Added Value of Blood Cells in Thrombin Generation Testing

Jun Wan; Joke Konings; Bas de Laat; Tilman M. Hackeng; Mark Roest

doi:10.1055/a-1450-8300

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2021; 121(12): 1574-1587
DOI: 10.1055/a-1450-8300

Review Article

Added Value of Blood Cells in Thrombin Generation Testing

Jun Wan

¹Synapse Research Institute, Maastricht, The Netherlands

²Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands

,

Joke Konings

¹Synapse Research Institute, Maastricht, The Netherlands

²Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands

,

Bas de Laat

¹Synapse Research Institute, Maastricht, The Netherlands

²Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands

,

Tilman M. Hackeng

²Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands

,

Mark Roest

¹Synapse Research Institute, Maastricht, The Netherlands

²Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands

› Institutsangaben

Abstract

The capacity of blood to form thrombin is a critical determinant of coagulability. Plasma thrombin generation (TG), a test that probes the capacity of plasma to form thrombin, has improved our knowledge of the coagulation system and shows promising utility in coagulation management. Although plasma TG gives comprehensive insights into the function of pro- and anticoagulation drivers, it does not measure the role of blood cells in TG. In this literature review, we discuss currently available continuous TG tests that can reflect the involvement of blood cells in coagulation, in particular the fluorogenic assays that allow continuous measurement in platelet-rich plasma and whole blood. We also provide an overview about the influence of blood cells on blood coagulation, with emphasis on the direct influence of blood cells on TG. Platelets accelerate the initiation and velocity of TG by phosphatidylserine exposure, granule content release and surface receptor interaction with coagulation proteins. Erythrocytes are also major providers of phosphatidylserine, and erythrocyte membranes trigger contact activation. Furthermore, leukocytes and cancer cells may be important players in cell-mediated coagulation because, under certain conditions, they express tissue factor, release procoagulant components and can induce platelet activation. We argue that testing TG in the presence of blood cells may be useful to distinguish blood cell–related coagulation disorders. However, it should also be noted that these blood cell–dependent TG assays are not clinically validated. Further standardization and validation studies are needed to explore their clinical usefulness.

