Contents

Search

venous thromboembolism (VTE)

Also see deep vein thrombosis & pulmonary embolism Etiology: risk factors 1) hypercoagulability, venous stasis & vascular injury interact to increase risk of venous thromboembolism 2) increasing age, age > 60 years [3] 3) major trauma [31] 4) recent surgery, within 6-12 months - hip fracture repair, hip arthroplasty, knee arthroplasty & cancer surgery are associated with high risk [3] - patients with prior venous thromboembolism, surgery is associated with increased risk for recurrence for up to 6 months [28] - recurrent VTE after surgery is 2.1% at 1 month, 3.3% at 3 months, & 4.6% at 6 months, compared 0.8% at 3 months without surgery [29] 5) pregnancy & the puerperium 6) immobility, travel [7] 7) medical conditions associated with hypercoagulability a) congestive heart failure [16] b) acute myocardial infarction c) acute respiratory failure [3] d) adenocarcinomas & other cancers [3,5] - 4-20 fold increased risk [3] - advanced stage cancers, myeloproliferative disorders or myelodysplastic syndrome at highest risk [15] - 1 in 20 patients with unprovoked venous thromboembolism will have cancer within 1 year [19] e) paresis or paralysis (stroke) f) obesity g) infection [10] 8) injection drug use 9) current oral contraceptive use, especially in connection with factor V Leiden mutation 10) postmenopausal hormone replacement 11) systemic lupus erythematosus 12) Behcet's disease 13) homocystinuria, hyperhomocysteinemia 14) myeloproliferative disorders a) polycythemia vera b) essential thrombocythemia 15) sickle cell anemia 16) nephrotic syndrome 17) antiphospholipid antibody syndrome - increases risk of recurrent VTE 8.2% vs 4.5% 18) abnormality or deficiency of coagulation factor a) activated protein C resistance - factor V Leiden mutation (most common inherited disorder) b) protein C deficiency c) protein S deficiency d) antithrombin III deficiency e) prothrombin 20210A f) activated protein C resistance g) dysfibrinogenemia (rare) 19) excessive coagulation factor(s) a) high levels of coagulation factor VIII b) high levels of coagulation factor IX c) high levels of coagulation factor XI 20) paroxysmal nocturnal hemoglobinuria 21) inflammatory bowel disease 22) heparin-induced thrombocytopenia 23) microalbuminuria (hazzard ratio = 2.0) [6] 24) blood transfusion [10,23] 25) erythropoiesis-stimulating agents [10] 26) chemotherapy [10] 27) non blood type-O [12] 28) history of venous thromboembolism [3] 29) also see risk of venous thromboembolism (QThrombosis) Epidemiology: - 1/2 of new venous thromboembolism diagnosed within 3 months of surgery or hospitalization [3] Pathology: - classification as deep vein thrombosis is a result of the assumption that superficial vein thrombosis (thrombophlebitis) do no embolize Laboratory: - see deep vein thrombosis &/or pulmonary embolism - most patients with unprovoked venous thromboembolism do not require - thrombophilia testing, since results will not affect management [3,20] - extensive screening for underlying cancer [3] - D-dimer in plasma - 5-year risk for recurrence ~30% in men with unprovoked VTE, despite negative D-dimer testing [29] - see ARUP consult [11] Radiology: - obtain imaging if Wells score (DVT) > 1 or Wells score (PE) > 4 [3] - duplex ultrasonography for DVT, pulmonary CT angiography for PE [3] - pulmonary CT angiography unnecessary if DVT has been diagnosed because treatments are the same [3] Complications: - 1/3 of patients with initial unprovoked venous thromboembolism who discontinue anticoagulation may experience recurrence within 10 years [30] - risk of recurrent venous thromboembolism increases with components of metabolic syndrome (hyperlipidemia, obesity, hypertension, diabetes mellitus) [32] - despite risk of intracranial hemorrhage, anticoagulation recommended [3] Management: - see deep vein thrombosis &/or pulmonary embolism - age- & sex-specific cancer screening [19] - extensive cancer screening unwarranted [19] - anticoagulation unless contraindicated - major GI bleeding from arteriovenous malformations or other etiologies requiring emergency surgery - temporary inferior vena cava filter appropriate in these circumstances - LMW heparin standard for venous thromboembolism anticoagulation in cancer patients [37] - LMW heparin with most evidence supporting use in cancer patients [37] - direct-acting oral anticoagulants (DOACs) better manage recurrent VTE at a cost of higher bleeding vs LMW heparin in patients with cancer [27] - direct-acting oral anticoagulants (DOACs) are treatment of choice in patients with or without cancer [36] - LMW heparin, fondaparonux, rivaroxaban or apixaban for hospitalized patients unless unstable & at risk for emergent surgery or thrombolytic therapy [3] - if warfarin is used, must be initially admnistered with at least 5 days of LMW heparin vs unfractionated heparin [3] - see special case of antiphospholipid antibody syndrome - duration of anticoagulation - 3-6 months of anticoagulation sufficient for provoked thrombosis - extended anticoagulation for unprovoked thrombosis in patients at low risk for bleeding or with irreversible risk factors [3] - major bleeding among patients who receive warfarin or DOACs are 1.7% & 1.1%, respectively per year. [34] - older age > 64 year: annual major bleeding risk 1.8 & 2.9 respectively - eGFR < 50 mL/min: annual major bleeding risk 2.8 & 3.7, respectively - history of bleeding: annual major bleeding risk 3.5 & 18.8, respectively - concurrent use of antiplatelet agent: annual major bleeding risk 2.9 & 17.2 - hemoglobin < 10 g/dL: annual major bleeding risk 6.5 & 17.4 - mortality among those with major bleeds: 8.3% for warfarin & 9.7% for DOAC [34] - rivaroxaban associated with low recurrence of VTE but higher rate of hemorrhage compared with dalteparin [22] - apixaban more effective with less major bleeding than rivaroxaban [25] - major bleeding similar with apixaban vs dalteparin (3.8% vs 4.0%) [33] - adding aspirin to warfarin associated with increased risk of bleeding without a benefit for thrombosis prevention [26]

