Was sollte der Rheumatologe über Hämostaseologie wissen?

Zusammenfassung

Entzündungs- wie Gerinnungsprozesse sind Teil komplexer Abwehrmechanismen zur Erhaltung der körperlichen Integrität und Homoiostase. Beide haben daher Gemeinsamkeiten, z. B. sind sie durch vielfältige Interaktionen auf zellulärer und humoraler Ebene vernetzt und nutzen schrittweise Amplifikationen. Von Bedeutung dabei ist, dass Entzündungs- und Gerinnungsaktivierung offenbar simultan im Rahmen von Abwehrprozessen erfolgen. Diese Verknüpfungen haben somit klinische Konsequenzen bzw. Korrelate, wie dies für Patienten mit akuten (Sepsis, Harnwegsinfekt, pulmonale Infekte, usw.) als auch chronischen (rheumatische Erkrankungen, entzündliche Darm- und Atemwegserkrankungen, usw.) Entzündungen durch erhöhte thromboembolische Morbiditäts- und Mortalitätsrisiken belegt werden kann. Die vorliegende Arbeit gibt einen Überblick zu klinischen und pathophysiologischen Aspekten der Wechselwirkung von Inflammation und Hyperkoagulabilität bei rheumatischen Systemerkrankungen (rheumatoide Arthritis, Kollagenosen, Vaskulitiden). Die insgesamt erhöhten Risiken für venöse thrombembolische Ereignisse und Lungenembolien (VTE) bei diesen Krankheiten bestehen v. a. in Phasen erhöhter Krankheitsaktivität, Immobilisation, die Notwendigkeit von operativen Eingriffen, Einsatz höherer Glukokortikoiddosen und sollte hinsichtlich einer strikten Thromboseprophylaxe berücksichtigt werden. Der rheumatologische Sonderfall Antiphospholipidsyndrom wird hinsichtlich seiner speziellen, klinischen Aspekte besprochen. Die Evidenz für einzelne VTE-Prophylaxemaßnahmen (physikalische, medikamentöse Maßnahmen) ist für rheumatische Erkrankungen unzureichend belegt und bedarf weiterer Untersuchungen. Schließlich werden aktuelle Aspekte der Antikoagulationsmöglichkeiten einschl. direkter oraler Antikoagulantien und möglicher Schnittstellen zu entzündlich-rheumatischen Erkrankungen diskutiert. Das deutlich erhöhte VTE-Risiko bei Patienten mit rheumatischen Erkrankungen erfordert dessen Berücksichtigung in der Prophylaxe, Diagnostik und Therapie.

Abstract

Inflammation as well as coagulation processes are part of complex defence mechanisms, which serve to maintain physical integrity and homeostasis. Therefore, they share a number of common features such as a network of manifold interactions on a cellular and humoral level or the use of stepwise amplification. Importantly, inflammation and coagulation are apparently activated simultaneously in the course of immune defence processes. These connections therefore have clinical implications or correlates, as has been proven for patients with acute (sepsis, urinary tract infections, pulmonary infections, etc.) and chronic (rheumatic diseases, inflammatory diseases of the intestinal and respiratory tract, etc.) inflammations, who are at an increased risk of morbidity and mortality due to thromboembolic events. This paper provides an overview of clinical and pathophysiological aspects of the interactions between inflammation and hypercoagulability in patients with systemic rheumatic diseases (rheumatoid arthritis, connective tissue diseases, vasculitis). The overall increased risks of venous thromboembolic events and pulmonary embolism (VTE) in these diseases most notably exist in phases of increased disease activity or immobilisation, or in phases in which surgical procedures are required or higher doses of glucocorticoids are used. These risks should be considered in decisions on strict thrombosis prophylaxis. The antiphospholipid syndrome, a special entity in rheumatology, will be discussed in the light of its specific clinical aspects. Evidence regarding individual measures to prevent VTE (physical measures, medication) is insufficient for rheumatic diseases and requires further investigation. Finally, current aspects of anticoagulation options will be discussed, including direct oral anticoagulants and possible interfaces with inflammatory rheumatic diseases. The clearly increased risk of VTE in patients with rheumatic diseases must be considered in the prevention, diagnosis and treatment of inflammatory rheumatic diseases.

