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22.09.2018 | Original Paper

Cardiovascular risk factors are important determinants of platelet-dependent thrombin generation in adult survivors of childhood cancer

verfasst von: Marina Panova-Noeva, Marie A. Neu, Susan Eckerle, Claudia Spix, Astrid Schneider, Irene Schmidtmann, Henri M. Spronk, Norbert Pfeiffer, Manfred Beutel, Karl J. Lackner, Thomas Münzel, Hugo ten Cate, Hiltrud Merzenich, Jörg Faber, Philipp S. Wild

Erschienen in: Clinical Research in Cardiology | Ausgabe 4/2019

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Abstract

Cardiovascular disease is the most frequent non-malignant cause of morbidity and mortality in adult survivors of childhood or adolescent cancer. Thrombin generation (TG) analysis gives insight in hypercoagulability as an important mechanism linked to cardiovascular risk factors (CVRFs). In 200 individuals, from the cardiac and vascular late sequelae in long-term survivors of childhood cancer study, TG in platelet-rich plasma (PRP) and platelet-free plasma (PFP) at 1pM tissue factor was investigated. Endogenous thrombin potential (ETP) and peak height were the analysed parameters of a TG curve. Sex-specific multivariable linear regression analysis adjusted for age and CVRFs was used to assess the clinical determinants of TG. Females presented with higher ETP and peak height compared to males, both in PRP and PFP. Hypertension (beta estimate, ß: 184.8 [90.7; 278.8]), obesity (ß: 161.9 [63.9; 259.5]), and HbA1c (ß: 715.6 [97.4; 1333.8]) were associated with higher ETP in PRP only. ETP in PRP was positively associated with obesity and HbA1c in both males and females and with dyslipidemia (ß: 253.07 [72.92; 433.22]) and systolic hypertension (ß: 436.7 [119.02; 754.39]) in females only. CVRFs showed no association with TG variables in PFP. In conclusion, this study presents an important relation between traditional CVRFs and TG in the presence of platelets only. Sex-specific differences in TG with females presenting with higher TG, particularly those with dyslipidemia and systolic hypertension, were demonstrated. These results highlight the potential of the platelet-coagulant function in identifying cancer survivors at higher risk for adverse cardiovascular events.

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Mulrooney DA, Yeazel MW, Kawashima T, Mertens AC, Mitby P, Stovall M, Donaldson SS, Green DM, Sklar CA, Robison LL, Leisenring WM (2009) Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. BMJ 339:b4606. https://doi.org/10.1136/bmj.b4606 CrossRefPubMedPubMedCentral

Tilemann LM, Heckmann MB, Katus HA, Lehmann LH, Muller OJ (2018) Cardio-oncology: conflicting priorities of anticancer treatment and cardiovascular outcome. Clin Res Cardiol 107(4):271–280. https://doi.org/10.1007/s00392-018-1202-x CrossRefPubMedPubMedCentral

Late Effects of Treatment for Childhood Cancer (PDQ(R)): Health Professional Version (2002) In: PDQ Cancer Information Summaries. Bethesda (MD)

Dengel DR, Kelly AS, Zhang L, Hodges JS, Baker KS, Steinberger J (2014) Signs of early sub-clinical atherosclerosis in childhood cancer survivors. Pediatr Blood Cancer 61(3):532–537. https://doi.org/10.1002/pbc.24829 CrossRefPubMed

Oeffinger KC, Buchanan GR, Eshelman DA, Denke MA, Andrews TC, Germak JA, Tomlinson GE, Snell LE, Foster BM (2001) Cardiovascular risk factors in young adult survivors of childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol 23(7):424–430CrossRefPubMed

Nuver J, Smit AJ, Wolffenbuttel BH, Sluiter WJ, Hoekstra HJ, Sleijfer DT, Gietema JA (2005) The metabolic syndrome and disturbances in hormone levels in long-term survivors of disseminated testicular cancer. J Clin Oncol 23(16):3718–3725. https://doi.org/10.1200/JCO.2005.02.176 CrossRefPubMed