Interactions

disease interactions

Related

deep vein thrombosis (DVT) prophylaxis for venous thromboembolism (VTE)

Specific

pulmonary embolism (PE) venous thromboembolism associated with malignancy venous thromboembolism associated with pregnancy

General

thromboembolism

References

  1. Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 829-39.
  2. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  4. Snow V, Qaseem A, Barry P, Hornbake ER, Rodnick JE, Tobolic T, Ireland B, Segal JB, Bass EB, Weiss KB, Green L, Owens DK; American College of Physicians; American Academy of Family Physicians Panel on Deep Venous Thrombosis/Pulmonary Embolism. Management of venous thromboembolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2007 Feb 6;146(3):204-10. Epub 2007 Jan 29. PMID: 17261857 (Corresponding NGC guideline withdrawn Dec 2012) - Snow V, Qaseem A, Barry P, Hornbake ER, Rodnick JE, Tobolic T, Ireland B, Segal J, Bass E, Weiss KB, Green L, Owens DK; The Joint American College Of Physicians/american Academy Of Family Physicians Panel On Deep Venous Thrombosis/pulmonary Embolism. Management of venous thromboembolism: a clinical practice guideline from the american college of physicians and the american academy of family physicians. Ann Fam Med. 2007 Jan-Feb;5(1):74-80. PMID: 17261867 (Corresponding NGC guideline withdrawn Dec 2012) - Qaseem A, Snow V, Barry P, Hornbake ER, Rodnick JE, Tobolic T, Ireland B, Segal J, Bass E, Weiss KB, Green L, Owens DK; Joint American Academy of Family Physicians/American College of Physicians Panel on Deep Venous Thrombosis/Pulmonary Embolism. Current diagnosis of venous thromboembolism in primary care: a clinical practice guideline from the American Academy of Family Physicians and the American College of Physicians. Ann Fam Med. 2007 Jan-Feb;5(1):57-62. PMID: 17261865 (Corresponding NGC guideline withdrawn Dec 2012) - Qaseem A, Snow V, Barry P, Hornbake ER, Rodnick JE, Tobolic T, Ireland B, Segal JB, Bass EB, Weiss KB, Green L, Owens DK; Joint American Academy of Family Physicians/American College of Physicians Panel on Deep Venous Thrombosis/Pulmonary Embolism. Current diagnosis of venous thromboembolism in primary care: a clinical practice guideline from the American Academy of Family Physicians and the American College of Physicians. Ann Intern Med. 2007 Mar 20;146(6):454-8. PMID: 17371890 (Corresponding NGC guideline withdrawn Dec 2012)
  5. Trujillo-Santos J et al, Clinical outcome in patients with venous thromboembolism and hidden cancer. Findings from the RIETE Registry. J Thromb Haemost 2008, 6:251 PMID: 18021305
  6. Mahmoodi BK et al Microalbuminuria and the risk of venous thromboembolism. JAMA 2009 May 6; 301:1790. PMID: 19417196
  7. Chandra D et al Travel and risk for venous thromboembolism. Ann Intern Med 2009 Aug 4; 151:180. PMID: 19581633
  8. Courtney DM et al. Clinical features from the history and physical examination that predict the presence or absence of pulmonary embolism in symptomatic emergency department patients: Results of a prospective, multicenter study. Ann Emerg Med 2010 Apr; 55:307. PMID: 20045580
  9. Prescriber's Letter 19(4): 2012 COMMENTARY: Venous Thromboembolism During Travel SPECIAL REPORT: Preventing Travel-Related Illnesses PATIENT EDUCATION HANDOUT: Preventing Blood Clots When You Travel Detail-Document#: 280424 (subscription needed) http://www.prescribersletter.com
  10. Rogers MAM et al. Triggers of hospitalization for venous thromboembolism. Circulation 2012 May 1; 125:2092 PMID: 22474264 - White RH. Identifying risk factors for venous thromboembolism. Circulation 2012 May 1; 125:2051. PMID: 22474263
