Hamostaseologie 2020; 40(03): 301-310
DOI: 10.1055/a-1177-5127
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Head, Neck, and Abdominopelvic Septic Thrombophlebitis: Current Evidence and Challenges in Diagnosis and Treatment

Luca Valerio
1   Center for Thrombosis and Hemostasis, University Medical Center Mainz, University of Mainz, Mainz, Germany
,
Nicoletta Riva
2   Department of Pathology and Anatomy, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
› Author Affiliations
Further Information

Publication History

17 February 2020

12 May 2020

Publication Date:
29 July 2020 (online)

Abstract

Septic thrombophlebitis (STP) is a complex, cross-disciplinary clinical condition that combines a localized infection with a neighboring venous thrombosis. STP can occur at several possible anatomic sites, such as dural sinuses, jugular vein (Lemierre syndrome), portal vein (pylephlebitis), and pelvic veins. Its high mortality in the preantibiotic era improved considerably with the introduction of modern antibiotics. However, little evidence exists to date to guide its clinical management. The incidence of STP or its risk factors may be increasing, and its mortality may still be considerable. These trends would have far-reaching implications, especially in the setting of increasing resistance to antimicrobial agents. No clinical assessment tools exist to support patient screening or guide treatment in STP. Few interventional studies exist on the efficacy and safety of anticoagulation. Recommendations on its indications, duration, and the agents of choice are mostly based on evidence derived from small observational studies. While all forms of STP pose similar challenges, future research may benefit from the distinction between bacteria-associated, virus-associated, and mycosis-associated thrombophlebitis. Addressing these gaps in evidence would enhance our ability to diagnose this condition and treat patients effectively.

