Akute Ischämie bei Tumorpatienten: Pathogenese, Therapie und Prävention

Zusammenfassung

Arterielle Thromboembolien machen ca. 10–30% aller tumorassoziierten thromboembolischen Komplikationen aus [1] und haben trotz Fortschritten in der medikamentösen und operativen Therapie der akuten peripheren Ischämie noch immer eine beträchtliche Mortalität bzw. Morbidität zur Folge [2]. Der vorliegende Beitrag schildert Pathophysiologie, Diagnostik und neueste Therapiemöglichkeiten der tumorassoziierten akuten Extremitätenischämie.

Abstract

Arterial thromboembolism accounts for approximately 10–30% of all tumour-associated thromboembolic complications and, despite advances in drug and surgical therapy of acute peripheral ischaemia, still results in considerable mortality and morbidity. This article describes the pathophysiology, diagnosis and latest therapeutic options for tumour-associated acute limb ischaemia.

Schlüsselwörter

Akute Extremitätenischämie - Tumorerkrankung - Pathogenese - Thrombektomie

Keywords

Acute limb ischemia - neoplastic disease - pathogenesis - thrombectomy

Publication History

Article published online:
29 September 2023

• Literatur

• 1 Sanon S, Lenihan DJ, Mouhayar E. Peripheral arterial ischemic events in cancer patients. Vasc Med 2011; 16: 119-130 DOI: 10.1177/1358863X10388346. (PMID: 21112902)
• 2 Navi BB, Reiner AS, Kamel H. et al. Risk of arterial thromboembolism in patients with cancer. J Am Coll Cardiol 2017; 70: 926-938
• 3 GBD 2016 Causes of Death Collaborators. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017; 390: 1151-1210 DOI: 10.1016/S0140-6736(17)32152-9. (PMID: 28919116)
• 4 Fitzmaurice C, Dicker D. Global Burden of Disease Cancer Collaboration. et al. The global burden of cancer 2013. JAMA Oncol 2015; 1: 505-527 DOI: 10.1001/jamaoncol.2015.0735.
• 5 Ferlay J, Colombet M, Soerjomataram I. et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer 2018; 103: 356-387 DOI: 10.1016/j.ejca.2018.07.005. (PMID: 30100160)
• 6 Navi BB, Reiner AS, Kamel H. et al. Arterial thromboembolic events preceding the diagnosis of cancer in older persons. Arterial thromboembolic events preceding the diagnosis of cancer in older persons. Blood 2019; 133: 781-789 DOI: 10.1182/blood-2018-06-860874. (PMID: 30578253)
• 7 Björck M, Earnshaw JJ, Acosta S. et al. European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the management of acute limb ischaemia. Eur J Vasc Endovasc Surg 2020; 59: 173e218 DOI: 10.1016/j.ejvs.2019.09.006. (PMID: 31899099)
• 8 Weijl NL, Rutten MFJ, Zwinderman AH. et al. Thromboembolic events during chemotherapy for germ cell cancer: a cohort study and review of the literature. J Clin Oncol 2000; 18: 2169-2178
• 9 Blann AD, Dunmore S. Arterial and venous thrombosis in cancer patients. Cardiol Res Pr 2011; 2011: 394740 DOI: 10.4061/2011/394740. (PMID: 21403876)
• 10 Mezouar S, Frère C, Darbousset R. et al. Role of platelets in cancer and cancer-associated thrombosis: experimental and clinical evidences. Thromb Res 2016; 139: 65-76 DOI: 10.1016/j.thromres.2016.01.006. (PMID: 26916298)
• 11 Seizer PMA. Platelets and matrix metalloproteinases. Thromb Haemost 2013; 110: 903-909 DOI: 10.1160/TH13-02-0113. (PMID: 23864155)
• 12 Gremmel T, Perkmann T, Seidinger D. et al. Differential impact of inflammation on six laboratory assays measuring residual arachidonic acid-inducible platelet reactivity during dual antiplatelet therapy. J Atheroscler Thromb 2013; 20: 630-645
