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Embolism and thrombosis

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Contents

Embolism and thrombosis is "a collective term for pathological conditions which are caused by the formation of a blood clot (thrombus) in a blood vessel, or by blocking of a blood vessel with an embolus, undissolved materials in the blood stream."[1]

The United States Surgeon General has announced a call to action to prevent Deep Vein Thrombosis and Pulmonary Embolism.[2]

Classification

Cause/etiology

The risk of venous thromboembolism can be estimated with http://www.qthrombosis.org/.

One risk factor is hypercoagulability due to cancer. Cancer can be found in up to 10% of patients within one year of embolism or thrombosis.[4]

Genetics

In a cohort study. the population attributable risk of venous thromboembolism was:[5]

In an older systematic review, the presence of Factor V Leiden (homozygotes or heterozygotes) but not prothrombin G20210A (heterozygoes; homozygotes not clear) increases risk of recurrence.[6]

Malignancy

The prevalence of malignancy is about:[7]

  • 3% of patients with first idiopathic venous thrombosis
  • 17% of patients with idiopathic, idiopathic venous thrombosis

The most common sites of cancer that is diagnosed at the time of, or later than the episode embolism and thrombosis of are:[8][9]

Diagnosis

Clinical practice guidelines address this for patients in general[10] and for patients who are pregnant[11].

Treatment

Embolism and thrombosis may be prevented by anticoagulation with anticoagulants. Clinical practice guidelines address this for patients in general[10] and for patients who are pregnant[11].

Dabigatran is given orally and may be as effective as warfarin and with less bleeding but increased dyspepsia for the treatment of embolism and thrombosis.[12]

Thrombolysis

Clinical practice guidelines address the management of severe forms of embolism and thrombosis which may require thrombolysis.[13]

Duration of treatment

This topic has been reviewed in a meta-analysis using individual patient data.[14]

Randomized controlled trials since 1995 of the duration of anticoagulation
  Patients Duration of
short course
Duration of
long course
findings
Campbell, 2007[15] DVT or PE without prior episode within 3 years 3 mos 6 mos Prolonged tended to do slightly better
Schulman, 2003[16] DVT or PE. 13% had prior VTE. 6 mos 24 mos Prolonged did better
Kearon, 2004[17] First episode of VTE due to transient risk factor 1 mo 3 mos Prolonged did better
Ridker, 2003[18] Idiopathic VTE. 30% had prior VTE 6 mos 2.1 yrs Prolonged did better
Agnelli, 2001[19] First episode of idiopathic DVT 3 mos 1 yr Prolonged did better while anticoagulated, but after two years there was no difference
Kearon, 1999[20] First episode of idiopathic VTE. 3 mos 2 yrs Prolonged did better
Pinede, 2001[21] DVT or PE without prior episode within 3 years 6 wks for distal DVT;
3 mos for proximal or PE
12 wks for distal DVT;
6 mos for proximal or PE
Prolonged tended to do slightly better
Levine, 1995[22] Acute DVT with normal normal impedance plethysmogram (IPG) after 4 weeks 1 mo 3 mos Prolonged tended to do better

Clinical practice guidelines by the American College of Chest Physicians address the duration of anticoagulation for deep venous thrombosis and pulmonary embolism.[10] Although initial trials suggested lack of benefit from prolonged anticoaguation[23], trials since 1995 favor longer anticoagulation. In patients who have had recurrent DVTs (two or more), anticoagulation is generally "life-long." The Cochrane Collaboration and others have meta-analyzed the risk and benefits of prolonged anti-coagulation.[24][23]

Recommendations by the American College of Chest Physicians for the Duration of Therapy[10]
Setting Recommended duration
Single DVT due to transient risk factor 3 months
Single unprovoked DVT at least 3 months (longer if favorable risks for anticoagulation)
Second episode of unprovoked VTE long-term treatment
DVT in patients with cancer LMWH for the first 3 to 6 months of long-term anticoagulant therapy

Using D-dimer to determine duration of treatment

For more information, see: D-dimer.