Keywords

thrombosis - haemorrhage - thrombin generation - blood cells - whole blood

Volltext

Referenzen

References
1 MacFarlane RG. An enzyme cascade in the blood clotting mechanism, and its function as a biochemical amplifier. Nature 1964; 202 (4931): 498-499
2 Davie EW, Ratnoff OD. Waterfall sequence for intrinsic blood clotting. Science 1964; 145 (3638): 1310-1312
3 van der Meijden PEJ, Munnix ICA, Auger JM. et al. Dual role of collagen in factor XII-dependent thrombus formation. Blood 2009; 114 (04) 881-890
4 Martin DM, Boys CWG, Ruf W. Tissue factor: molecular recognition and cofactor function. FASEB J 1995; 9 (10) 852-859
5 Wilcox JN, Smith KM, Schwartz SM, Gordon D. Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. Proc Natl Acad Sci U S A 1989; 86 (08) 2839-2843
6 Rousseau A, Larsen AK, Van Dreden P, Sabbah M, Elalamy I, Gerotziafas GT. Differential contribution of tissue factor and factor XII to thrombin generation triggered by breast and pancreatic cancer cells. Int J Oncol 2017; 51 (06) 1747-1756
7 Marchetti M, Diani E, ten Cate H, Falanga A. Characterization of the thrombin generation potential of leukemic and solid tumor cells by calibrated automated thrombography. Haematologica 2012; 97 (08) 1173-1180
8 Siddiqui FA, Desai H, Amirkhosravi A, Amaya M, Francis JL. The presence and release of tissue factor from human platelets. Platelets 2002; 13 (04) 247-253
9 Celi A, Pellegrini G, Lorenzet R. et al. P-selectin induces the expression of tissue factor on monocytes. Proc Natl Acad Sci U S A 1994; 91 (19) 8767-8771
10 Müller I, Klocke A, Alex M. et al. Intravascular tissue factor initiates coagulation via circulating microvesicles and platelets. FASEB J 2003; 17 (03) 476-478
11 Osterud B, Rapaport SI. Activation of factor IX by the reaction product of tissue factor and factor VII: additional pathway for initiating blood coagulation. Proc Natl Acad Sci U S A 1977; 74 (12) 5260-5264
12 Josso F, Prou-Wartelle O. Interaction of tissue factor and factor VII at the earliest phase of coagulation. Thromb Diath Haemorrh Suppl 1965; 17: 35-44
13 O'Donnell JS, O'Sullivan JM, Preston RJS. Advances in understanding the molecular mechanisms that maintain normal haemostasis. Br J Haematol 2019; 186 (01) 24-36
14 Versteeg HH, Heemskerk JW, Levi M, Reitsma PH. New fundamentals in hemostasis. Physiol Rev 2013; 93 (01) 327-358
15 Gailani D, Broze Jr GJ. Factor XI activation in a revised model of blood coagulation. Science 1991; 253 (5022): 909-912
16 Pieters J, Lindhout T, Hemker HC. In situ-generated thrombin is the only enzyme that effectively activates factor VIII and factor V in thromboplastin-activated plasma. Blood 1989; 74 (03) 1021-1024
17 Fulcher CA, Gardiner JE, Griffin JH, Zimmerman TS. Proteolytic inactivation of human factor VIII procoagulant protein by activated human protein C and its analogy with factor V. Blood 1984; 63 (02) 486-489
18 Walker FJ. Regulation of activated protein C by protein S. The role of phospholipid in factor Va inactivation. J Biol Chem 1981; 256 (21) 11128-11131
19 Comfurius P, Williamson P, Smeets EF, Schlegel RA, Bevers EM, Zwaal RF. Reconstitution of phospholipid scramblase activity from human blood platelets. Biochemistry 1996; 35 (24) 7631-7634
20 Bevers EM, Rosing J, Zwaal RF. Development of procoagulant binding sites on the platelet surface. Adv Exp Med Biol 1985; 192: 359-371
21 Monroe DM, Hoffman M, Roberts HR. Platelets and thrombin generation. Arterioscler Thromb Vasc Biol 2002; 22 (09) 1381-1389
22 Langdell RD, Wagner RH, Brinkhous KM. Effect of antihemophilic factor on one-stage clotting tests; a presumptive test for hemophilia and a simple one-stage antihemophilic factor assy procedure. J Lab Clin Med 1953; 41 (04) 637-647
