PTS was not captured by the ICHOM search strategy (search date 2011-2021). Another large study published in 2022 that included a large number of patients with residual complaints after pulmonary embolism (also not captured by ICHOM as the search date of ICHOM was between 2011-2021) were included.

Please note that the methodology that is followed here is a narrative review which cannot be used in the systematic process of rating the quality of the best available evidence as proposed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group.

Results

A total of 185 studies were initially selected based on the ICHOM search query. Of these 185 studies, n=106 studies were included as they reported on the outcome quality of life. Of these, the working group selected eight studies that were deemed most relevant for this module (Erickson, 2019; Haig, 2016; Kahn, 2017; Keller, 2019; Ljungqvist, 2018; Roman, 2013; Tabaoda, 2014; Tavoly, 2018). In addition one study (i.e., the first study, published in 2008, (Kahn, 2008) that reported on quality of life in patients with PTS which was not captured by the ICHOM search strategy (search date 2011-2021) and another large study published in 2022 that included a large amount of patients with residual complaints after pulmonary embolism (also not captured by ICHOM as the search date of ICHOM was between 2011-2021, (Valerio, 2022) were included.

The study characteristics are summarized in Table 1 below. Main results are fully shown in the forest plots. Risk of bias assessments are fully shown in the risk of bias table.

Tabel 1: Studies included in narrative review

				Exposure category, VTE with or without:
Study	Included in ICHOM	Study size, n	Condition	Psychosocial unwellness	Residual complaints	PTS	CTEPD without PH
Kahn, 2008	No	387	DVT			X
Haig, 2016	Yes	209	DVT			X
Ljungqvist, 2018	Yes	1040	VTE			x
Kahn, 2017	Yes	100	PE		X
Keller, 2019	Yes	101	PE		X
Tavoly, 2018	Yes	203	PE		X
Valerio, 2022	Yes	1017	PE		x
Roman, 2013	Yes	156	VTE				X
Taboada, 2014	Yes	42	VTE				X
Erickson, 2019	Yes	907	VTE	X
Keller, 2019	Yes	101	PE	X

^{CTEPD: chronic thromboembolic pulmonary disease; DVT: deep vein thrombosis; PE: pulmonary embolism; PH: pulmonary hypertension; PTS: postthrombotic syndrome; VTE: venous thromboembolism}

Exposure category PTS

Definitions exposure category

Kahn (2008) and Haig (2016) defined PTS by using the Villalta scale (higher scores indicate more severe PTS). A Villalta score of <5 was considered to represent no PTS.

Ljungqvist (2018) defined PTS by modified Villalta score with a kappa of 0.88 with the original Villalta score. A modified Villalta score of <5 was considered to represent no PTS.

Definitions outcome

Kahn (2008) defined quality of life (QOL) by using the Short-Form Health Survey-36 (SF-36PCS/MCS) and the VEINESQOL/Sym. Clinical relevance was non-defined.

Haig (2016) defined QOL by using the EQ-5D and the VEINES-QOL/Sym questionnaire. A mean difference in EQ-5D of 0·08 or more was defined as a clinically relevant difference. A mean difference in VEINES-QOL/Sym of four points or more was defined as a clinically relevant difference.

Ljungqvist (2018) defined QOL by SF-36PCS/MCS and the VEINESQOL/Sym. Clinical relevance was non-defined.

Kahn (2008) prospectively measured change in QOL during the two years after a diagnosis of acute DVT at eight hospitals in Canada. Among the 387 patients recruited, the average age was 56 years. The cumulative incidence of PTS was 47% at two years of follow-up. Patients who developed PTS had lower QOL scores for all questionnaires that were used (Figure 1). Since authors did not define a clinical relevant difference, we used the default threshold (> 0.5 SD). By using this threshold, none of the differences reached clinical relevance. The risk of bias was considered as ‘some concerns’ as it was unclear if excluded participants biased the results and if there was loss to follow-up.

Figure 1. Scores for Quality of life in patients with and without post thrombotic syndrome (PTS, Kahn (2008)

^{‘Mean’ depicted in the forest plot=’mean change’. PTS: post thrombotic syndrome}

Haig (2016) included patients who participated in an open-label clinical trial that was designed to evaluate the efficacy and safety of catheter-directed thrombolysis. Patients were aged 18–75 years with acute DVT located higher than the proximal half of the femoral vein. QOL results of intervention and comparator group were pooled after which prognosis of QOL was compared in patients with PTS vs non-PTS at 5 years of follow-up. Of 209 enrolled patients, 176 patients were available for analysis (missing data 16%). The average age was 56 years. For analysis on PTS, data was available for 163 patients (missing data 8%). The cumulative incidence of PTS was 63% at 5 years of follow-up. Patients who developed PTS had lower QOL scores for all questionnaires that were used. Outcomes on EQ-5D were 0.71 in PTS vs 0.88 in non-PTS, for VEINES-QOL 47.3 in PTS vs 53.6 in no PTS, for VEINES-Sym 46.6 in PTS vs 54.4 in no PTS. All differences were clinically relevant according to definitions of the study. The risk of bias was considered as ‘some concerns’ as it was unclear if excluded participants and missing data could have biased the results.

Ljungqvist (2018) conducted a cohort study, including 1040 females with a first episode of VTE. Patients were recruited from the "Thrombo Embolism Hormonal Study" (TEHS), a Swedish nation-wide case-control study on risk factors for venous thromboembolism in females 18-64 years of age. Among the 1040 patients recruited for follow-up, the average age was 49 years. The cumulative incidence of PTS was 20% after a median of six years of follow-up. Patients who developed PTS had lower QOL scores for all questionnaires that were used, i.e.:

-8.6 for SF-36 pcs, P<0.001
-4.9 for SF-36 mcs, P<0.001
-8.4 for VEINES/QoL, P<0.001
-10.6 for VEINES/Sym, P<0.001

Authors did not define a clinical relevant difference. The default threshold (> 0.5 SD) could not be used since SDs were not reported. The risk of bias was considered as ‘some concerns’ as it was unclear if non-participating patients for follow-up biased the results.

Exposure category Chronic thromboembolic pulmonary disease (CTEPD) without pulmonary hypertension (PH)/ Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Definitions exposure category

Roman (2012) defined PH and CTEPH as outpatients aged ≥18 years old who had a clinical diagnosis of PH or CTEPH, without further clarification.

Tabaoda (2012) defined CTEPD as patients with CTEPD and a mean pulmonary artery pressure (PAP) <25 mmHg at baseline that underwent pulmonary endarterectomy (PEA). Date of last venous thromboembolism (VTE) was collected from patient’s notes. Time from last VTE to diagnosis was defined as time from last pulmonary embolism to diagnosis of CTED.

Definitions outcome

Roman (2012) defined health related quality of life (QOL) by using the Short-Form Health Survey-36 (SF-36PCS/MCS) and EQ-5D-5L questionnaire. Clinical relevance was non-defined.

Tabaoda (2012) defined health related QOL with the CAMPHOR-questionnaire (a measure of health-related QoL for patients with CTEPD without PH). Clinical relevance was non-defined.

Roman (2014) recruited consecutive patients diagnosed with PAH or CTEPH in a multi-center study. Recruitment and data collection for analysis were carried out by a pharmaceutical company (Pfizer). One hundred fifty-six patients completed the evaluation at the baseline visit and 135 (86.5%) completed the end of study visit after six months. Overall, 71% were females, with a mean age of 52 years. N=139 (89%) had PAH and n=17 (11%) had CTEPH. Seventy-six patients (49%) had idiopathic PAH (IPAH) and 23 (17%) had connective tissue disease-associated PAH (CTD-PAH). Twenty percent of patients were diagnosed in the 12 months prior to the start of the study and 80% were diagnosed earlier. Mean scores (+/- SD) for the QoL outcomes are reported in Table 2.

Table 2. Mean scores (SD) for Quality of life in patients with IPAH, CTD-PAH and CTEPH (Roman, 2014)

	IPAH	CTD-PAH	CTEPH
SF-36 PCS	39 (9)	31 (8)	39 (9)
SF-36 MCS	47 (8)	48 (10)	47 (9)
EQ visual analogue scale	59 (21)	53 (17)	65 (17)

^{IPAH: idiopathic pulmonary arterial hypertension (PAH); CTD-PAH: connective tissue disease-associated PAH; CTEPD: chronic thromboembolic pulmonary disease; PCS: physical component summary; PH: pulmonary hypertension; MCS: mental component summary}

The health related QoL score were considered ‘worse than those published for the normal population’ but references or direct comparisons with the normal population were not provided. Since results were non-compared to a population without PH or CTEPH, we could not determine if findings were clinically relevant. The risk of bias was considered as ‘concerns’ as there were unclear definitions of the patient population, unclear definitions of exposure, and because recruitment and data collection for analysis were not carried out by the authors.

Tabaoda (2014) screened 1019 patients who underwent PEA at Papworth Hospital. Of those, 42 patients fulfilled the criteria of having CTED. In a before-after study patients were compared with themselves for the outcome health related QoL. Mean age of the patients was 49 years and 60% of the patients were females. 90% of the patients had a documented history of VTE, with a third of patients having more than one episode. All patients were symptomatic, the most frequent symptom was exertional breathlessness, and all presented with NYHA functional class II or III limitation.

An improvement in the total score (median [IQR]) and all three domains of the CAMPHOR- questionnaire was observed at 6 months and sustained at 1 year; the total score went from 40 (33) at baseline to 11 (30) at six months post-PEA (P<0.001) and 11 (37) at one year post PEA (P<0.001); symptoms went from 15 (13) to 4 (12) (P<0.001) and 5 (12) (P<0.001), respectively; activity went from 10 (9) to 5 (6) (P=0.002) and 4 (11) (P<0.001), respectively; and QoL went from 14 (14) to 2 (11) (P=0.003) and 1 (12) (P=0.001), respectively. Since results were shown without SDs, we could not use the default threshold (> 0.5 SD) to determine if findings were clinically relevant. The risk of bias was considered as ‘no concerns’.

Exposure category Residual complaints

Definitions exposure category

Kahn (2017) defined residual complaints by maximal aerobic capacity defined by peak oxygen uptake (Vo2) as a percentage of predicted maximal Vo2 (Vo2 peak) on cardiopulmonary exercise testing (CPET) at one year, with < 80% predicted Vo2 peak considered abnormal. CPET was interpreted in real time by a respirologist at each center who was blinded to patient information.

Keller (2018) defined residual complaints by New York Heart Association (NYHA) classes I-IV at six months of follow-up.

Tavoly (2018) defined residual complaints by NYHA class >1 (=persistent dyspnea) after a median follow of 3.6 years.

