Duration of Anticoagulation Therapy for Venous Thromboembolism

Abstract

Treatment of acute deep vein thrombosis and pulmonary embolism-often denominated together as venous thromboembolism (VTE)-consists of parenteral administration of heparin (usually low-molecularweight heparin or alternatively unfractionated heparin or fondaparinux) overlapped and followed by oral vitamin K antagonists that are administered for a certain period (usually 3 to 12 months). Recommended or suggested durations differ according to guidelines. Practically, the clinical decision in an individual patient depends upon the estimated risks of VTE recurrence and treatment-induced bleeding. The risk of VTE recurrence is higher in idiopathic events (about 10% per year during the first two years and 3% per year thereafter) (odds ratio of 2.4, compared to secondary events); in male subjects (at least before the age of 60, with an odds ratio of 2-4); in patients with persistently elevated D-dimer level (odds ratio of 2.3, compared with normal level); and during the first two years after discontinuation of treatment. The annual risk of major bleeding on anticoagulant treatment vary largely in observational studies with figures of 2% to 29%, depending on the patient characteristics. The case-fatality rate is 8% (DVT), 12% (PE) for recurrent VTE, and about 10% for major bleed. These figures do not support long-term anticoagulant therapy, except in those patients exhibiting a very high risk of recurrence and/or a very low risk of bleeding.New therapeutic aspects might impact on the duration of anticoagulant therapy after a venous thromboembolic event. They include the possibility of pursuing anticoagulant treatment at a reduced INR after an initial period with an INR 2-3, and the advent of new, more specific and orally active anticoagulants. These features might modify the risk-benefit balance of extending anticoagulant therapy beyond the usual, limited duration.

Procoagulant activity, but not number, of microparticles increases with age and in individuals after a single venous thromboembolism

“…Standard medical practice is that all VTE patients are prescribed prophylactic anticoagulants [4,5]. Complications of prolonged anticoagulation therapy can be serious, so patients who would not require treatment are exposed to unnecessary risk [6,7]. Known risk factors for recurrence of VTE include indications of ongoing thrombosis, such as a high D-dimer level, residual thrombosis detected by ultrasound and increased thrombin generation [8–13].…”

American Society of Nephrology Quiz and Questionnaire 2013

“…Furthermore, the low total iron binding capacity of 200 mg/dl (reference normal=230-430 mg/dl) is more consistent with inflammatory block rather than iron deficiency. In addition, his international normalized ratio (INR) is 1.8, which is slightly below the target level for treating a thrombus; this finding indicates that the warfarin level is subtherapeutic and not supratherapeutic, making bleeding, although not impossible, a bit less likely (20,21) (choice A is incorrect).…”

Assessing the overuse of medicines

“…And even when a drug is not new, controversy about duration can remain, as with the use of anticoagulants like Warfarin to treat those who have had an embolism. Guidelines varingly suggest that with a first embolism anticoagulants should be taken for either three or six months, with some evidence that there is no difference in outcome (Bounameaux and Perrier, 2008), suggesting many are prescribed for too long. As with the initial decision to prescribe, one reason for prescribing drugs for lengthy periods (now facilitated by the ease of requesting repeat prescription via the internet) is that doctors' risk avoidance may encourage them to continue treatment for longer than necessary, a tendency exacerbated by the care needed when taking someone off a medication where withdrawal effects can be severe.…”