23 Quick AJ. On various properties of thromboplastin (aqueous tissue extracts). Am J Physiol Legacy Content 1935; 114 (02) 282-296
24 Mann KG, Brummel K, Butenas S. What is all that thrombin for?. J Thromb Haemost 2003; 1 (07) 1504-1514
25 Tripodi A. Thrombin generation assay and its application in the clinical laboratory. Clin Chem 2016; 62 (05) 699-707
26 Tripodi A, Salerno F, Chantarangkul V. et al. Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests. Hepatology 2005; 41 (03) 553-558
27 Hézard N, Bouaziz-Borgi L, Remy MG, Nguyen P. Utility of thrombin-generation assay in the screening of factor V G1691A (Leiden) and prothrombin G20210A mutations and protein S deficiency. Clin Chem 2006; 52 (04) 665-670
28 MacFarlane RG, Biggs R. A thrombin generation test; the application in haemophilia and thrombocytopenia. J Clin Pathol 1953; 6 (01) 3-8
29 Hemker HC, Wielders S, Kessels H, Béguin S. Continuous registration of thrombin generation in plasma, its use for the determination of the thrombin potential. Thromb Haemost 1993; 70 (04) 617-624
30 Kelchtermans H, Pelkmans L, Bouwhuis A. et al. Simultaneous measurement of thrombin generation and fibrin formation in whole blood under flow conditions. Thromb Haemost 2016; 116 (01) 134-145
31 Kremers RMW, Wagenvoord RJ, Hemker HC. The effect of fibrin(ogen) on thrombin generation and decay. Thromb Haemost 2014; 112 (03) 486-494
32 Hemker HC, Giesen P, Al Dieri R. et al. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb 2003; 33 (01) 4-15
33 Ramjee MK. The use of fluorogenic substrates to monitor thrombin generation for the analysis of plasma and whole blood coagulation. Anal Biochem 2000; 277 (01) 11-18
34 Hemker HC, Giesen P, AlDieri R. et al. The calibrated automated thrombogram (CAT): a universal routine test for hyper- and hypocoagulability. Pathophysiol Haemost Thromb 2002; 32 (5–6): 249-253
35 Coen Hemker H, Hemker PW, Al Dieri R. The technique of measuring thrombin generation with fluorescent substrates: 4. The H-transform, a mathematical procedure to obtain thrombin concentrations without external calibration. Thromb Haemost 2009; 101 (01) 171-177
36 Kintigh J, Monagle P, Ignjatovic V. A review of commercially available thrombin generation assays. Res Pract Thromb Haemost 2017; 2 (01) 42-48
37 Al Dieri R, de Laat B, Hemker HC. Thrombin generation: what have we learned?. Blood Rev 2012; 26 (05) 197-203
38 Ten Cate H. Thrombin generation in clinical conditions. Thromb Res 2012; 129 (03) 367-370
39 Lutsey PL, Folsom AR, Heckbert SR, Cushman M. Peak thrombin generation and subsequent venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology (LITE) study. J Thromb Haemost 2009; 7 (10) 1639-1648
40 Hron G, Kollars M, Binder BR, Eichinger S, Kyrle PA. Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation. JAMA 2006; 296 (04) 397-402
41 Bosch Y, Al Dieri R, ten Cate H. et al. Preoperative thrombin generation is predictive for the risk of blood loss after cardiac surgery: a research article. J Cardiothorac Surg 2013; 8: 154
42 Santagostino E, Mancuso ME, Tripodi A. et al. Severe hemophilia with mild bleeding phenotype: molecular characterization and global coagulation profile. J Thromb Haemost 2010; 8 (04) 737-743
43 Zwaveling S, Bloemen S, de Laat B, Ten Cate H, Ten Cate-Hoek A. Calibrated Automated Thrombinography (CAT), a tool to identify patients at risk of bleeding during anticoagulant therapy: a systematic review. TH Open 2018; 2 (03) e291-e302
44 Curvers J, Thomassen MC, Rimmer J. et al. Effects of hereditary and acquired risk factors of venous thrombosis on a thrombin generation-based APC resistance test. Thromb Haemost 2002; 88 (01) 5-11
45 Rosing J, Tans G, Nicolaes GA. et al. Oral contraceptives and venous thrombosis: different sensitivities to activated protein C in women using second- and third-generation oral contraceptives. Br J Haematol 1997; 97 (01) 233-238