Valerio (2022) defined residual complaints by post-PE impairment (PPEI). The diagnosis of PPEI required deterioration in severity, or persistence of the highest severity, of at ≥ 1 ‘a’ (echocardiographic) and ≥ 1 ‘b’ (clinical, functional, or laboratory) parameter/abnormality. Deterioration or persistence was determined by comparison with the previous visit. For trichotomized (three-level) ‘a’ or ‘b’ parameters, the highest severity category was the one defined as ‘severe/high’; for dichotomized (two-level) parameters, it was the ‘moderate or severe/high’ category. Patients were considered to have reached the outcome ‘PPEI’ if they fulfilled the above criteria at the latest available follow-up visit (3, 12, or 24 months).

Definitions outcome

Kahn (2017) defined health related quality of life (QOL) by using the Short-Form Health Survey-36 (SF-36PCS/MCS). A difference of three points or more was defined as a clinically relevant difference.

Valerio (2022) defined health-related QoL using the EQ-5D-5L questionnaire and its corresponding visual analogue scale. Clinical relevance was non-defined.

Kahn (2017), Keller (2018), Tavoly (2017) and Valerio (2022) defined disease specific QOL by using the PEmb-QOL questionnaire. Clinical relevance was non-defined.

Kahn (2017) recruited out of n=984 patients with acute pulmonary embolism (PE), 100 patients at five hospitals. The average age was 50 years. At 1 year of follow-up, 40 of 86 patients (46%) had a percentage predicted Vo2 peak < 80% on CPET (i.e., residual complaints). Patients who had residual complaints had lower QOL for all questionnaires that were used. Differences for health related QOL were clinically relevant according to definitions of the study. Since authors could not define a clinical relevant difference for disease specific QOL, we used the default threshold (> 0.5 SD). By using this threshold, the difference for disease specific QOL was also clinically relevant, with some imprecision as confidence intervals were large. The risk of bias was considered as ‘some concerns’ as it was unclear if excluded participants biased the results.

Figure 2. Scores for Quality of life in patients with and without residual complaints (Kahn, 2017)

Keller (2018) recruited out of n=192 patients with acute PE, 101 patients at one outpatient clinic. The median age was 69 years. At six months of follow-up, (47%) had reported persisting dyspnea (NYHA class ≥II; of those, 19 patients (40.4%) were in NYHA class III/IV. Increasing NYHA classes were related to all PEmb‐QoL dimensions (see Table 3). authors did not define a clinical relevant difference for disease specific QOL. Since results were shown by regression techniques only (no SDs available) we could not use the default threshold (> 0.5 SD) to determine if findings were clinically relevant. The risk of bias was considered as ‘some concerns’ as it was unclear if excluded participants biased the results.

Table 3. Linear regression models for associations between PEmb-QoL dimensions and residual complaints categorized by NYHA classes at 6-months follow-up (Keller, 2018)

	Dyspnea categorized by NYHA-classes
	β (95% CI)	P-value
Frequency of complaints (FO)	0.5 (0.4-1.1)	<0.001
Activities of daily living limitations (AD)	0.8 (0.6-1.1)	<0.001
Work related problems (WR)	1.2 (0.8-1.5)	<0.001
Social limitations (SL)	0.4 (0.3-0.6)	<0.001
Intensity of complaints (IO)	0.4 (0.3-0.5)	<0.001
Emotional complaints (EC)	0.2 (0.0-0.4)	0.037

^{CI: confidence interval; NYHA: New York Heart Association}

Tavoly (2018) recruited consecutive patients diagnosed with PE in a single center study. After excluding 430 (51%) according to predefined exclusion criteria, 406 patients were found eligible and invited.

Of these, 203 patients completed the PEmb-QoL. After a median follow up of 3.6 (IQR 1.9–6.5) years, 96 (47%) patients reported dyspnea. The PEmb-QoL was higher (i.e., worse) in dyspneic patients (median score 12.5; IQR 9.9-15.0) compared to non-dyspneic patients (median score 8.0; IQR, 7.0-9.5), P<0.005. Since results were shown without SDs, we could not use the default threshold (> 0.5 SD) to determine if findings were clinically relevant. The risk of bias was considered as ‘some concerns’ as it was unclear if excluded participants biased the results.

Valerio (2022) included 1098 patients with PE at 17 study sites. For 81 patients, no follow-up data could be obtained after discharge. In total 880 patients could be assessed for PPEI. The median age was 64 years. At two years of follow-up, 16% had reported PPEI.

Patients who developed PPEI had worse QOL scores for all questionnaires that were used at 2 years of follow-up (Table 4).

Table 4. Scores for Quality of life in patients reporting post pulmonary embolism impairment (PPEI) and patients not reporting PPEI (Tavoly, 2018)

	No PPEI	PPEI	P-value
EQ-5D-L	0.94	0.92	0.3
EQ visual analogue scale	80	70	0.02
PEmb-QoL	9.8%	23.3%	0.003

^{PPEI: post pulmonary embolism impairment; Pemb-QoL: Pulmonary Embolism Quality of Life Questionnaire}

Since results were shown without SDs, we could not use the default threshold (> 0.5 SD) to determine if findings were clinically relevant. The risk of bias was considered as ‘some concerns’ as it was unclear if excluded participants biased the results.

Exposure category Psychosocial unwellness

Definitions exposure category

Erickson (2019) defined psychosocial unwellness as self-reported history of anxiety, or depression at time of enrollment.

Keller (2018) defined psychosocial unwellness as depression as confirmed diagnosis by a physician or administration of antidepressive drugs at 6 months of follow-up.

Definitions outcome

Erickson (2019) defined health related QoL by using the Short-Form Health Survey-12 PCS/MCS. In large national surveys of the entire U.S. population MCS scores have a mean of 50; thus, scores below 50 indicate worse health-related QoL than the typical U.S. person. Clinical relevance was non-defined.

Keller (2018) defined disease specific QOL by using the PEmb-QOL questionnaire. Clinical relevance was non-defined.

Erickson (2019) performed a cross-sectional survey in patients who self-reported VTE within the past two years before study enrollment. Patients diagnosed with cancer within the past two years were excluded. The study sample was recruited by a contract research agency (Hall & Partners, New York, New York, United States). Participants received an industry standard honorarium for their participation. A total of 971 patients accessed and completed the online survey. Data cleaning resulted in 64 patients being removed from the final data. The mean age of survey patients was 52 years, and most were female (57%). Self-reported VTE types were DVT (64%), PE alone (18%), or PE in combination with DVT (18%). The prevalence of anxiety was 27% and for depression 28%. The mean PCS and MCS scores were 41.7 and 46.7. Patients with a prior history of anxiety or depression were more likely to have below average QoL (anxiety 30% vs 16% and depression 33% vs 13% for PCS; anxiety 37% vs 13% and depression 41% vs 13% for MCS, all p-values <0.05). Since results on QoL were compared on an aggregate level (VTE vs the population), we could not determine if findings on anxiety/depression were clinically relevant. Risk of bias was considered as ‘concerns’ because of unclear definitions of patient population, self-reported definitions of exposure and because recruitment and data collection for analysis were not carried out by the authors.

Keller (2018) recruited out of n=192 patients with acute PE, 101 patients at one outpatient clinic. The median age was 69 years. At six months of follow-up, n=14 (16%) had reported depression. Depression was not consistently associated with QoL assessed by the PEmb‐QoL dimensions (point estimate from odds ratios between 1.0 to 2.6), but confidence intervals were wide for which reason it could not be determined if the effects were or were not clinically relevant. The risk of bias was considered as ‘some concerns’ as it was unclear if excluded participants biased the results.

Level of evidence of the literature

Summary

From the narrative review of a total of ten studies (from a selection of 106 unselected studies from the ICHOM analysis; Gwodz, 2022) that looked at chronic conditions that can arise after a VTE, the majority of these conditions were associated with a negative quality of life. As shown in Table 5, the prevalence of the chronic conditions was high.

Table 5. Results of the ten studies included in the narrative review, selection of studies from the ICHOM-analysis (Gwodz, 2022)

Study	Prevalence exposure	Difference	Statistical significant	Clinically relevant
Kahn, 2008	47%	Yes	Yes	No
Haig, 2016	63%	Yes	Yes	Yes
Ljungqvist, 2018	20%	Yes	Yes	CND
Kahn, 2017	46%	Yes	Yes	Yes
Keller, 2019	47%	Yes	Yes	CND
Tavoly, 2018	47%	Yes	Yes	CND
Valerio, 2022	16%	Yes	Yes	CND
Roman, 2013	CND	Yes	CND	CND
Taboada, 2014	CND	Yes	Yes	CND
Erickson, 2019	27%	CND	CND	CND
Keller, 2019	16%	Imprecise	No	CND

^{CND: could not be determined}

For CTEPD without PH/CTEPH, the prevalence could not be extracted from the studies discussed, but a recent publication has shown that the prevalence of CTEPH is 2-3% (Luijten, 2023). The results from the narrative review could not be assessed using the GRADE methodology, but were consistent and precise within the domains of GRADE (with the exception of the variable psychological unwell-being (Erickson, 2019; Keller, 2019), where numbers were small leading to imprecision), fit within the patient population as defined in the PICO and had the main methodological limitation that due to selection criteria it was not always clear how generalizable the study results are to the total population.

Zoeken en selecteren

A review of the literature was performed to answer the following question: Do long term complications of venous thromboembolism have an impact on quality of life?

P (Patients):	Patients aged > 18 years with venous thrombo-embolism (DVT and/or PE)
I (Intervention):	Residual complaints (pain, dyspnea), psychosocial unwellness, post thrombotic syndrome (PTS), chronic thromboembolic pulmonary disease (CTEPD) without pulmonary hypertension (PH), chronic thromboembolic pulmonary hypertension (CTEPH)
C (Comparison):	The absence of residual complaints (pain, dyspnea), no psychosocial unwellness, PTS, CTEPD without PH, CTEPH
O (Outcome):	Quality of life (QOL)

Definitions of exposure

The working group defined the presence (or absence) of exposure by using the definitions that were used in the study.

Relevant outcome measures

The guideline development group considered general quality of life and/or disease specific quality of life as crucial outcomes for decision making.

For general quality of life: Measured by SF-12 MCS/PCS, SF-36 MCS/PCS, EQ-5D (lower scores indicate poorer QOL for both questionnaires).

For disease specific quality of life: Measured by PEmb-QoL (higher scores indicate poorer QOL) and/or VEINES-QOL/Sym questionnaires (lower scores indicate poorer QOL) and/or CAMPHOR questionnaire (higher scores indicate poorer QOL).

The working group did not define a minimal clinically (patient) important difference for the outcomes. Therefore, definitions of studies were used. If studies did not define a clinically relevant finding default thresholds were used: 0.5SD for continuous outcomes and a 25% difference in relative risk (RR< 0.8 or RR>1.25) for dichotomous outcomes.