Neville KA, Cohn RJ, Steinbeck KS, Johnston K, Walker JL (2006) Hyperinsulinemia, impaired glucose tolerance, and diabetes mellitus in survivors of childhood cancer: prevalence and risk factors. J Clin Endocrinol Metab 91(11):4401–4407. https://doi.org/10.1210/jc.2006-0128 CrossRefPubMed

Hoffman KE, Derdak J, Bernstein D, Reynolds JC, Avila NA, Gerber L, Steinberg SM, Chrousos G, Mackall CL, Mansky PJ (2008) Metabolic syndrome traits in long-term survivors of pediatric sarcoma. Pediatr Blood Cancer 50(2):341–346. https://doi.org/10.1002/pbc.21363 CrossRefPubMed

Armstrong GT, Oeffinger KC, Chen Y, Kawashima T, Yasui Y, Leisenring W, Stovall M, Chow EJ, Sklar CA, Mulrooney DA, Mertens AC, Border W, Durand JB, Robison LL, Meacham LR (2013) Modifiable risk factors and major cardiac events among adult survivors of childhood cancer. J Clin Oncol 31(29):3673–3680. https://doi.org/10.1200/JCO.2013.49.3205 CrossRefPubMedPubMedCentral

10.

Hudson MM, Oeffinger KC, Jones K, Brinkman TM, Krull KR, Mulrooney DA, Mertens A, Castellino SM, Casillas J, Gurney JG, Nathan PC, Leisenring W, Robison LL, Ness KK (2015) Age-dependent changes in health status in the childhood cancer survivor cohort. J Clin Oncol 33(5):479–491. https://doi.org/10.1200/JCO.2014.57.4863 CrossRefPubMed

11.

Lipshultz SE, Lipsitz SR, Mone SM, Goorin AM, Sallan SE, Sanders SP, Orav EJ, Gelber RD, Colan SD (1995) Female sex and higher drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer. N Engl J Med 332(26):1738–1743. https://doi.org/10.1056/NEJM199506293322602 CrossRefPubMed

12.

Falanga A, Panova-Noeva M, Russo L (2009) Procoagulant mechanisms in tumour cells. Best Pract Res Clin Haematol 22(1):49–60. https://doi.org/10.1016/j.beha.2008.12.009 CrossRefPubMed

13.

Xu XR, Yousef GM, Ni H (2018) Cancer and platelet crosstalk: opportunities and challenges for aspirin and other antiplatelet agents. Blood 131(16):1777–1789. https://doi.org/10.1182/blood-2017-05-743187 CrossRefPubMed

14.

Drew DA, Cao Y, Chan AT (2016) Aspirin and colorectal cancer: the promise of precision chemoprevention. Nat Rev Cancer 16(3):173–186. https://doi.org/10.1038/nrc.2016.4 CrossRefPubMedPubMedCentral

15.

Kaplan ZS, Jackson SP (2011) The role of platelets in atherothrombosis. Hematol Am Soc Hematol Educ Progr 2011:51–61. https://doi.org/10.1182/asheducation-2011.1.51 CrossRef

16.

Morrell CN, Aggrey AA, Chapman LM, Modjeski KL (2014) Emerging roles for platelets as immune and inflammatory cells. Blood 123(18):2759–2767. https://doi.org/10.1182/blood-2013-11-462432 CrossRefPubMedPubMedCentral

17.

ten Cate H, Lowe G (2014) Coagulation proteases and cardiovascular disease. Thromb Haemost 112(5):858–859. https://doi.org/10.1160/TH14-09-0781 CrossRefPubMed

18.

Kossmann S, Lagrange J, Jackel S, Jurk K, Ehlken M, Schonfelder T, Weihert Y, Knorr M, Brandt M, Xia N, Li H, Daiber A, Oelze M, Reinhardt C, Lackner K, Gruber A, Monia B, Karbach SH, Walter U, Ruggeri ZM, Renne T, Ruf W, Munzel T, Wenzel P (2017) Platelet-localized FXI promotes a vascular coagulation-inflammatory circuit in arterial hypertension. Sci Transl Med. https://doi.org/10.1126/scitranslmed.aah4923 CrossRefPubMed

19.

