Venous and Arterial Thromboses: Two Sides of the Same Coin?

Abstract

Arterial and venous thromboses are sustained by development of intraluminal thrombi, respectively, within the venous and arterial systems. The composition and structure of arterial and venous thrombi have been historically considered as being very different. Arterial thrombi (conventionally defined as “white”) have been traditionally proposed to be composed mainly of fibrin and platelet aggregates, whilst venous thrombi (conventionally defined as “red”) have been proposed as mostly being enriched in fibrin and erythrocytes. This archaic dichotomy seems ever more questionable, since it barely reflects the pathophysiology of thrombus formation in vivo. Both types of thrombi are actually composed of a complex fibrin network but, importantly, also contain essentially the same blood-borne cells (i.e., red blood cells, leukocytes, and platelets), and it is only the relative content of these individual elements that differ between venous and arterial clots or, otherwise, between thrombi generated under different conditions of blood flow and shear stress. Convincing evidence now suggests that either white or red intracoronary thrombi may be present in patients with myocardial infarction and, even more importantly, red thrombi may be more prone to distal embolization during percutaneous coronary intervention than those with lower content of erythrocytes. Conversely, it is now accepted that components traditionally considered to be involved “only” in arterial thrombosis are also represented in venous thrombosis. Thus, platelets comprise important components of venous clots, although they may be present in lower amounts here than in arterial thrombi, and von Willebrand factor is also represented in both arterial and venous thrombi. Of importance, such evidence thus supports the concept that adjunctive treatment normally associated to prevention of arterial thrombosis (e.g., aspirin) may have a role also in prevention and treatment of venous thrombosis.

Keywords

hemostasis - thrombosis - cardiovascular disease - venous thromboembolism - arterial thrombosis - blood coagulation

• References

• 1 Lippi G, Franchini M, Targher G. Arterial thrombus formation in cardiovascular disease. Nat Rev Cardiol 2011; 8 (09) 502-512
• 2 Lippi G, Favaloro EJ, Cervellin G. Hemostatic properties of the lymph: relationships with occlusion and thrombosis. Semin Thromb Hemost 2012; 38 (02) 213-221
• 3 Leach RM, Treacher DF. Oxygen transport-2. Tissue hypoxia. BMJ 1998; 317 (7169): 1370-1373
• 4 Benjamin EJ, Blaha MJ, Chiuve SE. , et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation 2017; 135 (10) e146-e603
• 5 Comerota AJ, Thakur S. Deep venous thrombosis: upper and lower extremity. In: Kumar A, Ouriel K. , eds. Handbook of Endovascular Interventions. New York, NY: Springer; 2013
• 6 McKay DG, Linder MM, Cruse VK. Mechanism of thrombosis of the microcirculation. Am J Pathol 1971; 63 (02) 231-254
• 7 ten Cate H, Schoenmakers SH, Franco R. , et al. Microvascular coagulopathy and disseminated intravascular coagulation. Crit Care Med 2001; 29 (7, Suppl): S95-S97 , discussion S97–S98
• 8 George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med 2014; 371 (07) 654-666
• 9 Lippi G, Franchini M, Guidi GC. Diagnostic approach to inherited bleeding disorders. Clin Chem Lab Med 2007; 45 (01) 2-12
• 10 Lippi G, Favaloro EJ. Laboratory hemostasis: milestones in Clinical Chemistry and Laboratory Medicine. Clin Chem Lab Med 2013; 51 (01) 91-97
• 11 Lippi G, Pasalic L, Favaloro EJ. Detection of mild inherited disorders of blood coagulation: current options and personal recommendations. Expert Rev Hematol 2015; 8 (04) 527-542
• 12 Klarhöfer M, Csapo B, Balassy C, Szeles JC, Moser E. High-resolution blood flow velocity measurements in the human finger. Magn Reson Med 2001; 45 (04) 716-719