ICHOM-VTE

The systematic search of ICHOM VTE has been adopted for this search query (search date 8 March 2011- 8 March 2021; see attachments). All MEDLINE articles have been fully screened by 2 independent members of the ICHOM-VTE taskforce (Gwodz, 2022). The first 20 of the 110 unique non-MEDLINE hits were also viewed. When no new results were found, according to ICHOM-methodology, the point of saturation was reached and no further searches were made. The ICHOM-VTE-project was supported from unrestricted grants from Bayer, Boston Scientific, The Dutch Thrombosis Association, Leiden University Medical Center, Leo Pharma, and King’s College London. It was not reported whether and if so, how the sponsoring parties contributed – besides the financial support - to this project.

Referenties

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Boon GJAM, Ende-Verhaar YM, Bavalia R, et al. Non-invasive early exclusion of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: the InShape II study. Thorax. 2021;76(10):1002-1009. doi:10.1136/thoraxjnl-2020-216324.
Boon GJAM, Janssen SMJ, Barco S, et al. Efficacy and safety of a 12-week outpatient pulmonary rehabilitation program in Post-PE Syndrome. Thromb Res. 2021;206:66-75. doi:10.1016/j.thromres.2021.08.012.
Boon GJAM, van den Hout WB, Barco S, et al. A model for estimating the health economic impact of earlier diagnosis of chronic thromboembolic pulmonary hypertension. ERJ Open Res. 2021;7(3):00719-2020. Published 2021 Sep 6. doi:10.1183/23120541.00719-2020.
Delcroix M, Torbicki A, Gopalan D, et al. ERS statement on chronic thromboembolic pulmonary hypertension. Eur Respir J. 2021;57(6):2002828. Published 2021 Jun 17. doi:10.1183/13993003.02828-2020.
Ende-Verhaar YM, van den Hout WB, Bogaard HJ, et al. Healthcare utilization in chronic thromboembolic pulmonary hypertension after acute pulmonary embolism. J Thromb Haemost. 2018;16(11):2168-2174. doi:10.1111/jth.14266.
Erickson RM, Feehan M, Munger MA, Tak C, Witt DM. Understanding Factors Associated with Quality of Life in Patients with Venous Thromboembolism. Thromb Haemost. 2019;119(11):1869-1876. doi:10.1055/s-0039-1696717.
Gwozdz AM, de Jong CMM, Fialho LS, et al. Development of an international standard set of outcome measures for patients with venous thromboembolism: an International Consortium for Health Outcomes Measurement consensus recommendation. Lancet Haematol. 2022;9(9):e698-e706. doi:10.1016/S2352-3026(22)00215-0.
Haig Y, Enden T, Grøtta O, et al. Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT): 5-year follow-up results of an open-label, randomised controlled trial. Lancet Haematol. 2016;3(2):e64-e71. doi:10.1016/S2352-3026(15)00248-3.
Held M, Pfeuffer-Jovic E, Wilkens H, et al. Frequency and characterization of CTEPH and CTEPD according to the mPAP threshold > 20 mm Hg: Retrospective analysis from data of a prospective PE aftercare program. Respir Med. 2023;210:107177. doi:10.1016/j.rmed.2023.107177.
Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension [published correction appears in Eur Heart J. 2023 Apr 17;44(15):1312]. Eur Heart J. 2022;43(38):3618-3731. doi:10.1093/eurheartj/ehac237
Jervan Ø, Haukeland-Parker S, Gleditsch J, et al. The Effects of Exercise Training in Patients With Persistent Dyspnea Following Pulmonary Embolism: A Randomized Controlled Trial. Chest. 2023;164(4):981-991. doi:10.1016/j.chest.2023.04.042.
de Jong CMM, de Wit K, Black SA, et al. Use of patient-reported outcome measures in patients with venous thromboembolism: communication from the ISTH SSC Subcommittee on Predictive and Diagnostic Variables in Thrombotic Disease. J Thromb Haemost. 2023;21(10):2953-2962. doi:10.1016/j.jtha.2023.06.023.
Kahn SR, Shbaklo H, Lamping DL, et al. Determinants of health-related quality of life during the 2 years following deep vein thrombosis. J Thromb Haemost. 2008;6(7):1105-1112. doi:10.1111/j.1538-7836.2008.03002.x.
Kahn SR, Hirsch AM, Akaberi A, et al. Functional and Exercise Limitations After a First Episode of Pulmonary Embolism: Results of the ELOPE Prospective Cohort Study. Chest. 2017;151(5):1058-1068. doi:10.1016/j.chest.2016.11.030.
Keller K, Tesche C, Gerhold-Ay A, et al. Quality of life and functional limitations after pulmonary embolism and its prognostic relevance. J Thromb Haemost. 2019;17(11):1923-1934. doi:10.1111/jth.14589.
Klok FA, Huisman MV. Management of incidental pulmonary embolism. Eur Respir J. 2017;49(6):1700275. Published 2017 Jun 29. doi:10.1183/13993003.00275-2017.
Klok FA, Ageno W, Ay C, et al. Optimal follow-up after acute pulmonary embolism: a position paper of the European Society of Cardiology Working Group on Pulmonary Circulation and Right Ventricular Function, in collaboration with the European Society of Cardiology Working Group on Atherosclerosis and Vascular Biology, endorsed by the European Respiratory Society. Eur Heart J. 2022;43(3):183-189. doi:10.1093/eurheartj/ehab816.
Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41(4):543-603. doi:10.1093/eurheartj/ehz405.
Ljungqvist M, Holmström M, Kieler H, Lärfars G. Long-term quality of life and postthrombotic syndrome in women after an episode of venous thromboembolism. Phlebology. 2018;33(4):234-241. doi:10.1177/0268355517698620.
Luijten D, Talerico R, Barco S, et al. Incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: an updated systematic review and meta-analysis. Eur Respir J. 2023;62(1):2300449. Published 2023 Jul 7. doi:10.1183/13993003.00449-2023.
Roman A, Barbera JA, Castillo MJ, Muñoz R, Escribano P. Health-related quality of life in a national cohort of patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Arch Bronconeumol. 2013;49(5):181-188. doi:10.1016/j.arbres.2012.12.007.
Taboada D, Pepke-Zaba J, Jenkins DP, et al. Outcome of pulmonary endarterectomy in symptomatic chronic thromboembolic disease. Eur Respir J. 2014;44(6):1635-1645. doi:10.1183/09031936.00050114.
Tavoly M, Wik HS, Sirnes PA, et al. The impact of post-pulmonary embolism syndrome and its possible determinants. Thromb Res. 2018;171:84-91. doi:10.1016/j.thromres.2018.09.048.
Ten Cate-Hoek AJ. Diagnosis and prevention of the post-thrombotic syndrome. Ned Tijdschr Hematol. 2018;15:319-25.
Valerio L, Mavromanoli AC, Barco S, et al. Chronic thromboembolic pulmonary hypertension and impairment after pulmonary embolism: the FOCUS study. Eur Heart J. 2022;43(36):3387-3398. doi:10.1093/eurheartj/ehac206.

Evidence tabellen

Risk of bias table for cohort studies based on risk of bias tool by the CLARITY Group at McMaster University

Author, year

Selection of participants

Was selection of exposed and non-exposed cohorts drawn from the same population?

Exposure

Can we be confident in the assessment of exposure?

Outcome of interest

Can we be confident that the outcome of interest was not present at start of study?

Confounding-assessment

Can we be confident in the assessment of confounding factors?

Confounding-analysis

Did the study match exposed and unexposed for all variables that are associated with the outcome of interest or did the statistical analysis adjust for these confounding variables?

Assessment of outcome

Can we be confident in the assessment of outcome?

Follow up

Was the follow up of cohorts adequate? In particular, was outcome data complete or imputed?

Co-interventions

Were co-interventions similar between groups?

Overall Risk of bias

Definitely yes, probably yes, probably no, definitely no

Low, Some concerns, High

Kahn, 2008

Probably yes

Reason: Participants were selected consecutively from outpatienst clinics, but there were exclusion criteria.

Probably yes

Reason: questionnaire data with ascertainment rules were used.

Not applicable

Reason: Outcome concerned quality of life

Not applicable

Reason: The stdy design was prognostic

Not applicable

Reason: The stdy design was prognostic

Definitely yes

Reason: validated questionnaire data with ascertainment rules were used.

Probably yes

Reason: Follow up was up to 2 years after acute DVT. Of 387 enrolled participants, 260 attended the final visit. Cumulative incidences were obtained through Kaplan Meier, suggesting that censoring at a calendar end date. took place No loss to follow-up was described

Not applicable

Reason: The stdy design was prognostic

Some concerns

Unclear if excluded participants biased the results. Unclear if there was loss to follow-up

Haig, 2016

Probably yes

Reason: participants from an open label clinical trial were included. There were some dropouts over 5 year follow-up

Probably yes

Reason: questionnaire data with ascertainment rules were used.

Not applicable

Reason: Outcome concerned quality of life

Not applicable

Reason: The study design was prognostic

Not applicable

Reason: The study design was prognostic

Definitely yes

Reason: validated questionnaire data with ascertainment rules were used.

Probably yes

Reason: follow up was up to 5 years after acute DVT. Of 209 enrolled patients, 176 patients were available for analysis (missing data 16%). For analysis on PTS, data was available for 163 patients (missing data 8%).

Not applicable

Reason: The stdy design was prognostic

Some concerns

Unclear if excluded participants biased the results. Missing data nearing 20% of total

Ljunqvist, 2018

Probably yes

Reason: Participants were selected from outpatienst clinics, through consent. For follow-up approximately 25% did not consent or provided information needed for follow-up

Probably yes

Reason: questionnaire data with ascertainment rules were used.

Not applicable

Reason: Outcome concerned quality of life

Not applicable

Reason: Outcome concerned quality of life

Not applicable

Reason: The stdy design was prognostic

Definitely yes

Reason: validated questionnaire data with ascertainment rules were used.

Probably yes

Reason: Median follow was 6 years after VTE. Of 1050 enrolled patients, 1040 patients were available for analysis (missing data n=10) patients (missing data 8%).

Not applicable

Reason: The study design was prognostic

Some concerns

Unclear if excluded participants (nearing 25% of total) biased the results.

Kahn, 2017

Probably yes

Reason: Participants were selected consecutively from outpatient clinics, but there were exclusion

Definitely yes

Reason: Objective measures were used ( maximal Vo2) on cardiopulmonary exercise testing (CPET)and interpreted in real time by a respirologist at who was blinded to patient information.

Not applicable

Reason: Outcome concerned quality of life

Not applicable

Reason: The study design was prognostic

Not applicable

Reason: The study design was prognostic

Definitely yes

Reason: validated questionnaire data with ascertainment rules were used.

