Henri Spronk

Associate professor

Initially trained in Biochemistry and Molecular Biology at Nijmegen University, Dr Henri Spronk obtained a PhD in Biochemistry on the effects of impaired vitamin K-dependent protein carboxylation.

The focus of his current work is on the bidirectional relation between coagulation and inflammation, as well as on the applicability of functional plasma assays such as thrombin generation, for atherothrombotic risk prediction. He has a special interest in the role of active coagulation factors, mainly thrombin, in activation of protein-activated receptors (PARs) which can regulate the balance between vascular protective and disruptive. Overall, knowledge on the non-haemostatic functions of thrombin and factor Xa enables pharmacological interference in cellular processes contributing to the the development and progression of atherosclerosis or atrial fibrillation.

Department of Biochemistry
Department of Internal Medicine
Universiteitssingel 50, 6229 ER Maastricht
PO Box 616, 6200 MD Maastricht
Room number: 4.326
T: +31(0)43 388 42 61

  • 2020
    • Mastenbroek, T. G., Karel, M. F. A., Nagy, M., Chayoua, W., Korsten, E. I. J., Coenen, D. M., Debets, J., Konings, J., Brouns, A. E., Leenders, P. J. A., van Essen, H., van Oerle, R., Heitmeier, S., Spronk, H. M., Kuijpers, M. J. E., & Cosemans, J. M. E. M. (2020). Vascular protective effect of aspirin and rivaroxaban upon endothelial denudation of the mouse carotid artery. Scientific Reports, 10(1), [19360]. https://doi.org/10.1038/s41598-020-76377-8
    • Panova-Noeva, M., Wagner, B., Nagler, M., Koeck, T., ten Cate, V., Prochaska, J. H., Heitmeier, S., Meyer, I., Gerdes, C., Laux, V., Konstantinides, S., Spronk, H. M., Muenzel, T., Lackner, K. J., Leineweber, K., ten Cate, H., & Wild, P. S. (2020). Comprehensive platelet phenotyping supports the role of platelets in the pathogenesis of acute venous thromboembolism - results from clinical observation studies. EBioMedicine, 60, [102978]. https://doi.org/10.1016/j.ebiom.2020.102978
    • Lagrange, J., Wagner, B., Nagler, M., ten Cate, V., Pallares Robles, A., Koeck, T., Rapp, S., Prochaska, J. H., Spronk, H. M., Wenzel, P., Ruf, W., ten Cate, H., Wild, P. S., & Panova-Noeva, M. (2020). Characterization of Thrombin Generation Curve Shape in Presence of Platelets from Acute Venous Thromboembolism Patients. Journal of Clinical Medicine, 9(9), [2892]. https://doi.org/10.3390/jcm9092892
    • Kremers, B., Wubbeke, L., Mees, B., ten Cate, H., Spronk, H., & ten Cate-Hoek, A. (2020). Plasma Biomarkers to Predict Cardiovascular Outcome in Patients With Peripheral Artery Disease A Systematic Review and Meta-Analysis. Arteriosclerosis Thrombosis and Vascular Biology, 40(9), 2018-2032. https://doi.org/10.1161/ATVBAHA.120.314774
    • van Paridon, P. C. S., Panova-Noeva, M., van Oerle, R., Schultz, A., Hermanns, I. M., Prochaska, J. H., Arnold, N., Binder, H., Schmidtmann, I., Beutel, M. E., Pfeiffer, N., Münzel, T., Lackner, K. J., Ten Cate, H., Wild, P. S., & Spronk, H. M. H. (2020). Thrombin generation in cardiovascular disease and mortality - results from the Gutenberg Health Study. Haematologica-the Hematology Journal, 105(9), 2327-2334. https://doi.org/10.3324/haematol.2019.221655