 
  • References

  • 1 Turner AL, Reynolds FE. Furuncle of the right nasal vestibule; septic thrombosis of the cavernous sinus; lepto-meningitis; death; autopsy. (with microscopic examination of the orbits, cavernous blood sinuses, meninges, ethmoidal and sphenoidal air sinuses). Proc R Soc Med 1926; 19 (Laryngol Sect): 10
  • 2 Baker CC, Petersen SR, Sheldon GF. Septic phlebitis: a neglected disease. Am J Surg 1979; 138 (01) 97-103
  • 3 Esmon CT. Basic mechanisms and pathogenesis of venous thrombosis. Blood Rev 2009; 23 (05) 225-229
  • 4 Lotze EC, Kaufman RH, Kaplan AL. Postpartum ovarian vein thrombophlebitis. Obstet Gynecol Surv 1966; 21 (06) 853-870
  • 5 Mermel LA, Allon M, Bouza E. , et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis 2009; 49 (01) 1-45
  • 6 Silvis SM, de Sousa DA, Ferro JM, Coutinho JM. Cerebral venous thrombosis. Nat Rev Neurol 2017; 13 (09) 555-565
  • 7 Sacco C, Zane F, Granziera S. , et al; Lemierre Study Group. Lemierre syndrome: clinical update and protocol for a systematic review and individual patient data meta-analysis. Hamostaseologie 2019; 39 (01) 76-86
  • 8 Brown CE, Stettler RW, Twickler D, Cunningham FG. Puerperal septic pelvic thrombophlebitis: incidence and response to heparin therapy. Am J Obstet Gynecol 1999; 181 (01) 143-148
  • 9 Belhassen-García M, Gomez-Munuera M, Pardo-Lledias J. , et al. Pylephlebitis: incidence and prognosis in a tertiary hospital. Enferm Infecc Microbiol Clin 2014; 32 (06) 350-354
  • 10 Antoniak S. The coagulation system in host defense. Res Pract Thromb Haemost 2018; 2 (03) 549-557
  • 11 Scully M, Levi M. How we manage haemostasis during sepsis. Br J Haematol 2019; 185 (02) 209-218
  • 12 Levi M, Sivapalaratnam S. Disseminated intravascular coagulation: an update on pathogenesis and diagnosis. Expert Rev Hematol 2018; 11 (08) 663-672
  • 13 Branchford BR, Carpenter SL. The role of inflammation in venous thromboembolism. Front Pediatr 2018; 6: 142
  • 14 Antoniak S, Mackman N. Multiple roles of the coagulation protease cascade during virus infection. Blood 2014; 123 (17) 2605-2613
  • 15 Riley TV. Heparinase production by anaerobic bacteria. J Clin Pathol 1987; 40 (04) 384-386
  • 16 Forrester LJ, Campbell BJ, Berg JN, Barrett JT. Aggregation of platelets by Fusobacterium necrophorum. J Clin Microbiol 1985; 22 (02) 245-249
  • 17 Ward PA, Fattahi F. New strategies for treatment of infectious sepsis. J Leukoc Biol 2019; 106 (01) 187-192
  • 18 Mendoza-Pinto C, García-Carrasco M, Cervera R. Role of infectious diseases in the antiphospholipid syndrome (including its catastrophic variant). Curr Rheumatol Rep 2018; 20 (10) 62
  • 19 Abdel-Wahab N, Lopez-Olivo MA, Pinto-Patarroyo GP, Suarez-Almazor ME. Systematic review of case reports of antiphospholipid syndrome following infection. Lupus 2016; 25 (14) 1520-1531
  • 20 Pongas G, Dasgupta SK, Thiagarajan P. Antiplatelet factor 4/heparin antibodies in patients with gram negative bacteremia. Thromb Res 2013; 132 (02) 217-220
  • 21 Iba T, Levi M, Levy JH. Sepsis-induced coagulopathy and disseminated intravascular coagulation. Semin Thromb Hemost 2020; 46 (01) 89-95
  • 22 Frick IM, Shannon O, Neumann A, Karlsson C, Wikström M, Björck L. Streptococcal inhibitor of complement (SIC) modulates fibrinolysis and enhances bacterial survival within fibrin clots. J Biol Chem 2018; 293 (35) 13578-13591
  • 23 Riordan T. Human infection with Fusobacterium necrophorum (Necrobacillosis), with a focus on Lemierre's syndrome. Clin Microbiol Rev 2007; 20 (04) 622-659
  • 24 Dunnihoo DR, Gallaspy JW, Wise RB, Otterson WN. Postpartum ovarian vein thrombophlebitis: a review. Obstet Gynecol Surv 1991; 46 (07) 415-427
