Loose Fibrin Clot Structure and Increased Susceptibility to Lysis Characterize Patients with Central Acute Pulmonary Embolism: The Impact of Isolated Embolism

Michał Ząbczyk; Joanna Natorska; Agnieszka Janion-Sadowska; Agnieszka Metzgier-Gumiela; Mateusz Polak; Krzysztof Plens; Marianna Janion; Grzegorz Skonieczny; Katarzyna Mizia-Stec; Anetta Undas

doi:10.1055/s-0040-1718762

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2021; 121(04): 529-537
DOI: 10.1055/s-0040-1718762

Stroke, Systemic or Venous Thromboembolism

Loose Fibrin Clot Structure and Increased Susceptibility to Lysis Characterize Patients with Central Acute Pulmonary Embolism: The Impact of Isolated Embolism

Michał Ząbczyk

¹Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland

²Krakow Center for Medical Research and Technologies, John Paul II Hospital, Krakow, Poland

,

Joanna Natorska

¹Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland

²Krakow Center for Medical Research and Technologies, John Paul II Hospital, Krakow, Poland

,

Agnieszka Janion-Sadowska

³2nd Department of Cardiology, The Faculty of Medicine and Health Sciences, The Jan Kochanowski University, Kielce, Poland

,

Agnieszka Metzgier-Gumiela

⁴Intensive Care Cardiology Unit, Provincial Polyclinical Hospital, Torun, Poland

,

Mateusz Polak

⁵First Department of Cardiology, Leszek Giec Upper-Silesian Medical Centre of the Silesian Medical University in Katowice, Poland

,

Krzysztof Plens

⁶KCRI, Krakow, Poland

,

Marianna Janion

³2nd Department of Cardiology, The Faculty of Medicine and Health Sciences, The Jan Kochanowski University, Kielce, Poland

,

Grzegorz Skonieczny

⁴Intensive Care Cardiology Unit, Provincial Polyclinical Hospital, Torun, Poland

,

Katarzyna Mizia-Stec

⁵First Department of Cardiology, Leszek Giec Upper-Silesian Medical Centre of the Silesian Medical University in Katowice, Poland

,

Anetta Undas

¹Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland

²Krakow Center for Medical Research and Technologies, John Paul II Hospital, Krakow, Poland

› Institutsangaben

Abstract

Background Prothrombotic fibrin clot properties are associated with higher early mortality risk in acute pulmonary embolism (PE) patients. It is unknown whether different types of PE are associated with particular clot characteristics.

Methods We assessed 126 normotensive, noncancer acute PE patients (median age: 59 [48–70] years; 52.4% males), who were categorized into central versus peripheral PE with or without concomitant deep vein thrombosis (DVT). Plasma fibrin clot permeability (K _s), clot lysis time (CLT), thrombin generation, platelet-derived markers, and fibrinolytic parameters were measured on admission. Plasma fibrin clot morphology was assessed by scanning electron microscopy (SEM).

Results Patients with central PE (n = 76; 60.3%) compared with peripheral PE (n = 50; 39.7%) had 17.8% higher K _s and 14.3% shortened CLT (both p < 0.01 after adjustment for potential confounders including fibrinogen), with no differences between segmental and subsegmental PE. SEM analysis demonstrated larger fibrin fiber diameter and pore size in central PE compared with peripheral PE (both p < 0.01). For isolated PE, there was 23.3% higher K _s in central PE than in peripheral PE (n = 24; 19%) with no differences in other variables. Central PE combined with DVT (n = 45; 35.7%), as compared with central isolated PE (n = 31; 24.6%), was associated with shortened CLT (all p < 0.05).

Conclusion Our findings suggest that looser fibrin networks composed of thicker fibers with increased susceptibility to lysis characterize patients with central PE, suggesting that fibrin clot phenotype affects the size of thrombi occluding the pulmonary arteries, highlighting the role of fibrin structures in thrombus formation and stability.