    • Heuberger, J. A. A. C., Posthuma, J. J., Ziagkos, D., Rotmans, J., Daniels, J. M. A., Gal, P., Stuurman, F. E., Spronk, H. M. H., Cate, H. T., Burggraaf, J., Moerland, M., & Cohen, A. F. (2020). Additive effect of erythropoietin use on exercise-induced endothelial activation and hypercoagulability in athletes. European Journal of Applied Physiology, 120(8), 1893-1904. https://doi.org/10.1007/s00421-020-04419-0
    • De With, R. R., Erkuner, O., Rienstra, M., Nguyen, B-O., Korver, F. W. J., Linz, D., Ten, H. C., Spronk, H., Kroon, A. A., Maass, A. H., Blaauw, Y., Tieleman, R. G., Hemels, M. E. W., de Groot, J. R., Elvan, A., de Melis, M., Scheerder, C. O. S., Al-Jazairi, M. I. H., Schotten, U., ... RACE V Investigators (2020). Temporal patterns and short-term progression of paroxysmal atrial fibrillation data from RACE V. EP Europace, 22(8), 1162-1172. https://doi.org/10.1093/europace/euaa123
    • Brouns, S. L. N., van Geffen, J. P., Campello, E., Swieringa, F., Spiezia, L., van Oerle, R., Provenzale, I., Verdoold, R., Farndale, R. W., Clemetson, K. J., Spronk, H. M. H., van der Meijden, P. E. J., Cavill, R., Kuijpers, M. J. E., Castoldi, E., Simioni, P., & Heemskerk, J. W. M. (2020). Platelet-primed interactions of coagulation and anticoagulation pathways in flow-dependent thrombus formation. Scientific Reports, 10(1), 11910. [11910]. https://doi.org/10.1038/s41598-020-68438-9
    • Visser, M., Heitmeier, S., ten Cate, H., & Spronk, H. M. H. (2020). Role of Factor XIa and Plasma Kallikrein in Arterial and Venous Thrombosis. Thrombosis and Haemostasis, 120(6), 883-893. https://doi.org/10.1055/s-0040-1710013
    • d'Alessandro, E., Becker, C., Bergmeier, W., Bode, C., Bourne, J. H., Brown, H., Buller, H. R., ten Cate-Hoek, A. J., ten Cate, V., van Cauteren, Y. J. M., Cheung, Y. F. H., Cleuren, A., Coenen, D., Crijns, H. J. G. M., de Simone, I., Dolleman, S. C., Klein, C. E., Fernandez, D. I., Granneman, L., ... Scientific Reviewer Committee (2020). Thrombo-Inflammation in Cardiovascular Disease: An Expert Consensus Document from the Third Maastricht Consensus Conference on Thrombosis. Thrombosis and Haemostasis, 120(4), 538-564. https://doi.org/10.1055/s-0040-1708035
    • Grover, S. P., Schmedes, C. M., Auriemma, A. C., Butler, E., Parrish, M. L., Miszta, A., Cleuren, A. C., Visser, M., Heitmeier, S., Posma, J. J., Spronk, H. M., Antoniak, S., Wolberg, A. S., Pawlinski, R., Gailani, D., & Mackman, N. (2020). Differential roles of factors IX and XI in murine placenta and hemostasis under conditions of low tissue factor. Blood advances, 4(1), 207-216. https://doi.org/10.1182/bloodadvances.2019000921
    • Visser, M., van Oerle, R., ten Cate, H., Laux, V., Mackman, N., Heitmeier, S., & Spronk, H. M. H. (2020). Plasma Kallikrein Contributes to Coagulation in the Absence of Factor XI by Activating Factor IX. Arteriosclerosis Thrombosis and Vascular Biology, 40(1), 103-111. https://doi.org/10.1161/ATVBAHA.119.313503
  • 2019
    • Panova-Noeva, M., Wagner, B., Nagler, M., Arnold, N., Prochaska, J. H., Eckerle, S., Spronk, H. M., Merzenich, H., Wingerter, A., Schneider, A., Danckwardt, S., ten Cate, H., Faber, J., & Wild, P. S. (2019). Relation between platelet coagulant and vascular function, sex-specific analysis in adult survivors of childhood cancer compared to a population-based sample. Scientific Reports, 9, [20090]. https://doi.org/10.1038/s41598-019-56626-1
    • Heestermans, M., de Jong, A., van Tilburg, S., Reitsma, P. H., Versteeg, H. H., Spronk, H. M., & van Vlijmen, B. J. M. (2019). Use of "C9/11 Mismatch" Control Small Interfering RNA Reveals Sequence-Related Off-Target Effect on Coagulation of an Small Interfering RNA Targeting Mouse Coagulation Factor XII. Nucleic Acid Therapeutics, 29(4), 218-223. https://doi.org/10.1089/nat.2018.0767
