Hamostaseologie 2024; 44(02): 150-154
DOI: 10.1055/a-2173-7729
Review Article

Recurrent Venous Thromboembolism in Patients on Anticoagulation: An Update Based on the Revised AWMF S2k Guideline

Robert Klamroth
1   Department of Internal Medicine and Vascular Medicine, Vivantes Hospital in Friedrichshain, Berlin, Germany
,
Hanno Riess
2   Department of Haematology, Oncology and Tumour Immunology, Charité – University Medicine Berlin, Berlin, Germany
,
Jan Beyer-Westendorf
3   Department for Hematology, Medical Faculty, University Hospital Carl Gustav – Carus, Dresden, Germany
,
Birgit Linnemann
4   Department for Cardiology III – Angiology, University Hospital of the Johannes – Gutenberg University, Mainz, Germany
› Author Affiliations

Abstract

In the recently updated German S2k Guideline “Diagnostics and Therapy of Venous Thrombosis and Pulmonary Embolism,” a new chapter was incorporated about recurrent venous thromboembolism (VTE) in patients on anticoagulation treatment. Despite the high efficacy of anticoagulation in most patients, approximately 2% experience a recurrent VTE event while receiving anticoagulant drugs. The proper diagnosis of the recurrent VTE is important and possible only with the knowledge of localization and thrombus burden of the primary VTE event. Possible reasons for recurrent VTE events in patients on anticoagulation are non-adherence to medication, sub-therapeutic drug levels due to resorption disorders or drug interactions, or concomitant disease with high thrombogenicity. Cancer is the most common underlying disease, but it is important to investigate and understand possible other causes whenever a breakthrough VTE event occurs. This results in the recommendation that in patients with VTE recurrence on therapeutic anticoagulation, in particular, the presence of malignant disease, antiphospholipid syndrome, and rare diseases like paroxysmal nocturnal hemoglobinuria or Behçet's disease should be considered. For VTE recurrence during heparin therapy, heparin-induced thrombocytopenia type II needs to be ruled out, even if platelet counts are within the normal range. Although the mechanisms of recurrence on anticoagulation can be evaluated in a certain degree, clinical evidence for the management of recurrent VTE in anticoagulated patients is minimal and mainly based on expert opinion. Switching anticoagulant medication and intensifying anticoagulant treatment are possible options.



Publication History

Received: 15 August 2023

Accepted: 07 September 2023

Article published online:
30 April 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Linnemann B, Blank W, Doenst T. et al. Diagnostics and Therapy of Venous Thrombosis and Pulmonary Embolism. The revised AWMF S2k Guideline. Vasa. 2023 Oct; 52(S111): 1–146. PMID: 37904504. DOI: 10.1024/0301-1526/a001089
  • 2 van Es N, Coppens M, Schulman S, Middeldorp S, Büller HR. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood 2014; 124 (12) 1968-1975
  • 3 van Es J, Cheung YW, van Es N. et al. Short-term prognosis of breakthrough venous thromboembolism in anticoagulated patients. Thromb Res 2020; 187: 125-130
  • 4 Nijkeuter M, Hovens MMC, Davidson BL, Huisman MV. Resolution of thromboemboli in patients with acute pulmonary embolism: a systematic review. Chest 2006; 129 (01) 192-197
  • 5 Donadini MP, Ageno W, Antonucci E. et al. Prognostic significance of residual venous obstruction in patients with treated unprovoked deep vein thrombosis: a patient-level meta-analysis. Thromb Haemost 2014; 111 (01) 172-179
  • 6 Ageno W, Squizzato A, Wells PS, Büller HR, Johnson G. The diagnosis of symptomatic recurrent pulmonary embolism and deep vein thrombosis: guidance from the SSC of the ISTH. J Thromb Haemost 2013; 11 (08) 1597-1602
  • 7 Steffel J, Collins R, Antz M. et al. External Reviewers. 2021 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Europace 2021; 23 (10) 1612-1676
  • 8 Wiggins BS, Dixon DL, Neyens RR, Page II RL, Gluckman TJ. Select drug-drug interactions with direct oral anticoagulants: JACC review topic of the week. J Am Coll Cardiol 2020; 75 (11) 1341-1350
  • 9 Douxfils J, Adcock DM, Bates SM. et al. 2021 Update of the International Council for Standardization in Haematology Recommendations for laboratory measurement of direct oral anticoagulants. Thromb Haemost 2021; 121 (08) 1008-1020
  • 10 Schulman S. How I treat recurrent venous thromboembolism in patients receiving anticoagulant therapy. Blood 2017; 129 (25) 3285-3293
  • 11 Hillmen P, Muus P, Dührsen U. et al. Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria. Blood 2007; 110 (12) 4123-4128
  • 12 Khorana AA, Noble S, Lee AYY. et al. Role of direct oral anticoagulants in the treatment of cancer-associated venous thromboembolism: guidance from the SSC of the ISTH. J Thromb Haemost 2018; 16 (09) 1891-1894
  • 13 Carrier M, Prandoni P. Controversies in the management of cancer-associated thrombosis. Expert Rev Hematol 2017; 10 (01) 15-22
  • 14 Li A, Garcia DA, Lyman GH, Carrier M. Direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for treatment of cancer associated thrombosis (CAT): a systematic review and meta-analysis. Thromb Res 2019; 173: 158-163
  • 15 Rézig S, Mao RL, Couturaud F, Lacut K, Delluc A. Incidence of cancer after a second unprovoked venous thromboembolic event. Thromb Haemost 2019; 119 (03) 490-495
  • 16 Cohen H, Hunt BJ, Efthymiou M. et al. RAPS Trial Investigators. Rivaroxaban versus warfarin to treat patients with thrombotic antiphospholipid syndrome, with or without systemic lupus erythematosus (RAPS): a randomised, controlled, open-label, phase 2/3, non-inferiority trial. Lancet Haematol 2016; 3 (09) e426-e436
  • 17 Pengo V, Denas G, Zoppellaro G. et al. Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Blood 2018; 132 (13) 1365-1371
  • 18 Ordi-Ros J, Sáez-Comet L, Pérez-Conesa M. et al. Rivaroxaban versus vitamin K antagonist in antiphospholipid syndrome: a randomized noninferiority trial. Ann Intern Med 2019; 171 (10) 685-694
  • 19 Bauersachs R, Langer F, Kalka C. et al. Treatment of the antiphospholipid syndrome with direct oral anticoagulants. Position statement of German societies. Vasa 2019; 48 (06) 483-486
  • 20 Arachchillage DRJ, Laffan M. What is the appropriate anticoagulation strategy for thrombotic antiphospholipid syndrome?. Br J Haematol 2020; 189 (02) 216-227
  • 21 Petri M. Use of hydroxychloroquine to prevent thrombosis in systemic lupus erythematosus and in antiphospholipid antibody-positive patients. Curr Rheumatol Rep 2011; 13 (01) 77-80
  • 22 Rodger MA, Le Gal G, Anderson DR. et al. REVERSE II Study Investigators. Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: multinational prospective cohort management study. BMJ 2017; 356: j1065
  • 23 Linnemann B, Beyer-Westendorf J, Espinola-Klein C. et al. Management of Lower-Extremity Deep Vein Thrombosis — An Update based on the revised AWMF S2k guideline. Hamostaseologie 2024; 44: 97-110
  • 24 Opitz CF, Meyer FJ. Pulmonary embolism — an update based on the revised AWMF-S2k guideline. Hamostaseologie 2024; 44: 111-118