Keywords

fibrin clot - thrombus location - prothrombotic - fibrinolysis - acute pulmonary embolism

Volltext

Referenzen

References
1 Huisman MV, Barco S, Cannegieter SC. et al. Pulmonary embolism. Nat Rev Dis Primers 2018; 4: 18028
2 Cohen AT, Agnelli G, Anderson FA. VTE Impact Assessment Group in Europe (VITAE). et al. Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost 2007; 98 (04) 756-764
3 Konstantinides SV, Meyer G, Becattini C. The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). Eur Respir J 2019; 54 (03) 1901647
4 Pena E, Kimpton M, Dennie C, Peterson R, LE Gal G, Carrier M. Difference in interpretation of computed tomography pulmonary angiography diagnosis of subsegmental thrombosis in patients with suspected pulmonary embolism. J Thromb Haemost 2012; 10 (03) 496-498
5 Girard P, Sanchez O, Leroyer C. Evaulation du Scanner Spiralé dans l'Embolie Pulmonaire Study Group. et al. Deep venous thrombosis in patients with acute pulmonary embolism: prevalence, risk factors, and clinical significance. Chest 2005; 128 (03) 1593-1600
6 Margaglione M, Brancaccio V, De Lucia D. et al. Inherited thrombophilic risk factors and venous thromboembolism: distinct role in peripheral deep venous thrombosis and pulmonary embolism. Chest 2000; 118 (05) 1405-1411
7 Cha SI, Shin KM, Lee JW. et al. Clinical characteristics of patients with peripheral pulmonary embolism. Respiration 2010; 80 (06) 500-508
8 Undas A, Natorska J. Improving fibrinolysis in venous thromboembolism: impact of fibrin structure. Expert Rev Hematol 2019; 12 (08) 597-607
9 Undas A, Zawilska K, Ciesla-Dul M. et al. Altered fibrin clot structure/function in patients with idiopathic venous thromboembolism and in their relatives. Blood 2009; 114 (19) 4272-4278
10 Zabczyk M, Plens K, Wojtowicz W, Undas A. Prothrombotic fibrin clot phenotype is associated with recurrent pulmonary embolism after discontinuation of anticoagulant therapy. Arterioscler Thromb Vasc Biol 2017; 37 (02) 365-373
11 Cieslik J, Mrozinska S, Broniatowska E, Undas A. Altered plasma clot properties increase the risk of recurrent deep vein thrombosis: a cohort study. Blood 2018; 131 (07) 797-807
12 Undas A. Fibrin clot properties and their modulation in thrombotic disorders. Thromb Haemost 2014; 112 (01) 32-42
13 Martinez MR, Cuker A, Mills AM. et al. Enhanced lysis and accelerated establishment of viscoelastic properties of fibrin clots are associated with pulmonary embolism. Am J Physiol Lung Cell Mol Physiol 2014; 306 (05) L397-L404
14 Ząbczyk M, Natorska J, Janion-Sadowska A. et al. Prothrombotic fibrin clot properties associated with NETs formation characterize acute pulmonary embolism patients with higher mortality risk. Sci Rep 2020; 10 (01) 11433
15 Ząbczyk M, Natorska J, Janion-Sadowska A, Malinowski KP, Janion M, Undas A. Elevated lactate levels in acute pulmonary embolism are associated with prothrombotic fibrin clot properties: contribution of NETs formation. J Clin Med 2020; 9 (04) E953
16 Mazur P, Gawęda B, Natorska J. et al. Fibrin structure in organized thrombotic material removed during pulmonary artery endarterectormy: the effect of vessel calibre. J Thromb Thrombolysis 2016; 42 (02) 212-217
17 Kupis RW, Goldman-Mazur S, Polak M, Ząbczyk M, Undas A. Faster fibrin clot degradation characterizes patients with central pulmonary embolism at a low risk of recurrent peripheral embolism. Sci Rep 2019; 9 (01) 72
18 Baglin T, Gray E, Greaves M. British Committee for Standards in Haematology. et al. Clinical guidelines for testing for heritable thrombophilia. Br J Haematol 2010; 149 (02) 209-220
