Häufigkeit thromboembolischer Komplikationen bei Patienten mit Lungenkarzinom^[*]

Zusammenfassung

Hintergrund: Thromboembolische Komplikationen bei Lungenkrebspatienten gelten als häufig, jedoch liegen nur wenige Daten über deren Inzidenz vor. Zur Klärung der Häufigkeit thromboembolischer Ereignisse im arteriellen und venösen System wurden die in unserem Hause mit einem Lungenkarzinom diagnostizierten Patienten retrospektiv bezüglich des Auftretens thromboembolischer Ereignisse ausgewertet.

Patienten/Methode: Alle Patienten mit Erstdiagnose eines Lungenkarzinoms wurden seit 1/2008 prospektiv erfasst und hier bis 12/2010 retrospektiv bezüglich thromboembolischer Komplikationen im venösen und arteriellen System ausgewertet unter Berücksichtigung von Tumorstadium, Histologie und platinhaltiger Chemotherapie. Bei den venösen thromboembolischen Komplikationen wurden Lungenarterienembolien und tiefe Venenthrombosen berücksichtigt, bei den arteriellen thromboembolischen Komplikationen Myokardinfarkt, mesenteriale Ischämie, peripher-arterielle Ischämie, Nierenarterienischämie und ischämischer Apoplex.

Ergebnisse: In den 36 Monaten wurde in unserem Zentrum bei 1940 Patienten (1209 Männer, 731 Frauen) die Erstdiagnose eines Lungenkarzinoms gestellt, 156 kleinzellige Lungenkarzinome (SCLC; 8 %) und 1784 nichtkleinzellige Lungenkarzinome (NSCLC; 92 %). Insgesamt traten bisher bei 190/1940 Patienten (9,8 %) thromboembolische Komplikationen auf; bei 148/190 (78 %) venöse und bei 51/190 (27 %) arterielle thromboembolische Komplikationen. Wir dokumentierten 82/148 (55 %) tiefe Venenthrombosen, 98/148 (66 %) Lungenarterienembolien sowie arterielle thromboembolische Ereignisse: ischämischer Apoplex 23/51 (45 %), Koronararterien 14/51 (28 %), Extremitätenarterien 12/51 (24 %), Mesenterialarterien 4/51 (7,8 %), extrakranielle hirnversorgende Arterien 3/51 (5,9 %).

Diskussion/Schlussfolgerungen: Thromboembolische Ereignisse sind eine häufige Komplikation bei Patienten mit Lungenkarzinom. Auf dem Boden dieser Ergebnisse sollte der Stellenwert einer entsprechenden Primärprophylaxe erneut diskutiert werden.

Abstract

Background: Clinicians are frequently confronted by thromboembolic events in patients with lung cancer, yet few data are available about their incidence. In order to obtain data on the frequency of thromboembolic events in the venous and arterial systems, all patients with lung cancer diagnosed in our hospital were retrospectively evaluated with regard to such an event.

Patients/Methods: All patients with a primary diagnosis of lung cancer between January 2008 and December 2010 were prospectively recorded within our tumour registry and retrospectively evaluated with regard to tumour stage, histology and platinum-based chemotherapy. Thromboembolic complications of the arterial and the venous system were included (pulmonary embolism, deep venous thrombosis, myocardial infarction, mesenterial ischaemia, acute limb ischaemia, ischaemia of the renal artery and ischaemic stroke).

Results: Within those 36 months 1940 patients (1209 men, 731 women) were diagnosed with lung cancer. SCLC and NSCLC in 156 (8 %) and 1784 cases (92 %), respectively. Thromboembolic events were documented in 190/1940 (9.8 %) cases, venous thromboembolic complications in 148/190 patients (78 %), arterial thromboembolic complications in 51/190 patients (27 %). We documented 82/148 (55 %) deep venous thrombosis, 98/148 (66 %) pulmonary embolisms and arterial thromboembolic events: ischaemic stroke 23/51 (45 %), coronary arteries 14/51 (28 %), peripheral arteries 12/51 (24 %), mesenterial arteries 4/51 (7.8 %), extracranial cerebral arteries 3/51 (5.9 %).

Conclusions: Thromboembolic complications are a common event in patients with lung cancer. Thus, the benefit of primary prevention anticoagulation in lung cancer patients should be prospectively evaluated.

^* Diese Veröffentlichung ist Teil der Promotion von Herrn Markus Samulowski an der Ruhr-Universität Bochum. Die Studie wurde von der Stiftung Oskar-Helene-Heim unterstützt.