• 13 Alonso-Escolano D, Strongin AY, Chung AW. et al. Membrane type-1 matrix metalloproteinase stimulates tumor cell-induced platelet aggregation: role of receptor glycoproteins. Br J Pharmacol 2004; 141: 241-252
• 14 Heinmöller E, Weinel RJ, Heidtmann HH. et al. Studies on tumor-cell-induced platelet aggregation in human lung cancer cell lines. J Cancer Res ClinOncol 1996; 122: 735-744 DOI: 10.1007/BF01209121. (PMID: 8954171)
• 15 Pavo N, Raderer M, Hülsmann M. et al. Cardiovascular biomarkers in patients with cancer and their association with all-cause mortality. Heart 2015; 101: 1874-1880
• 16 Herrmann JLA. The endothelium: dysfunction and beyond. J Nucl Cardiol 2001; 8: 197-206 DOI: 10.1067/mnc.2001.114148. (PMID: 11295698)
• 17 Herrmann JLA. The endothelium – the cardiovascular health barometer. Herz 2008; 33: 343-353 DOI: 10.1007/s00059-008-3088-2. (PMID: 18773154)
• 18 Kleiman NS, Lehane DE, Geyer Jr CE. et al. Prinzmetalʼs angina during 5-fluorouracil chemotherapy. Am J Med 1987; 82: 566-568
• 19 Collins C, Weiden PL. Cardiotoxicity of 5-fluorouracil. Cancer Treat Rep 1987; 71: 733-736 (PMID: 3300968)
• 20 Schnetzler B, Popova N, Collao Lamb C. et al. Coronary spasm induced by capecitabine. Ann Oncol 2001; 12: 723-724
• 21 Mosseri M, Fingert HJ, Varticovski L. et al. In vitro evidence that myocardial ischemia resulting from 5-fluorouracil chemotherapy is due to protein kinase C-mediated vasoconstriction of vascular smooth muscle. Cancer Res 1993; 53: 3028-3033
• 22 Sekijima T, Tanabe A, Maruoka R. et al. Impact of platinum-based chemotherapy on the progression of atherosclerosis. Climacteric 2011; 14: 31-40 DOI: 10.3109/13697137.2010.522278. (PMID: 21067421)
• 23 Thijs AM, van Herpen CML, Sweep FCGJ. et al. Role of endogenous vascular endothelial growth factor in endothelium-dependent vasodilation in humans. Hypertension 2013; 61: 1060-1065 DOI: 10.1161/HYPERTENSIONAHA.111.00841.
• 24 Vaughn DJ, Palmer SC, Carver JR. et al. Cardiovascular risk in long-term survivors of testicular cancer. Cancer 2008; 112: 1949-1953 DOI: 10.1002/cncr.23389. (PMID: 18338810)
• 25 Gugic J, Zaletel LZ, Oblak I. Treatment-related cardiovascular toxicity in long-term survivors of testicular cancer. Radiol Oncol 2017; 51: 221-227 DOI: 10.1515/raon-2016-0021. (PMID: 28740458)
• 26 Haugnes HS, Oldenburg J, Bremnes RM. Pulmonary and cardiovascular toxicity in long-term testicular cancer survivors. Urol Oncol 2015; 33: 399-406 DOI: 10.1016/j.urolonc.2014.11.012. (PMID: 25554583)
• 27 Ishioka J, Fujii Y, Kageyama Y. et al. Cardiovascular events in survivors of high-dose chemotherapy for germ cell tumors. Int J Urol 2008; 15: 642-645 DOI: 10.1111/j.1442-2042.2008.02066.x. (PMID: 18643784)
• 28 Winnik S, Lohmann C, Siciliani G. et al. Systemic VEGF inhibition accelerates experimental atherosclerosis and disrupts endothelial homeostasis – implications for cardiovascular safety. Int J Cardiol 2013; 168: 2453-2461 DOI: 10.1016/j.ijcard.2013.03.010. (PMID: 23561917)
• 29 Herrmann J, Lerman LO, Mukhopadhyay D. et al. Angiogenesis in atherogenesis. Arterioscler Thromb Vasc Biol 2006; 26: 1948-1957 DOI: 10.1161/01.ATV.0000233387.90257.9b. (PMID: 16794218)
• 30 Stewart FA, Heeneman S, Te Poele J. et al. Ionizing radiation accelerates the development of atherosclerotic lesions in ApoE-/-mice and predisposes to an inflammatory plaque phenotype prone to hemorrhage. Am J Pathol 2006; 168: 649-658 DOI: 10.2353/ajpath.2006.050409.
