Over het LUMC— Afdelingen— Trombose en Hemostase— Prevention, treatment and prognosis of thrombosis
Trombose en Hemostase

Prevention, treatment and prognosis of thrombosis

Venous thrombosis (deep vein thrombosis and pulmonary embolism) is a frequent and potentially fatal condition. Throughout the clinical course of venous thrombosis, several choices regarding diagnostic and therapeutic management must be tailored to the individual patient to achieve optimal treatment results and hence, prognosis. Furthermore, knowledge on risk factors and predictors of thrombosis will lead to optimal prevention strategies.

Focus on making a difference for patients

Our research activities focus on making the best management decisions throughout the entire patient pathway, including prevention of disease. We lead and participate in large national and international clinical trials within the Dutch Thrombosis Network, PEITHO network and INVENT VTE. Studies that are performed within our research group all have a very clear focus on solving current uncertainties in clinical decision making and improving long-term quality of life. The results of these studies change international guidelines and clinical practice.

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Focus on making a difference for patients

Our research activities focus on making the best management decisions throughout the entire patient pathway, including prevention of disease. We lead and participate in large national and international clinical trials within the Dutch Thrombosis Network, PEITHO network and INVENT VTE. Studies that are performed within our research group all have a very clear focus on solving current uncertainties in clinical decision making and improving long-term quality of life. The results of these studies change international guidelines and clinical practice.

Innovation in care for patients with venous thrombosis

Novel treatment possibilities for venous thrombosis, both interventional as well as pharmacological, have been introduced in the past years or are about to be introduced. We run study programs to determine which patients may benefit most from these novel treatment modalities. Moreover, we have a strong focus on long-term outcomes, including persistent symptoms of pain or dyspnea, but also functional outcomes, quality of life and psychosocial sequala such as anxiety and depression. Our research group is word-leading in developing and validating tools to measure these long-term complications, implementing these tools in routine practice and studying interventions aimed at improving quality of life.

Optimal prevention of venous thrombosis

Ultimately, prevention of venous thrombosis will most effectively reduce burden of disease. For several situations where we know that the risk of venous thrombosis is increased, anticoagulant treatment is given, which is fairly effective in reducing this high risk. However, the drawback of such treatment is a high risk of bleeding.

In our studies we apply state-of-the-art statistical techniques to large datasets that consist of both clinical and laboratory data. This way, individual risk profiles can be developed that identify persons at high risk of thrombosis. Based on these profiles, individual prevention strategies can be developed, to reduce both venous thrombosis and bleeding complications.

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PROGNOSIS AND OPTIMAL MANAGEMENT OF VENOUS THROMBOSIS
SERENITY
IDENTIFICATION OF PATIENTS AT HIGH RISK OF VENOUS THROMBOSIS

PROGNOSIS AND OPTIMAL MANAGEMENT OF VENOUS THROMBOSIS

Our group has a leading role in several randomized controlled trials that aim to improve short- and long-term prognosis of patients with venous thrombosis, such as the SAFE-SSPE to study the relevance of treating subsegmental pulmonary embolism, the L-TRRiP study to evaluate the optimal duration of anticoagulation for venous thrombosis based on individualized assessment of the risk of recurrent thrombosis and bleeding, and the HI-PEITHO and PEITHO 3 randomized clinical trials in which novel reperfusion strategies are evaluated in patients with severe but not yet high-risk pulmonary embolism, i.e., catheter directed thrombolysis and half-dose systemic thrombolysis, respectively.

In addition and in close collaboration with patient representatives, we develop new instruments to measure the outcome of venous thrombosis treatment, e.g. the post-VTE functional status scale, and constructed a standard set of outcome parameters that capture all outcomes that matter most to patients and healthcare professionals taking care of patients with venous thrombosis: ICHOM VTE. These sets are being integrated in the routine care for patients with venous thrombosis, as well as in the above mentioned trials. This increases knowledge on the impact of different management decisions on the long term, and better allows for shared decision making.

SERENITY

Advance care planning for patients with terminal and life limiting illness has become the standard of care across Europe. One component of this multi-professional process includes rationalization of pharmacotherapy, including the deprescribing of medicines that are no longer necessary and/or potentially harmful. Despite the fact that antithrombotic therapy (ATT), comprising anticoagulant or antiplatelet agents, has little or even negative effects on cancer patients’ wellbeing, stopping ATT near the end of life is rare in clinical practice. Due to the overall lack of evidence, many healthcare professionals feel uncertain about timing of deprescription of ATT and lack the tools to objectively assess the relevant risks for a given patient, with a tendency to overestimate the risk of cardiovascular complications in the short term and underestimate the risk of bleeding events. Individual expectations of patients may also interact with clinician perception of the benefit of ATT. As a result of this lack of knowledge and tendency to overemphasize the benefits of ATT, it is often reluctantly continued until death or until the patient has developed a relevant bleeding complication,  contributing to an increased disease burden for patients already experiencing a highly stressful and emotional palliative care period.