  11. ARUP Consult: Venous Thromboembolism The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/venous-thromboembolism
  12. Sode BF et al. Risk of venous thromboembolism and myocardial infarction associated with factor V Leiden and prothrombin mutations and blood type. CMAJ 2013 Mar 19; 185:E229. PMID: 23382263
  13. Lijfering WM, Rosendaal FR, Cannegieter SC. Risk factors for venous thrombosis - current understanding from an epidemiological point of view. Br J Haematol. 2010 Jun;149(6):824-33 PMID: 20456358
  14. Noble S, Pasi J. Epidemiology and pathophysiology of cancer-associated thrombosis. Br J Cancer. 2010 Apr 13;102 Suppl 1:S2-9 PMID: 20386546 - White RH. The epidemiology of venous thromboembolism. Circulation. 2003 Jun 17;107(23 Suppl 1):I4-8. PMID: 12814979
  15. Chee CE et al. Predictors of venous thromboembolism recurrence and bleeding among active cancer patients: A population-based cohort study. Blood 2014 Apr 2 PMID: 24782507 http://bloodjournal.hematologylibrary.org/content/early/2014/04/29/blood-2014-01-549733
  16. Tang L, Wu YY, Lip GY, Yin P, Hu Y Heart failure and risk of venous thromboembolism: a systematic review and meta-analysis. The Lancet Haematology. Dec 3, 2015 PMID: 26765646 http://thelancet.com/journals/lanhae/article/PIIS2352-3026%2815%2900228-8/abstract
  17. Kearon C et al Antithrombotic Therapy for VTE Disease: CHEST Guideline. Chest. January 2016 PMID: 26867832 http://journal.publications.chestnet.org/article.aspx?articleid=2479255
  18. Johnson SA, Eleazer GP, Rondina MT. Pathogenesis, diagnosis, and treatment of venous thromboembolism in older adults. J Am Geriatr Soc. 2016;64(9):1869-1878 PMID: 27556937
  19. van Es N, Le Gal G, Otten HM et al. Screening for occult cancer in patients with unprovoked venous thromboembolism: A systematic review and meta-analysis of individual patient data. Ann Intern Med 2017 Aug 22; PMID: 28828492 - Merli G, Weitz H. Venous thrombosis and cancer: What would Dr. Trousseau teach today? Ann Intern Med 2017 Aug 22; [e-pub]. PMID: 28828491
  20. Connors JM Thrombophilia Testing and Venous Thrombosis. N Engl J Med 2017; 377:1177-1187. September 21, 2017 PMID: 28930509 http://www.nejm.org/doi/full/10.1056/NEJMra1700365
  21. Kearon C, Parpia S, Spencer FA, et al. Antiphospholipid antibodies and recurrent thrombosis after a first unprovoked venous thromboembolism. Blood 2018 Feb 28 PMID: 29490924 http://www.bloodjournal.org/content/early/2018/02/27/blood-2017-09-805689
  22. Young AM, Marshall A, Thirlwall J et al. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: Results of a randomized trial (SELECT-D). J Clin Oncol 2018 Jul 10; 36:2017 PMID: 29746227
  23. Goel R et al. Association of perioperative red blood cell transfusions with venous thromboembolism in a North American registry. JAMA Surg 2018 Sep 1; 153:826 PMID: 29898202
  24. Meyer MR, Witt DM, Delate T et al Thrombophilia testing patterns amongst patients with acute venous thromboembolism. Thromb Res. 2015 Dec;136(6):1160-4. PMID: 26477821 Free PMC Article
  25. Dawwas GK, Brown J, Dietrich E, Park H. Effectiveness and safety of apixaban versus rivaroxaban for prevention of recurrent venous thromboembolism and adverse bleeding events in patients with venous thromboembolism: A retrospective population-based cohort analysis. Lancet Haematol 2019 Jan; 6:e20 PMID: 30558988 https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(18)30191-1/fulltext - Dawwas GK, Leonard CE, Lewis JD et al. Risk for recurrent venous thromboembolism and bleeding with apixaban compared with rivaroxaban: An analysis of real-world data. Ann Intern Med 2021 Dec 7; [e-pub]. PMID: 34871048 https://www.acpjournals.org/doi/10.7326/M21-0717