Probably yes

Reason: Follow up was up to 1 year after acute PE.

Not applicable

Reason: The study design was prognostic

Some concerns

Unclear if excluded participants biased the results.

Keller, 2018

Probably yes

Reason: Participants were selected consecutively from one outpatient clinic (n=192), but there were exclusion criteria

Definitely yes

Reason: Objective measures were used.

Not applicable

Reason: Outcome concerned quality of life

Not applicable

Reason: The study design was prognostic

Not applicable

Reason: The study design was prognostic

Definitely yes

Reason: validated questionnaire data with ascertainment rules was used.

Probably yes

Reason: Follow up was up to 0.5 years after acute PE.

Not applicable

Reason: The study design was prognostic

Some concerns

Unclear if excluded participants biased the results.

Tavoly, 2018

Probably yes

Reason: Participants were selected consecutively from one outpatient clinic, but there were exclusion criteria (and not all participated.

Definitely yes

Reason: Objective measures were used.

Not applicable

Reason: Outcome concerned quality of life

Not applicable

Reason: The study design was prognostic

Not applicable

Reason: The study design was prognostic

Definitely yes

Reason: validated questionnaire data with ascertainment rules was used.

Probably yes

Reason: Median Follow up was 3.6 years after acute PE.

Not applicable

Reason: The study design was prognostic

Some concerns

Unclear if excluded participants biased the results.

Valerio, 2022

Probably yes

Reason: The FOCUS prospectively enrolled consecutive unselected patients with confirmed diagnosis of acute symptomatic PE. The study was performed at 17 hospitals in Germany. Patients were excluded if the diagnosis of PE was an incidental finding during diagnostic work up for another disease; if they had

A documented history of confirmed CTEPH; or if they had already been

enrolled in this study in the past

Definitely yes

Reason: Objective measures were used.

Not applicable

Reason: Outcome concerned quality of life

Not applicable

Reason: The study design was prognostic

Not applicable

Reason: The study design was prognostic

Definitely yes

Reason: validated questionnaire data with ascertainment rules was used.

Probably yes

Reason: Maximum Follow up was 2 years after acute PE. Of 1098 patienmts included 81 patienst did not provide follow-up data (7%). PPEI could be evaluated in 880 patients

Not applicable

Reason: The study design was prognostic

Some concerns

Unclear if missing data biased the results.

Roman, 2012

Unclear

Reason: consecutive patients diagnosed with PAH or CTEPH in a multi-center study, further undefined.

Definitely no

Reason: the exposure was not defined

Not applicable

Reason: Outcome concerned quality of life

Not applicable

Reason: The study design was prognostic

Not applicable

Reason: The study design was prognostic

Definitely yes

Reason: validated questionnaire data with ascertainment rules was used.

Probably yes

Reason: Follow up was 6 months. Of 156 patients included 21 patienst did not provide follow-up data (13%).

Not applicable

Reason: The study design was prognostic

Concerns. Unclear definitions of patient population, unclear definitions of exposure. Recruitment and data collection for analysis were not carried out by the authors

Tabaoda, 2014

Probably yes

Authors screened 1019 patients who underwent PEA at Papworth Hospital. Of those, 42

patients fulfilled the criteria of having CTED

Definitely yes

Reason: Objective measures were used.

Not applicable

Reason: Outcome concerned quality of life

Not applicable

Reason: The study design was prognostic

Not applicable

Reason: The study design was prognostic

Definitely yes

Reason: validated questionnaire data with ascertainment rules was used.

Definitely yes

Reason: Follow up was up to 1 year after PEA. There was no loss to follow-up

Not applicable

Reason: The study design was prognostic

No concerns

Erickson, 2019

Probably no

Reason: This was a survey with an unknown response rate (but determined bu authors as ‘less than ideal’) that relied on patient self-report for index VTE identification and could only compare outcomes with aggregate findings drom a normal population. Recruitment went through a contract research agency

Probably yes

Reason: the exposure was identified through self-report (potential information bias)

Not applicable

Reason: Outcome concerned quality of life

Not applicable

Reason: The study design was prognostic

Not applicable

Reason: The study design was prognostic

Definitely yes

Reason: validated questionnaire data with ascertainment rules was used.

Probably yes

Reason: This was a a cross-sectional survey in patients who self-reported VTE within the past 2 years before study enrollment. A total of 971 patients accessed and completed the online survey. Data cleaning resulted in 64 patients (6.5%) being removed from the final data.

Concerns. Unclear definitions of patient population, self-reported definitions of exposure. Recruitment and data collection for analysis were not carried out by the authors.

