Impact of ABO Blood Group on Thromboembolic and Bleeding Complications in Patients with Left Ventricular Assist Devices

Maximilian Tscharre; Franziska Wittmann; Daniela Kitzmantl; Thomas Schlöglhofer; Philip Cichra; Silvia Lee; Beate Eichelberger; Patricia P. Wadowski; Günther Laufer; Dominik Wiedemann; Simon Panzer; Daniel Zimpfer; Thomas Gremmel

doi:10.1055/a-1983-0676

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2023; 123(03): 336-346
DOI: 10.1055/a-1983-0676

Stroke, Systemic or Venous Thromboembolism

Impact of ABO Blood Group on Thromboembolic and Bleeding Complications in Patients with Left Ventricular Assist Devices

Maximilian Tscharre

¹Department of Internal Medicine, Cardiology and Nephrology, Landesklinikum Wiener Neustadt, Wiener Neustadt, Austria

²Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria

,

Franziska Wittmann

³Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria

,

Daniela Kitzmantl

²Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria

,

Thomas Schlöglhofer

³Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria

,

Philip Cichra

³Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria

,

Silvia Lee

²Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria

,

Beate Eichelberger

⁴Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria

,

Patricia P. Wadowski

²Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria

,

Günther Laufer

³Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria

,

Dominik Wiedemann

³Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria

,

Simon Panzer

⁴Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria

,

Daniel Zimpfer

³Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria

,

Thomas Gremmel

²Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria

⁵Department of Internal Medicine I, Cardiology and Intensive Care Medicine, Landesklinikum Mistelbach-Gänserndorf, Mistelbach, Austria

⁶Institute of Cardiovascular Pharmacotherapy and Interventional Cardiology, Karl Landsteiner Society, St. Pölten, Austria

› Author Affiliations

Abstract

Background The ABO blood group system is linked to hemostasis via its relationship with von Willebrand factor (VWF) and factor VIII (FVIII). In the current study, we investigated the association of the ABO system with clinical outcomes as well as VWF and platelet function in patients with left ventricular assist devices (LVADs).

Methods Bleeding and thromboembolic complications were assessed in 111 patients during 1 year after LVAD implantation. In 67 LVAD patients, VWF antigen, VWF activity, VWF ristocetin cofactor, VWF collagen-binding, and FVIII activity were assessed. Platelet surface P-selectin and activated glycoprotein IIb/IIIa were determined by flow cytometry, and soluble P-selectin was measured with an enzyme-linked immunoassay. Platelet aggregation was assessed by light transmission and impedance aggregometry.

Results Thirty-six patients (32.4%) experienced a bleeding and 22 patients (19.8%) a thromboembolic event. In univariate analyses, patients with blood group O had numerically more bleeding complications and less thromboembolic events as compared to patients with blood group non-O (both p ≥ 0.05). After multivariable adjustment, blood group O was significantly associated with a higher risk of bleeding (hazard ratio 2.42 [95% confidence interval 1.03–5.70], p = 0.044) but not linked to thromboembolic complications.

Conclusion Patients with blood group O had significantly lower levels of VWF and FVIII (all p < 0.05), whereas P-selectin expression in response to thrombin-receptor activating peptide and soluble P-selectin were higher as compared to patients with blood group non-O (both p < 0.05). LVAD patients with blood group O are at an increased bleeding risk, potentially due to lower VWF and FVIII levels.

Keywords

left ventricular assist device - ABO group system - von Willebrand factor - bleeding complications - thromboembolic complications