  • 25 Dotters-Katz SK, Smid MC, Grace MR, Thompson JL, Heine RP, Manuck T. Risk factors for postpartum septic pelvic thrombophlebitis: a multicenter cohort. Am J Perinatol 2017; 34 (11) 1148-1151
  • 26 Choudhry AJ, Baghdadi YM, Amr MA, Alzghari MJ, Jenkins DH, Zielinski MD. Pylephlebitis: a review of 95 cases. J Gastrointest Surg 2016; 20 (03) 656-661
  • 27 Garcia J, Aboujaoude R, Apuzzio J, Alvarez JR. Septic pelvic thrombophlebitis: diagnosis and management. Infect Dis Obstet Gynecol 2006; 2006: 15614
  • 28 Weed JC. Indications and techniques of ligation of the inferior vena cava. Surg Clin North Am 1953; 33 (04) 967-974
  • 29 Talaie T, Drucker C, Aicher B. , et al. Endovascular thrombectomy of septic thrombophlebitis of the inferior vena cava: case report and review of the literature. Vasc Endovascular Surg 2018; 52 (08) 641-647
  • 30 Josey WE, Staggers Jr SR. Heparin therapy in septic pelvic thrombophlebitis: a study of 46 cases. Am J Obstet Gynecol 1974; 120 (02) 228-233
  • 31 Einhäupl KM, Villringer A, Meister W. , et al. Heparin treatment in sinus venous thrombosis. Lancet 1991; 338 (8767): 597-600
  • 32 de Bruijn SF, Stam J. Randomized, placebo-controlled trial of anticoagulant treatment with low-molecular-weight heparin for cerebral sinus thrombosis. Stroke 1999; 30 (03) 484-488
  • 33 Einhäupl K, Stam J, Bousser MG. , et al; European Federation of Neurological Societies. EFNS guideline on the treatment of cerebral venous and sinus thrombosis in adult patients. Eur J Neurol 2010; 17 (10) 1229-1235
  • 34 Misra UK, Kalita J, Chandra S, Kumar B, Bansal V. Low molecular weight heparin versus unfractionated heparin in cerebral venous sinus thrombosis: a randomized controlled trial. Eur J Neurol 2012; 19 (07) 1030-1036
  • 35 Afshari D, Moradian N, Nasiri F, Razazian N, Bostani A, Sariaslani P. The efficacy and safety of low-molecular-weight heparin and unfractionated heparin in the treatment of cerebral venous sinus thrombosis. Neurosciences (Riyadh) 2015; 20 (04) 357-361
  • 36 Southwick FS, Richardson Jr EP, Swartz MN. Septic thrombosis of the dural venous sinuses. Medicine (Baltimore) 1986; 65 (02) 82-106
  • 37 Zuurbier SM, Coutinho JM, Stam J. , et al; ISCVT Investigators. Clinical outcome of anticoagulant treatment in head or neck infection-associated cerebral venous thrombosis. Stroke 2016; 47 (05) 1271-1277
  • 38 Wu M, Schuster M, Tadros M. Update on management of portal vein thrombosis and the role of novel anticoagulants. J Clin Transl Hepatol 2019; 7 (02) 154-164
  • 39 Golpe R, Marín B, Alonso M. Lemierre's syndrome (necrobacillosis). Postgrad Med J 1999; 75 (881) 141-144
  • 40 Doyle KJ, Jackler RK. Otogenic cavernous sinus thrombosis. Otolaryngol Head Neck Surg 1991; 104 (06) 873-877
  • 41 Lustig LR, Cusick BC, Cheung SW, Lee KC. Lemierre's syndrome: two cases of postanginal sepsis. Otolaryngol Head Neck Surg 1995; 112 (06) 767-772
  • 42 Valerio L, Zane F, Sacco C. , et al. Patients with Lemierre syndrome have a high risk of new thromboembolic complications, clinical sequelae and death: an analysis of 712 cases. J Intern Med 2020; (e-pub ahead of print) DOI: 10.1111/joim.13114.
  • 43 van der Poel NA, Mourits MP, de Win MML, Coutinho JM, Dikkers FG. Prognosis of septic cavernous sinus thrombosis remarkably improved: a case series of 12 patients and literature review. Eur Arch Otorhinolaryngol 2018; 275 (09) 2387-2395
  • 44 Stawicki SP, Firstenberg MS, Lyaker MR. , et al. Septic embolism in the intensive care unit. Int J Crit Illn Inj Sci 2013; 3 (01) 58-63
  • 45 Goswami U, Brenes JA, Punjabi GV, LeClaire MM, Williams DN. Associations and outcomes of septic pulmonary embolism. Open Respir Med J 2014; 8: 28-33