    • Olie, R. H., van der Meijden, P. E. J., Spronk, H. M. H., van Oerle, R., Barvik, S., Bonarjee, V. V. S., Ten Cate, H., & Nilsen, D. W. T. (2019). Effects of the PAR-1 Antagonist Vorapaxar on Platelet Activation and Coagulation Biomarkers in Patients with Stable Coronary Artery Disease. TH open : companion journal to thrombosis and haemostasis, 3(3), e259-e262. https://doi.org/10.1055/s-0039-1695710
    • Heestermans, M., Salloum-Asfar, S., Streef, T., Laghmani, E. H., Salvatori, D., Luken, B. M., Zeerleder, S. S., Spronk, H. M. H., Korporaal, S. J., Kirchhofer, D., Wagenaar, G. T. M., Versteeg, H. H., Reitsma, P. H., Renne, T., & van Vlijmen, B. J. M. (2019). Mouse venous thrombosis upon silencing of anticoagulants depends on tissue factor and platelets, not FXII or neutrophils. Blood, 133(19), 2090-2099. https://doi.org/10.1182/blood-2018-06-853762
    • Kremers, B. M. M., Birocchi, S., van Oerle, R., Zeerleder, S., Spronk, H. M. H., Mees, B. M. E., Luken, B. M., ten Cate, H., & ten Cate-Hoek, A. J. (2019). Searching for a Common Thrombo-Inflammatory Basis in Patients With Deep Vein Thrombosis or Peripheral Artery Disease. Frontiers in cardiovascular medicine, 6, 1-11. [33]. https://doi.org/10.3389/fcvm.2019.00033
    • Panova-Noeva, M., Neu, M. A., Eckerle, S., Spix, C., Schneider, A., Schmidtmann, I., Spronk, H. M., Pfeiffer, N., Beutel, M., Lackner, K. J., Muenzel, T., ten Cate, H., Merzenich, H., Faber, J., & Wild, P. S. (2019). Cardiovascular risk factors are important determinants of platelet-dependent thrombin generation in adult survivors of childhood cancer. Clinical research in cardiology, 108(4), 438-447. https://doi.org/10.1007/s00392-018-1374-4
    • Posthuma, J. J., Posma, J. J. N., Schep, G., Bender, M. M. H., van Oerle, R., van der Wal, A. C., Ten Cate, H., & Spronk, H. M. H. (2019). Protease-activated receptors are potential regulators in the development of arterial endofibrosis in high-performance athletes. Journal of Vascular Surgery, 69(4), 1243-1250. https://doi.org/10.1016/j.jvs.2018.05.220
    • Posthuma, J. J., Posma, J. J. N., van Oerle, R., Leenders, P., van Gorp, R. H., Jaminon, A. M. G., Mackman, N., Heitmeier, S., Schurgers, L. J., ten Cate, H., & Spronk, H. M. H. (2019). Targeting Coagulation Factor Xa Promotes Regression of Advanced Atherosclerosis in Apolipoprotein-E Deficient Mice. Scientific Reports, 9, [3909]. https://doi.org/10.1038/s41598-019-40602-w
    • Grottke, O., van Ryn, J., Zentai, C., Gan, G., Honickel, M., Rossaint, R., Ten Cate, H., & Spronk, H. M. H. (2019). Volume replacement strategies do not impair the binding of dabigatran to idarucizumab: Porcine model of hemodilution. PLOS ONE, 14(1), e0209350. [0209350]. https://doi.org/10.1371/journal.pone.0209350
    • Benedikter, B. J., Bouwman, F. G., Heinzmann, A. C. A., Vajen, T., Mariman, E. C., Wouters, E. F. M., Savelkoul, P. H. M., Koenen, R. R., Rohde, G. G. U., van Oerle, R., Spronk, H. M., & Stassen, F. R. M. (2019). Proteomic analysis reveals procoagulant properties of cigarette smoke-induced extracellular vesicles. Journal of Extracellular Vesicles , 8(1), [1585163]. https://doi.org/10.1080/20013078.2019.1585163