46 Lisman T, Bakhtiari K, Adelmeijer J, Meijers JC, Porte RJ, Stravitz RT. Intact thrombin generation and decreased fibrinolytic capacity in patients with acute liver injury or acute liver failure. J Thromb Haemost 2012; 10 (07) 1312-1319
47 Dargaud Y, Wolberg AS, Luddington R. et al. Evaluation of a standardized protocol for thrombin generation measurement using the calibrated automated thrombogram: an international multicentre study. Thromb Res 2012; 130 (06) 929-934
48 Dargaud Y, Wolberg AS, Gray E, Negrier C, Hemker HC. Subcommittee on Factor VIII, Factor IX, and Rare Coagulation Disorders. Proposal for standardized preanalytical and analytical conditions for measuring thrombin generation in hemophilia: communication from the SSC of the ISTH. J Thromb Haemost 2017; 15 (08) 1704-1707
49 Dargaud Y, Luddington R, Baglin TP. Elimination of contact factor activation improves measurement of platelet-dependent thrombin generation by calibrated automated thrombography at low-concentration tissue factor. J Thromb Haemost 2006; 4 (05) 1160-1161
50 De Smedt E, Hemker HC. Thrombin generation is extremely sensitive to preheating conditions. J Thromb Haemost 2011; 9 (01) 233-234
51 Subcommittee on Control of Anticoagulation of the SSC of the ISTH. Towards a recommendation for the standardization of the measurement of platelet-dependent thrombin generation. J Thromb Haemost 2011; 9 (09) 1859-1861
52 Dargaud Y, Luddington R, Gray E. et al. Standardisation of thrombin generation test: which reference plasma for TGT? An international multicentre study. Thromb Res 2010; 125 (04) 353-356
53 van Veen JJ, Gatt A, Makris M. Thrombin generation testing in routine clinical practice: are we there yet?. Br J Haematol 2008; 142 (06) 889-903
54 Hoffman M, Monroe III DM. A cell-based model of hemostasis. Thromb Haemost 2001; 85 (06) 958-965
55 Reverter JC, Béguin S, Kessels H, Kumar R, Hemker HC, Coller BS. Inhibition of platelet-mediated, tissue factor-induced thrombin generation by the mouse/human chimeric 7E3 antibody. Potential implications for the effect of c7E3 Fab treatment on acute thrombosis and “clinical restenosis”. J Clin Invest 1996; 98 (03) 863-874
56 Sang Y, Roest M, de Laat B, de Groot PG, Huskens D. Interplay between platelets and coagulation. Blood Rev 2021; 46: 100733
57 Swieringa F, Spronk HMH, Heemskerk JWM, van der Meijden PEJ. Integrating platelet and coagulation activation in fibrin clot formation. Res Pract Thromb Haemost 2018; 2 (03) 450-460
58 Morrissey JH, Choi SH, Smith SA. Polyphosphate: an ancient molecule that links platelets, coagulation, and inflammation. Blood 2012; 119 (25) 5972-5979
59 Verhoef JJF, Barendrecht AD, Nickel KF. et al. Polyphosphate nanoparticles on the platelet surface trigger contact system activation. Blood 2017; 129 (12) 1707-1717
60 Winckers K, Thomassen S, Ten Cate H, Hackeng TM. Platelet full length TFPI-α in healthy volunteers is not affected by sex or hormonal use. PLoS One 2017; 12 (02) e0168273
61 Preston RJS, Tran S, Johnson JA. et al. Platelet factor 4 impairs the anticoagulant activity of activated protein C. J Biol Chem 2009; 284 (09) 5869-5875
62 Camire RM, Kalafatis M, Simioni P, Girolami A, Tracy PB. Platelet-derived factor Va/Va Leiden cofactor activities are sustained on the surface of activated platelets despite the presence of activated protein C. Blood 1998; 91 (08) 2818-2829
63 Brambilla M, Facchinetti L, Canzano P. et al. Human megakaryocytes confer tissue factor to a subset of shed platelets to stimulate thrombin generation. Thromb Haemost 2015; 114 (03) 579-592
64 Panes O, Matus V, Sáez CG, Quiroga T, Pereira J, Mezzano D. Human platelets synthesize and express functional tissue factor. Blood 2007; 109 (12) 5242-5250