Elevated d-dimer levels at the end of treatment predict recurrence.[25]

Using Ultrasonography to determine duration of treatment

Ultrasonography, using the following protocol may[26] or may not[27] help determine when to stop anticoaguation[26]:

"If veins had not recanalized, we invited patients to have further ultrasonography after 3 and 9 months in patients with secondary DVT and after 3, 9, 15, and 21 months in those with unprovoked DVT. Anticoagulation was discontinued when the veins had recanalized, along with further ultrasonography"


Reducing the risk of recurrence after an unprovoked deep venous thrombosis.[28] [29] [25] [30] [31]
  Treatment or testRisk if treated or test result is favorableRisk if not treated or test result is unfavorableComments
Randomized controlled trial[28] Aspirin 100 mg daily for 2 years6% per year11.2% per year0.5% major bleeding
Randomized controlled trial[29] Rivaroxaban for 6-12 months1% over 6-12 months7% over 6-12 months0.7% major bleeding
Systematic review of a diagnostic test[25][31] Normal d-dimer4% per year9% per year
Systematic review of a diagnostic test[30] Recanalization of veins (no residual vein obstruction or RVO)Insignificant difference

Extending treatment with aspirin

Two trials have examined this idea.[32][28]

Randomized controlled trials of aspirin after discontinuation of anticoagulants.[32][28]
Trial Patients InterventionComparison OutcomeResultsComment
InterventionControl
ASPIRE, 2012[32] 822 patients
• first-ever, unprovoked venous thromboembolism
• completed initial anticoagulant
Aspirin 100 mg/dayPlacebo venous thromboembolism at 37 months 4.8% 6.5% relative risk ratio = 0.74 (95% CI: 0.52 to 1.05; P=0.09)
WARFASA, 2012[28] 502 patients
• first-ever, unprovoked venous thromboembolism
• completed initial anticoagulant
Aspirin 100 mg/dayPlacebovenous thromboembolism at 24 months 6.6% 11.2%

0.58 (95% CI: 0.36 to 0.93)

Prognosis

A systematic review of cohort studies found:[33]

  • During the initial 3 months of anticoagulation
    • Recurrent VTE = 3.4%
      • Recurrent fatal VTE was 0.4% (case-fatalityrate was 11.3%)
    • Major bleeding was 1.6%
      • Fatal major bleeding events was 0.2% (case-fatalityrate of 11.3%)
  • After anticoagulation
    • Recurrent VTE = 7.6% per 100 patient-years
      • Recurrent fatal VTE was 0.3% per 100 patient-years (case-fatality rate was 3.6%)

Elevated d-dimer levels at the end of treatment predict recurrence.[25]

The presence of Factor V Leiden but not prothrombin G20210A increases risk of recurrence.[6]

Prevention

Among patients with cancer, anticoagulation does not help in the primary prevention of embolism and thrombosis.[34]

Rosuvastatin, a hydroxymethylglutaryl-coenzyme A reductase inhibitor (statin), may reduce embolism and thrombosis according to the Jupiter randomized controlled trial.[35]

