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Infection as cause of immobility and occurrence of venous thromboembolism: analysis of 1635 medical cases from the RIETE registry

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Abstract

Several risk assessment models include infection and immobility among the items to be considered for venous thromboembolism (VTE) prevention. However, information on patients with infection leading to immobility and developing VTE are limited, as well as on the role of specific types of infection. Data were collected from the worldwide RIETE registry, including patients with symptomatic objectively confirmed VTE, and followed-up for at least 3 months. The overall population of RIETE at June 2013 (n = 47,390) was considered. Acute infection leading to immobility was reported in 3.9 % of non-surgical patients. Compared with patients immobilized due to dementia, patients with infection had a shorter duration of immobilization prior to VTE (less than 4 weeks in 94.2 vs. 25.9 % of cases; p < 0.001). During the 3-month follow-up, VTE patients with infection versus those with dementia had a lower rate of fatal bleeding (0.5 vs. 1.1 %; p < 0.05) or fatal PE (1.7 vs. 3.5 %; p < 0.01). Patients with respiratory tract infections had more likely PE as initial VTE presentation than other types of infection (62.3 vs. 37.7 %; p < 0.001). Significantly more patients with pneumonia than those with other respiratory infections had received VTE prophylaxis (50.2 vs. 30.6 %; p < 0.001). Following VTE, patients with sepsis showed a significantly higher risk of fatal bleeding. Based on our real-world data, infection seems to contribute to the pathogenesis of VTE by accelerating the effects of immobility. Its role as VTE risk factor probably deserves further attention and specific assessment in order to optimize VTE prophylaxis and treatment.

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Abbreviations

DVT:

Deep vein thrombosis

PE:

Pulmonary embolism

VTE:

Venous thromboembolism

RIETE:

Registro Informatizado de la Enfermedad TromboEmbolica

Helical CT scan:

Helical computerized tomography scan

SD:

Standard deviation

VKA:

Vitamin K antagonist

LMWH:

Low molecular weight heparin

IU:

International unit

COPD:

Chronic obstructive pulmonary disease

NS:

Not significant

References

  1. Smeeth L, Cook C, Thomas S, Hall AJ, Hubbard R, Vallance P (2006) Risk of deep vein thrombosis and pulmonary embolism after infection in a community setting. Lancet 367:1075–1079

    Article  PubMed  Google Scholar 

  2. Bhagat K, Moss R, Collier J, Vallance P (1996) Endothelial “stunning” following a brief exposure to endotoxin: a mechanism to link infection and infarction. Cardiovasc Res 32:822–829

    CAS  PubMed  Google Scholar 

  3. Bhagat K, Vallance P (1997) Inflammatory cytokines impair endothelium-dependent dilatation in human veins in vivo. Circulation 96:3042–3047

    Article  CAS  PubMed  Google Scholar 

  4. Grainge MJ, West J, Card TR (2010) Venous thromboembolism during active disease and remission in inflammatory bowel disease: a cohort study. Lancet 375:657–663

    Article  PubMed  Google Scholar 

  5. Semeraro N, Ammollo CT, Semeraro F, Colucci M (2012) Sepsis, thrombosis and organ dysfunction. Thromb Res 129:290–295

    Article  CAS  PubMed  Google Scholar 

  6. Schmidt M, Horvath-Puho E, Thomsen RW, Smeeth L, Sorensen HT (2012) Acute infection and venous thromboembolism. J Intern Med 271:608–618

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gardlund B, The Heparin Prophylaxis Study Group (1996) Randomised, controlled trial of low-dose heparin for prevention of fatal pulmonary embolism in patients with infectious diseases. Lancet 347:1357–1361

    Article  CAS  PubMed  Google Scholar 

  8. Samama MM (2000) An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients: the Sirius study. Arch Intern Med 160:3415–3420

    Article  CAS  PubMed  Google Scholar 

  9. Alikhan R, Cohen AT, Combe S, Samama MM, Desjardins L, Eldor A et al (2003) Prevention of venous thromboembolism in medical patients with enoxaparin: a subgroup analysis of the MEDENOX study. Blood Coagul Fibrinolysis 14:341–346

    Article  CAS  PubMed  Google Scholar 

  10. Alikhan R, Cohen AT, Combe S, Samama MM, Desjardins L, Eldor A et al (2004) Risk factors for venous thromboembolism in hospitalized patients with acute medical illness: analysis of the MEDENOX study. Arch Intern Med 164:963–968

    Article  PubMed  Google Scholar 

  11. Barba R, Di Micco P, Blanco-Molina A, Delgado C, Cisneros E, Villalta J et al (2011) Fever and deep venous thrombosis. Findings from the RIETE registry. J Thromb Thrombolysis 32:288–292