    • Posma, J. J., Grover, S. P., Hisada, Y., Owens, A. P., Antoniak, S., Spronk, H. M., & Mackman, N. (2019). Roles of Coagulation Proteases and PARs (Protease-Activated Receptors) in Mouse Models of Inflammatory Diseases. Arteriosclerosis Thrombosis and Vascular Biology, 39(1), 13-24. https://doi.org/10.1161/ATVBAHA.118.311655
  • 2018
    • Mulder, B. A., Geelhoed, B., van der Harst, P., Spronk, H. M., Van Gelder, I. C., Asselbergs, F. W., & Rienstra, M. (2018). Plasminogen activator inhibitor-1 and tissue plasminogen activator and incident AF: Data from the PREVEND study. International Journal of Cardiology, 272, 208-210. https://doi.org/10.1016/j.ijcard.2018.08.029
    • Tilburg, J., Adili, R., Nair, T. S., Hawley, M. E., Tuk, D. C., Jackson, M., Spronk, H. M., Versteeg, H. H., Carey, T. E., van Vlijmen, B. J. M., Maracle, C. X., & Holinstat, M. (2018). Characterization of hemostasis in mice lacking the novel thrombosis susceptibility gene Slc44a2. Thrombosis Research, 171, 155-159. https://doi.org/10.1016/j.thromres.2018.09.057
    • Eggebrecht, L., Prochaska, J. H., Schulz, A., Arnold, N., Juenger, C., Goebel, S., Laubert-Reh, D., Binder, H., Beutel, M. E., Pfeiffer, N., Blankenberg, S., Lackner, K. J., Spronk, H. M., ten Cate, H., Muenzel, T., & Wild, P. S. (2018). Intake of Vitamin K Antagonists and Worsening of Cardiac and Vascular Disease: Results From the Population-Based Gutenberg Health Study. Journal of the American Heart Association, 7(17), [008650]. https://doi.org/10.1161/JAHA.118.008650
    • Crombag, G. A. J. C., Spronk, H. M., Nelemans, P., Schreuder, F. H. B. M., Truijman, M. T. B., van Dijk, A. C., de Rotte, A. A. J., Liem, M. I., Daemen, M. J. A. P., van der Steen, A. F. W., Mess, W. H., Nederkoorn, P. J., Hendrikse, J., van der Lugt, A., Wildberger, J. E., ten Cate, H., van Oostenbrugge, R. J., & Kooi, M. E. (2018). No Association between Thrombin Generation and Intra-Plaque Haemorrhage in Symptomatic Carotid Atherosclerotic Plaques: The Plaque at RISK (PARISK) Study. Thrombosis and Haemostasis, 118(8), 1461-1469. https://doi.org/10.1055/s-0038-1666858
    • Kremers, B. M. M., Ten Cate, H., & Spronk, H. M. H. (2018). Pleiotropic effects of the hemostatic system. Journal of Thrombosis and Haemostasis, 16(8), 1464-1473. https://doi.org/10.1111/jth.14161
    • D'Alessandro, E., Posma, J. J. N., Spronk, H. M. H., & ten Cate, H. (2018). Tissue factor (:Factor VIIa) in the heart and vasculature: More than an envelope. Thrombosis Research, 168, 130-137. https://doi.org/10.1016/j.thromres.2018.06.020
    • Swieringa, F., Spronk, H. M. H., Heemskerk, J. W. M., & van der Meijden, P. E. J. (2018). Integrating platelet and coagulation activation in fibrin clot formation. Research and practice in thrombosis and haemostasis, 2(3), 450-460. https://doi.org/10.1002/rth2.12107
    • Panova-Noeva, M., Schulz, A., Spronk, H. M., Beicht, A., Laubert-Reh, D., van Oerle, R., Arnold, N., Prochaska, J. H., Blettner, M., Beutel, M., Pfeiffer, N., Munzel, T., Lackner, K. J., ten Cate, H., & Wild, P. S. (2018). Clinical Determinants of Thrombin Generation Measured in Presence and Absence of Platelets-Results from the Gutenberg Health Study. Thrombosis and Haemostasis, 118(5), 873-882. https://doi.org/10.1055/s-0038-1641565
    • Panova-Noeva, M., Schulz, A., Arnold, N., Hermanns, M. I., Prochaska, J. H., Laubert-Reh, D., Spronk, H. M., Blettner, M., Beutel, M., Pfeiffer, N., Munzel, T., Lackner, K. J., ten Cate, H., & Wild, P. S. (2018). Coagulation and inflammation in long-term cancer survivors: results from the adult population. Journal of Thrombosis and Haemostasis, 16(4), 699-708. https://doi.org/10.1111/jth.13975