Steliarova-Foucher E, Stiller C, Lacour B, Kaatsch P (2005) International classification of childhood cancer, third edition. Cancer 103(7):1457–1467. https://doi.org/10.1002/cncr.20910 CrossRefPubMed

20.

Panova-Noeva M, Schulz A, Spronk HM, Beicht A, Laubert-Reh D, van Oerle R, Arnold N, Prochaska JH, Blettner M, Beutel M, Pfeiffer N, Munzel T, Lackner KJ, Ten Cate H, Wild PS (2018) Clinical determinants of thrombin generation measured in presence and absence of platelets-results from the gutenberg health study. Thromb Haemost. https://doi.org/10.1055/s-0038-1641565 CrossRefPubMed

21.

Panova-Noeva M, Marchetti M, Spronk HM, Russo L, Diani E, Finazzi G, Salmoiraghi S, Rambaldi A, Barbui T, Ten Cate H, Falanga A (2011) Platelet-induced thrombin generation by the calibrated automated thrombogram assay is increased in patients with essential thrombocythemia and polycythemia vera. Am J Hematol 86(4):337–342. https://doi.org/10.1002/ajh.21974 CrossRefPubMed

22.

Loeffen R, Kleinegris MC, Loubele ST, Pluijmen PH, Fens D, van Oerle R, ten Cate H, Spronk HM (2012) Preanalytic variables of thrombin generation: towards a standard procedure and validation of the method. J Thromb Haemost JTH 10(12):2544–2554. https://doi.org/10.1111/jth.12012 CrossRefPubMed

23.

Panova-Noeva M, Schulz A, Spronk HM, Beicht A, Laubert-Reh D, van Oerle R, Arnold N, Prochaska JH, Blettner M, Beutel M, Pfeiffer N, Munzel T, Lackner KJ, Ten Cate H, Wild PS (2018) Clinical determinants of thrombin generation measured in presence and absence of platelets-results from the gutenberg health study. Thromb Haemost 118(5):873–882. https://doi.org/10.1055/s-0038-1641565 CrossRefPubMed

24.

Faber J, Wingerter A, Neu MA, Henninger N, Eckerle S, Munzel T, Lackner KJ, Beutel ME, Blettner M, Rathmann W, Peters A, Meisinger C, Linkohr B, Neuhauser H, Kaatsch P, Spix C, Schneider A, Merzenich H, Panova-Noeva M, Prochaska JH, Wild PS (2018) Burden of cardiovascular risk factors and cardiovascular disease in childhood cancer survivors: data from the German CVSS-study. Eur Heart J 39(17):1555–1562. https://doi.org/10.1093/eurheartj/ehy026 CrossRefPubMed

25.

Westhoff CL, Pike MC, Cremers S, Eisenberger A, Thomassen S, Rosing J (2017) Endogenous thrombin potential changes during the first cycle of oral contraceptive use. Contraception 95(5):456–463. https://doi.org/10.1016/j.contraception.2017.01.001 CrossRefPubMedPubMedCentral

26.

Tchaikovski SN, Thomassen MC, Costa SD, Bremme K, Rosing J (2014) Changes in haemostatic parameters during the menstrual cycle and subsequent use of drospirenone-containing oral contraceptives. Thromb Res 134(5):1032–1037. https://doi.org/10.1016/j.thromres.2014.09.008 CrossRefPubMed

27.

Ruhl H, Schroder L, Muller J, Sukhitashvili S, Welz J, Kuhn WC, Oldenburg J, Rudlowski C, Potzsch B (2014) Impact of hormone-associated resistance to activated protein C on the thrombotic potential of oral contraceptives: a prospective observational study. PLoS One 9(8):e105007. https://doi.org/10.1371/journal.pone.0105007 CrossRefPubMedPubMedCentral

28.