• 13 Lippi G, Franchini M. Pathogenesis of venous thromboembolism: when the cup runneth over. Semin Thromb Hemost 2008; 34 (08) 747-761
• 14 Rumbaut RE, Thiagarajan P. Arterial, venous, and microvascular hemostasis/thrombosis. Platelet-Vessel Wall Interactions in Hemostasis and Thrombosis. Chap 6. San Rafael, CA: Morgan & Claypool Life Sciences; 2010
• 15 Wohner N. Role of cellular elements in thrombus formation and dissolution. Cardiovasc Hematol Agents Med Chem 2008; 6 (03) 224-228
• 16 Cimmino G, Ciccarelli G, Golino P. Role of tissue factor in the coagulation network. Semin Thromb Hemost 2015; 41 (07) 708-717
• 17 Falanga A, Schieppati F, Russo D. Cancer tissue procoagulant mechanisms and the hypercoagulable state of patients with cancer. Semin Thromb Hemost 2015; 41 (07) 756-764
• 18 von Brühl ML, Stark K, Steinhart A. , et al. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med 2012; 209 (04) 819-835
• 19 van Es N, Bleker S, Sturk A, Nieuwland R. Clinical significance of tissue factor-exposing microparticles in arterial and venous thrombosis. Semin Thromb Hemost 2015; 41 (07) 718-727
• 20 Gale AJ. Continuing education course #2: current understanding of hemostasis. Toxicol Pathol 2011; 39 (01) 273-280
• 21 Smith SA, Travers RJ, Morrissey JH. How it all starts: initiation of the clotting cascade. Crit Rev Biochem Mol Biol 2015; 50 (04) 326-336
• 22 Versteeg HH, Heemskerk JW, Levi M, Reitsma PH. New fundamentals in hemostasis. Physiol Rev 2013; 93 (01) 327-358
• 23 Fogelson AL, Hussain YH, Leiderman K. Blood clot formation under flow: the importance of factor XI depends strongly on platelet count. Biophys J 2012; 102 (01) 10-18
• 24 Vercauteren E, Gils A, Declerck PJ. Thrombin activatable fibrinolysis inhibitor: a putative target to enhance fibrinolysis. Semin Thromb Hemost 2013; 39 (04) 365-372
• 25 Curnow J, Pasalic L, Favaloro EJ. Treatment of von Willebrand disease. Semin Thromb Hemost 2016; 42 (02) 133-146
• 26 Peyvandi F, Garagiola I, Baronciani L. Role of von Willebrand factor in the haemostasis. Blood Transfus 2011; 9 (Suppl. 02) s3-s8
• 27 Danese E, Montagnana M, Lippi G. Factor XII in hemostasis and thrombosis: active player or (innocent) bystander?. Semin Thromb Hemost 2016; 42 (06) 682-688
• 28 Chapin JC, Hajjar KA. Fibrinolysis and the control of blood coagulation. Blood Rev 2015; 29 (01) 17-24
• 29 Mackman N. Triggers, targets and treatments for thrombosis. Nature 2008; 451 (7181): 914-918
• 30 Silvain J, Collet JP, Nagaswami C. , et al. Composition of coronary thrombus in acute myocardial infarction. J Am Coll Cardiol 2011; 57 (12) 1359-1367
• 31 Ramaiola I, Padró T, Peña E. , et al. Changes in thrombus composition and profilin-1 release in acute myocardial infarction. Eur Heart J 2015; 36 (16) 965-975
• 32 Sadowski M, Ząbczyk M, Undas A. Coronary thrombus composition: links with inflammation, platelet and endothelial markers. Atherosclerosis 2014; 237 (02) 555-561
• 33 Zalewski J, Bogaert J, Sadowski M. , et al. Plasma fibrin clot phenotype independently affects intracoronary thrombus ultrastructure in patients with acute myocardial infarction. Thromb Haemost 2015; 113 (06) 1258-1269
• 34 Silvain J, Collet JP, Guedeney P. , et al. Thrombus composition in sudden cardiac death from acute myocardial infarction. Resuscitation 2017; 113: 108-114
• 35 Sato Y, Hatakeyama K, Yamashita A, Marutsuka K, Sumiyoshi A, Asada Y. Proportion of fibrin and platelets differs in thrombi on ruptured and eroded coronary atherosclerotic plaques in humans. Heart 2005; 91 (04) 526-530
• 36 Kramer MC, van der Wal AC, Koch KT. , et al. Presence of older thrombus is an independent predictor of long-term mortality in patients with ST-elevation myocardial infarction treated with thrombus aspiration during primary percutaneous coronary intervention. Circulation 2008; 118 (18) 1810-1816