65 Camera M, Frigerio M, Toschi V. et al. Platelet activation induces cell-surface immunoreactive tissue factor expression, which is modulated differently by antiplatelet drugs. Arterioscler Thromb Vasc Biol 2003; 23 (09) 1690-1696
66 Bouchard BA, Gissel MT, Whelihan MF, Mann KG, Butenas S. Platelets do not express the oxidized or reduced forms of tissue factor. Biochim Biophys Acta 2014; 1840 (03) 1188-1193
67 Østerud B, Olsen JO. Human platelets do not express tissue factor. Thromb Res 2013; 132 (01) 112-115
68 Bouchard BA, Krudysz-Amblo J, Butenas S. Platelet tissue factor is not expressed transiently after platelet activation. Blood 2012; 119 (18) 4338-4339
69 Bouchard BA, Mann KG, Butenas S. No evidence for tissue factor on platelets. Blood 2010; 116 (05) 854-855
70 Brambilla M, Rossetti L, Zara C. et al. Do methodological differences account for the current controversy on tissue factor expression in platelets?. Platelets 2018; 29 (04) 406-414
71 Østerud B, Bouchard BA. Detection of tissue factor in platelets: why is it so troublesome?. Platelets 2019; 30 (08) 957-961
72 Duckers C, Simioni P, Spiezia L. et al. Residual platelet factor V ensures thrombin generation in patients with severe congenital factor V deficiency and mild bleeding symptoms. Blood 2010; 115 (04) 879-886
73 Brunet JG, Sharma T, Tasneem S. et al. Thrombin generation abnormalities in Quebec platelet disorder. Int J Lab Hematol 2020; 42 (06) 801-809
74 Vanschoonbeek K, Feijge MAH, Van Kampen RJW. et al. Initiating and potentiating role of platelets in tissue factor-induced thrombin generation in the presence of plasma: subject-dependent variation in thrombogram characteristics. J Thromb Haemost 2004; 2 (03) 476-484
75 Panova-Noeva M, van der Meijden PEJ, Ten Cate H. Clinical applications, pitfalls, and uncertainties of thrombin generation in the presence of platelets. J Clin Med 2019; 9 (01) E92
76 Shenkman B, Livnat T, Misgav M, Budnik I, Einav Y, Martinowitz U. The in vivo effect of fibrinogen and factor XIII on clot formation and fibrinolysis in Glanzmann's thrombasthenia. Platelets 2012; 23 (08) 604-610
77 Béguin S, Keularts I, Al Dieri R, Bellucci S, Caen J, Hemker HC. Fibrin polymerization is crucial for thrombin generation in platelet-rich plasma in a VWF-GPIb-dependent process, defective in Bernard-Soulier syndrome. J Thromb Haemost 2004; 2 (01) 170-176
78 Pike GN, Cumming AM, Hay CRM, Bolton-Maggs PH, Burthem J. Sample conditions determine the ability of thrombin generation parameters to identify bleeding phenotype in FXI deficiency. Blood 2015; 126 (03) 397-405
79 Hemker HC. Thrombin generation: biochemical possibilities and clinical reality. Blood 2015; 126 (03) 288-289
80 Kroll MH, Harris TS, Moake JL, Handin RI, Schafer AI. von Willebrand factor binding to platelet GpIb initiates signals for platelet activation. J Clin Invest 1991; 88 (05) 1568-1573
81 Pelkmans L, Miszta A, Al Dieri R, de Laat B, Kelchtermans H. Thrombin generation in the presence of platelets is sensitive to the activation status of von Willebrand factor. Thromb Haemost 2015; 113 (01) 209-211
82 Leebeek FW, Eikenboom JC. Von Willebrand's Disease. N Engl J Med 2016; 375 (21) 2067-2080
83 Rugeri L, Beguin S, Hemker C. et al. Thrombin-generating capacity in patients with von Willebrand's disease. Haematologica 2007; 92 (12) 1639-1646
84 Szanto T, Nummi V, Jouppila A, Brinkman HJM, Lassila R. Platelets compensate for poor thrombin generation in type 3 von Willebrand disease. Platelets 2020; 31 (01) 103-111
85 Neunert C, Lim W, Crowther M, Cohen A, Solberg Jr L, Crowther MA. American Society of Hematology. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 2011; 117 (16) 4190-4207