  • 46 Plemmons RM, Dooley DP, Longfield RN. Septic thrombophlebitis of the portal vein (pylephlebitis): diagnosis and management in the modern era. Clin Infect Dis 1995; 21 (05) 1114-1120
  • 47 Centor RM. Expand the pharyngitis paradigm for adolescents and young adults. Ann Intern Med 2009; 151 (11) 812-815
  • 48 Mayne ES, Louw S. Good fences make good neighbors: human immunodeficiency virus and vascular disease. Open Forum Infect Dis 2019; 6 (11) ofz303
  • 49 Lodigiani C, Iapichino G, Carenzo L. , et al; Humanitas COVID-19 Task Force. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res 2020; 191: 9-14
  • 50 Paccoud O, Fontaine H, Bougnoux ME, Lortholary O, Suarez F, Lanternier F. Portal vein thrombosis as a long-term complication of chronic hepatosplenic candidiasis in an allogeneic haematopoietic stem-cell transplant recipient. Clin Microbiol Infect 2020; 26 (07) 967-968
  • 51 Fardini Y, Wang X, Témoin S. , et al. Fusobacterium nucleatum adhesin FadA binds vascular endothelial cadherin and alters endothelial integrity. Mol Microbiol 2011; 82 (06) 1468-1480
  • 52 Kasper DL, Sahani D, Misdraji J. Case records of the Massachusetts General Hospital. Case 25-2005. A 40-year-old man with prolonged fever and weight loss. N Engl J Med 2005; 353 (07) 713-722
  • 53 Murphy EC, Mörgelin M, Cooney JC, Frick IM. Interaction of bacteroides fragilis and Bacteroides thetaiotaomicron with the kallikrein-kinin system. Microbiology 2011; 157 (Pt 7): 2094-2105
  • 54 Meda MS, Lopez AJ, Guyot A. Candida inferior vena cava filter infection and septic thrombophlebitis. Br J Radiol 2007; 80 (950) e48-e49
  • 55 Maulat C, Lapierre L, Migueres I, Chaufour X, Martin-Blondel G, Muscari F. Caval replacement with parietal peritoneum tube graft for septic thrombophlebitis after hepatectomy: a case report. World J Hepatol 2019; 11 (01) 133-137
  • 56 Caccese R, Carfagna P, Pistilli N, Massetti AP, Falcone M, Venditti M. Candidal thrombophlebitis of central veins: case report and review. Med Mycol 2012; 50 (03) 299-304
  • 57 Rabah F, El-Banna N, Abdel-Baki M. , et al. Postvaricella thrombosis-report of two cases and literature review. Pediatr Infect Dis J 2012; 31 (09) 985-987
  • 58 Driesen Y, Verweij M, De Maeseneer M, De Dooy J, Wojciechowski M, Van Den Akker M. Vascular complications of varicella: description of 4 Cases and a Review of Literature. Pediatr Infect Dis J 2015; 34 (11) 1256-1259
  • 59 Khan R, Yasmeen A, Pandey AK, Al Saffar K, Narayanan SR. Cerebral venous thrombosis and acute pulmonary embolism following varicella infection. Eur J Case Rep Intern Med 2019; 6 (10) 001171
  • 60 Musselwhite LW, Sheikh V, Norton TD. , et al. Markers of endothelial dysfunction, coagulation and tissue fibrosis independently predict venous thromboembolism in HIV. AIDS 2011; 25 (06) 787-795
  • 61 Bai C, Ding J, Da Z. , et al. Probable risk factors of internal jugular vein stenosis in Chinese patients-A real-world cohort study. Clin Neurol Neurosurg 2020; 191: 105678
  • 62 Plastini T, Henry D, Dunleavy K. Ovarian vein thrombus: to treat or not to treat?. Blood Adv 2017; 1 (15) 1120-1123
  • 63 Riva N, Donadini MP, Ageno W. Epidemiology and pathophysiology of venous thromboembolism: similarities with atherothrombosis and the role of inflammation. Thromb Haemost 2015; 113 (06) 1176-1183
  • 64 Cassinelli G, Naggi A. Old and new applications of non-anticoagulant heparin. Int J Cardiol 2016; 212 (Suppl. 01) S14-S21
  • 65 Young E. The anti-inflammatory effects of heparin and related compounds. Thromb Res 2008; 122 (06) 743-752
  • 66 Di Nisio M, Wichers IM, Middeldorp S. Treatment for superficial thrombophlebitis of the leg. Cochrane Database Syst Rev 2018; 2 (02) CD004982
  • 67 Ungprasert P, Srivali N, Wijarnpreecha K, Charoenpong P, Knight EL. Non-steroidal anti-inflammatory drugs and risk of venous thromboembolism: a systematic review and meta-analysis. Rheumatology (Oxford) 2015; 54 (04) 736-742