Schlüsselwörter

Rheumatoide Arthritis - Thrombose - Koagulation - Lungenembolie

Key words

rheumatoid arthritis - thrombosis - coagulation - pulmonary embolism

• References

• 1 Hoppe B, Dorner T. Coagulation and the fibrin network in rheumatic disease: a role beyond haemostasis. Nature Reviews Rheumatology 2012; 8: 738-746
• 2 Hoppe B, Haupl T, Skapenko A et al. Fibrinogen and factor XIII A-subunit genotypes interactively influence C-reactive protein levels during inflammation. Annals of the Rheumatic Diseases 2012; 71: 1163-1169
• 3 Lee JJ, Pope JE. A Meta-Analysis of the Risk of Venous Thromboembolism in Inflammatory Rheumatic Diseases. Arthritis & Rheumatology 2014; 66: S473-S474
• 4 Zoller B, Li XJ, Sundquist J et al. Risk of pulmonary embolism in patients with autoimmune disorders: a nationwide follow-up study from Sweden. Lancet 2012; 379: 244-249
• 5 Veetil BMA, Bongartz T. Perioperative care for patients with rheumatic diseases. Nature Reviews Rheumatology 2012; 8: 32-41
• 6 Lee JJ, Pope JE. A meta-analysis of the risk of venous thromboembolism in inflammatory rheumatic diseases. Arthritis Research & Therapy. 2014; 16
• 7 Fischer LM, Schlienger RG, Matter C et al. Effect of rheumatoid arthritis or systemic lupus erythematosus on the risk of first-time acute myocardial infarction. American Journal of Cardiology 2004; 93: 198-200
• 8 Merkel PA, Lo GH, Holbrook JT et al. Brief communication: High incidence of venous thrombotic events among patients with Wegener granulomatosis: The Wegener's clinical occurrence of thrombosis (WeCLOT) study. Annals of Internal Medicine 2005; 142: 620-626
• 9 Ingegnoli F, Fantini F, Griffini S et al. Anti-tumour necrosis factor alpha therapy normalises fibrinolysis impairment in patients with active rheumatoid arthritis. Clinical and Experimental Rheumatology 2010; 28: 254-257
• 10 Ingegnoli F, Fantini F, Favalli E et al. Activation of inflammation, coagulation and fibrinolysis in patients with rheumatoid arthritis: Inhibition by tumour necrosis factor alpha blockade. Annals of the Rheumatic Diseases 2008; 67: A30
• 11 Ingegnoli F, Cugno M, Favalli EG et al. Treatment with infliximab is associated with reduction of prothrombotic and inflammatory biomarkers in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases 2007; 66: 173-174
• 12 Cervera R, Khamashta MA, Font J et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period – A comparison of early and late manifestations in a cohort of 1,000 patients. Medicine 2003; 82: 299-308
• 13 Haga HJ, Jacobsen EM, Peen E. Incidence of thromboembolic events in patients with primary Sjogren’s syndrome. Scandinavian Journal of Rheumatology 2008; 37: 127-129
• 14 AWMF S2 Leitlinie zur Prophylaxe der venösen Thromboembolie. www.awmf.de Stand 3.8.2015 Gültigkeit abgelaufen, wird derzeit überarbeitet
• 15 AWMF S3 Leitlinien zur Prophylaxe der venösen Thromboembolien. www.awmf.de Stand 3.8.2015 Gültigkeit abgelaufen, wird derzeit überarbeitet
• 16 Bates SM, Jaeschke R, Stevens SM et al. Diagnosis of DVT: Antithrombotic therapy and prevention of thrombosis, 9^th edition: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 141: e351S-e418S
• 17 Ingegnoli F, Fantini F, Favalli EG et al. Inflammatory and prothrombotic biomarkers in patients with rheumatoid arthritis: Effects of tumor necrosis factor-alpha blockade. Journal of Autoimmunity 2008; 31: 175-179
• 18 Wallberg-Jonsson S, Cvetkovic JT, Sundqvist KG et al. Activation of the immune system and inflammatory activity in relation to markers of atherothrombotic disease and atherosclerosis in rheumatoid arthritis. Journal of Rheumatology 2002; 29: 875-882
• 19 Miyakis S, Lockshin MD, Atsumi T et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). Journal of Thrombosis and Haemostasis 2006; 4: 295-306
• 20 Roggenbuck D, Egerer K, von Landenberg P et al. Antiphospholipid antibody profiling – Time for a new technical approach?. Autoimmunity Reviews 2012; 11: 821-826