86 Tardy-Poncet B, Piot M, Chapelle C. et al. Thrombin generation and heparin-induced thrombocytopenia. J Thromb Haemost 2009; 7 (09) 1474-1481
87 Wan J, Konings J, Yan Q. et al. A novel assay for studying the involvement of blood cells in whole blood thrombin generation. J Thromb Haemost 2020; 18 (06) 1291-1301
88 Panova-Noeva M, Schulz A, Spronk HM. et al. Clinical determinants of thrombin generation measured in presence and absence of platelets: results from the Gutenberg Health Study. Thromb Haemost 2018; 118 (05) 873-882
89 Makowski M, Smorag I, Makowska J. et al. Platelet reactivity and mean platelet volume as risk markers of thrombogenesis in atrial fibrillation. Int J Cardiol 2017; 235: 1-5
90 Giannini EG, Savarino V. Thrombocytopenia in liver disease. Curr Opin Hematol 2008; 15 (05) 473-480
91 Tripodi A, Primignani M, Chantarangkul V. et al. Thrombin generation in patients with cirrhosis: the role of platelets. Hepatology 2006; 44 (02) 440-445
92 Krüger-Genge A, Blocki A, Franke RP, Jung F. Vascular endothelial cell biology: an update. Int J Mol Sci 2019; 20 (18) E4411
93 de Laat-Kremers RMW, Ninivaggi M, Devreese KMJ. et al. Towards standardization of thrombin generation assays: inventory of thrombin generation methods based on results of an International Society of Thrombosis and Haemostasis Scientific Standardization Committee survey. J Thromb Haemost 2020; 18 (08) 1893-1899
94 Ljungkvist M, Lövdahl S, Zetterberg E, Berntorp E. Low agreement between fresh and frozen-thawed platelet-rich plasma in the calibrated automated thrombogram assay. Haemophilia 2017; 23 (03) e214-e218
95 Rand MD, Lock JB, van't Veer C, Gaffney DP, Mann KG. Blood clotting in minimally altered whole blood. Blood 1996; 88 (09) 3432-3445
96 Thuerlemann C, Haeberli A, Alberio L. Monitoring thrombin generation by electrochemistry: development of an amperometric biosensor screening test for plasma and whole blood. Clin Chem 2009; 55 (03) 505-512
97 Tappenden KA, Gallimore MJ, Evans G, Mackie IJ, Jones DW. Thrombin generation: a comparison of assays using platelet-poor and -rich plasma and whole blood samples from healthy controls and patients with a history of venous thromboembolism. Br J Haematol 2007; 139 (01) 106-112
98 Al Dieri R, Hemker CH. Thrombin generation in whole blood. Br J Haematol 2008; 141 (06) 895
99 Ninivaggi M, Apitz-Castro R, Dargaud Y, de Laat B, Hemker HC, Lindhout T. Whole-blood thrombin generation monitored with a calibrated automated thrombogram-based assay. Clin Chem 2012; 58 (08) 1252-1259
100 Prior SM, Mann KG, Freeman K, Butenas S. Continuous thrombin generation in whole blood: new applications for assessing activators and inhibitors of coagulation. Anal Biochem 2018; 551: 19-25
101 Weisel JW, Litvinov RI. Red blood cells: the forgotten player in hemostasis and thrombosis. J Thromb Haemost 2019; 17 (02) 271-282
102 Byrnes JR, Wolberg AS. Red blood cells in thrombosis. Blood 2017; 130 (16) 1795-1799
103 Sorlie PD, Garcia-Palmieri MR, Costas Jr R, Havlik RJ. Hematocrit and risk of coronary heart disease: the Puerto Rico Health Program. Am Heart J 1981; 101 (04) 456-461
104 Eischer L, Tscholl V, Heinze G, Traby L, Kyrle PA, Eichinger S. Hematocrit and the risk of recurrent venous thrombosis: a prospective cohort study. PLoS One 2012; 7 (06) e38705
105 Sparkenbaugh E, Pawlinski R. Prothrombotic aspects of sickle cell disease. J Thromb Haemost 2017; 15 (07) 1307-1316
106 Du VX, Huskens D, Maas C, Al Dieri R, de Groot PG, de Laat B. New insights into the role of erythrocytes in thrombus formation. Semin Thromb Hemost 2014; 40 (01) 72-80
107 Helms CC, Marvel M, Zhao W. et al. Mechanisms of hemolysis-associated platelet activation. J Thromb Haemost 2013; 11 (12) 2148-2154