• 37 Mizuno K, Satomura K, Miyamoto A. , et al. Angioscopic evaluation of coronary-artery thrombi in acute coronary syndromes. N Engl J Med 1992; 326 (05) 287-291
• 38 Abela GS, Eisenberg JD, Mittleman MA. , et al. Detecting and differentiating white from red coronary thrombus by angiography in angina pectoris and in acute myocardial infarction. Am J Cardiol 1999; 83 (01) 94-97 , A8
• 39 Uchida Y, Uchida Y, Sakurai T, Kanai M, Shirai S, Morita T. Characterization of coronary fibrin thrombus in patients with acute coronary syndrome using dye-staining angioscopy. Arterioscler Thromb Vasc Biol 2011; 31 (06) 1452-1460
• 40 Quadros AS, Cambruzzi E, Sebben J. , et al. Red versus white thrombi in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: clinical and angiographic outcomes. Am Heart J 2012; 164 (04) 553-560
• 41 Yunoki K, Naruko T, Inoue T. , et al. Relationship of thrombus characteristics to the incidence of angiographically visible distal embolization in patients with ST-segment elevation myocardial infarction treated with thrombus aspiration. JACC Cardiovasc Interv 2013; 6 (04) 377-385
• 42 Fokkema ML, Vlaar PJ, Svilaas T. , et al. Incidence and clinical consequences of distal embolization on the coronary angiogram after percutaneous coronary intervention for ST-elevation myocardial infarction. Eur Heart J 2009; 30 (08) 908-915
• 43 Marder VJ, Chute DJ, Starkman S. , et al. Analysis of thrombi retrieved from cerebral arteries of patients with acute ischemic stroke. Stroke 2006; 37 (08) 2086-2093
• 44 Liebeskind DS, Sanossian N, Yong WH. , et al. CT and MRI early vessel signs reflect clot composition in acute stroke. Stroke 2011; 42 (05) 1237-1243
• 45 Niesten JM, van der Schaaf IC, van Dam L. , et al. Histopathologic composition of cerebral thrombi of acute stroke patients is correlated with stroke subtype and thrombus attenuation. PLoS One 2014; 9 (02) e88882
• 46 Ahn SH, Hong R, Choo IS. , et al. Histologic features of acute thrombi retrieved from stroke patients during mechanical reperfusion therapy. Int J Stroke 2016; 11 (09) 1036-1044
• 47 Simons N, Mitchell P, Dowling R, Gonzales M, Yan B. Thrombus composition in acute ischemic stroke: a histopathological study of thrombus extracted by endovascular retrieval. J Neuroradiol 2015; 42 (02) 86-92
• 48 Kovács A, Sótonyi P, Nagy AI. , et al. Ultrastructure and composition of thrombi in coronary and peripheral artery disease: correlations with clinical and laboratory findings. Thromb Res 2015; 135 (04) 760-766
• 49 Stein PD, Evans H. An autopsy study of leg vein thrombosis. Circulation 1967; 35 (04) 671-681
• 50 Grossman ZD, Wistow BW, McAfee JG. , et al. Platelets labeled with oxine complexes of Tc-99m and In-111. Part 2. Localization of experimentally induced vascular lesions. J Nucl Med 1978; 19 (05) 488-491
• 51 Quarmby J, Smith A, Collins M, Cederholm-Williams S, Burnand K. A model of in vivo human venous thrombosis that confirms changes in the release of specific soluble cell adhesion molecules in experimental venous thrombogenesis. J Vasc Surg 1999; 30 (01) 139-147
• 52 Burches B, Karnicki K, Wysokinski W, McBane II RD. Immunohistochemistry of thrombi following iliac venous stenting: a novel model of venous thrombosis. Thromb Haemost 2006; 96 (05) 618-622
• 53 Shaydakov M, Comerota A, Lurie F. , et al. The structure of venous thrombus depends on blood flow: insights from animal models. J Vasc Surg Venous Lymphat Disord 2017; 5 (01) 145-146
• 54 Undas A, Ariëns RA. Fibrin clot structure and function: a role in the pathophysiology of arterial and venous thromboembolic diseases. Arterioscler Thromb Vasc Biol 2011; 31 (12) e88-e99
• 55 Undas A. Fibrin clot properties and their modulation in thrombotic disorders. Thromb Haemost 2014; 112 (01) 32-42
• 56 Aleman MM, Walton BL, Byrnes JR, Wolberg AS. Fibrinogen and red blood cells in venous thrombosis. Thromb Res 2014; 133 (Suppl. 01) S38-S40