• 21 Roggenbuck D, Egerer K, Feist E et al. Antiphospholipid antibody profiling: Association with the clinical phenotype of antiphospholipid syndrome? Comment on the article by Otomo et al. Arthritis and Rheumatism 2012; 64: 2807-2808
• 22 Roggenbuck D, Somma V, Schierack P et al. Autoantibody profiling in APS. Lupus 2014; 23: 1262-1264
• 23 Alexandrova E, Reshetnyak TM, Seredavkina NV et al. Comparison of Multi-Line Dot Assay and Enzyme-Linked Immunosorbent Assay for Detection of Autoantibody Profile in Antiphospholipid Syndrome. Annals of the Rheumatic Diseases 2013; 72: 907-908
• 24 Cervera R, Piette JC, Font J et al. Antiphospholipid syndrome – Clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis and Rheumatism 2002; 46: 1019-1027
• 25 Cohen D, Berger SP, Steup-Beekman GM et al. Diagnosis and management of the antiphospholipid syndrome. British Medical Journal. 2010 340.
• 26 Guyatt GH, Akl EA, Crowther M et al. Introduction to the Ninth Edition Antithrombotic Therapy and Prevention of Thrombosis, 9^th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: 48S-52S
• 27 Bates SM, Greer IA, Middeldorp S et al. Screening for Antiphospholipid Antibodies in Women With Pregnancy Complications Response. Chest 2012; 142: 545-546
• 28 Visser J, Ulander VM, Helmerhorst FM et al. Thromboprophylaxis for recurrent miscarriage in women with or without thrombophilia HABENOX: A randomised multicentre trial. Thrombosis and Haemostasis 2011; 105: 295-301
• 29 Clark P, Walker ID, Langhorne P et al. SPIN (Scottish Pregnancy Intervention) study: a multicenter, randomized controlled trial of low-molecular-weight heparin and low-dose aspirin in women with recurrent miscarriage. Blood 2010; 115: 4162-4167
• 30 Schleussner E, Kamin G, Seeliger G et al. Low-molecidar-weight heparin in recurrent pregnancy loss – Results of the ETHIG II study. Thrombosis Research 2013; 131: S73
• 31 Clark P, Walker ID, Langhorne P et al. SPIN (Scottish Pregnancy Intervention) study: a multicenter, randomized controlled trial of low-molecular-weight heparin and low-dose aspirin in women with recurrent miscarriage. Blood 2010; 115: 4162-4167
• 32 Martinez-Zamora MA, Peralta S, Creus M et al. Risk of thromboembolic events after recurrent spontaneous abortion in antiphospholipid syndrome: a case-control study. Annals of the Rheumatic Diseases 2012; 71: 61-66
• 33 Gris JC, Bouvier S, Molinari N et al. Comparative incidence of a first thrombotic event in purely obstetric antiphospholipid syndrome with pregnancy loss: the NOH-APS observational study. Blood 2012; 119: 2624-2632
• 34 https://clinicaltrials.gov/ct2/show/NCT02116036?term=raps&rank=12 besucht am 22. Juli 2015
• 35 Caldeira D, Costa J, Ferreira JJ et al. Non-vitamin K antagonist oral anticoagulants in the cardioversion of patients with atrial fibrillation: systematic review and meta-analysis. Clinical Research in Cardiology 2015; 104: 582-590
• 36 Kakkos SK, Kirkilesis GI, Tsolakis IA Editor’s Choice – Efficacy and Safety of the New Oral Anticoagulants Dabigatran, Rivaroxaban, Apixaban, and Edoxaban in the Treatment and Secondary Prevention of Venous Thromboembolism: A Systematic Review and Meta-analysis of Phase III Trials. European Journal of Vascular and Endovascular Surgery 2014; 48: 565-575
• 37 Beyer-Westendorf J, Forster K, Pannach S et al. Rates, management, and outcome of rivaroxaban bleeding in daily care: results from the Dresden NOAC registry. Blood 2014; 124: 955-962
• 38 Tamayo S, Peacock WF, Patel M et al. Characterizing Major Bleeding in Patients With Nonvalvular Atrial Fibrillation: A Pharmacovigilance Study of 27 467 Patients Taking Rivaroxaban. Clinical Cardiology 2015; 38: 63-68
• 39 Chang HY, Zhou MJ, Tang WZ et al. Risk of gastrointestinal bleeding associated with oral anticoagulants: population based retrospective cohort study. BMJ-British Medical Journal. 2015 350. h1585
• 40 Matta F, Singala R, Yaekoub AY et al. Risk of venous thromboembolism with rheumatoid arthritis. Thrombosis and Haemostasis 2009; 101: 134-138
• 41 Delvaeye M, Conway EM. Coagulation and innate immune responses: can we view them separately?. Blood 2009; 114: 2367-2374