  • 68 Malmberg S, Petrén S, Gunnarsson R, Sundvall PD, Hedin K. The likelihood that Fusobacterium necrophorum is linked to uncomplicated pharyngotonsillitis in primary care patients - a systematic with meta analysis. PROSPERO 2018; CRD4201810680
  • 69 Miranda B, Aaron S, Arauz A. , et al. The benefit of EXtending oral antiCOAgulation treatment (EXCOA) after acute cerebral vein thrombosis (CVT): EXCOA-CVT cluster randomized trial protocol. Int J Stroke 2018; 13 (07) 771-774
  • 70 Keshari RS, Silasi R, Popescu NI. , et al. Fondaparinux pentasaccharide reduces sepsis coagulopathy and promotes survival in the baboon model of Escherichia coli sepsis. J Thromb Haemost 2020; 18 (01) 180-190
  • 71 Peetermans M, Liesenborghs L, Peerlinck K. , et al; Staphylothrombin Investigators. Targeting coagulase activity in Staphylococcus aureus bacteraemia: a randomized controlled single-centre trial of staphylothrombin inhibition. Thromb Haemost 2018; 118 (05) 818-829
  • 72 Sexton TR, Zhang G, Macaulay TE. , et al. Ticagrelor reduces thromboinflammatory markers in patients with pneumonia. JACC Basic Transl Sci 2018; 3 (04) 435-449
  • 73 Storey RF, James SK, Siegbahn A. , et al. Lower mortality following pulmonary adverse events and sepsis with ticagrelor compared to clopidogrel in the PLATO study. Platelets 2014; 25 (07) 517-525
  • 74 Lancellotti P, Musumeci L, Jacques N. , et al. Antibacterial activity of ticagrelor in conventional antiplatelet dosages against antibiotic-resistant gram-positive bacteria. JAMA Cardiol 2019; 4 (06) 596-599
  • 75 Papareddy P, Rossnagel M, Doreen Hollwedel F. , et al. A human antithrombin isoform dampens inflammatory responses and protects from organ damage during bacterial infection. Nat Microbiol 2019; 4 (12) 2442-2455
  • 76 Chen J, Li X, Li L. , et al. Coagulation factors VII, IX and X are effective antibacterial proteins against drug-resistant Gram-negative bacteria. Cell Res 2019; 29 (09) 711-724
  • 77 Najem MY, Couturaud F, Lemarié CA. Cytokine and chemokine regulation of venous thromboembolism. J Thromb Haemost 2020; 18 (05) 1009-1019
  • 78 Ali RA, Gandhi AA, Meng H. , et al. Adenosine receptor agonism protects against NETosis and thrombosis in antiphospholipid syndrome. Nat Commun 2019; 10 (01) 1916
  • 79 Paciullo F, Momi S, Gresele P. PCSK9 in haemostasis and thrombosis: possible pleiotropic effects of PCSK9 inhibitors in cardiovascular prevention. Thromb Haemost 2019; 119 (03) 359-367
  • 80 Berger JM, Loza Valdes A, Gromada J, Anderson N, Horton JD. Inhibition of PCSK9 does not improve lipopolysaccharide-induced mortality in mice. J Lipid Res 2017; 58 (08) 1661-1669
  • 81 Heinzl MW, Resl M, Klammer C, Egger M, Dieplinger B, Clodi M. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is not induced in artificial human inflammation and is not correlated with inflammatory response. Infect Immun 2020; 88 (03) e00842-19
  • 82 Mahmoudpour SH, Jankowski M, Valerio L. , et al. Safety of low-dose subcutaneous recombinant interleukin-2: systematic review and meta-analysis of randomized controlled trials. Sci Rep 2019; 9 (01) 7145
  • 83 Bochenek ML, Leidinger C, Rosinus NS. , et al. Activated endothelial TGFβ1 signaling promotes venous thrombus nonresolution in mice via endothelin-1: potential role for chronic thromboembolic pulmonary hypertension. Circ Res 2020; 126 (02) 162-181
  • 84 Laridan E, Martinod K, De Meyer SF. Neutrophil extracellular traps in arterial and venous thrombosis. Semin Thromb Hemost 2019; 45 (01) 86-93
  • 85 Southwick FS. Septic thrombophlebitis of major dural venous sinuses. Curr Clin Top Infect Dis 1995; 15: 179-203