    • Mackman, N., Spronk, H. M. H., Stouffer, G. A., & ten Cate, H. (2018). Dual Anticoagulant and Antiplatelet Therapy for Coronary Artery Disease and Peripheral Artery Disease Patients. Arteriosclerosis Thrombosis and Vascular Biology, 38(4), 726-732. https://doi.org/10.1161/ATVBAHA.117.310048
    • Borst, O., Munzer, P., Alnaggar, N., Geue, S., Tegtmeyer, R., Rath, D., Droppa, M., Seizer, P., Heitmeier, S., Heemskerk, J. W. M., Jennings, L. K., Storey, R. F., Angiolillo, D. J., Rocca, B., Spronk, H., Ten Cate, H., Gawaz, M., & Geisler, T. (2018). Inhibitory mechanisms of very low-dose rivaroxaban in non-ST-elevation myocardial infarction. Blood advances, 2(6), 715-730. https://doi.org/10.1182/bloodadvances.2017013573
    • Spronk, H. M. H., Padro, T., Siland, J. E., Prochaska, J. H., Winters, J., van der Wal, A. C., Posthuma, J. J., Lowe, G., d'Alessandro, E., Wenzel, P., Coenen, D. M., Reitsma, P. H., Ruf, W., van Gorp, R. H., Koenen, R. R., Vajen, T., Alshaikh, N. A., Wolberg, A. S., Macrae, F. L., ... ten Cate, H. (2018). Atherothrombosis and Thromboembolism: Position Paper from the Second Maastricht Consensus Conference on Thrombosis. Thrombosis and Haemostasis, 118(2), 229-250. https://doi.org/10.1160/TH17-07-0492
    • Henskens, Y. M. C., Gulpen, A. J. W., van Oerle, R., Wetzels, R., Verhezen, P., Spronk, H., Schalla, S., Crijns, H. J., ten Cate, H., & ten Cate-Hoek, A. (2018). Detecting clinically relevant rivaroxaban or dabigatran levels by routine coagulation tests or thromboelastography in a cohort of patients with atrial fibrillation. Thrombosis Journal, 16, [3]. https://doi.org/10.1186/s12959-017-0160-2
  • 2017
    • Honickel, M., Spronk, H. M., Rossaint, R., Stoppe, C., van Ryn, J., ten Cate, H., & Grottke, O. (2017). Dose requirements for idarucizumab reversal of dabigatran in a lethal porcine trauma model with continuous bleeding. Thrombosis and Haemostasis, 117(7), 1370-1378. https://doi.org/10.1160/TH16-11-0824
    • Kleinegris, M-C. F., Konings, J., Daemen, J. W., Henskens, Y., de Laat, B., Spronk, H. M. H., ten Cate-Hoek, A. J., & ten Cate, H. (2017). Increased Clot Formation in the Absence of Increased Thrombin Generation in Patients with Peripheral Arterial Disease: A Case-Control Study. Frontiers in cardiovascular medicine, 4, [23]. https://doi.org/10.3389/fcvm.2017.00023
    • Hobbelt, A. H., Spronk, H. M., Crijns, H. J. G. M., Ten Cate, H., Rienstra, M., & Van Gelder, I. C. (2017). Prethrombotic State in Young Very Low- Risk Patients With Atrial Fibrillation. Journal of the American College of Cardiology, 69(15), 1990-1992. https://doi.org/10.1016/j.jacc.2017.01.057
    • Panova-Noeva, M., Arnold, N., Hermanns, M. I., Prochaska, J. H., Schulz, A., Spronk, H. M., Binder, H., Pfeiffer, N., Beutel, M., Blankenberg, S., Zeller, T., Lotz, J., Muenzel, T., Lackner, K. J., ten Cate, H., & Wild, P. S. (2017). Mean Platelet Volume and Arterial Stiffness - Clinical Relationship and Common Genetic Variability. Scientific Reports, 7, [40229]. https://doi.org/10.1038/srep40229
    • Spronk, H. M. H., De Jong, A. M., Verheule, S., De Boer, H. C., Maass, A. H., Lau, D. H., Rienstra, M., van Hunnik, A., Kuiper, M., Lumeij, S., Zeemering, S., Linz, D., Kamphuisen, P. W., ten Cate, H., Crijns, H. J., Van Gelder, I. C., van Zonneveld, A. J., & Schotten, U. (2017). Hypercoagulability causes atrial fibrosis and promotes atrial fibrillation. European Heart Journal, 38(1), 38-50. https://doi.org/10.1093/eurheartj/ehw119