108 Peyrou V, Lormeau JC, Hérault JP, Gaich C, Pfliegger AM, Herbert JM. Contribution of erythrocytes to thrombin generation in whole blood. Thromb Haemost 1999; 81 (03) 400-406
109 Whelihan MF, Mooberry MJ, Zachary V. et al. The contribution of red blood cells to thrombin generation in sickle cell disease: meizothrombin generation on sickled red blood cells. J Thromb Haemost 2013; 11 (12) 2187-2189
110 Horne III MK, Cullinane AM, Merryman PK, Hoddeson EK. The effect of red blood cells on thrombin generation. Br J Haematol 2006; 133 (04) 403-408
111 Walton BL, Lehmann M, Skorczewski T. et al. Elevated hematocrit enhances platelet accumulation following vascular injury. Blood 2017; 129 (18) 2537-2546
112 Wan J, Roberts LN, Hendrix W. et al. Whole blood thrombin generation profiles of patients with cirrhosis explored with a near patient assay. J Thromb Haemost 2020; 18 (04) 834-843
113 Whelihan MF, Lim MY, Mooberry MJ. et al. Thrombin generation and cell-dependent hypercoagulability in sickle cell disease. J Thromb Haemost 2016; 14 (10) 1941-1952
114 Kawakami S, Kaibara M, Kawamoto Y, Yamanaka K. Rheological approach to the analysis of blood coagulation in endothelial cell-coated tubes: activation of the intrinsic reaction on the erythrocyte surface. Biorheology 1995; 32 (05) 521-536
115 Van Der Meijden PE, Van Schilfgaarde M, Van Oerle R, Renné T, ten Cate H, Spronk HM. Platelet- and erythrocyte-derived microparticles trigger thrombin generation via factor XIIa. J Thromb Haemost 2012; 10 (07) 1355-1362
116 Iwata H, Kaibara M. Activation of factor IX by erythrocyte membranes causes intrinsic coagulation. Blood Coagul Fibrinolysis 2002; 13 (06) 489-496
117 Noubouossie DF, Henderson MW, Mooberry M. et al. Red blood cell microvesicles activate the contact system, leading to factor IX activation via 2 independent pathways. Blood 2020; 135 (10) 755-765
118 Kearney KJ, Butler J, Posada OM. et al. Kallikrein directly interacts with and activates Factor IX, resulting in thrombin generation and fibrin formation independent of factor XI. Proc Natl Acad Sci U S A 2021; 118 (03) e2014810118
119 Visser M, van Oerle R, Ten Cate H. et al. Plasma kallikrein contributes to coagulation in the absence of factor XI by activating factor IX. Arterioscler Thromb Vasc Biol 2020; 40 (01) 103-111
120 Reimers RC, Sutera SP, Joist JH. Potentiation by red blood cells of shear-induced platelet aggregation: relative importance of chemical and physical mechanisms. Blood 1984; 64 (06) 1200-1206
121 Hermand P, Gane P, Huet M. et al. Red cell ICAM-4 is a novel ligand for platelet-activated α IIbbeta 3 integrin. J Biol Chem 2003; 278 (07) 4892-4898
122 Klatt C, Krüger I, Zey S. et al. Platelet-RBC interaction mediated by FasL/FasR induces procoagulant activity important for thrombosis. J Clin Invest 2018; 128 (09) 3906-3925
123 Cermak J, Key NS, Bach RR, Balla J, Jacob HS, Vercellotti GM. C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood 1993; 82 (02) 513-520
124 Basavaraj MG, Gruber FX, Sovershaev M. et al. The role of TFPI in regulation of TF-induced thrombogenicity on the surface of human monocytes. Thromb Res 2010; 126 (05) 418-425
125 Maugeri N, Brambilla M, Camera M. et al. Human polymorphonuclear leukocytes produce and express functional tissue factor upon stimulation. J Thromb Haemost 2006; 4 (06) 1323-1330
126 Darbousset R, Thomas GM, Mezouar S. et al. Tissue factor-positive neutrophils bind to injured endothelial wall and initiate thrombus formation. Blood 2012; 120 (10) 2133-2143
127 Egorina EM, Sovershaev MA, Olsen JO, Østerud B. Granulocytes do not express but acquire monocyte-derived tissue factor in whole blood: evidence for a direct transfer. Blood 2008; 111 (03) 1208-1216
128 Swystun LL, Liaw PC. The role of leukocytes in thrombosis. Blood 2016; 128 (06) 753-762