Table ICHOM-studies that reported on the outcome quality of life

ICHOM ID	First author	Year	Title
5	Chen	2019	Long-Term Clinical Outcomes of Complicated Retrievable Inferior Vena Cava Filter for Deep Venous Thrombosis Patients: Safety and Effectiveness
7	Clay	2018	Cost-effectiveness of edoxaban compared to warfarin for the treatment and secondary prevention of venous thromboembolism in the UK
9	Guercini	2016	The management of patients with venous thromboembolism in Italy: insights from the PREFER in VTE registry
16	Kumar	2014	Health-Related Quality of Life in Children and Young Adults With Post-Thrombotic Syndrome: Results From a Cross-Sectional Study
25	Staniszewska	2020	The good, bad and the ugly of the Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis trial from the viewpoint of clinicians
27	Svedman	2019	Deep venous thrombosis after Achilles tendon rupture is associated with poor patient‐reported outcome
28	Wagenhäuser	2019	Clinical outcomes after direct and indirect surgical venous thrombectomy for inferior vena cava thrombosis
31	Vedantham	2017	Pharmacomechanical Catheter-Directed Thrombolysis for Deep- Vein Thrombosis
32	Schmitz	2019	Deep venous thrombosis and pulmonary embolism after anterior cruciate ligament reconstruction INCIDENCE, OUTCOME, AND RISK FACTORS
34	Kahn	2020	Quality of life after pharmacomechanical catheter-directed thrombolysis for proximal deep vein thrombosis
35	Wu	2018	The association between major complications of immobility during hospitalization and quality of life among bedridden patients: A 3 month prospective multi-center study
36	Haig	2016	Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT): 5-year follow-up results of an open-label, randomised controlled trial
40	Monreal	2019	Deep Vein Thrombosis in Europe—Health- Related Quality of Life and Mortality
42	Weinberg	2019	Relationships Between the Use of Pharmacomechanical Catheter-Directed Thrombolysis, Sonographic Findings, and Clinical Outcomes in Patients with Acute Proximal DVT: Results from the ATTRACT Multicenter Randomized Trial
47	Eirckson	2019	Understanding Factors Associated with Quality of Life in Patients with Venous Thromboembolism
56	Garcia	2020	Ultrasound-accelerated thrombolysis and venoplasty for the treatment of the postthrombotic syndrome: Results of the ACCESS PTS Study
59	Dumantepe	2019	Endophlebectomy of the common femoral vein and endovascular iliac vein recanalization for chronic iliofemoral venous occlusion
62	Bradbury	2019	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)
64	Chuang	2019	Comparison of quality of life measurements: EQ-5D-5L versus disease/treatment-specific measures in pulmonary embolism and deep vein thrombosis
66	Sebastian	2020	Early clinical outcomes for treatment of post-thrombotic syndrome and common iliac vein compression with a hybrid oblique self-expanding nitinol stent – the TOPOS study
67	Razavi	2020	Correlation between Post-Procedure Residual Thrombus and Clinical Outcome in Deep Vein Thrombosis Patients Receiving Pharmacomechanical Thrombolysis in a Multicenter Randomized Trial
69	Engeseth	2019	Does the Villalta scale capture the essence of postthrombotic syndrome? A qualitative study of patient experience and expert opinion
70	Gombert	2018	Patency rate and quality of life after ultrasound-accelerated catheter-directed thrombolysis for deep vein thrombosis
71	Chuang	2018	Deep-vein thrombosis in Europe — Burden of illness in relationship to healthcare resource utilization and return to work
73	Strijkers	2015	Validation of the LET classification
74	Lutsey	2020	Long-Term Association of Venous Thromboembolism With Frailty, Physical Functioning, and Quality of Life: The Atherosclerosis Risk in Communities Study
76	Siddiqui	2020	Predictors of Poor Quality of Life after Primary Lower Limb Deep Venous Thrombosis: A Perspective from a Developing Nation
80	Utne	2018	Rivaroxaban versus warfarin for the prevention of post-thrombotic syndrome
82	Alibaz-Oner	2016	Post-thrombotic syndrome and venous disease-specific quality of life in patients with vascular Behçet’s disease
90	Qian	2020	The perplexity of catheter‑directed thrombolysis for deep venous thrombosis: the approaches play an important role
91	Ruihua	2017	Technique and Clinical Outcomes of Combined Stent Placement for Postthrombotic Chronic Total Occlusions of the Iliofemoral Veins
92	Ljungqvist	2018	Long-term quality of life and postthrombotic syndrome in women after an episode of venous thromboembolism
96	Jiang	2017	Mid-term outcome of endovascular treatment for acute lower extremity deep venous thrombosis
97	Wagenhäuser	2018	Open surgery for iliofemoral deep vein thrombosis with temporary arteriovenous fistula remains valuable
99	Hogg	2014	Validity of standard gamble estimated quality of life in acute venous thrombosis
104	Catarinella	2015	Quality-of-life in interventionally treated patients with post-thrombotic syndrome
107	Marvig	2015	Quality of life in patients with venous thromboembolism and atrial fibrillation treated with coumarin anticoagulants
108	Pesser	2020	Same Admission Hybrid Treatment of Primary Upper Extremity Deep Venous Thrombosis with Thrombolysis, Transaxillary Thoracic Outlet Decompression, and Immediate Endovascular Evaluation
110	Bi	2019	Long-term outcome and quality of life in patients with iliac vein compression syndrome after endovascular treatment
113	Engelberger	2017	Ultrasound-assisted versus conventional catheter-directed thrombolysis for acute iliofemoral deep vein thrombosis: 1-year follow-up data of a randomized-controlled trial
114	Dumantepe	2018	The effect of Angiojet rheolytic thrombectomy in the endovascular treatment of lower extremity deep venous thrombosis
115	Tichelaar	2016	A Retrospective Comparison of Ultrasound-Assisted Catheter-Directed Thrombolysis and Catheter-Directed Thrombolysis Alone for Treatment of Proximal Deep Vein Thrombosis
116	Nawasrah	2021	Incidence and severity of postthrombotic syndrome after iliofemoral thrombosis – results of the Iliaca-PTS – Registry
121	Lozano Sanchez	2013	Negative impact of deep venous thrombosis on chronic venous disease
123	Holmes	2014	Efficacy of a short course of complex lymphedema therapy or graduated compression stocking therapy in the treatment of post-thrombotic syndrome
124	Mol	2016	One versus two years of elastic compression stockings for prevention of post-thrombotic syndrome (OCTAVIA study): randomised controlled trial
128	Mean	2014	The VEINES-QOL/Sym questionnaire is a reliable and valid disease-specific quality of life measure for deep vein thrombosis in elderly patients
129	Broholm	2011	Postthrombotic syndrome and quality of life in patients with iliofemoral venous thrombosis treated with catheter-directed thrombolysis
135	Persson	2011	Deep venous thrombosis after surgery for achilles tendon rupture: a provoked transient event with minor long-term sequelae
136	Keita	2017	Assessment of quality of life, satisfaction with anticoagulation therapy, and adherence to treatment in patients receiving long-course vitamin K antagonists or direct oral anticoagulants for venous thromboembolism
141	Vogel	2012	Common femoral endovenectomy with iliocaval endoluminal recanalization improves symptoms and quality of life in patients with postthrombotic iliofemoral obstruction
142	Lee	2015	Role of coexisting contralateral primary venous disease in development of post-thrombotic syndrome following catheter-based treatment of iliofemoral deep venous thrombosis
145	Zhang	2013	A prospective randomized trial of catheter-directed thrombolysis with additional balloon dilatation for iliofemoral deep venous thrombosis: a single-center experience
150	Meng	2013	Stenting of iliac vein obstruction following catheter-directed thrombolysis in lower extremity deep vein thrombosis
152	Ast	2014	Clinical outcomes of patients with non-fatal VTE after toral knee arthroplasty
155	Lee	2021	Performance of two clinical scales to assess quality of life in patients with post-thrombotic syndrome
159	Ye	2016	Outcomes of stent placement for chronic occlusion of a filter-bearing inferior vena cava in patients with severe post-thrombotic syndrome
160	Enden	2013	Symptom burden and job absenteeism after treatment with additional catheter-direced thrombolysis for deep vein thrombosis
161	Roberts	2014	Post-thrombotic syndrome is an independent determinant of health-related quality of life following both first proximal and sital deep vein thrombosis
162	Kearon	2019	Pharmacomechanical catheter-directed thrombolysis in acute femoral-popliteal deep vein thrombosis: analysis from a stratified randomized trial
163	Yuan	2019	Diagnosis and treatment of acquired ateriovenous fistula after lower extremity deep vein thrombosis
166	Warner	2013	Functional outcomes following catheter-based iliac vein stent placement
170	Yu	2018	The midterm effect of iliac vein stenting following catheter-directed thrombolysis for the treatment of deep vein thrombosis
171	Sarici	2013	Our early experience with iliofemoral vein stenting in patients with post-thrombotic syndrome
172	Ye	2014	Technical details and clinical outcomes of transpopliteal venoous stent placement for postthrombotic chronic total occlusion of the iliofemoral vein
173	Comerota	2019	Endovascular thrombus reomval for acute iliofemoral deep vein thrombosis: analysis from a stratified multicenter randomized trial
8	Filipppo Corsi	2017	Life-threatening massive pulmonary embolism rescued by venoarterial- extracorporeal membrane oxygenation
33	Kline	2013	Treatment of submassive pulmonary embolism with tenecteplase or placebo: cardiopulmonary outcomes at 3 months: multicenter double-blind, placebo-controlled randomized trial
37	Rolving	2020	Effect of a Physiotherapist-Guided Home-Based Exercise Intervention on Physical Capacity and Patient-Reported Outcomes Among Patients With Acute Pulmonary Embolism A Randomized Clinical Trial
41	Kahn, S.	2017	Functional and Exercise Limitations After a First Episode of Pulmonary Embolism Results of the ELOPE Prospective Cohort Study
44	Keller, K.	2018	Quality of life and functional limitations after pulmonary embolism and its prognostic relevance
48	Tavoly, M.	2018	The impact of post-pulmonary embolism syndrome and its possible determinants
49	Stoller	2019	Clinical presentation and outcomes in elderly patients with symptomatic isolated subsegmental pulmonary embolism
50	Hoole	2020	Balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension: the UK experience
51	Kamenskaya	2020	Long‑term health‑related quality of life after surgery in patients with chronic thromboembolic pulmonary hypertension
52	Notten	2020	Prevalence of venous obstructions in (recurrent) venous thromboembolism: a case-control study
54	Taboada	2014	Outcome of pulmonary endarterectomy in symptomatic chronic thromboembolic disease
55	Cires-Drouet	2020	Safety of exercise therapy after acute pulmonary embolism
60	Chuang	2019	Health‐related quality of life and mortality in patients with pulmonary embolism: a prospective cohort study in seven European countries
65	Jeong	2019	Relationship of Lower-extremity Deep Venous Thrombosis Density at CT Venography to Acute Pulmonary Embolism and the Risk of Postthrombotic Syndrome
68	Kamenskaya	2017	Factors affecting the quality of life before and after surgery in patients with chronic thromboembolic pulmonary hypertension
72	Darocha	2017	Improvement in Quality of Life and Hemodynamics in Chronic Thromboembolic Pulmonary Hypertension Treated With Balloon Pulmonary Angioplasty
75	Tavoly	2016	Health-related quality of life after pulmonary embolism: a cross-sectional study
77	Walen	2017	Safety, feasibility and patient reported outcome measures of outpatient treatment of pulmonary embolism
78	Knox	2019	Preservation of Cardiopulmonary Function in Patients Treated with Ultrasound-Accelerated Thrombolysis in the Setting of Submassive Pulmonary Embolism
79	Rao	2019	Ultrasound-assisted versus conventional catheter-directed thrombolysis for acute pulmonary embolism: A multicenter comparison of patient-centered outcomes
81	Ivarsson	2018	Health-related quality of life, treatment adherence and psychosocial support in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension
93	van Es	2013	Quality of life after pulmonary embolism as assessed with SF-36 and PEmb-QoL
98	Fukui	2016	Efficacy of cardiac rehabilitation after balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension
102	Urushibara	2015	Effects of Surgical and Medical Treatment on Quality of Life for Patients With Chronic Thromboembolic Pulmonary Hypertension
103	Piazza	2020	One-Year Echocardiographic, Functional, and Quality of Life Outcomes After Ultrasound-Facilitated Catheter-Based Fibrinolysis for Pulmonary Embolism
105	Akaberi	2018	Determining the minimal clinically important difference for the PEmbQoL questionnaire, a measure of pulmonary embolism-specific quality of life
117	Harzheim	2013	Anxiety and depression disorders in patients with pulmonary arterial hypertension and chronic thromboemoblic pulmonary hypertension
118	Sertic	2020	Mid-term outcomes with the use of extracorporeal membrane oxygenation for cardiopulmonary failure secondary to massive pulmonary emoblism
122	Inagaki	2014	Home-based pulmonary rehabilitation in patients with inoperable or residual chronic thromboembolic pulmonary hypertension: A preliminary study
125	Kahn	2017	Quality of life, dyspnea, and functional exercise capacity following a first episode of pulmonary embolism: Results of the ELOPE Cohort Study
132	Barco	2021	Survival and quality of life after early discharge in low-risk pulmonary embolism
133	Stewart	2015	Contribution of fibrinolysis to the physical component summary of the SF-36 after acute submassive pulmonary embolism
138	Nagel	2012	Exercise training improves exercise capacity and quality of life in patients with inoperable or residual chronic thromboembolic pulmonary hypertension
139	Roman	2013	Health-related quality of life in a national cohort of patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension
144	Marshall	2011	Surgical pumonary embolectomy: mid-terms outcomes
148	Kline	2016	Outpatient treatment of low-risk venous thromboembolism with monotherapy oral anticoagulation: patient quality of life outcomes and clinician acceptance
149	Tavoly	2015	Quality of life after pulmonary embolism: first cross-cultural evaluation of the pulmonary embolism quality-of-life (PEmb-QoL_ questionnaire in a Norwegian cohort
157	Valerio	2021	Quality of life three and twelve months after acute pulmonary embolism: analysis from a prospective multicenter cohort study
164	Berlier	2019	Real-life experience with Selexipag as an add-on therapy to oral combination therapy in patients with pulmonary arterial or distal chronic thromboembolic pulmonary hypertension: a retrospective analysis
165	Guth	2018	Exercise right heart catheterisation before and after pulmonary endarterectomy in patients with chronic thromboemoblic disease

Verantwoording

Beoordelingsdatum en geldigheid

Laatst beoordeeld : 23-09-2025

Initiatief en autorisatie

Initiatief:

Nederlandse Internisten Vereniging

Geautoriseerd door:

Nederlands Huisartsen Genootschap
Nederlandse Internisten Vereniging
Nederlandse Orthopaedische Vereniging
Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose
Nederlandse Vereniging van Maag-Darm-Leverartsen
Nederlandse Vereniging voor Anesthesiologie
Nederlandse Vereniging voor Cardiologie
Nederlandse Vereniging voor Dermatologie en Venereologie
Nederlandse Vereniging voor Heelkunde
Nederlandse Vereniging voor Kindergeneeskunde
Nederlandse Vereniging voor Klinische Geriatrie
Nederlandse Vereniging voor Neurologie
Nederlandse Vereniging voor Thoraxchirurgie
Nederlandse Vereniging van Ziekenhuisapothekers
Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie
Nederlandse Vereniging voor Klinische Chemie en Laboratoriumgeneeskunde
Nederlandse Vereniging voor Intensive Care
Nederlandse Vereniging voor Mond- Kaak- en Aangezichtschirurgie
Harteraad

Algemene gegevens

Voor meer details over de gebruikte richtlijnmethodologie verwijzen wij u naar de Werkwijze. Relevante informatie voor de ontwikkeling/herziening van deze richtlijnmodule is hieronder weergegeven.

De ontwikkeling/herziening van deze richtlijnmodule werd ondersteund door het Kennisinstituut van de Federatie Medisch Specialisten (www.demedischspecialist.nl/kennisinstituut) en werd gefinancierd uit de Stichting Kwaliteitsgelden Medisch Specialisten (SKMS). Patiëntenparticipatie bij deze richtlijn werd medegefinancierd uit de Kwaliteitsgelden Patiënten Consumenten (SKPC) binnen het programma KIDZ. De financier heeft geen enkele invloed gehad op de inhoud van de richtlijnmodule.

Samenstelling werkgroep

Voor het ontwikkelen van de richtlijnmodule is in 2021 een multidisciplinaire werkgroep ingesteld, bestaande uit vertegenwoordigers van alle relevante specialismen (zie hiervoor de Samenstelling van de werkgroep) die betrokken zijn bij de zorg voor patiënten die antitrombotische therapie dan wel tromboseprofylaxe gebruiken.

