Q J Med 2014; 107:495–497 doi:10.1093/qjmed/hcu084 Advance Access Publication 11 April 2014

Commentary How long to anticoagulate? J. THACHIL From the Department of Haematology, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK Address correspondence to Dr Jecko Thachil, Department of Haematology, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK. email: [email protected]

women using combined oral contraceptive remains increased 4–8 folds regardless the number of years of use).3 In the absence of these dilemmas, the presence of a clearly identifiable risk factor which precipitated the VTE would mean a 3-month period of anticoagulation, even if the presenting diagnosis was a PE.2 Is 3 months anticoagulation however adequate for patients with PE? This issue was addressed in a pooled analysis of individual participants’ data from seven randomized trials, which included nearly 3000 men or women with a first VTE.4 After 24 months of follow-up, the investigators identified VTE recurrence was similar if anticoagulation treatment was stopped at 3 months compared with 6 months or later and higher if stopped at 4–6 weeks compared with 3 months. In other words, regardless of the initial location of VTE, there is no benefit of continuing to treat for more than 3 months especially, if there is a clear identifiable risk factor. This study also provides clarity to the confusion of treating isolated calf vein thrombosis for 4–6 weeks, which probably is not entirely safe and ideally should be for 3 months. Despite these studies clearly demonstrating the appropriate duration, it is still common practice to continue receive 6 months of anticoagulation, which has both financial and social implications in addition to an increase in bleeding risk from a treatment which was not necessary. If there are no precipitating factors for VTE which are clearly identifiable and possible to be removed (e.g., stopping oestrogen treatment), the anticoagulant treatment should be ‘extended’ (the preferred term to life-long or long-term).5 However, before

! The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: [email protected]

Downloaded from by guest on November 13, 2015

Anticoagulant drugs have dramatically decreased the morbidity and mortality associated with venous thromboembolism (VTE). Although early antithrombotic treatment is straightforward, doubts still exist in the decision process of ‘how long to anticoagulate?’ It is common practice among physicians to stop anticoagulation in those who had one episode of VTE; deep vein thrombosis or pulmonary embolism (PE), after 3–6 months and recommend long-term anticoagulation in those who had a second event. Recent studies have however identified risk stratification models which could help in determining the duration of anticoagulation. The decision on the duration of anticoagulant treatment should be based on the balance between benefits of preventing a recurrent VTE episode and the risks of bleeding from the drugs. The first step in this regard is to identify if there has been a precipitating factor for the VTE. These commonly are surgery, periods of immobilization like after needing a plaster cast and hormonal treatments like oral contraceptive pill. In these patients, the risk of VTE recurrence is 5% in the first year after stopping anticoagulant therapy. The latest American College of Chest Physicians guidance on VTE management consider this risk to be low enough to discontinue anticoagulant therapy at the end of 3 months.1,2 The only practical point in this scenario is how confidently the precipitating factor can be linked to the VTE event. For example, if the thrombotic episode occurred more than 3 months after the surgery, can this be considered as a provoked event? If the female develops a PE after being on the pill for a number of years, can oestrogen be considered causative? (Despite the fact that risk of VTE in

496

J. Thachil Two other related points of interest are (i) those patients who develop thrombosis in relation to cancer which were excluded in many of the studies; and (ii) the role of tests for heritable thrombophilia in determining the duration of anticoagulation. The current recommendation for patients who develop thrombosis while being treated for a malignancy is to continue low molecular weight heparin until the cancer has been cured or in remission and chemotherapy has been completed, as long as at least 3 months of treatment has elapsed.10 If otherwise, continuation of anticoagulation with warfarin or low molecular weight heparin (choice based on patient preference) is recommended. Testing for heritable thrombophilic defects is usually not helpful in predicting recurrence after a first VTE episode of VTE.5 In the latest guidance from the British Society of Haematology, it is stated that ‘decisions regarding duration of anticoagulation in unselected patients should be made with reference to whether or not a first episode of venous thrombosis was provoked or not, regardless of heritable thrombophilia.11 In summary, the decision on how long to anticoagulate should follow a three-step process, firstly, determining if there was a clearly defined risk factor or not, secondly, what is the risk of bleeding and lastly, adoption of a risk stratification model for those who may considered to benefit from extended duration of anticoagulation (Figure 1). Duration of anticoagulation is either 3 months or extended period based on these factors. It is also good practice to undertake regular assessments in the patients on extended anticoagulation to identify any new contraindications or to allow discussions on advances in thrombosis risk prediction or treatment.

Transient risk factors present Distal Lower limb thrombus

No Yes

Bleeding risk* DVT or PE High

Low

Prediction scoring

3 months

3 months

3 months

Extended*

Figure 1. Algorithm for decision making process for the duration of anticoagulation. Asterisk denotes periodic reassessment.

Downloaded from by guest on November 13, 2015

embarking on extended therapy, a careful assessment of the bleeding risk should be considered (the second step in decision making). A risk-scoring system like the popular HAS-BLED score widely used in patients receiving anticoagulation for atrial fibrillation has not yet been validated for patients with VTE. It is useful in this context to have frank discussion about the risk–benefit balance for anticoagulation with the patients who sustained unprovoked VTE before deciding on the duration.6 A common question here is can the risk of recurrence be determined? Despite an overall high recurrence risk being present, the majority of patients with a first unprovoked VTE will not have a repeat episode in the absence of anticoagulation but will continually be exposed to the risk of bleeding, if the treatment is continued.7 Therefore, recently, several risk stratification scores have been developed to assist in predicting the recurrence rate of VTE. These would help in ‘selecting’ patients who may need continuation of anticoagulation and differentiating them from those who could be at low risk of recurrence. The first among these is the ‘Men continue and HER DOO2’.8 In this multicentre, prospective cohort study of 646 patients with a first, unprovoked major VTE over a 4-year period, the presence of none or one of the following characteristics in women: hyperpigmentation (H), edema (E) or redness (R) of either leg; D-dimer 5250 mg/l while taking warfarin; body mass index 530 kg/m2; or age 565 years, had an annual risk of 1.6% while women who had two or more of these findings had an annual risk of 14.1%. This criterion did not apply to men, while women with 0 or 1 risk factor could safely discontinue anticoagulation therapy following a first unprovoked VTE. In the Vienna prediction model, the combination of location of the initial VTE event and the patient’s sex together with D-dimer was validated to discriminate between low- and high-risk patients.7 This model was particularly beneficial in identifying patients at low risk of recurrence for example, women with isolated calf deep vein thrombosis, and low levels of D-dimer could have an annual recurrence rate was as low as 1.9%. Lastly, the most recent DASH scoring system was determined from 1818 cases of unprovoked VTE treated for at least 3 months.9 Abnormal D-dimer after stopping anticoagulation (D), age

How long to anticoagulate?

How long to anticoagulate? - PDF Download Free
83KB Sizes 2 Downloads 3 Views