Full Text

References

References
1 Shah P, Yuzefpolskaya M, Hickey GW. et al. Twelfth Interagency Registry for Mechanically Assisted Circulatory Support Report: readmissions after left ventricular assist device. Ann Thorac Surg 2022; 113 (03) 722-737
2 Potapov EV, Antonides C, Crespo-Leiro MG. et al. 2019 EACTS Expert Consensus on long-term mechanical circulatory support. Eur J Cardiothorac Surg 2019; 56 (02) 230-270
3 Kirklin JK, Naftel DC, Pagani FD. et al. Seventh INTERMACS annual report: 15,000 patients and counting. J Heart Lung Transplant 2015; 34 (12) 1495-1504
4 Dentali F, Sironi AP, Ageno W. et al. Relationship between ABO blood group and hemorrhage: a systematic literature review and meta-analysis. Semin Thromb Hemost 2013; 39 (01) 72-82
5 Franchini M, Mannucci PM. ABO blood group and thrombotic vascular disease. Thromb Haemost 2014; 112 (06) 1103-1109
6 Gill JC, Endres-Brooks J, Bauer PJ, Marks Jr WJ, Montgomery RR. The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood 1987; 69 (06) 1691-1695
7 Franchini M, Crestani S, Frattini F, Sissa C, Bonfanti C. Clin Chem Lab Med. ABO blood group and von Willebrand factor: biological implications. Clin Chem Lab Med 2014; 52 (09) 1273-1276
8 Lenting PJ, Christophe OD, Denis CV. von Willebrand factor biosynthesis, secretion, and clearance: connecting the far ends. Blood 2015; 125 (13) 2019-2028
9 Tscharre M, Michelson AD, Gremmel T. Novel antiplatelet agents in cardiovascular disease. J Cardiovasc Pharmacol Ther 2020; 25 (03) 191-200
10 Tscharre M, Tentzeris I, Vogel B. et al. Von Willebrand factor and ADAMTS13 and long-term outcomes in patients undergoing percutaneous coronary intervention. Thromb Res 2020; 196: 31-37
11 Mehic D, Hofer S, Jungbauer C. et al. Association of ABO blood group with bleeding severity in patients with bleeding of unknown cause. Blood Adv 2020; 4 (20) 5157-5164
12 Hansen SM, Sprogøe U, Möller S. et al. ABO blood group is related to bleeding in cardiac surgery. Acta Anaesthesiol Scand Blackwell Munksgaard 2021; 65: 466-472
13 Mazzeffi M, Gupta R, Lonergan T, Pasrija C, Kon Z, Tanaka K. ABO type and bleeding during adult ECMO. Intensive Care Med 2017; 43 (02) 275-276
14 Garcia AA, van der Heijden JF, Meijers JC, Rosendaal FR, Reitsma PH. The relationship between ABO blood group and the risk of bleeding during vitamin K antagonist treatment. J Thromb Haemost 2006; 4 (06) 1418-1420
15 Tscharre M, Wittmann F, Kitzmantl D. et al. Platelet activation and aggregation in different centrifugal-flow left ventricular assist devices. Platelets 2022; 33 (02) 249-256
16 Tscharre M, Wittmann F, Kitzmantl D. et al. Growth differentiation factor-15 correlates inversely with protease-activated receptor-1-mediated platelet reactivity in patients with left ventricular assist devices. Pharmaceuticals (Basel) 2022; 15 (04) 484
17 Schlöglhofer T, Zapusek L, Wiedemann D. et al. International normalized ratio test frequency in left ventricular assist device patients affects anticoagulation quality and adverse events. ASAIO J 2021; 67 (02) 157-162
18 Gremmel T, Koppensteiner R, Panzer S. Comparison of aggregometry with flow cytometry for the assessment of agonists'-induced platelet reactivity in patients on dual antiplatelet therapy. PLoS One 2015; 10 (06) e0129666
19 Gremmel T, Eslam RB, Koppensteiner R, Lang IM, Panzer S. Prasugrel reduces agonists′ inducible platelet activation and leukocyte-platelet interaction more efficiently than clopidogrel. Cardiovasc Ther 2013; 31: e40-5
20 Gremmel T, Calatzis A, Steiner S. et al. Is TRAP-6 suitable as a positive control for platelet reactivity when assessing response to clopidogrel?. Platelets 2010; 21 (07) 515-521
21 Gremmel T, Steiner S, Seidinger D, Koppensteiner R, Panzer S, Kopp CW. Comparison of methods to evaluate aspirin-mediated platelet inhibition after percutaneous intervention with stent implantation. Platelets 2011; 22 (03) 188-195
22 Gremmel T, Kopp CW, Seidinger D. et al. The formation of monocyte-platelet aggregates is independent of on-treatment residual agonists'-inducible platelet reactivity. Atherosclerosis 2009; 207 (02) 608-613
23 Interagency Registry for Mechanically Assisted Circulatory Support—Appendix A—Adverse event definitions 4.0. Accessed May 23, 2022, at: https://www.uab.edu/medicine/intermacs/intermacs-documents
24 Gross C, Dimitrov K, Riebandt J. et al. Validation of intrinsic left ventricular assist device data tracking algorithm for early recognition of centrifugal flow pump thrombosis. Life (Basel) 2022; 12 (04) 563
25 Katz JN, Adamson RM, John R. et al; TRACE study. Safety of reduced anti-thrombotic strategies in HeartMate II patients: a one-year analysis of the US-TRACE Study. J Heart Lung Transplant 2015; 34 (12) 1542-1548