Kerngroep

Prof. dr. M.V. (Menno) Huisman, internist-vasculaire geneeskunde, LUMC, NIV (voorzitter)
Dr. M.J.H.A. (Marieke) Kruip, internist-hematoloog, Erasmus MC, NIV, NVVH (Nederlandse Vereniging voor Hematologie)
Prof. Dr. F.A. (Erik) Klok, internist-vasculaire geneeskunde, LUMC, NIV
Dr. J. (Jenneke) Leentjens, internist-vasculaire geneeskunde, RadboudUMC, NIV (vanaf 2023)
Dr. N. (Nick) van Es, internist-vasculaire geneeskunde, Amsterdam UMC, NIV (vanaf 2023)
Dr. M.A. (Marc) Brouwer, cardioloog, RadboudUMC, NVVC
Dr. H.B. (Harmen) Ettema, orthopedisch chirurg, Isala, NOV
Dr. B. (Banne) Nemeth, aios orthopedie, LUMC, NOV
Dr. A.M. (Arno) Wiersema, vaatchirurg, Dijklander Ziekenhuis, NVVH (tot 2023)
Dr. M.C. (Michiel) Warlé, vaatchirurg, RadboudUMC, NVVH (vanaf 2024)
Dr. M.E. (Maarten) Tushuizen, maag-darm-leverarts, LUMC, NVMDL
Dr. J.M. (Jonathan) Coutinho, neuroloog, Amsterdam UMC, NVN
Drs. M.H. (Monique) Suijker, kinderarts-hematoloog, UMC Utrecht, NVK
Drs. P (Paul) Smits, huisarts/ Kaderhuisarts HVZ, NHG

Klankbordgroep

Dr. J.J.C.M. (Sjef) van de Leur, arts klinische chemie, Isala, NVKC
Dr. M.G. (Mariëlle) van Pampus, gynaecoloog, OLVG, NVOG
Drs. R.J. (Rutger) Lely, radioloog, Amsterdam UMC, NVVR
Dr. C. (Bibi) van Montfrans, dermatoloog, Erasmus MC, NVDV
Dr. R.A. (Richard) Faaij, klinisch geriater, Diakonessenhuis, NVKG
Dr. B. (Baucke) van Minnen, kaakchirurg, UMCG, NVMKA
Drs. N. (Noa) Rosenberg, beleidsadviseur, Harteraad (vanaf mei 2024)
I.G.J. (Ilse) Verstraaten MSc, beleidsadviseur, Harteraad (tot 2024)
Dr. N. (Nakisa) Khorsand, ziekenhuisapotheker, OLVG, NVZA
Dr. M.F. (Margreet) van Herwaarden, openbaar apotheker, KNMP
Dr. E.T.T.L. (Eric) Tjwa, MDL-arts, RadboudUMC, NVMDL
Dr. L.M. (Linda) de Heer, cardio-thoracaal chirurg, UMC Utrecht, NVT
Prof. dr. S. (Saskia) Middeldorp, internist-vasculaire geneeskunde, Radboudumc, NIV
Dr. J.M.M.B. (Hans-Martin) Otten, internist-oncoloog, Meander MC, NIV
Dr. E.J. (Esther) Nossent, longarts, Amsterdam UMC, NVALT
Dr. C.H. (Heleen) van Ommen, kinderarts-hematoloog, Erasmus MC, NVK
Dr. K.M.J. (Katja) Heitink, kinderarts-oncoloog, Prinses Maxima Centrum, NVK
Prof. dr. N.P. (Nicole) Juffermans, intensivist, Amsterdam UMC, NVIC
Dr. M.C.A. (Marcella) Muller, intensivist, Amsterdam UMC, NVIC

Met ondersteuning van

H. (Hanneke) Olthuis, adviseur, Kennisinstituut van de Federatie Medisch Specialisten
H.J. (Harm-Jan) van der Hart, adviseur, Kennisinstituut van de Federatie Medisch Specialisten

Belangenverklaringen

Een overzicht van de belangen van werkgroepleden en het oordeel over het omgaan met eventuele belangen vindt u in onderstaande tabel. De ondertekende belangenverklaringen zijn op te vragen bij het secretariaat van het Kennisinstituut van de Federatie Medisch Specialisten via secretariaat@kennisinstituut.nl.

Werkgroeplid	Functie	Nevenfuncties	Gemelde belangen	Ondernomen actie
Huisman (voorzitter)	Internist vasculaire geneeskunde	voorzitter Dutch Thrombosis Network – onbetaald voorzitter Nationaal Kennisplatform Antistollingszorg – onbetaald medisch leider Trombosedienst Leiden - detachering LUMC	ZonMW Dutch Healthcare Fund – herseninfarct na covid-19 en register van patienten met atrium fibrilleren NHS – herseninfarct na covid-19 Boehringer Ingelheim – register atriumfibrilleren – afgesloten Bristol-Myers Squibb/Pfizer – VTE behandeling bij patienten met maligniteit – afgesloten Bayer Health Care - VTE behandeling bij patienten met maligniteit – afgesloten Aspen – webinar anti-Xa bepaling bij LMWH – afgesloten Daiichi-Sankyo – deelname studie cancer associated thrombosis – afgesloten à op geen van deze projecten projectleider, betreft unrestricted grants en veelal financiering promotietrajecten.	Geen restricties
Banne Nemeth	Orthopedisch chirurg in opleiding	Postdoc klinische epidemiologie en orthopedie, LUMC	Trombosestichting - “VTE following total hip and knee arthroplasty: prediction is the future“	Geen restricties
Harmen Ettema	Orthopedisch chirurg Isala zwolle	Geen	Gemeld bij herbevestiging in 2025: ZonMW, Distinct trial, tromboseprofylaxe bij orthopedische ingrepen, geen projectleider	Geen restricties
Jonathan Coutinho	neuroloog Amsterdam UMC	Geen	Bayer - Pacific stroke en Oceanic stroke study, onderzoek naar inzet van nieuw middel bij patienten met een beroerte, national leader en SC member) Boehringer Ingelheim - RESPECT CVT, vergelijking dabigatran Etexilate met Warfarin, SC member, AstraZeneca, Portola - ANNEXA-I studie, onderzoek naar inzet van Andexanet alfa bij patienten met intracraniele bloeding, national leader Gemeld bij herbevestiging in 2025: ZonMw, Hartstichting, Eurostars, Trombosestichting, Europese Unie, Health-Holland, NWO, onderzoek naar diagnostiek en behandeling van een beroerte Co-founder TrianecT BV fellow European Stroke Organization lid richtlijn commissie ESO over cerebrale sinustrombose editorial board member Stroke en Journal of Neurology leadership International cerebral venous thrombosis consortium	Restricties t.a.v. besluitvorming modules over andexanet alfa bij bloedingen geen restricties ten gevolge van rol pacific stroke study en dabigatran etixilate/warfarin bij CVT, aangezien deze patientengroepen geen onderwerp zijn van deze richtlijnherziening.
Klok	Internist vasculaire geneeskunde LUMC Leiden	Bestuur NVIVG Bestuur ESC werkgroep pulmonale circulatie Bestuur ISTH SSC werkgroep diagnostische en predictieve variabelen (tot 2024) Bestuur Dutch Thrombosis Network Gastwetenschapper Universiteit Mainz (Duitsland) Gemeld bij herbevestiging in 2024: Medisch leider Trombosedienst Leiden (tot 1-1-25)	Bayer, Leo Pharma en BSCI – voorzitter van een internationale werkgroep om een standaard set van uitkomsten (ICHOM) te maken voor VTE – inmiddels afgesloten Actelion en The Netherlands Organisation for Health Research and Development - mede-aanvrager van 3 ZonMw beurzen voor onderzoek naar voorkomen van VTE en herseninfarcten bij COVID-19 patiënten (DC&TC en CORONIS consortium - DC&TC wordt ook ondersteund door TSN en een unrestricted grant van Actelion voor diagnostiek deel - afgesloten The Dutch Thrombosis Association -onderzoek naar nieuwe beeldvormende technieken van trombose The Dutch Heart Foundation - lange termijn prognose van longembolie - afgesloten the Horizon Europe Program - voorzitter van een Europees consortium dat tot doel heeft het gebruik van antitrombotische medicatie in de laatste levensfase te optimaliseren	Geen restricties
Kruip	Hematoloog Gemeld bij herbevestiging in 2024: Directeur Kwaliteit & Patientenzorg, Erasmus MC, betaald	Medisch leider trombosedienst Star-shl (0.2FTE), gedetacheerd vanuit Erasmus MC, betaald voorzitter Federatie Nederlandse Trombosediensten (FNT), onbetaald Gemeld bij herbevestiging in 2024: RvC Lenticure, onbetaald RvT Trombosestichting, onbetaald	Horizon Europe programme Trombosestichting/ZonMw Sprekers vergoedingen gehad van Sobi, Roche en Bristol Myers Squibb; betaling aan het Erasmus MC	Geen restricties
Maarten Tushuizen	MDL-arts LUMC	Geen	Maag-Lever-Darmstichting (MLDS)	Geen restricties
Marc Brouwer	Cardioloog Radboudumc	Geen	Nee	Geen restricties
Paul Smits	huisarts, zelfstandig	Coördinator onderwijscommissie harvaatHAG	geen	Geen restricties
Monique Suijker	Kinderarts-hematoloog werkzaam bij Van Creveldkliniek, UMCU	Geen	Geen lopende studies Bayer en Janssen - Einstein Jr studie - gebruik Rivaroxaban bij kinderen – afgesloten	Geen restricties
Arno Wiersema (teruggetrokken, tot 2024)	Vaatchirurg, Dijklander ziekenhuis	Geen	ZonMw, Amsterdam UMC, Dijklander zh en Medtronic - www.action-1.nl - betreft onderzoek naar rol van heparine bij een open buikslagader operatie, rol als projectleider	Restricties ten aanzien van besluitvorming over heparine.
Michiel Warlé (vanaf 2024)	Vaatchirurg Radboudumc	Werkgroep Landelijk Kennisplatform Antistolling	ZEGG/ZonMw- GENPAD studie (Cyp2c19 genotypering bij Clopidogrel en perifeer arterieel vaatlijden – hoofdonderzoeker Gemeld bij herbevestiging in 2025: NWO-OTP, Wireless clot retriever, projectleider	Geen restricties
Nick van Es (vanaf 2023)	Internist-vasculaire geneeskunde, Amsterdam UMC, locatie AMC	Geen	Trombosestichting – PREVENT (PREdicting VENous Thromboembolism in pancreatic cancer patients) NWO - Blood vessels-on-chip to understand and target COVID-19 intravascular coagulation Gemeld bij herbevestiging in 2024: Deelname Podcast LEO Pharma (2024) Sprekersvergoeding Werfen en Amgen (2024) Eenmalige adviesraad Pfizer (2019) Anthos Therapeutics, ASTER-study en MAGNOLIA-study, effectiviteit en veiligheid van abelacimab (niet geregistreerd middel) in patienten met kankergerelateerde trombose, rol als national lead investigator. NWO, Atherosclerotic cardiovascular disease induced by immune checkpoint inhibitors, rol als projecteleider	Geen restricties
Leentjens (vanaf 2023)	Internist-vasculair geneeskundige, Radboudumc	Geen	Astra Zeneca - scientific steering comité van database studie over bloedingen bij ptn die Xa remmers gebruiken (apixaban, edoxaban Adviesraad Viatris (tot begin 2024) Synapse B.V. – studie naar interactie tussen hemostase en inflammatie bij patiënten met een herseninfarct op jonge leeftijd	Geen restricties
Actieve klankbordgroepleden
Esther Nossent	Longarts Amsterdam UMC	Geen	Janssen, Bayer, MSD, United Therapeutics, Ferrer - OPTICS Boehringer Ingelheim B.V., AbbVie, PEXAS – P402 ILD-extension Gemeld bij herbevestiging in 2025: Deelnemer ICHOM-project, internationale werkgroep om een standaardset van uitkomsten te maken voor VTE Sprekersvergoedingen voor onderwijsevents in afgelopen 5 jaar: Astra Zeneca, Janssen, Bayer/ MSD, Boehringer Ingelheim B.V., Chiesi, GlaxoSmithKline B.V., Novartis, Roche, United Therapeutics/Ferrer Deelname adviesraden: Bayer/MSD (lopend) en Boehringer Ingelheim (afgesloten)	Geen restricties
Heleen van Ommen	Hoofd afd. Kinderhematologie & kinderoncologie Erasmus MC Sophia Kinderziekenhuis	Geen	Daiicho Sankyo - Fase 3 trial effectiviteit van edoxaban voor behandeling van trombose bij kinderen, local PI en steeringCie - afgesloten Octopharma - Microscopic evaluation of clots in ECMO systems, rol als PI BI/BMS en INVENT – chair IPTN ThromPED registry (international observational registry/study of children with thrombosis, Adviseur voor verschillende farmaceuten voor ontwikkeling van onderzoek van antistollingsmiddelen of antidota bij kinderen zoals Asundexian (Bayer BV), andexanet (Astra Zeneca) – tot deelname clusterstuurgroep	Geen restricties
Eric Tjwa	MDL arts, Radboudumc	Geen	Geen Gemeld bij herbevestiging in 2025: Geen betrokkenheid bij onderzoeken die direct/indirect verband houden met de inhoud van de richtlijn	Geen restricties
Hans-Martin Otten (vanaf 2024)	Internist Meander MC	Lid METC UMCU, betaald	Eenmalig advies aan Leo Pharma: standpunten over de zorg bij patiënten met VTE en kanker in NL (19-11-2019) ANT-007 & ANT-008 multi-center studies, abelcimab vs apixaban bij kankergerelateerde VTE, participatie in Meander MC Hukusai-study, participatie - afgesloten Einstein-study, adjudicatie-cie - afgesloten	Geen restricties
Noa Rosenberg (vanaf 2024)	Beleidsadviseur		Geen	Geen restricties
Katja Heitink – Pollé	Kinderoncoloog Prinses Máxima Centrum	Landelijke werkgroep trombose bij kinderen	geen	Geen restricties