    Article  PubMed  Google Scholar 

  12. Rogers MAM, Levine DA, Blumberg N, Flanders SA, Chopra V, Langa KM (2012) Triggers of hospitalization for venous thromboembolism. Circulation 125:2092–2099

    Article  PubMed  PubMed Central  Google Scholar 

  13. Clayton TC, Gaskin M, Meade TW (2011) Recent respiratory infection and risk of venous thromboembolism: case-control study through a general practice database. Int J Epidemiol 40:819–827

    Article  PubMed  PubMed Central  Google Scholar 

  14. Geerts WH, Pineo GF, Heit JA, Bergqvist D, Lassen MR, Colwell CW et al (2004) Prevention of venous thromboembolism: the seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 126:338S–400S

    Article  CAS  PubMed  Google Scholar 

  15. Barbar S, Noventa F, Rossetto V, Ferrari A, Brandolin B, Perlati M et al (2010) A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost 8:2450–2457

    Article  CAS  PubMed  Google Scholar 

  16. Chen JY, Chao TH, Guo YL, Hsu CH, Huang YY, Chen JH et al (2006) A simplified clinical model to predict pulmonary embolism in patients with acute dyspnea. Int Heart J 47:259–271

    Article  PubMed  Google Scholar 

  17. Tan KK, Koh WP, Chao AKH (2007) Risk factors and presentation of deep venous thrombosis among Asian patients: a hospital-based case-control study in Singapore. Ann Vasc Surg 21:490–495

    Article  PubMed  Google Scholar 

  18. Lowe GD (2003) Virchow’s triad revisited: abnormal flow. Pathophysiol Haemost Thromb 33:455–457

    Article  PubMed  Google Scholar 

  19. Leibson CL, Petterson TM, Bailey KR, Melton LJ 3rd, Heit JA (2008) Risk factors for venous thromboembolism in nursing home residents. Mayo Clin Proc 83:151–157

    Article  Google Scholar 

  20. Pottier P, Hardouin JB, Lejeune S, Jolliet P, Gillet B, Planchon B (2009) Immobilization and the risk of venous thromboembolism. A meta-analysis on epidemiological studies. Thromb Res 124:468–476

    Article  CAS  PubMed  Google Scholar 

  21. Piazza G, Goldhaber SZ, Lessard DM, Goldberg RJ, Emery C, Spencer FA (2011) Venous thromboembolism in heart failure: preventable deaths during and after hospitalization. Am J Med 124:252–259

    Article  PubMed  Google Scholar 

  22. Monreal M, Kakkar AK, Caprini JA, Barba R, Uresandi F, Valle R, RIETE Investigators et al (2004) The outcome after treatment of venous thromboembolism is different in surgical and acutely ill medical patients. Findings from the RIETE registry. J Thromb Haemost 2:1892–1898

    Article  CAS  PubMed  Google Scholar 

  23. Monreal M, Trujillo-Santos J (2009) Lessons from VTE registries: the RIETE experience. Best Pract Res Clin Haematol 22:25–33

    Article  PubMed  Google Scholar 

  24. Nunez MJ, Villalba JC, Cebrian E, Visonà A, Lopez-Jimenez L, Nunez M, RIETE Investigators et al (2012) Venous thromboembolism in immobilized patients with dementia. Findings from the RIETE registry. Thromb Res 130:173–177

    Article  CAS  PubMed  Google Scholar 

  25. Kahn SR, Lim W, Dunn AS, Cushman M, Dentali F, Akl EA et al (2012) Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 141:e195S–e226S

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Fu C, Chute DJ, Farag ES, Garakian J, Cummings JL, Vinters HV (2004) Co-morbidity in dementia. An autopsy study. Arch Pathol Lab Med 128:32–38

    PubMed  Google Scholar 

  27. Brunnstrom HR, Englund EM (2009) Cause of death in patients with dementia disorders. Eur J Neurol 16:488–492

    Article  CAS  PubMed  Google Scholar 

  28. Mejer N, Westh H, Schonheyder HC, Jensen AG, Larsen AR et al (2014) Increased risk of venous thromboembolism within the first year after Staphylococcus aureus bacteraemia: a nationwide observational matched controlled study. J Intern Med 275:387–397

    Article  CAS  PubMed  Google Scholar 

  29. Chen YG, Lin TY, Huang WY, Lin CL, Dai MS, Kao CH (2015) Association between pneumococcal pneumonia and venous thromboembolism in hospitalized patients: a nationwide-population based study. Respirology 20:799–804

    Article  PubMed  Google Scholar 

  30. Stam J (2005) Thrombosis of the cerebral veins and sinuses. N Engl J Med 352:1791–1798

    Article  CAS  PubMed  Google Scholar 

  31. Torbicki A, Perrier A, Konstantinides S et al (2008) Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology. Eur Heart J 29:2276–2315