26 Nascimbene A, Neelamegham S, Frazier OH, Moake JL, Dong J-F. Acquired von Willebrand syndrome associated with left ventricular assist device. Blood 2016; 127 (25) 3133-3341
27 Bansal A, Uriel N, Colombo PC. et al. Effects of a fully magnetically levitated centrifugal-flow or axial-flow left ventricular assist device on von Willebrand factor: a prospective multicenter clinical trial. J Heart Lung Transplant 2019; 38 (08) 806-816
28 Campos M, Sun W, Yu F. et al. Genetic determinants of plasma von Willebrand factor antigen levels: a target gene SNP and haplotype analysis of ARIC cohort. Blood 2011; 117 (19) 5224-5230
29 Campos M, Buchanan A, Yu F. et al. Influence of single nucleotide polymorphisms in factor VIII and von Willebrand factor genes on plasma factor VIII activity: the ARIC Study. Blood 2012; 119 (08) 1929-1934
30 Ward SE, O'Sullivan JM, O'Donnell JS. The relationship between ABO blood group, von Willebrand factor, and primary hemostasis. Blood 2020; 136 (25) 2864-2874
31 Berti S, Bartorelli AL, Koni E. et al; From the RISPEVA registry. Impact of high body mass index on vascular and bleeding complications after transcatheter aortic valve implantation. Am J Cardiol 2021; 155: 86-95
32 Darzi AJ, Karam SG, Charide R. et al. Prognostic factors for VTE and bleeding in hospitalized medical patients: a systematic review and meta-analysis. Blood 2020; 135 (20) 1788-1810
33 Braekkan SK, van der Graaf Y, Visseren FLJ, Algra A. Obesity and risk of bleeding: the SMART study. J Thromb Haemost 2016; 14 (01) 65-72
34 He M, Wolpin B, Rexrode K. et al. ABO blood group and risk of coronary heart disease in two prospective cohort studies. Arterioscler Thromb Vasc Biol 2012; 32 (09) 2314-2320
35 Schunkert H, König IR, Kathiresan S. et al; Cardiogenics, CARDIoGRAM Consortium. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet 2011; 43 (04) 333-338
36 Christiansen MK, Larsen SB, Nyegaard M. et al. The ABO locus is associated with increased platelet aggregation in patients with stable coronary artery disease. Int J Cardiol 2019; 286: 152-158
37 Chen Y, Chen C, Ke X. et al. Analysis of circulating cholesterol levels as a mediator of an association between ABO blood group and coronary heart disease. Circ Cardiovasc Genet 2014; 7 (01) 43-48
38 Gum PA, Kottke-Marchant K, Welsh PA, White J, Topol EJ. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol 2003; 41 (06) 961-965
39 Sibbing D, Schulz S, Braun S. et al. Antiplatelet effects of clopidogrel and bleeding in patients undergoing coronary stent placement. J Thromb Haemost 2010; 8 (02) 250-256
40 Gremmel T, Steiner S, Seidinger D, Koppensteiner R, Panzer S, Kopp CW. In vivo and protease-activated receptor-1-mediated platelet activation but not response to antiplatelet therapy predict two-year outcomes after peripheral angioplasty with stent implantation. Thromb Haemost 2014; 111 (03) 474-482
41 Gremmel T, Ay C, Riedl J. et al. Platelet-specific markers are associated with monocyte-platelet aggregate formation and thrombin generation potential in advanced atherosclerosis. Thromb Haemost 2016; 115 (03) 615-621
42 Shattil SJ, Hoxie JA, Cunningham M, Brass LF. Changes in the platelet membrane glycoprotein IIb.IIIa complex during platelet activation. J Biol Chem 1985; 260 (20) 11107-11114
43 Matetzky S, Shenkman B, Guetta V. et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 2004; 109 (25) 3171-3175
44 Mayer K, Bernlochner I, Braun S. et al. Aspirin treatment and outcomes after percutaneous coronary intervention: results of the ISAR-ASPI registry. J Am Coll Cardiol 2014; 64 (09) 863-871
45 Sibbing D, Morath T, Braun S. et al. Clopidogrel response status assessed with Multiplate point-of-care analysis and the incidence and timing of stent thrombosis over six months following coronary stenting. Thromb Haemost 2010; 103 (01) 151-159
46 Barbalic M, Dupuis J, Dehghan A. et al. Large-scale genomic studies reveal central role of ABO in sP-selectin and sICAM-1 levels. Hum Mol Genet 2010; 19 (09) 1863-1872
47 Chen Y, Zhuo X, Lin Y. et al. Association of ABO blood group with P-selectin levels in Chinese Han healthy volunteers. Transfusion 2015; 55 (11) 2759-2765
48 Blann AD, Daly RJ, Amiral J. The influence of age, gender and ABO blood group on soluble endothelial cell markers and adhesion molecules. Br J Haematol 1996; 92 (02) 498-500
49 Gremmel T, Michelson AD, Frelinger III AL, Bhatt DL. Novel aspects of antiplatelet therapy in cardiovascular disease. Res Pract Thromb Haemost 2018; 2 (03) 439-449
50 Patrono C, García Rodríguez LA, Landolfi R, Baigent C. Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med 2005; 353 (22) 2373-2383