Inbreng patiëntenperspectief

De werkgroep besteedde aandacht aan het patiëntenperspectief door uitnodigen van Stichting Harteraad voor de schriftelijke knelpuntenanalyse en door een patiëntvertegenwoordiger van Stichting Harteraad toe te voegen aan de klankbordgroep. De verkregen input is meegenomen bij het opstellen van de uitgangsvragen, de keuze voor de uitkomstmaten en bij het opstellen van de overwegingen (zie alinea waarden en voorkeuren van patiënten). De conceptrichtlijn is tevens voor commentaar voorgelegd aan Stichting Harteraad en Stichting Kind en Ziekenhuis en de eventueel aangeleverde commentaren zijn bekeken en verwerkt.

Kwalitatieve raming van mogelijke financiële gevolgen in het kader van de Wkkgz

Bij de richtlijnmodule voerde de werkgroep conform de Wet kwaliteit, klachten en geschillen zorg (Wkkgz) een kwalitatieve raming uitom te beoordelen of de aanbevelingen mogelijk leiden tot substantiële financiële gevolgen. Bij het uitvoeren van deze beoordeling is de richtlijnmodule op verschillende domeinen getoetst (zie het stroomschema bij Werkwijze).

Module	Uitkomst raming	Toelichting
Follow-up VTE	geen financiële gevolgen	Hoewel uit de toetsing volgt dat de aanbevelingen breed toepasbaar zijn (5.000-40.000 patiënten), volgt ook uit de toetsing dat het overgrote deel (±90%) van de zorgaanbieders en zorgverleners al aan de norm voldoet. Er worden daarom geen substantiële financiële gevolgen verwacht.

Zoekverantwoording

ICHOM-search 08-03-2021

PubMed search 08-03-2021: 584 resultaten, met gebruik van filters ’English language’ en ’Publication in past 10 years’.

Daarnaast 420 non-PubMed resultaten:

Embase: 601 - 346 uniek
Web of Science: 130 - 21 uniek
Cochrane Library: 109 - 53 uniek (waaronder 29 clinicaltrialregister-items)

PubMed

((("venous thrombo-embolism"[tw] OR "venous thromboembolism"[tw] OR "deep venous thrombosis"[tw] OR "DVT"[tw] OR "Venous Thrombosis"[mesh] OR "venous thrombosis"[tw] OR "Pulmonary Embolism"[mesh] OR "pulmonary embolism"[tw]) AND ("Patient Reported Outcome Measures"[Mesh] OR "PROMS"[tw] OR "patient-reported"[tw] OR "patient reported"[tw] OR "patient-relevant"[tw] OR "patient relevant"[tw]) NOT (("Case Reports"[ptyp] OR "case report"[ti] OR "Clinical Trial Protocol"[ptyp] OR "protocol"[ti]) NOT ("Review"[ptyp] OR "review"[ti] OR "Clinical Study"[ptyp] OR "trial"[ti] OR "RCT"[ti])) NOT (("Child"[Mesh] OR "child"[ti] OR "children"[ti] OR "Infant"[Mesh] OR "infant"[ti] OR "infants"[ti] OR "infancy"[ti] OR "pediatr*"[ti] OR "paediatr*"[ti]) NOT ("Adult"[mesh] OR "adult"[ti] OR "adults"[ti] OR "elderly"[ti] OR "Adolescent"[Mesh] OR "adolescent"[ti] OR "adolescents"[ti] OR "adolescence"[ti])) NOT (("Animals"[mesh] OR "veterinary"[ti] OR "rabbit"[ti] OR "rabbits"[ti] OR "animal"[ti] OR "animals"[ti] OR "mouse"[ti] OR "mice"[ti] OR "rodent"[ti] OR "rodents"[ti] OR "rat"[ti] OR "rats"[ti] OR "pig"[ti] OR "pigs"[ti] OR "porcine"[ti] OR "horse"[ti] OR "horses"[ti] OR "equine"[ti] OR "cow"[ti] OR "cows"[ti] OR "bovine"[ti] OR "goat"[ti] OR "goats"[ti] OR "sheep"[ti] OR "ovine"[ti] OR "canine"[ti] OR "dog"[ti] OR "dogs"[ti] OR "feline"[ti] OR "cat"[ti] OR "cats"[ti]) NOT "Humans"[mesh])) OR (("venous thrombo-embolism"[ti] OR "venous thromboembolism"[ti] OR "deep venous thrombosis"[ti] OR "DVT"[ti] OR "Venous Thrombosis"[majr] OR "venous thrombosis"[ti] OR "Pulmonary Embolism"[majr] OR "pulmonary embolism"[ti]) AND ("Treatment Outcome"[majr] OR "Treatment Outcome"[tiab] OR "Disease-Free Survival"[tiab] OR "Early Termination of Clinical Trials"[tiab] OR "Progression-Free Survival"[tiab] OR "Therapeutic Index"[tiab] OR "Treatment Failure"[tiab] OR "Patient Reported Outcome Measures"[majr] OR "PROMS"[tiab] OR "patient-reported"[tiab] OR "patient reported"[tiab] OR "patient-relevant"[tiab] OR "patient relevant"[tiab] OR "Quality of Life"[majr] OR "Quality of life"[tiab] OR "QoL"[tiab] OR "HRQoL"[tiab]) NOT (("Case Reports"[ptyp] OR "case report"[ti] OR "Clinical Trial Protocol"[ptyp] OR "protocol"[ti]) NOT ("Review"[ptyp] OR "review"[ti] OR "Clinical Study"[ptyp] OR "trial"[ti] OR "RCT"[ti])) NOT (("Child"[Mesh] OR "child"[ti] OR "children"[ti] OR "Infant"[Mesh] OR "infant"[ti] OR "infants"[ti] OR "infancy"[ti] OR "pediatr*"[ti] OR "paediatr*"[ti]) NOT ("Adult"[mesh] OR "adult"[ti] OR "adults"[ti] OR "elderly"[ti] OR "Adolescent"[Mesh] OR "adolescent"[ti] OR "adolescents"[ti] OR "adolescence"[ti])) NOT (("Animals"[mesh] OR "veterinary"[ti] OR "rabbit"[ti] OR "rabbits"[ti] OR "animal"[ti] OR "animals"[ti] OR "mouse"[ti] OR "mice"[ti] OR "rodent"[ti] OR "rodents"[ti] OR "rat"[ti] OR "rats"[ti] OR "pig"[ti] OR "pigs"[ti] OR "porcine"[ti] OR "horse"[ti] OR "horses"[ti] OR "equine"[ti] OR "cow"[ti] OR "cows"[ti] OR "bovine"[ti] OR "goat"[ti] OR "goats"[ti] OR "sheep"[ti] OR "ovine"[ti] OR "canine"[ti] OR "dog"[ti] OR "dogs"[ti] OR "feline"[ti] OR "cat"[ti] OR "cats"[ti]) NOT "Humans"[mesh])))

Embase

http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=main&MODE=ovid&D=oemezd