    Article  CAS  PubMed  Google Scholar 

  32. Sabit R, Thomas P, Shale DJ, Collins P, Linnane SJ et al (2010) The effects of hypoxia on markers of coagulation and systemic inflammation in patients with COPD. Chest 138:47–51

    Article  CAS  PubMed  Google Scholar 

  33. Sidney S, Sorel M, Quesenberry CP Jr, DeLuise C, Lanes S, Eisner MD et al (2005) COPD and incident cardiovascular disease hospitalizations and mortality: Kaiser Permanent Medical Care Program. Chest 128:2068–2075

    Article  PubMed  Google Scholar 

  34. Stein PD, Beemath A, Meyers FA, Olson RE et al (2007) Pulmonary embolism and deep venous thrombosis in hospitalized adults with chronic obstructive pulmonary disease. J Cardiovasc Med (Hagerstown) 8:253–257

    Article  Google Scholar 

  35. Schneider C, Bothner U, Jick SS, Meier CR et al (2010) Chronic obstructive pulmonary disease and the risk of cardiovascular diseases. Eur J Epidemiol 25:253–260

    Article  PubMed  Google Scholar 

  36. Curkendall SM, DeLuise C, Jones JK, Lanes S, Stang MR, Goehring E Jr et al (2006) Cardiovascular disease in patients with chronic obstructive pulmonary disease, Saskatchewan Canada cardiovascular disease in COPD patients. Ann Epidemiol 16:63–70

    Article  PubMed  Google Scholar 

  37. Bertoletti L, Quenet S, Mismetti P, Hernandez L, Martin-Villasclaras JJ, Tolosa C, RIETE Investigators et al (2012) Clinical presentation and outcome of venous thromboembolism in COPD. Eur Resp J 39:862–868

    Article  CAS  Google Scholar 

  38. Tapson VF, Decousus H, Pini M, Chong BH, Froelich JB, Monreal M et al (2007) Venous thromboembolism prophylaxis in acutely ill hospitalized medical patients. Findings from the International Medical Prevention Registry on Venous Thromboembolism. Chest 132:936–945

    Article  PubMed  Google Scholar 

  39. Anderson FA Jr, Zayaruzny M, Heit JA, Fidan D, Cohen AT (2007) Estimated annual numbers of US acute-care hospital patients at risk for venous thromboembolism. Am J Hematol 82:777–782

    Article  PubMed  Google Scholar 

  40. Cohen AT, Tapson VF, Bergmann JF, Goldhaber SZ, Kakkar AK, Deslandes B et al (2008) Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-sectional study. Lancet 371:387–394

    Article  PubMed  Google Scholar 

  41. Jancar P, Morgan T, Mrhar A, Kosnik M, Lainscak M (2009) Venous thromboembolism prophylaxis in hospitalized patients with pneumonia: a prospective survey. Wien Klin Wochenschr 121:318–323

    Article  PubMed  Google Scholar 

  42. Hull RD (2012) Relevance of immobility and importance of risk assessment management for medically ill patients. Clin Appl Thromb Hemost 19:268–276

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We express our gratitude to Sanofi Spain for supporting this Registry with an unrestricted educational grant. We also express our gratitude to Bayer Pharma AG for supporting this Registry. Bayer Pharma AG’s support was limited to the part of RIETE outside Spain, which accounts for a 19.76 % of the total patients included in the RIETE Registry. We also thank the RIETE Registry Coordinating Center, S & H Medical Science Service, for their quality control, logistic and administrative support and Prof. Salvador Ortiz, Universidad Autónoma de Madrid and Statistical Advisor S & H Medical Science Service for the statistical analysis of the data presented in this paper.

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical standard

RIETE registry is realized in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Informed consent has been obtained from each enrolled patient.