  26. Schaefer JK, Li Y, Gu X et al Association of Adding Aspirin to Warfarin Therapy Without an Apparent Indication With Bleeding and Other Adverse Events. JAMA Intern Med. Published online March 4, 2019. PMID: 30830172 https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2726050
  27. Rossel A, Robert-Ebadi H, Combescure C et al. Anticoagulant therapy for acute venous thrombo-embolism in cancer patients: A systematic review and network meta-analysis. PLoS One 2019 Mar 21; 14:e0213940 PMID: 30897142 Free PMC Article https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213940
  28. Nemeth B, Lijfering WM, MD, Nelissen RGHH Risk and Risk Factors Associated With Recurrent Venous Thromboembolism Following Surgery in Patients With History of Venous Thromboembolism. JAMA Netw Open. 2019;2(5):e193690 PMID: 31074822 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2733182
  29. Kearon C, Parpia S, Spencer FA et al. Long-term risk of recurrence in patients with a first unprovoked venous thromboembolism managed according to D-dimer results: A cohort study. J Thromb Haemost 2019 Apr 29; PMID: 31033194 https://onlinelibrary.wiley.com/doi/abs/10.1111/jth.14458
  30. Khan F, Rahman A, Carrier M et al Long term risk of symptomatic recurrent venous thromboembolism after discontinuation of anticoagulant treatment for first unprovoked venous thromboembolism event: systematic review and meta-analysis. BMJ 2019;366:l4363 PMID: 31340984 https://www.bmj.com/content/366/bmj.l4363 - Bikdeli B, Krumholz HM, Hines HH Jr. Minimizing recurrent venous thromboembolism. BMJ 2019;366:l4686 PMID: 31345836 https://www.bmj.com/content/366/bmj.l4686
  31. Rothaus C Vena Cava Filters in Severely Injured Patients. NEJM Resident 360. July 24, 2019 https://resident360.nejm.org/clinical-pearls/vena-cava-filters-in-severely-injured-patients
  32. Stewart LK, Kline JA. Metabolic syndrome increases risk of venous thromboembolism recurrence after acute deep vein thrombosis. Blood Adv 2020 Jan 14; 4:127. PMID: 31917844 Free PMC Article
  33. Agnelli G et al. Apixaban for the treatment of venous thromboembolism associated with cancer. N Engl J Med 2020 Mar 29; PMID: 32223112 https://www.nejm.org/doi/10.1056/NEJMoa1915103 - Lee AYY. Anticoagulant therapy for venous thromboembolism in cancer. N Engl J Med 2020 Mar 29 PMID: 32223115 https://www.nejm.org/doi/10.1056/NEJMe2004220
  34. Khan F, Tritschler T, Kimptonet M et al. Long-term risk for major bleeding during extended oral anticoagulant therapy for first unprovoked venous thromboembolism: A systematic review and meta-analysis. Ann Intern Med 2021 Sep 14; [e-pub] PMID: 34516270 https://www.acpjournals.org/doi/10.7326/M21-1094
  35. Goldenberg NA et al. Effect of anticoagulant therapy for 6 weeks vs 3 months on recurrence and bleeding events in patients younger than 21 years of age with provoked venous thromboembolism: The Kids-DOTT randomized clinical trial. JAMA 2022 Jan 11; 327:129 PMID: 35015038 PMCID: PMC8753509 (available on 2022-07-11) https://jamanetwork.com/journals/jama/fullarticle/2787908
  36. Stevens SM, Woller SC, Baumann Kreuziger L et al. Executive summary: Antithrombotic therapy for VTE disease: Second update of the CHEST guideline and expert panel report. Chest. 2021;160:2247-2259. PMID: 34352279 https://journal.chestnet.org/article/S0012-3692(21)01507-5/fulltext
  37. NEJM Knowledge+
  38. American Society of Hematology ASH Clinical Practice Guidelines on Venous Thromboembolism. http://www.hematology.org/VTE/