19 Pieters M, Philippou H, Undas A, de Lange Z, Rijken DC, Mutch NJ. Subcommittee on Factor XIII and Fibrinogen, and the Subcommittee on Fibrinolysis. An international study on the feasibility of a standardized combined plasma clot turbidity and lysis assay: communication from the SSC of the ISTH. J Thromb Haemost 2018; 16 (05) 1007-1012
20 Colle JP, Mishal Z, Lesty C. et al. Abnormal fibrin clot architecture in nephrotic patients is related to hypofibrinolysis: influence of plasma biochemical modifications: a possible mechanism for the high thrombotic tendency?. Thromb Haemost 1999; 82 (05) 1482-1489
21 Meltzer ME, Lisman T, de Groot PG. et al. Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1. Blood 2010; 116 (01) 113-121
22 Longstaff C, Kolev K. Basic mechanisms and regulation of fibrinolysis. J Thromb Haemost 2015; 13 (Suppl. 01) S98-S105
23 Collet JP, Lesty C, Montalescot G, Weisel JW. Dynamic changes of fibrin architecture during fibrin formation and intrinsic fibrinolysis of fibrin-rich clots. J Biol Chem 2003; 278 (24) 21331-21335
24 Undas A, Topór-Madry R, Tracz W. Simvastatin increases clot permeability and susceptibility to lysis in patients with LDL cholesterol below 3.4 mmol/l. Pol Arch Med Wewn 2009; 119 (06) 354-359
25 Pai M, Evans NS, Shah SJ, Green D, Cook D, Crowther MA. Statins in the prevention of venous thromboembolism: a meta-analysis of observational studies. Thromb Res 2011; 128 (05) 422-430
26 Li L, Zhang P, Tian JH, Yang K. Statins for primary prevention of venous thromboembolism. Cochrane Database Syst Rev 2014; , Issue 12. Art. No.: CD008203.
27 Biere-Rafi S, Hutten BA, Squizzato A. et al. Statin treatment and the risk of recurrent pulmonary embolism. Eur Heart J 2013; 34 (24) 1800-1806
28 Glynn RJ, Danielson E, Fonseca FA. et al. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med 2009; 360 (18) 1851-1861
29 Wu ZY, Li H, Tang YJ. Effect of simvastatin on the SIRT2/NF-κB pathway in rats with acute pulmonary embolism. Pharm Biol 2018; 56 (01) 511-518
30 van Langevelde K, Srámek A, Vincken PW, van Rooden JK, Rosendaal FR, Cannegieter SC. Finding the origin of pulmonary emboli with a total-body magnetic resonance direct thrombus imaging technique. Haematologica 2013; 98 (02) 309-315
31 Salonen EM, Vartio T, Hedman K, Vaheri A. Binding of fibronectin by the acute phase reactant C-reactive protein. J Biol Chem 1984; 259 (03) 1496-1501
32 Kwasny-Krochin B, Gluszko P, Undas A. Unfavorably altered fibrin clot properties in patients with active rheumatoid arthritis. Thromb Res 2010; 126 (01) e11-e16
33 Undas A, Szułdrzynski K, Stepien E. et al. Reduced clot permeability and susceptibility to lysis in patients with acute coronary syndrome: effects of inflammation and oxidative stress. Atherosclerosis 2008; 196 (02) 551-557
34 Ząbczyk M, Stachowicz A, Natorska J, Olszanecki R, Wiśniewski JR, Undas A. Plasma fibrin clot proteomics in healthy subjects: relation to clot permeability and lysis time. J Proteomics 2019; 208: 103487
35 Stępniewski J, Kopeć G, Magoń W, Sobczyk D, Musiałek P, Podolec P. Ultrasound‑assisted, catheter‑directed, low‑dose thrombolysis for the treatment of acute intermediate‑high risk pulmonary embolism. Pol Arch Intern Med 2018; 128 (06) 394-395
36 Kopytek M, Zabczyk M, Natorska J. et al. Viscoelastic properties of plasma fibrin clots are similar in patients on rivaroxaban and vitamin K antagonists. J Physiol Pharmacol 2019; 70 (01) 70
37 Białas AJ, Kornicki K, Ciebiada M. et al. Monocyte to large platelet ratio as a diagnostic tool for pulmonary embolism in patients with acute exacerbation of chronic obstructive pulmonary disease. Pol Arch Intern Med 2018; 128 (01) 15-23

Zusatzmaterial

Supplementary Material