References

  1. Anonymous (2014), Embolism and thrombosis (English). Medical Subject Headings. U.S. National Library of Medicine.
  2. The Surgeon General's Call to Action to Prevent Deep Vein Thrombosis and Pulmonary Embolism. Office of Public Health and Science (2008).
  3. Decousus H, Quéré I, Presles E, Becker F, Barrellier MT, Chanut M et al. (2010). "Superficial venous thrombosis and venous thromboembolism: a large, prospective epidemiologic study.". Ann Intern Med 152 (4): 218-24. DOI:10.1059/0003-4819-152-4-201002160-00006. PMID 20157136. Research Blogging.
  4. Carrier M, Le Gal G, Wells PS, Fergusson D, Ramsay T, Rodger MA (September 2008). "Systematic review: the Trousseau syndrome revisited: should we screen extensively for cancer in patients with venous thromboembolism?". Annals of internal medicine 149 (5): 323–33. PMID 18765702[e]
  5. Sode BF, Allin KH, Dahl M, Gyntelberg F, Nordestgaard BG (2013). "Risk of venous thromboembolism and myocardial infarction associated with factor V Leiden and prothrombin mutations and blood type.". CMAJ 185 (5): E229-37. DOI:10.1503/cmaj.121636. PMID 23382263. PMC PMC3602271. Research Blogging.
  6. 6.0 6.1 Segal JB, Brotman DJ, Necochea AJ, et al. (June 2009). "Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review". JAMA 301 (23): 2472–85. DOI:10.1001/jama.2009.853. PMID 19531787. Research Blogging.
  7. Prandoni P, Lensing AW, Büller HR, Cogo A, Prins MH, Cattelan AM et al. (1992). "Deep-vein thrombosis and the incidence of subsequent symptomatic cancer.". N Engl J Med 327 (16): 1128-33. PMID 1528208.
  8. Sørensen HT, Mellemkjaer L, Olsen JH, Baron JA (2000). "Prognosis of cancers associated with venous thromboembolism.". N Engl J Med 343 (25): 1846-50. PMID 11117976. <
  9. Sørensen HT, Mellemkjaer L, Steffensen FH, Olsen JH, Nielsen GL (1998). "The risk of a diagnosis of cancer after primary deep venous thrombosis or pulmonary embolism.". N Engl J Med 338 (17): 1169-73. PMID 9554856.
  10. 10.0 10.1 10.2 10.3 Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ (June 2008). "Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)". Chest 133 (6 Suppl): 454S–545S. DOI:10.1378/chest.08-0658. PMID 18574272. Research Blogging.
  11. 11.0 11.1 (2011) "Practice bulletin no. 123: thromboembolism in pregnancy.". Obstet Gynecol 118 (3): 718-29. DOI:10.1097/AOG.0b013e3182310c4c. PMID 21860313. Research Blogging.
  12. Schulman S, Kearon C, Kakkar AK, Mismetti P, Schellong S, Eriksson H et al. (2009). "Dabigatran versus warfarin in the treatment of acute venous thromboembolism.". N Engl J Med 361 (24): 2342-52. DOI:10.1056/NEJMoa0906598. PMID 19966341. Research Blogging. Review in: Ann Intern Med. 2010 Apr 20;152(8):JC4-7
  13. Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ et al. (2011). "Management of Massive and Submassive Pulmonary Embolism, Iliofemoral Deep Vein Thrombosis, and Chronic Thromboembolic Pulmonary Hypertension: A Scientific Statement From the American Heart Association.". Circulation. DOI:10.1161/CIR.0b013e318214914f. PMID 21422387. Research Blogging.
  14. Boutitie F, Pinede L, Schulman S, Agnelli G, Raskob G, Julian J et al. (2011). "Influence of preceding length of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping treatment: analysis of individual participants' data from seven trials.". BMJ 342: d3036. DOI:10.1136/bmj.d3036. PMID 21610040. PMC PMC3100759. Research Blogging.
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  16. Schulman S, Wåhlander K, Lundström T, Clason SB, Eriksson H (October 2003). "Secondary prevention of venous thromboembolism with the oral direct thrombin inhibitor ximelagatran". N. Engl. J. Med. 349 (18): 1713–21. DOI:10.1056/NEJMoa030104. PMID 14585939. Research Blogging.
  17. Kearon C, Ginsberg JS, Anderson DR, et al (May 2004). "Comparison of 1 month with 3 months of anticoagulation for a first episode of venous thromboembolism associated with a transient risk factor". J. Thromb. Haemost. 2 (5): 743–9. DOI:10.1046/j.1538-7836.2004.00698.x. PMID 15099280. Research Blogging.
  18. Ridker PM, Goldhaber SZ, Danielson E, et al (April 2003). "Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism". N. Engl. J. Med. 348 (15): 1425–34. DOI:10.1056/NEJMoa035029. PMID 12601075. Research Blogging.
  19. Agnelli G, Prandoni P, Santamaria MG, et al (July 2001). "Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis. Warfarin Optimal Duration Italian Trial Investigators". N. Engl. J. Med. 345 (3): 165–9. PMID 11463010[e]
