Two Weeks of Low Molecular Weight Heparin for Isolated Symptomatic Distal Vein Thrombosis (TWISTER study)

Eileen Merriman; Sanjeev Chunilal; Tim Brighton; Vivien Chen; Simon McRae; Paul Ockelford; Jennifer Curnow; Huy Tran; Beng Chong; Mark Smith; Gordon Royle; Helen Crowther; Alison Slocombe; Huyen Tran

doi:10.1016/j.thromres.2021.09.004

Two Weeks of Low Molecular Weight Heparin for Isolated Symptomatic Distal Vein Thrombosis (TWISTER study)

Thromb Res. 2021 Nov:207:33-39. doi: 10.1016/j.thromres.2021.09.004. Epub 2021 Sep 11.

Authors

Eileen Merriman¹, Sanjeev Chunilal², Tim Brighton³, Vivien Chen⁴, Simon McRae⁵, Paul Ockelford⁶, Jennifer Curnow⁷, Huy Tran⁸, Beng Chong⁹, Mark Smith¹⁰, Gordon Royle¹¹, Helen Crowther¹², Alison Slocombe¹³, Huyen Tran¹⁴

Affiliations

¹ Haematology Department, North Shore Hospital, Auckland, New Zealand. Electronic address: eileen.merriman@waitematadhb.govt.nz.
² Department of Clinical Haematology, Monash Medical Centre, Melbourne, Australia.
³ Department of Haematology, New South Wales Health Pathology Randwick, Prince of Wales Hospital Randwick, NSW, Australia.
⁴ Department of Haematology, Concord Hospital, NW, Australia.
⁵ SA Pathology, Royal Adelaide Hospital, Adelaide, Australia.
⁶ Department of Haematology, Auckland City Hospital, Auckland, New Zealand.
⁷ Department of Haematology, Westmead Hospital, NSW, Australia.
⁸ Department of Haematology, Frankston Hospital, Victoria, Australia.
⁹ Department of Haematology, St George's Hospital, NSW, Australia.
¹⁰ Department of Haematology, Christchurch Hospital, New Zealand.
¹¹ Department of Haematology, Middlemore Hospital, Auckland, New Zealand.
¹² Department of Haematology, Blacktown Hospital, NSW, Australia.
¹³ Department of Haematology, Box Hill Hospital, Victoria, Australia.
¹⁴ Department of Clinical Haematology, Monash Medical Centre, Melbourne, Australia; The Alfred Hospital, Melbourne, Australia; Australian Centre for Blood Diseases, Melbourne, Australia.

PMID: 34530387
DOI: 10.1016/j.thromres.2021.09.004

Abstract

Background: Treatment of low-risk patients with isolated symptomatic distal deep vein thrombi (IDDVT) is uncertain.

Objective: assess whether two weeks of therapeutic anticoagulation is efficacious/safe for IDDVT.

Primary outcome: symptomatic three-month venous thromboembolism (VTE) incidence in the two-week anticoagulation group. Secondary outcomes included post-thrombotic syndrome (PTS) and bleeding.

Methods: Prospective multicentre cohort study. Consecutive low-risk IDDVT patients enrolled within 72 h of diagnosis and treated with therapeutic dose enoxaparin or rivaroxaban. At two weeks, patients had repeat complete whole leg compression ultrasound (CUS)/clinical review. If resolution of leg symptoms AND no radiological evidence of thrombus extension, anticoagulation was stopped. If ongoing symptoms and/or radiographic extension within distal veins, anticoagulation was continued for four more weeks. Patients with extension into the popliteal vein on two-week ultrasound were treated off-study. Patients were reviewed at three and six months.

Findings/interpretation: 241 eligible patients received ≥2 weeks anticoagulation. 167/241 (69%) were assigned to the 2-week anticoagulation group; 71/241 (30%) to the six-week anticoagulation group; 3/241 patients (1%) had extension into the popliteal vein on two-week CUS. Two patients in the two-week anticoagulation group had symptomatic IDDVT recurrence in ≤3 months; VTE recurrence 2/156; 1.3%(95% CI 0.05-4.85%). 69% of patients had complete resolution of symptoms within two weeks. Six-month PTS rates were 8/184, 4.4%(95% CI 2.1-8.5%). No major bleeding was reported. Our findings suggest it's safe/efficacious to stop therapeutic anticoagulation at two weeks in low-risk IDDVT patients with resolution of symptoms/no extension on ultrasound. This could replace 6-12 weeks of anticoagulation for ambulatory, low-risk IDDVT patients.

Trial registration: ClinicalTrials.govNCT01252420.

Keywords: Anticoagulants; Calf vein thrombosis; Distal deep vein thrombosis; Pulmonary embolism; Venous thromboembolism.

Associated data

ClinicalTrials.gov/NCT01252420