Wolf M, Ewen S, Mahfoud F, Bohm M (2018) Hypertension: history and development of established and novel treatments. Clin Res Cardiol 107(Suppl 2):16–29. https://doi.org/10.1007/s00392-018-1299-y CrossRefPubMed

29.

Kulenthiran S, Ewen S, Bohm M, Mahfoud F (2017) Hypertension up to date: SPRINT to SPYRAL. Clin Res Cardiol 106(7):475–484. https://doi.org/10.1007/s00392-017-1095-0 CrossRefPubMed

30.

Lip GY, Skjoth F, Overvad K, Rasmussen LH, Larsen TB (2015) Blood pressure and prognosis in patients with incident heart failure: the diet, cancer and health (DCH) cohort study. Clin Res Cardiol 104(12):1088–1096. https://doi.org/10.1007/s00392-015-0878-4 CrossRefPubMed

31.

Overbeek A, van den Berg MH, van Leeuwen FE, Kaspers GJ, Lambalk CB, van Dulmen-den Broeder E (2017) Chemotherapy-related late adverse effects on ovarian function in female survivors of childhood and young adult cancer: a systematic review. Cancer Treat Rev 53:10–24. https://doi.org/10.1016/j.ctrv.2016.11.006 CrossRefPubMed

32.

Johnson L, Sammel MD, Schanne A, Lechtenberg L, Prewitt M, Gracia C (2016) Female cancer survivors exposed to alkylating-agent chemotherapy have unique reproductive hormone profiles. Fertil Steril 106(7):1793–1799. https://doi.org/10.1016/j.fertnstert.2016.08.041 CrossRefPubMedPubMedCentral

33.

Patti G, De Caterina R, Abbate R, Andreotti F, Biasucci LM, Calabro P, Cioni G, Davi G, Di Sciascio G, Golia E, Golino P, Malatesta G, Mangiacapra F, Marcucci R, Nusca A, Parato VM, Pengo V, Prisco D, Pulcinelli F, Renda G, Ricottini E, Ruggieri B, Santilli F, Sofi F, Zimarino M (2014) Platelet function and long-term antiplatelet therapy in women: is there a gender-specificity? A ‘state-of-the-art’ paper. Eur Heart J 35(33):2213–2223. https://doi.org/10.1093/eurheartj/ehu279 (Working Group on Thrombosis of the Italian Society of C) CrossRefPubMed

34.

Boese AC, Kim SC, Yin KJ, Lee JP, Hamblin MH (2017) Sex differences in vascular physiology and pathophysiology: estrogen and androgen signaling in health and disease. Am J Physiol Heart Circ Physiol AJPHEART 00217:02016. https://doi.org/10.1152/ajpheart.00217.2016 CrossRef

35.

Sowers MR, Matthews KA, Jannausch M, Randolph JF, McConnell D, Sutton-Tyrrell K, Little R, Lasley B, Pasternak R (2005) Hemostatic factors and estrogen during the menopausal transition. J Clin Endocrinol Metab 90(11):5942–5948. https://doi.org/10.1210/jc.2005-0591 CrossRefPubMed

Titel: Cardiovascular risk factors are important determinants of platelet-dependent thrombin generation in adult survivors of childhood cancer
verfasst von: Marina Panova-Noeva
Marie A. Neu
Susan Eckerle
Claudia Spix
Astrid Schneider
Irene Schmidtmann
Henri M. Spronk
Norbert Pfeiffer
Manfred Beutel
Karl J. Lackner
Thomas Münzel
Hugo ten Cate
Hiltrud Merzenich
Jörg Faber
Philipp S. Wild
Publikationsdatum: 22.09.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Clinical Research in Cardiology / Ausgabe 4/2019
Print ISSN: 1861-0684
Elektronische ISSN: 1861-0692
DOI: https://doi.org/10.1007/s00392-018-1374-4

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