(((exp *"venous thromboembolism"/ OR "venous thrombo-embolism".ti,ab OR "venous thromboembolism".ti,ab OR "deep venous thrombosis".ti,ab OR "DVT".ti,ab OR *"Vein Thrombosis"/ OR "venous thrombosis".ti,ab OR exp *"Lung Embolism"/ OR "pulmonary embolism".ti,ab) AND ("patient-reported outcome"/ OR "PROMS".ti,ab OR "patient-reported".ti,ab OR "patient reported".ti,ab OR "patient-relevant".ti,ab OR "patient relevant".ti,ab) NOT (("Case Report"/ OR "case report".ti OR "Clinical Trial Protocol"/ OR "protocol".ti) NOT (exp "Review"/ OR "review".ti OR "Clinical Study"/ OR exp "Clinical Trial"/ OR "trial".ti OR "RCT".ti)) NOT ((exp "Child"/ OR "child".ti OR "children".ti OR exp "Infant"/ OR "infant".ti OR "infants".ti OR "infancy".ti OR "pediatr*".ti OR "paediatr*".ti) NOT (exp "Adult"/ OR "adult".ti OR "adults".ti OR "elderly".ti OR exp "Adolescent"/ OR "adolescent".ti OR "adolescents".ti OR "adolescence".ti)) NOT ((exp "Animals"/ OR "veterinary".ti OR "rabbit".ti OR "rabbits".ti OR "animal".ti OR "animals".ti OR "mouse".ti OR "mice".ti OR "rodent".ti OR "rodents".ti OR "rat".ti OR "rats".ti OR "pig".ti OR "pigs".ti OR "porcine".ti OR "horse".ti OR "horses".ti OR "equine".ti OR "cow".ti OR "cows".ti OR "bovine".ti OR "goat".ti OR "goats".ti OR "sheep".ti OR "ovine".ti OR "canine".ti OR "dog".ti OR "dogs".ti OR "feline".ti OR "cat".ti OR "cats".ti) NOT exp "Humans"/)) OR ((exp *"venous thromboembolism"/ OR "venous thrombo-embolism".ti OR "venous thromboembolism".ti OR "deep venous thrombosis".ti OR "DVT".ti OR *"Vein Thrombosis"/ OR "venous thrombosis".ti OR exp *"Lung Embolism"/ OR "pulmonary embolism".ti) AND (exp *"Treatment Outcome"/ OR "Treatment Outcome".ti,ab OR "Disease-Free Survival".ti,ab OR "Early Termination of Clinical Trials".ti,ab OR "Progression-Free Survival".ti,ab OR "Therapeutic Index".ti,ab OR "Treatment Failure".ti,ab OR *"patient-reported outcome"/ OR "PROMS".ti,ab OR "patient-reported".ti,ab OR "patient reported".ti,ab OR "patient-relevant".ti,ab OR "patient relevant".ti,ab OR exp *"Quality of Life"/ OR "Quality of life".ti OR "QoL".ti OR "HRQoL".ti) NOT (("Case Report"/ OR "case report".ti OR "Clinical Trial Protocol"/ OR "protocol".ti) NOT (exp "Review"/ OR "review".ti OR "Clinical Study"/ OR exp "Clinical Trial"/ OR "trial".ti OR "RCT".ti)) NOT ((exp "Child"/ OR "child".ti OR "children".ti OR exp "Infant"/ OR "infant".ti OR "infants".ti OR "infancy".ti OR "pediatr*".ti OR "paediatr*".ti) NOT (exp "Adult"/ OR "adult".ti OR "adults".ti OR "elderly".ti OR exp "Adolescent"/ OR "adolescent".ti OR "adolescents".ti OR "adolescence".ti)) NOT ((exp "Animals"/ OR "veterinary".ti OR "rabbit".ti OR "rabbits".ti OR "animal".ti OR "animals".ti OR "mouse".ti OR "mice".ti OR "rodent".ti OR "rodents".ti OR "rat".ti OR "rats".ti OR "pig".ti OR "pigs".ti OR "porcine".ti OR "horse".ti OR "horses".ti OR "equine".ti OR "cow".ti OR "cows".ti OR "bovine".ti OR "goat".ti OR "goats".ti OR "sheep".ti OR "ovine".ti OR "canine".ti OR "dog".ti OR "dogs".ti OR "feline".ti OR "cat".ti OR "cats".ti) NOT exp "Humans"/))) NOT (conference review or conference abstract).pt

Web of Science

http://isiknowledge.com/wos

((ab=("venous thromboembolism" OR "venous thrombo-embolism" OR "venous thromboembolism" OR "deep venous thrombosis" OR "DVT" OR "Vein Thrombosis" OR "venous thrombosis" OR "Lung Embolism" OR "pulmonary embolism") AND ti=("patient-reported outcome" OR "PROMS" OR "patient-reported" OR "patient reported" OR "patient-relevant" OR "patient relevant") NOT ti=(("Case Report" OR "case report" OR "Clinical Trial Protocol" OR "protocol") NOT ("Review" OR "review" OR "Clinical Study" OR "Clinical Trial" OR "trial" OR "RCT")) NOT ti=(("Child" OR "child" OR "children" OR "Infant" OR "infant" OR "infants" OR "infancy" OR "pediatr*" OR "paediatr*") NOT ("Adult" OR "adult" OR "adults" OR "elderly" OR "Adolescent" OR "adolescent" OR "adolescents" OR "adolescence")) NOT ti=("Animals" OR "veterinary" OR "rabbit" OR "rabbits" OR "animal" OR "animals" OR "mouse" OR "mice" OR "rodent" OR "rodents" OR "rat" OR "rats" OR "pig" OR "pigs" OR "porcine" OR "horse" OR "horses" OR "equine" OR "cow" OR "cows" OR "bovine" OR "goat" OR "goats" OR "sheep" OR "ovine" OR "canine" OR "dog" OR "dogs" OR "feline" OR "cat" OR "cats")) OR (ti=("venous thromboembolism" OR "venous thrombo-embolism" OR "venous thromboembolism" OR "deep venous thrombosis" OR "DVT" OR "Vein Thrombosis" OR "venous thrombosis" OR "Lung Embolism" OR "pulmonary embolism") AND ti=("Treatment Outcome" OR "Treatment Outcome" OR "Disease-Free Survival" OR "Early Termination of Clinical Trials" OR "Progression-Free Survival" OR "Therapeutic Index" OR "Treatment Failure" OR "patient-reported outcome" OR "PROMS" OR "patient-reported" OR "patient reported" OR "patient-relevant" OR "patient relevant" OR "Quality of Life" OR "Quality of life" OR "QoL" OR "HRQoL") NOT ti=(("Case Report" OR "case report" OR "Clinical Trial Protocol" OR "protocol") NOT ("Review" OR "review" OR "Clinical Study" OR "Clinical Trial" OR "trial" OR "RCT")) NOT ti=(("Child" OR "child" OR "children" OR "Infant" OR "infant" OR "infants" OR "infancy" OR "pediatr*" OR "paediatr*") NOT ("Adult" OR "adult" OR "adults" OR "elderly" OR "Adolescent" OR "adolescent" OR "adolescents" OR "adolescence")) NOT ti=("Animals" OR "veterinary" OR "rabbit" OR "rabbits" OR "animal" OR "animals" OR "mouse" OR "mice" OR "rodent" OR "rodents" OR "rat" OR "rats" OR "pig" OR "pigs" OR "porcine" OR "horse" OR "horses" OR "equine" OR "cow" OR "cows" OR "bovine" OR "goat" OR "goats" OR "sheep" OR "ovine" OR "canine" OR "dog" OR "dogs" OR "feline" OR "cat" OR "cats")) OR (ti=("venous thromboembolism" OR "venous thrombo-embolism" OR "venous thromboembolism" OR "deep venous thrombosis" OR "DVT" OR "Vein Thrombosis" OR "venous thrombosis" OR "Lung Embolism" OR "pulmonary embolism") AND ab=("patient-reported outcome" OR "PROMS" OR "patient-reported" OR "patient reported" OR "patient-relevant" OR "patient relevant") NOT ti=(("Case Report" OR "case report" OR "Clinical Trial Protocol" OR "protocol") NOT ("Review" OR "review" OR "Clinical Study" OR "Clinical Trial" OR "trial" OR "RCT")) NOT ti=(("Child" OR "child" OR "children" OR "Infant" OR "infant" OR "infants" OR "infancy" OR "pediatr*" OR "paediatr*") NOT ("Adult" OR "adult" OR "adults" OR "elderly" OR "Adolescent" OR "adolescent" OR "adolescents" OR "adolescence")) NOT ti=("Animals" OR "veterinary" OR "rabbit" OR "rabbits" OR "animal" OR "animals" OR "mouse" OR "mice" OR "rodent" OR "rodents" OR "rat" OR "rats" OR "pig" OR "pigs" OR "porcine" OR "horse" OR "horses" OR "equine" OR "cow" OR "cows" OR "bovine" OR "goat" OR "goats" OR "sheep" OR "ovine" OR "canine" OR "dog" OR "dogs" OR "feline" OR "cat" OR "cats")) OR (ti=("venous thromboembolism" OR "venous thrombo-embolism" OR "venous thromboembolism" OR "deep venous thrombosis" OR "DVT" OR "Vein Thrombosis" OR "venous thrombosis" OR "Lung Embolism" OR "pulmonary embolism") AND ti=("patient-reported outcome" OR "PROMS" OR "patient-reported" OR "patient reported" OR "patient-relevant" OR "patient relevant") NOT ti=(("Case Report" OR "case report" OR "Clinical Trial Protocol" OR "protocol") NOT ("Review" OR "review" OR "Clinical Study" OR "Clinical Trial" OR "trial" OR "RCT")) NOT ti=(("Child" OR "child" OR "children" OR "Infant" OR "infant" OR "infants" OR "infancy" OR "pediatr*" OR "paediatr*") NOT ("Adult" OR "adult" OR "adults" OR "elderly" OR "Adolescent" OR "adolescent" OR "adolescents" OR "adolescence")) NOT ti=("Animals" OR "veterinary" OR "rabbit" OR "rabbits" OR "animal" OR "animals" OR "mouse" OR "mice" OR "rodent" OR "rodents" OR "rat" OR "rats" OR "pig" OR "pigs" OR "porcine" OR "horse" OR "horses" OR "equine" OR "cow" OR "cows" OR "bovine" OR "goat" OR "goats" OR "sheep" OR "ovine" OR "canine" OR "dog" OR "dogs" OR "feline" OR "cat" OR "cats"))) NOT dt=(meeting abstract)

Richtlijnendatabase

Antitrombotisch beleid

Antitrombotisch beleid

Follow-up VTE

Uitgangsvraag

Aanbeveling

Overwegingen

Onderbouwing

Achtergrond

Conclusies / Summary of Findings

Samenvatting literatuur

Zoeken en selecteren

Referenties

Evidence tabellen

Verantwoording

Beoordelingsdatum en geldigheid

Initiatief en autorisatie

Algemene gegevens

Samenstelling werkgroep

Belangenverklaringen

Inbreng patiëntenperspectief

Module

Zoekverantwoording

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