Author information

Authors and Affiliations

  1. Department of Clinical Research, FADOI Foundation, Piazzale L. Cadorna, 15, Milan, Italy

    Stefania Frasson & Gualberto Gussoni

  2. Emergency Room, Department of Internal Medicine, Fatebenefratelli Hospital of Naples, Naples, Italy

    Pierpaolo Di Micco

  3. Department of Internal Medicine, Hospital Rey Juan Carlos, Móstoles, Madrid, Spain

    Raquel Barba

  4. Department of Medicine and Therapeutic, Hôpital Nord, University Hospital of Saint-Etienne, Saint-Étienne, France

    Laurent Bertoletti

  5. Department of Internal Medicine, Complejo Hospitalario de Pontevedra, Pontevedra, Spain

    Manuel J. Nuñez

  6. Department of Internal Medicine, Hospital General Universitario de Alicante, Alicante, Spain

    Beatriz Valero

  7. Department of Internal Medicine, Hospital Reina Sofía de Tudela, Tudela, Navarra, Spain

    Angel Luis Samperiz

  8. Department of Pneumology, Hospital Txagorritxu, Vitoria-Gasteiz, Álava, Spain

    Agustina Rivas

  9. Department of Internal Medicine, Hospital Universitari Germans Trias I Pujol, Badalona, Barcelona, Spain

    Manuel Monreal

Authors
  1. Stefania Frasson
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  2. Gualberto Gussoni
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  3. Pierpaolo Di Micco
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  4. Raquel Barba
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  5. Laurent Bertoletti
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  6. Manuel J. Nuñez
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  7. Beatriz Valero
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  8. Angel Luis Samperiz
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  9. Agustina Rivas
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  10. Manuel Monreal
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Consortia

The RIETE Investigators

Corresponding author

Correspondence to Stefania Frasson.

Additional information

A full list of RIETE Investigators is given in the Appendix.

Appendices

Appendix

Coordinator of the RIETE Registry: Dr. Manuel Monreal (Spain); RIETE Steering Committee Members: Dr. Hervè Decousus (France), Dr. Paolo Prandoni (Italy), Dr. Benjamin Brenner (Israel); RIETE National Coordinators: Dr. Raquel Barba (Spain), Dr. Pierpaolo Di Micco (Italy), Dr. Laurent Bertoletti (France), Dr. Sebastian Schellong (Germany), Dr. Manolis Papadakis (Greece), Dr. Inna Tzoran (Israel), Dr. Abilio Reis (Portugal), Dr. Marijan Bosevski (R.Macedonia), Dr. Henri, Bounameaux (Switzerland), Dr. Radovan Malý (Czech Republic); RIETE Registry Coordinating Center: S & H Medical Science Service

Members of the RIETE Group

SPAIN: Adarraga MD, Arcelus JI, Arroyo-Cozar M, Ballaz A, Barba R, Barrón M, Barrón-Andrés B, Bascuñana J, Blanco-Molina A, Bueso T, Casado I, Conget F, del Molino F, del Toro J, Falgá C, Fernández-Capitán C, Font L, Fuentes MI, Gallego P, García-Bragado F, García-Lorenzo MD, Gómez V, González J, González-Bachs E, Grau E, Guil M, Gutiérrez J, Hernández L, Hernández-Huerta S, Hernando-López E, Isern V, Jaras MJ, Jiménez D, Lecumberri R, Lobo JL, López-Jiménez L, López-Montes L, López-Reyes R, López-Sáez JB, Lorente MA, Lorenzo A, Luque JM, Madridano O, Marchena PJ, Martín M, Monreal M, Mora JM, Nauffal D, Nieto JA, Núñez MJ, Ogea JL, Pedrajas JM, Peris ML, Porras JA, Riera-Mestre A, Rivas A, Rodríguez-Dávila MA, Román P, Rosa V, Ruiz-Giménez N, Ruiz J, Sahuquillo JC, Samperiz A, Sánchez Muñoz-Torrero JF, Soler S, Suriñach JM, Tiberio G, Tilvan RM, Tolosa C, Trujillo-Santos J, Uresandi F, Valdés M, Valero B, Valle R, Vela J, Vidal G, Villalta J, BELGIUM: Verhamme P, Peerlinck K, BRAZIL: Gadelha T, CZECH REPUBLIC: Malý R, Hirmerova J, Kaletova M, Tomko T, FRANCE: Bertoletti L, Bura-Riviere A, Farge-Bancel D, Hij A, Mahe I, Merah A, GERMANY: Schellong S, GREECE: Babalis D, Papadakis M, Tzinieris I, ISRAEL: Braester A, Brenner B, Tzoran I, Zeltser D, ITALY: Amitrano M, Barillari G, Ciammaichella M, Di Micco P, Duce R, Giorgi-Pierfranceschi M, Gussoni G, Pasca S, Pesavento R, Piovella C, Poggio R, Prandoni P, Quintavalla R, Rocci A, Rota L, Schenone A, Tiraferri E, Tonello D, Tufano A, Visonà A, Zalunardo B, PORTUGAL: Barbosa AL, Miranda D, Santos M, Sousa MS, REPUBLIC OF MACEDONIA: Bosevski M, Kovacevic D, SWITZERLAND: Alatri A, Bounameaux H, Calanca L, Mazzolai L.

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Frasson, S., Gussoni, G., Di Micco, P. et al. Infection as cause of immobility and occurrence of venous thromboembolism: analysis of 1635 medical cases from the RIETE registry. J Thromb Thrombolysis 41, 404–412 (2016). https://doi.org/10.1007/s11239-015-1242-2

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