Our group is leading the Horizon-Europe funded Serenity project that aims to lay the foundation for optimal ATT in cancer patients at the end of life, with the ultimate goal to improve their QoL and satisfaction through patient empowerment and the reduction of disease burden by preventing bleeding events but -through careful risk prediction- without an increase in cardiovascular complications. The main objective is to develop, test, validate, and widely implement the state-of-the-art SERENITY intervention: a user-friendly, easily accessible, web-based shared decision support tool, taking all relevant psychosocial, socioeconomic, cultural, religious, and other aspects into account.

IDENTIFICATION OF PATIENTS AT HIGH RISK OF VENOUS THROMBOSIS

It is well known that certain clinical conditions and situations are associated with an, on average, increased risk of venous thrombosis. Examples are pregnancy, oral contraceptive use, trauma, surgery and cancer. In our research we combine extensive laboratory and clinical data from several sources, which allows development of algorithms that, by integrating all this knowledge, can estimate individual thrombosis risks in such high risk situations.  

In several ongoing projects we study this amongst others for cancer patients, for patients who need hip- or knee replacement, for exposure to hormones (endogenous and exogenous), and for patients with Covid-19. These studies use data from the MEGA-study, the AT-AGE-study, THE-VTE-study, the POT-(K)CAST study and the L-TRRiP study, but also nationwide data from several registries.

Themes for Innovation

Cardio-Vascular
Cancer

Team Members

  • Dr. M.V. Huisman, Internist-Vascular Medicine
  • Dr. F.A. Klok, Internist-Vascular Medicine
  • Dr. S.C Cannegieter
  • H.J. Kaptein, MD – PhD fellow
  • M.M. de Jong, MD – PhD fellow
  • Luijten, MD - PhD fellow
  • S.L. Martens, MD - PhD fellow
  • F.B. van der Horst, MD - PhD fellow
  • L.I Burggraaf, MD – PhD fellow
  • Camilleri, MD – PhD fellow
  • J.S. Anijs, PhD fellow
  • M.J.R. Smeets, MD – PhD fellow

Key publications

Risk for Recurrent Venous Thromboembolism in Patients With Subsegmental Pulmonary Embolism Managed Without Anticoagulation : A Multicenter Prospective Cohort Study.
Chronic thromboembolic pulmonary hypertension and impairment after pulmonary embolism: the FOCUS study.
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.
Triaging acute pulmonary embolism for home treatment by Hestia or simplified PESI criteria: the HOME-PE randomized trial.
Early switch to oral anticoagulation in patients with acute intermediate-risk pulmonary embolism (PEITHO-2): a multinational, multicentre, single-arm, phase 4 trial.
Non-invasive early exclusion of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: the InShape II study.
Incidence of thrombotic complications in critically ill ICU patients with COVID-19.
Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer.
How I assess and manage the risk of bleeding in patients treated for venous thromboembolism.
Prediction of recurrent venous thrombosis in all patients with a first venous thrombotic event: The Leiden Thrombosis Recurrence Risk Prediction model (L-TRRiP).
Differential impact of syncope on the prognosis of patients with acute pulmonary embolism: a systematic review and meta-analysis.
Idarucizumab for Dabigatran Reversal - Full Cohort Analysis.
Thromboprophylaxis after Knee Arthroscopy and Lower-Leg Casting.
One versus two years of elastic compression stockings for prevention of post-thrombotic syndrome (OCTAVIA study): randomised controlled trial.
Efficacy and Safety of Outpatient Treatment Based on the Hestia Clinical Decision Rule with or without N-Terminal Pro-Brain Natriuretic Peptide Testing in Patients with Acute Pulmonary Embolism. A Randomized Clinical Trial.
Idarucizumab for Dabigatran Reversal.
Risk profile and clinical outcome of symptomatic subsegmental acute pulmonary embolism.
Patient outcomes after acute pulmonary embolism. A pooled survival analysis of different adverse events.
Risk of arterial cardiovascular events in patients after pulmonary embolism.
Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty.
Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism: a systematic review and meta-analysis.
Targeted proteomics for evaluating risk of venous thrombosis following traumatic lower‐leg injury or knee arthroscopy
Glucocorticoid use and risk of first and recurrent venous thromboembolism: self-controlled case-series and cohort study
Effect of gender-affirming hormone use on coagulation profiles in transmen and transwomen
High risk of venous thromboembolism after orthopedic surgery in patients with thrombophilia
Association Between Hepatic Triglyceride Content and Coagulation Factors: The Netherlands Epidemiology of Obesity Study
Preventing VTE following total hip and knee arthroplasty: Is prediction the future?
The joint effect of genetic risk factors and different types of combined oral contraceptives on venous thrombosis risk
Clinical risk assessment model to predict venous thromboembolism risk after immobilization for lower-limb trauma
Individualized Thromboprophylaxis in Patients with Lower-Leg Cast Immobilization-A Validation and Subgroup Analysis in the POT-CAST Trial
Risk prediction of recurrent venous thrombosis; where are we now and what can we add?