  • 2016
    • Zentai, C., Solomon, C., van der Meijden, P. E. J., Spronk, H. M. H., Schnabel, J., Rossaint, R., & Grottke, O. (2016). Effects of Fibrinogen Concentrate on Thrombin Generation, Thromboelastometry Parameters, and Laboratory Coagulation Testing in a 24-Hour Porcine Trauma Model. Clinical and Applied Thrombosis-Hemostasis, 22(8), 749-759. https://doi.org/10.1177/1076029615584662
    • Posma, J. J. N., Posthuma, J. J., & Spronk, H. M. H. (2016). Coagulation and non-coagulation effects of thrombin. Journal of Thrombosis and Haemostasis, 14(10), 1908-1916. https://doi.org/10.1111/jth.13441
    • Loeffen, R. A., van Oerle, R., Leers, M. P. G., Kragten, J. A., Crijns, H., Spronk, H. M. H., & ten Cate, H. (2016). Factor XIa and Thrombin Generation Are Elevated in Patients with Acute Coronary Syndrome and Predict Recurrent Cardiovascular Events. PLOS ONE, 11(7), [e0158355]. https://doi.org/10.1371/journal.pone.0158355
    • Zentai, C., van der Meijden, P. E. J., Braunschweig, T., Hueck, N., Honickel, M., Spronk, H. M. H., Rossaint, R., & Grottke, O. (2016). Hemostatic Therapy Using Tranexamic Acid and Coagulation Factor Concentrates in a Model of Traumatic Liver Injury. Anesthesia and Analgesia, 123(1), 38-48. https://doi.org/10.1213/ANE.0000000000001379
    • van Beers, J. J. B. C., van Egmond, L. T., Wetzels, R. J. H., Verhezen, P. W. M., Beckers, E. A. M., van Oerle, R., Spronk, H. M. H., Straat, R. J. M. H. E., & Henskens, Y. M. C. (2016). Increased coagulation and fibrinolytic potential of solvent-detergent plasma: a comparative study between Omniplasma and fresh frozen plasma. Vox Sanguinis, 111(1), 33-42. https://doi.org/10.1111/vox.12395
    • Heestermans, M., Salloum-Asfar, S., Salvatori, D., Laghmani, E. H., Luken, B. M., Zeerleder, S. S., Spronk, H. M. H., Korporaal, S. J., Wagenaar, G. T. M., Reitsma, P. H., & van Vlijmen, B. J. M. (2016). Role of platelets, neutrophils, and factor XII in spontaneous venous thrombosis in mice. Blood, 127(21), 2630-2637. https://doi.org/10.1182/blood-2015-10-672766
    • Cheung, Y. W., Bouman, A. C., Castoldi, E., Wielders, S. J., Spronk, H. M. H., ten Cate, H., Hoek - ten Cate, A., & ten Wolde, M. (2016). Toll-like receptor 9 gene expression in the post-thrombotic syndrome, residual thrombosis and recurrent deep venous thrombosis: A case-control study. Thrombosis Research, 140, 106-109. https://doi.org/10.1016/j.thromres.2016.02.025
    • Honickel, M., Maron, B., van Ryn, J., Braunschweig, T., ten Cate, H., Spronk, H. M. H., Rossaint, R., & Grottke, O. (2016). Therapy with activated prothrombin complex concentrate is effective in reducing dabigatran-associated blood loss in a porcine polytrauma model. Thrombosis and Haemostasis, 115(2), 271-284. https://doi.org/10.1160/TH15-03-0266
    • Panova-Noeva, M., Schulz, A., Hermanns, M. I., Grossmann, V., Pefani, E., Spronk, H. M. H., Laubert-Reh, D., Binder, H., Beutel, M., Pfeiffer, N., Blankenberg, S., Zeller, T., Muenzel, T., Lackner, K. J., ten Cate, H., & Wild, P. S. (2016). Sex-specific differences in genetic and nongenetic determinants of mean platelet volume: results from the Gutenberg Health Study. Blood, 127(2), 251-259. https://doi.org/10.1182/blood-2015-07-660308