  20. Kearon C, Gent M, Hirsh J, et al (March 1999). "A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism". N. Engl. J. Med. 340 (12): 901–7. PMID 10089183[e]
  21. Pinede L, Ninet J, Duhaut P, et al (May 2001). "Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep vein thrombosis or pulmonary embolism and comparison of 6 and 12 weeks of therapy after isolated calf deep vein thrombosis". Circulation 103 (20): 2453–60. PMID 11369685[e]
  22. Levine MN, Hirsh J, Gent M, et al (August 1995). "Optimal duration of oral anticoagulant therapy: a randomized trial comparing four weeks with three months of warfarin in patients with proximal deep vein thrombosis". Thromb. Haemost. 74 (2): 606–11. PMID 8584992[e]
  23. 23.0 23.1 Ost D, Tepper J, Mihara H, Lander O, Heinzer R, Fein A (August 2005). "Duration of anticoagulation following venous thromboembolism: a meta-analysis". JAMA 294 (6): 706–15. DOI:10.1001/jama.294.6.706. PMID 16091573. Research Blogging.
  24. Hutten BA, Prins MH (2006). "Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism". Cochrane database of systematic reviews (Online) (1): CD001367. DOI:10.1002/14651858.CD001367.pub2. PMID 16437432. Research Blogging.
  25. 25.0 25.1 25.2 25.3 Douketis J, Tosetto A, Marcucci M, Baglin T, Cushman M, Eichinger S et al. (2010). "Patient-level meta-analysis: effect of measurement timing, threshold, and patient age on ability of D-dimer testing to assess recurrence risk after unprovoked venous thromboembolism.". Ann Intern Med 153 (8): 523-31. DOI:10.1059/0003-4819-153-8-201010190-00009. PMID 20956709. Research Blogging.
  26. 26.0 26.1 Prandoni, Paolo; Martin H. Prins, Anthonie W.A. Lensing, Angelo Ghirarduzzi, Walter Ageno, Davide Imberti, Gianluigi Scannapieco, Giovanni B. Ambrosio, Raffaele Pesavento, Stefano Cuppini, Roberto Quintavalla, Giancarlo Agnelli, for the AESOPUS Investigators (2009-05-05). "Residual Thrombosis on Ultrasonography to Guide the Duration of Anticoagulation in Patients With Deep Venous Thrombosis: A Randomized Trial". Ann Intern Med 150 (9): 577-585. PMID 19414836. Retrieved on 2009-05-06.
  27. Robinson KS, Anderson DR, Gross M, et al. (September 1997). "Ultrasonographic screening before hospital discharge for deep venous thrombosis after arthroplasty: the post-arthroplasty screening study. A randomized, controlled trial". Ann. Intern. Med. 127 (6): 439–45. PMID 9313000[e]
  28. 28.0 28.1 28.2 28.3 28.4 Becattini C, Agnelli G, Schenone A, Eichinger S, Bucherini E, Silingardi M et al. (2012). "Aspirin for preventing the recurrence of venous thromboembolism.". N Engl J Med 366 (21): 1959-67. DOI:10.1056/NEJMoa1114238. PMID 22621626. Research Blogging.
  29. 29.0 29.1 EINSTEIN Investigators. Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H et al. (2010). "Oral rivaroxaban for symptomatic venous thromboembolism.". N Engl J Med 363 (26): 2499-510. DOI:10.1056/NEJMoa1007903. PMID 21128814. Research Blogging. Review in: Evid Based Med. 2011 Oct;16(5):139-40
  30. 30.0 30.1 Carrier M, Rodger MA, Wells PS, Righini M, LE Gal G (2011). "Residual vein obstruction to predict the risk of recurrent venous thromboembolism in patients with deep vein thrombosis: a systematic review and meta-analysis.". J Thromb Haemost 9 (6): 1119-25. DOI:10.1111/j.1538-7836.2011.04254.x. PMID 21382171. Research Blogging.
  31. 31.0 31.1 Tosetto A, Iorio A, Marcucci M, Baglin T, Cushman M, Eichinger S et al. (2012). "Predicting disease recurrence in patients with previous unprovoked venous thromboembolism: a proposed prediction score (DASH).". J Thromb Haemost 10 (6): 1019-25. DOI:10.1111/j.1538-7836.2012.04735.x. PMID 22489957. Research Blogging.
  32. 32.0 32.1 32.2 Brighton, Timothy A.; John W. Eikelboom, Kristy Mann, Rebecca Mister, Alexander Gallus, Paul Ockelford, Harry Gibbs, Wendy Hague, Denis Xavier, Rafael Diaz, Adrienne Kirby, John Simes. "Low-Dose Aspirin for Preventing Recurrent Venous Thromboembolism". New England Journal of Medicine. DOI:10.1056/NEJMoa1210384. ISSN 0028-4793. Retrieved on 2012-11-05. Research Blogging.
  33. Carrier M, Le Gal G, Wells PS, Rodger MA (2010). "Systematic review: case-fatality rates of recurrent venous thromboembolism and major bleeding events among patients treated for venous thromboembolism.". Ann Intern Med 152 (9): 578-89. DOI:10.1059/0003-4819-152-9-201005040-00008. PMID 20439576. Research Blogging.
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