• Literatur

• 1 Heit JA, Silverstein MD, Mohr DN et al. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 2000; 160: 809-815
• 2 Chew HK, Wun T, Harvey D et al. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med 2006; 166: 458-64
• 3 Blom J, Vanderschoot J, Oostindiër M et al. Incidence of venous thrombosis in a large cohort of 66 329 cancer patients: results of a record linkage study. J Thromb Haemost 2006; 4: 529-535
• 4 Silverstein MD, Heit JA, Mohr DN et al. Trends in the Incidence of Deep Vein Thrombosis and Pulmonary Embolism. Arch Intern Med 1998; 158: 585-593
• 5 Lee AYY, Levine MN. Venous thromboembolism and cancer: risks and outcomes. Circulation 2003; 107: I17-21
• 6 Trousseau A. Phlegmasia alba dolens. In: Clinique Medicale De l’Hotel-Dieu De Paris. 03. Vol. 2nd Ed. 1865: 654-712
• 7 Shen VS, Pollak EW. Fatal pulmonary embolism in cancer patients: is heparin prophylaxis justified?. The Southern Medical Journal 1980; 73: 841-843
• 8 Hettiarachchi RJ, Lok J, Prins MH et al. Undiagnosed malignancy in patients with deep vein thrombosis: incidence, risk indicators, and diagnosis. Cancer 1998; 83: 180-185
• 9 Hach-Wunderle V, Schellong S, Encke ANT. AWMF online Diagnostik und Therapie der Venenthrombose und der Lungenembolie. AWMF Online 2010;
• 10 Sørensen HT, Mellemkjaer L, Steffensen FH et al. The risk of a diagnosis of cancer after primary deep venous thrombosis or pulmonary embolism. N Engl J Med 1998; 338: 206-207
• 11 Levitan N, Dowlati A, Remick SC et al. Rates of Initial and Recurrent Thromboembolic Disease Among Patients with Malignancy Versus Those without Malignancy. Medicine 1999; 78: 285-291
• 12 Khorana AA, Francis CW, Culakova E et al. Risk factors for chemotherapy-associated venous thromboembolism in a prospective observational study. Cancer 2005; 104: 2822-2829
• 13 Barni S, Labianca R, Agnelli G et al. Chemotherapy-associated thromboembolic risk in cancer outpatients and effect of nadroparin thromboprophylaxis: results of a retrospective analysis of the PROTECHT study. J Transl Med 2011; 9: 179
• 14 Lee A. Cancer and thromboembolic disease: pathogenic mechanisms. Cancer Treatment Reviews 2002; 7372: 137-140
• 15 Blom JW, Osanto S, Rosendaal FR. The risk of a venous thrombotic event in lung cancer patients: higher risk for adenocarcinoma than squamous cell carcinoma. J Thromb Haemost 2004; 2: 1760-1765
• 16 Moore RA, Adel N, Riedel E et al. High incidence of thromboembolic events in patients treated with cisplatin-based chemotherapy: a large retrospective analysis. J Clin Oncol 2011; 29: 3466-3473
• 17 Roger VL, Go AS, Lloyd-Jones DM et al. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation 2012; 125: e2-e220
• 18 Wiesner G, Grimm J, Bittner E et al. Zum Herzinfarktgeschehen in der Bundesrepublik Deutschland: Prävalenz, Inzidenz, Trend, Ost-West-Vergleich. Gesundheitswesen 1999; 61: 72-78
• 19 Khorana AA, Francis CW, Culakova E et al. Thromboembolism in hospitalized neutropenic cancer patients. J Clin Oncol 2006; 24: 484-490
• 20 Goldstein LB, Bushnell CD, Adams RJ et al. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42: 517-584
• 21 Diener HC. Primär- und Sekundärprävention der zerebralen Ischämie. In: Leitlinien Für Diagnostik und Therapie in der Neurologie. 4.. überarbeitete Auflage. Stuttgart: Georg Thieme Verlag Stuttgart; 2008: 654 ff
• 22 Camm aJ, Kirchhof P, Lip GYH et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). European Heart Journal 2010; 31: 2369-2429
• 23 Bona R, Hickey A, Wallace D. Warfarin is safe as secondary prophylaxis in patients with cancer and a previous episode of venous thrombosis. Am J Clin Oncol 2000; 23: 71-73
• 24 Hutten BBA, Prins MH, Gent M et al. Incidence of Recurrent Thromboembolic and Bleeding Thromboembolism in Relation to Both Malignancy and Achieved International Normalized Ratio: A Retrospective Analysis. J Clin Oncol 2000; 18: 3078-3083
• 25 Pabinger I, Alt-Epping B, Biasutti F. Venöse Thrombembolien bei Tumorpatienten. Hämostaseologie 2011; 281-290
• 26 Guyatt GH, Akl EA, Crowther M et al. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: 7S-47S
• 27 Lyman GH, Khorana AA, Kuderer NM et al. Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 2013; 31: 1-17
• 28 Mandal M, Labianca R. Venous thromboembolism (VTE) in cancer patients. ESMO Clinical Recommendations for prevention and management 2010; 2: 117-119
• 29 Hirsh J, Fuster V, Ansell J et al. American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. Circulation 2003; 107: 1692-1711
• 30 Gitter MJ, Jaeger TM, Petterson TM et al. Bleeding and thromboembolism during anticoagulant therapy: a population-based study in Rochester, Minnesota. Mayo Clinic Proceedings. Mayo Clinic 1995; 70: 725-733
• 31 White R, Beyth R, Zhou H et al. Major bleeding after hospitalization for deep-venous thrombosis. Am J Med 1999; 107: 414-424
• 32 Agnelli G, George DJ, Kakkar AK et al. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med 2012; 366: 601-609
• 33 Levine MN, Gu C, Liebman HA et al. A randomized phase II trial of apixaban for the prevention of thromboembolism in patients with metastatic cancer. J Thromb Haemost 2012; 10: 807-814
• 34 Agnelli G, Buller H, Cohen A. Apixaban for extended treatment of venous thromboembolism. N Engl J Med 2013; 368: 699-708