129 Brinkmann V, Reichard U, Goosmann C. et al. Neutrophil extracellular traps kill bacteria. Science 2004; 303 (5663): 1532-1535
130 Elaskalani O, Abdol Razak NB, Metharom P. Neutrophil extracellular traps induce aggregation of washed human platelets independently of extracellular DNA and histones. Cell Commun Signal 2018; 16 (01) 24
131 Barranco-Medina S, Pozzi N, Vogt AD, Di Cera E. Histone H4 promotes prothrombin autoactivation. J Biol Chem 2013; 288 (50) 35749-35757
132 Medeiros SK, Zafar N, Liaw PC, Kim PY. Purification of silica-free DNA and characterization of its role in coagulation. J Thromb Haemost 2019; 17 (11) 1860-1865
133 Smith SA, Baker CJ, Gajsiewicz JM, Morrissey JH. Silica particles contribute to the procoagulant activity of DNA and polyphosphate isolated using commercial kits. Blood 2017; 130 (01) 88-91
134 Ghasemzadeh M, Hosseini E. Platelet-leukocyte crosstalk: linking proinflammatory responses to procoagulant state. Thromb Res 2013; 131 (03) 191-197
135 Young A, Chapman O, Connor C, Poole C, Rose P, Kakkar AK. Thrombosis and cancer. Nat Rev Clin Oncol 2012; 9 (08) 437-449
136 Blom JW, Doggen CJ, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 2005; 293 (06) 715-722
137 Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton III LJ. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 2000; 160 (06) 809-815
138 Reddel CJ, Tan CW, Chen VM. Thrombin generation and cancer: contributors and consequences. Cancers (Basel) 2019; 11 (01) E100
139 Lundbech M, Krag AE, Christensen TD, Hvas AM. Thrombin generation, thrombin-antithrombin complex, and prothrombin fragment F1+2 as biomarkers for hypercoagulability in cancer patients. Thromb Res 2020; 186: 80-85
140 Adesanya MA, Maraveyas A, Madden L. Differing mechanisms of thrombin generation in live haematological and solid cancer cells determined by calibrated automated thrombography. Blood Coagul Fibrinolysis 2017; 28 (08) 602-611
141 Hudák R, Debreceni IB, Deák I. et al. Laboratory characterization of leukemic cell procoagulants. Clin Chem Lab Med 2017; 55 (08) 1215-1223
142 Al Saleh HA, Haas-Neill S, Al-Hashimi A. et al. Thrombotic characteristics of extracellular vesicles derived from prostate cancer cells. Prostate 2018; 78 (13) 953-961
143 Rousseau A, Van Dreden P, Khaterchi A, Larsen AK, Elalamy I, Gerotziafas GT. Procoagulant microparticles derived from cancer cells have determinant role in the hypercoagulable state associated with cancer. Int J Oncol 2017; 51 (06) 1793-1800
144 Gheldof D, Mullier F, Bailly N. et al. Microparticle bearing tissue factor: a link between promyelocytic cells and hypercoagulable state. Thromb Res 2014; 133 (03) 433-439
145 Thomas GM, Panicot-Dubois L, Lacroix R, Dignat-George F, Lombardo D, Dubois C. Cancer cell-derived microparticles bearing P-selectin glycoprotein ligand 1 accelerate thrombus formation in vivo. J Exp Med 2009; 206 (09) 1913-1927
146 Raasi S, Mielicki WP, Gordon SG, Korte W. Properties of proteins in cancer procoagulant preparations that are detected by anti-tissue factor antibodies. Arch Biochem Biophys 2004; 428 (02) 131-135
147 Gordon SG, Franks JJ, Lewis B. Cancer procoagulant A: a factor X activating procoagulant from malignant tissue. Thromb Res 1975; 6 (02) 127-137
148 Abdol Razak NB, Jones G, Bhandari M, Berndt MC, Metharom P. Cancer-associated thrombosis: an overview of mechanisms, risk factors, and treatment. Cancers (Basel) 2018; 10 (10) 380
149 Panteleev MA, Hemker HC. Global/integral assays in hemostasis diagnostics: promises, successes, problems and prospects. Thromb J 2015; 13 (01) 5
150 Benes J, Zatloukal J, Kletecka J. Viscoelastic methods of blood clotting assessment: a multidisciplinary review. Front Med (Lausanne) 2015; 2: 62