Predicting Recurrent Venous Thromboembolism After Discontinuing Anticoagulants

Warfarin (generic name for type of blood thinner) is an anticoagulant used to prevent the formation of blood clots in the blood vessels and their migration elsewhere in the body. Warfarin is commonly prescribed for treatment of atrial fibrillation, deep venous thrombosis, and pulmonary embolism.
A recent study sought to refine international risk classification guidelines on preventing VTE after discontinuation of anticoagulation therapy.

Recent research suggests that the ISTH classification for XXX for patients who stop anticoagulation after a first VTE would benefit from refinement;

A recent study suggested the need for refining the International Society of Thrombosis and Haemostasis (ISTH) risk classification rubric for VTE recurrence and anticoagulation therapy so that certain risk factors are re-categorized to take into account study findings regarding VTE recurrence risks. The study findings were recently reported in the European Respiratory Journal.

The prevalent treatment for venous thromboembolism (VTE) is anticoagulation for a minimum of 3 months to reduce risk of recurrent VTE. Current international guidelines suggest: 1) stopping anticoagulant therapy if VTE was provoked by a major transient risk factor, such as surgery; 2) prolonging the therapy for recurrent VTE that is unprovoked by either major nor minor risk factors; 3) prolonging VTE that is associated with a major persistent risk factor (ie, active cancer). The decision to prolong anticoagulation is difficult in patients with a first VTE occurring without major risk factors, as the impact of minor risk factors remains uncertain, so guidelines diverge, presenting a challenge for the clinician and often confusion for the patient.

Researchers aimed to validate and refine current risk classification guidelines on VTE recurrence. Toward that end, they conducted a post-hoc prospective study, recruiting patients between 2001 and 2019 for a multicenter cohort that included 1881 patients (18 years of age or older; 56.9±19.3 years; 55.4% female) with a first symptomatic VTE. These patients were prospectively followed after ceasing anticoagulation therapy that had lasted for 3 months or longer. The primary study outcome was symptomatic recurrent VTE during follow-up. The secondary outcome was all-cause mortality.

In the 4.8-year median follow-up, symptomatic recurrent VTE occurred in 230 (12.2%) patients. Using the definitions of the ISTH classification, researchers found that patients with major or minor persistent risk factors or unprovoked VTE had a 2-fold increased recurrence risk vs patients with VTE associated with a major transient risk factor. In patients with a minor transient risk factor, recurrence was not increased (hazard ratio [HR] 1.31; 95% CI, 0.84-2.06).

A secondary analysis of individual risk factors suggested 2 risk factors needing to be reclassified. Hormone-related VTE had a particularly low recurrence rate (pregnancy: HR 0.26; 95% CI, 0.08-0.82; estrogens: HR 0.25; 95% CI, 0.14-0.47), leading researchers to reclassify pregnancy and estrogen factors as “major transient,” and amyotrophic lateral sclerosis (ALS) was associated with high risk of recurrence (HR 5.84; 95% CI, 1.82-18.70), such that researchers reclassified this factor to “major persistent.”

Researchers also sought to confirm the influence of what the ISTH classification defined as major transient risk factors. This assessment found a 2- to 3-fold reduced risk of VTE recurrence in patients with prolonged hospitalization and plaster cast, and found that major surgery was not associated with a lower risk of recurrence.

The investigators concluded that for patients with a first episode VTE who stopped anticoagulation after 3 months of therapy or longer, refining the ISTH classification, such that it was based only the recurrence risk intensity of individual risk factors, would allow clinicians to better discriminate between patients at low vs high recurrence risk. Specifically, they concluded that hormone-related VTE should be reclassified as a major transient risk for VTE and that ALS should be reclassified as a major persistent risk for VTE.

Researchers noted significant limitations to their study, including: 1) selection bias, given that almost 50% of patients in the entire cohort could not be included in the analysis; 2) a small sample size that rendered the study too underpowered to obtain certain precise estimates; 3) anticoagulant therapy duration was systematically adjusted in all analyses; and 4) imaging and biological parameters were not evaluated.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Le Mao R, Orione C, de Moreuil C, et al. Risk stratification for predicting recurrent venous thromboembolism after discontinuation of anticoagulation: A post-hoc analysis of a French prospective multicenter study. Eur Respir J. Published online February 24, 2022. doi:10.1183/13993003.03002-2021