• 57 Aleman MM, Byrnes JR, Wang JG. , et al. Factor XIII activity mediates red blood cell retention in venous thrombi. J Clin Invest 2014; 124 (08) 3590-3600
• 58 Byrnes JR, Duval C, Wang Y. , et al. Factor XIIIa-dependent retention of red blood cells in clots is mediated by fibrin α-chain crosslinking. Blood 2015; 126 (16) 1940-1948
• 59 Litvinov RI, Weisel JW. Role of red blood cells in haemostasis and thrombosis. ISBT Sci Ser 2017; 12 (01) 176-183
• 60 Tan KT, Lip GY. Red vs white thrombi: treating the right clot is crucial. Arch Intern Med 2003; 163 (20) 2534-2535 , author reply 2535
• 61 Sobieszczyk P, Fishbein MC, Goldhaber SZ. Acute pulmonary embolism: don't ignore the platelet. Circulation 2002; 106 (14) 1748-1749
• 62 Kwaan HC, Mazar AP. Biologic role of the plasminogen-plasmin system: thrombolysis, bleeding, and beyond. Semin Thromb Hemost 2013; 39 (04) 327-328
• 63 Orme R, Judge HM, Storey RF. Monitoring antiplatelet therapy. Semin Thromb Hemost 2017; 43 (03) 311-319
• 64 Bounameaux H, Fontana P. Aspirin for venous thromboembolism prevention and treatment: a renewal?. Pol Arch Med Wewn 2012; 122 (10) 461-463
• 65 Simes J, Becattini C, Agnelli G. , et al; INSPIRE Study Investigators (International Collaboration of Aspirin Trials for Recurrent Venous Thromboembolism). Aspirin for the prevention of recurrent venous thromboembolism: the INSPIRE collaboration. Circulation 2014; 130 (13) 1062-1071
• 66 Marik PE, Cavallazzi R. Extended anticoagulant and aspirin treatment for the secondary prevention of thromboembolic disease: a systematic review and meta-analysis. PLoS One 2015; 10 (11) e0143252
• 67 Weitz JI, Lensing AWA, Prins MH. , et al; EINSTEIN CHOICE Investigators. Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism. N Engl J Med 2017; 376 (13) 1211-1222
• 68 Anderson DR, Dunbar MJ, Bohm ER. , et al. Aspirin versus low-molecular-weight heparin for extended venous thromboembolism prophylaxis after total hip arthroplasty: a randomized trial. Ann Intern Med 2013; 158 (11) 800-806
• 69 Eikelboom JW, Kearon C, Guyatt G. , et al. Perioperative aspirin for prevention of venous thromboembolism: the PeriOperative ISchemia Evaluation-2 Trial and a Pooled Analysis of the Randomized Trials. Anesthesiology 2016; 125 (06) 1121-1129
• 70 Jackson SP. Arterial thrombosis--insidious, unpredictable and deadly. Nat Med 2011; 17 (11) 1423-1436
• 71 Minnerup J, Kleinschnitz C. Visualization of clot composition in ischemic stroke: do we get what we see?. Stroke 2011; 42 (05) 1193-1194
• 72 Favaloro EJ, Lippi G. Laboratory testing in the era of direct or non-vitamin K antagonist oral anticoagulants: a practical guide to measuring their activity and avoiding diagnostic errors. Semin Thromb Hemost 2015; 41 (02) 208-227
• 73 Cervellin G, Benatti M, Bonfanti L, Lippi G. Quality and safety issues of direct oral anticoagulants in the emergency department. Semin Thromb Hemost 2015; 41 (03) 348-354
• 74 Favaloro EJ, Pasalic L, Curnow J, Lippi G. Laboratory monitoring or measurement of direct oral anticoagulants (DOACs): advantages, limitations and future challenges. Curr Drug Metab 2017
• 75 Chin PK. Which patients may benefit from dose adjustment of non-vitamin K antagonist oral anticoagulants?. Semin Thromb Hemost 2015; 41 (02) 195-207
• 76 Timp JF, Lijfering WM, Flinterman LE. , et al. Predictive value of factor VIII levels for recurrent venous thrombosis: results from the MEGA follow-up study. J Thromb Haemost 2015; 13 (10) 1823-1832
• 77 Franchini M, Lippi G. Relative risks of thrombosis and bleeding in different ABO blood groups. Semin Thromb Hemost 2016; 42 (02) 112-117
• 78 Franchini M, Marano G, Vaglio S, Catalano L, Pupella S, Liumbruno GM. The role of ABO blood type in thrombosis scoring systems. Semin Thromb Hemost 2017; 43 (05) 525-529