Evaluating changes in anticoagulation management and the impact on the future of thrombosis care in the Netherlands

Thrombosis, often misunderstood and underestimated, is the formation of a blood clot in the blood vessels. These clots can obstruct normal blood flow, leading to serious complications, such as stroke or heart attack, depending on location.¹

Risk factors for thrombosis include lifestyle elements such as smoking, physical inactivity, and poor diet quality, so modification of activities plays a critical role in reducing cardiovascular risk.² However, some individuals may still develop clots, without any identifiable risk factors, necessitating medical intervention.³

Patients who exhibit an increased risk of thrombosis are treated with anticoagulants which reduce the blood's ability to clot. The primary goal of this treatment is to prevent the existing clot from enlarging and/or to prevent the formation of new clots. For some individuals, lifelong medication may be required, making effective anticoagulation management essential to minimize the risk of thrombosis.⁴

In a recent webinar Dr. Melchior Nierman, Chief Medical Officer at Unilabs and head of an anticoagulation clinic in the Netherlands, discussed the evolving landscape of anticoagulation treatment and its implications for the future of thrombosis care.

Goal setting in anticoagulation management 

The primary goal of anticoagulation care is to minimize the risk of thrombosis while managing the increased risk of bleeding associated with treatment. Healthcare providers use the international normalized ratio (INR) to guide therapy, aiming to keep patients within INR range of between 2.0 - 3.0 for the low therapeutic range, or 2.5 - 3.5 for the high therapeutic range.⁵ Patients with an INR below the target range may be prone to clotting, whereas those above this target range are at risk of bleeding.⁶

A critical measure in anticoagulation management is the ‘time in therapeutic range’ (TTR), which represents the percentage of time a patient’s INR remains within the ideal range for their condition. Achieving a high TTR, typically between 65-75%, is representative of high-quality anticoagulation management.⁷ The goal is to maximize TTR to ensure optimal treatment efficacy and safety.

Dr. Nierman notes a concerning global trend of suboptimal  TTR levels, ‘There is a significant variation in TTR among countries, with an average of 60% in daily practice globally’ ⁸, he observes. Despite this, he is optimistic about the actual potential for improvement. In the Netherlands, various therapeutic strategies have resulted in TTRs as high as 80%, demonstrating the potential for significant enhancement in anticoagulation management worldwide.⁹

A changed treatment landscape  

For decades, vitamin K antagonists (VKAs) were the cornerstone of anticoagulation management. VKAs reduce the production of four key clotting factors in the blood (factor II, VII, IX, X). However, VKAs have notable limitations, including interactions with vitamin K-rich foods and various medications, as well as the need for frequent INR checks to monitor and adjust dosing.^10,11

The introduction of direct oral anticoagulants (DOACs) in 2011 marked a significant advancement in anticoagulation therapy.¹² DOACs which target either Xa or IIa/thrombin, offer several advantages over VKAs: they appear to have almost no interaction with foods, have fewer medication interactions, and crucially, do not require regular INR checks. These benefits have simplified the management of anticoagulation therapy for many patients.^13-15

In the Netherlands, DOACs were incorporated into clinical guidelines in 2016, and have since become the first-line treatment option for thrombosis.^16,17 Dr. Nierman highlights that DOACs are associated with a lower incidence of severe bleeding compared to VKAs, making them a preferable choice for many patients.¹⁸

Although DOACs have revolutionized anticoagulation management¹², and despite the benefits, DOACs are not suitable for all patients. The FRAIL-AF study, published in 2023, revealed that frail older patients experienced a 69% increase in clinically relevant bleeding when switched from VKAs to DOACs.¹⁹ This finding underscores the importance of individualized treatment plans and careful consideration of patient-specific factors when choosing an anticoagulation strategy.

A changed clinical need

Despite the cautious use of DOACs in vulnerable patients, their increased adoption in the Netherlands has significantly reduced the number of patients visiting anticoagulation clinics. In 2015, over 460,000 patients attended these clinics, but by 2022 this number had dropped to just over 200,000.⁹

For patients on VKAs, INR monitoring remains essential. A key development in clinical practice is the introduction of new monitoring technology. Traditionally, patients needed to visit an outpatient clinic to have a blood sample taken and sent to a laboratory for INR testing, with results taking several hours. These results then required interpretation by a healthcare professional before being communicated to the patient.²⁰ Now, with the use of handheld devices that require only a drop of blood, INR results can be obtained in around one minute.²¹ This technology is useful for point of care testing (POCT) in clinics, and for self-monitoring by patients, showing clear benefits. POCT reduces the time medical staff spend on VKA management and enhances patient care by increasing the time they spend in their therapeutic range, with fewer treatment-related complications, thus easing the burden on clinics.^22,23

In the Netherlands, patients who use self-monitoring can further streamline their care by sharing their INR values via a self-measurement portal which provides dosing guidance for self-management of their medication. This technology has led to a 10% increase in  self-measurement and/or management from 2018 to 2022.⁹

These advancements have prompted a re-evaluation of clinic operations across the country. Whereas clinics were previously managed locally, they are now organized on a regional basis with a core collaboration center, for instance, the Center for Anticoagulation & Thrombosis Care (CAT). Dr. Nierman asserts they have developed ‘a model for future-proof anticoagulation management’, which includes a Knowledge Centre, a Self-Measurement Centre, a Central Dosing Centre, and an Emergency Consultation Centre.^24,25 This model, supports 100,000 patients in the Netherlands, producing 1.7 million INR values, with nearly 30% of these patients managed through self-management programs.^9,26

Future Focus

With fully digitized self-measurement and self-management techniques already widely used in Holland, Dr. Niemer aims to further reduce the number of patients reliant on anticoagulation clinics and laboratories for INR testing and reporting. He aspires to transform over 50% of the patient population towards self-measuring and thus managing their anticoagulation therapy in the next few years. To support this goal, several initiatives are planned including digital training and online consultations to empower patients with the knowledge and confidence to effectively participate in their self-measurement programs. 

Another objective of the CAT model is to enhance the quality of care by focusing on what Dr. Nierman calls the ‘T50 population’. These patients exhibit TTR values of below 50 and spend more than half of the time outside the optimal therapeutic range.⁹ By targeting these patients with interventions to improve medication adherence, or by adjusting their medication regimens, the team has achieved significant improvements with TTR values of up to 74%.²⁷ The team plans to continue prioritizing this area to further enhance patient outcomes.

For further details on anticoagulation management and future-proofing thrombosis care, you can watch Dr. Nierman’s full presentation here.