• 31 Hoving S, Heeneman S, Gijbels MJJ. et al. Single-dose and fractionated irradiation promote initiation and progression of atherosclerosis and induce an inflammatory plaque phenotype in ApoE-/-mice. Int J Radiat Oncol Biol Phys 2008; 71: 848-857 DOI: 10.1016/j.ijrobp.2008.02.031. (PMID: 18514779)
• 32 Stasi R, Stipa E, Masi M. et al. Antiphospholipid antibodies: prevalence, clinical significance and correlation to cytokine levels in acute myeloid leukemia and non-Hodgkinʼs lymphoma. Thromb Haemost 1993; 70: 568-572
• 33 Stern JJ, Ng RH, Triplett DA. et al. Incidence of antiphospholipid antibodies in patients with monoclonal gammopathy of undetermined significance. Am J Clin Pathol 1994; 101: 471-474 DOI: 10.1093/ajcp/101.4.471.
• 34 Zuckerman E, Toubi E, Golan TD. et al. Increased thromboembolic incidence in anti-cardiolipin-positive patients with malignancy. Br J Cancer 1995; 72: 447-451
• 35 Nicolajsen CW, Dickenson MH, Budtz-Lilly J. et al. Frequency of cancer in patients operated on for acute peripheral arterial thrombosis and the impact on prognosis. J Vasc Surg 2015; 62: 1598e606 DOI: 10.1016/j.jvs.2015.06.223. (PMID: 26384760)
• 36 Working Party on Thrombolysis in the Management of Limb Ischemia. Thrombolysis in the management of lower limb peripheral arterial occlusion – a consensus document. J Vasc Interv Radiol 2003; 14: S337-S349
• 37 Ouriel K, Shortell CK, DeWeese JA. et al. A comparison of thrombolytic therapy with operative revascularization in the initial treatment of acute peripheral arterial ischemia. J Vasc Surg 1994; 19: 1021-1030
• 38 Tsang JS, Naughton PA, OʼDonnell J. et al. Acute limb ischemia in patients with cancer: Should we surgically intervene?. Ann Vasc Surg 2011; 25: 954-996
• 39 Javid M, Magee TR, Galland RB. Arterial thrombosis associated with malignant disease. Eur J Vasc Endovasc Surg 2008; 35: 84-87 DOI: 10.1016/j.ejvs.2007.08.014. (PMID: 17931915)
• 40 Argyriou A, Kafetzakis A, Saratzis A. et al. Revascularization outcomes in patients with acute limb ischemia and active neoplastic disease. J Endovasc Ther 2021; 28: 100-106
• 41 Lee AY, Levine MN, Baker RI. et al. Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349: 146-153
• 42 Raskob GE, van Es N, Verhamme P. et al. Hokusai VTE Cancer Investigators. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med 2018; 378: 615-624
• 43 Marshall A, Levine M, Hill C. et al. Treatment of cancer-associated venous thromboembolism: 12-month outcomes of the placebo versus rivaroxaban randomization of the SELECT-D Trial (SELECT-D: 12m). J Thromb Haemost 2020; 18: 905-915 DOI: 10.1111/jth.14752. (PMID: 31995662)
• 44 Mangiafico RA, Mangiafico M. Medical treatment of critical limb ischemia: current state and future directions. Curr Vasc Pharmacol 2011; 9: 658-676 DOI: 10.2174/157016111797484107. (PMID: 21595626)
• 45 Antithrombotic Trialistsʼ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324: 71-86 DOI: 10.1136/bmj.324.7329.71. (PMID: 11786451)
• 46 Zeller T, Frank U, Bürgelin K. et al. Langzeitergebnisse nach Rekanalisation akuter und subakuter thrombotischer arterieller Verschlüsse der unteren Extremitäten mit einem Rotations-Thrombektomiekatheter. Röfo 2002; 174: 1559-1565
• 47 Leung DA, Blitz LR, Nelson T. et al. Rheolytic pharmacomechanical thrombectomy for the management of acute limb ischemia: results from the PEARL Registry. J Endovasc Ther 2015; 22: 546-557
• 48 de Donato G, Pasqui E, Sponza M. et al. INDIAN trial collaborators. Safety and efficacy of vacuum assisted thrombo-aspiration in patients with acute lower limb ischaemia: the INDIAN Trial. Eur J Vasc Endovasc Surg 2021; 61: 820-828