Top

Published in:

22-12-2022 | Warfarin | Research

Utility of the Total Thrombus-Formation Analysis System as a Tool for Evaluating Thrombogenicity and Monitoring Antithrombotic Therapy in Pediatric Fontan Patients

Authors: Osamu Matsuo, Masanobu Ishii, Koichi Kaikita, Jun Morinaga, Fumiya Miyamura, Shiro Matsumoto, Kenichi Tsujita, Kimitoshi Nakamura

Published in: Pediatric Cardiology | Issue 5/2023

Abstract

Background

There is no consensus regarding thromboprophylaxis after Fontan procedure, and novel tools to assess thrombogenicity are needed to establish optimal thromboprophylaxis. The Total Thrombus-formation Analysis System (T-TAS) was developed for the quantitative analysis of thrombus formation using microchips with thrombogenic surfaces. This prospective study evaluated the utility of T-TAS in the assessment of thrombogenicity in pediatric Fontan patients.

Methods and Results

The participants included 20 consecutive Fontan patients who underwent cardiac catheterization and 30 healthy controls. Blood samples collected without and with antithrombotic therapy (aspirin or aspirin and warfarin) were used for T-TAS to compute the area under the curve (AUC) in the atheroma (AR₁₀-AUC₃₀) and platelet (PL₁₈-AUC₁₀) chips. A higher AUC indicates higher thrombogenicity.

T-TAS values showed that patients in the Fontan group without antithrombotic therapy had lower thrombogenicity than those in the control group [PL₁₈-AUC₁₀, median (interquartile range) 356 (313–394) vs. 408 (392–424); AR₁₀-AUC₃₀, median (interquartile range) 1270 (1178–1351) vs. 1382 (1338–1421)]. Aspirin and warfarin therapies significantly decreased PL₁₈-AUC₁₀ and AR₁₀-AUC₃₀, respectively, compared with those of patients without antithrombotic therapy (P < 0.001 for each comparison). Subgroup analysis divided by low (< 9 mmHg) or high (≥ 9 mmHg) central venous pressure (CVP) showed that CVP affects the reduction in AR₁₀-AUC₃₀ with antithrombotic therapy.

Conclusions

T-TAS may be a useful tool for monitoring thrombogenicity and antithrombotic therapy in Fontan patients.

Van Den Helm S, Sparks CN, Ignjatovic V, Monagle P, Attard C (2022) Increased risk for thromboembolism after Fontan surgery: considerations for thromboprophylaxis. Front Pediatr 10:803408. https://doi.org/10.3389/fped.2022.803408CrossRefPubMed

Firdouse M, Agarwal A, Chan AK, Mondal T (2014) Thrombosis and thromboembolic complications in Fontan patients: a literature review. Clin Appl Thromb Hemost 20:484–492. https://doi.org/10.1177/1076029613520464CrossRefPubMed

Monagle P, Chan AKC, Goldenberg NA, Ichord RN, Journeycake JM, NowakGöttl U, Vesely SK (2012) Antithrombotic therapy in neonates and children: antithrombotic therapy and prevention of thrombosis, ninth ed: American college of chest physicians evidence-based clinical practice guidelines. Chest 141:e737S-e801S. https://doi.org/10.1378/chest.11-2308CrossRefPubMedPubMedCentral

Stout KK, Daniels CJ, Aboulhosn JA, Bozkurt B, Broberg CS, Colman JM, Crumb SR et al (2019) 2018 AHA/ACC guideline for the management of adults with congenital heart disease: a report of the American college of cardiology/american heart association task force on clinical practice guidelines. Circulation 139:e698–e800. https://doi.org/10.1161/CIR.0000000000000603CrossRefPubMed

Monagle P, Cochrane A, Roberts R, Manlhiot C, Weintraub R, Szechtman B, Hughes M, Andrew M, Mccrindle BW (2011) Fontan anticoagulation study group, a multicenter, randomized trial comparing heparin/warfarin and acetylsalicylic acid as primary thromboprophylaxis for 2 years after the Fontan procedure in children. J Am Coll Cardiol 58:645–651. https://doi.org/10.1016/j.jacc.2011.01.061CrossRefPubMed

Ohuchi H, Yasuda K, Miyazaki A, Ono S, Hayama Y, Negishi J, Noritake K et al (2015) Prevalence and predictors of haemostatic complications in 412 Fontan patients: their relation to anticoagulation and haemodynamics. Eur J Cardiothorac Surg 47:511–519. https://doi.org/10.1093/ejcts/ezu145CrossRefPubMed

Jahangiri M, Kreutzer J, Zurakowski D, Bacha E, Jonas RA (2000) Evaluation of hemostatic and coagulation factor abnormalities in patients undergoing the Fontan operation. J Thorac Cardiovasc Surg 120:778–782. https://doi.org/10.1067/mtc.2000.108903CrossRefPubMed

Chaloupecký V, Svobodová I, Hadaćová I, Tomek V, Hučín B, Tláskal T, Janoušek J et al (2005) Coagulation profile and liver function in 102 patients after total cavopulmonary connection at mid term follow up. Heart 91:73–79. https://doi.org/10.1136/hrt.2003.026419CrossRefPubMedPubMedCentral

Odegard KC, McGowan FX, Zurakowski D, DiNardo JA, Castro RA, del Nido PJ, Laussen PC (2002) Coagulation factor abnormalities in patients with single-ventricle physiology immediately prior to the Fontan procedure. Ann Thorac Surg 73:1770–1777. https://doi.org/10.1016/S0003-4975(02)03580-4CrossRefPubMed

10.

Idorn L, Jensen AS, Juul K, Reimers JI, Johansson PI, Sørensen KE, Ostrowski SR et al (2013) Thromboembolic complications in Fontan patients: population-based prevalence and exploration of the etiology. Pediatr Cardiol 34:262–272. https://doi.org/10.1007/s00246-012-0431-4CrossRefPubMed

11.

Hosokawa K, Ohnishi T, Kondo T, Fukasawa M, Koide T, Maruyama I, Tanaka KA (2011) A novel automated microchip flow-chamber system to quantitatively evaluate thrombus formation and antithrombotic agents under blood flow conditions. J Thromb Haemost 9:2029–2037. https://doi.org/10.1111/j.1538-7836.2011.04464.xCrossRefPubMed

12.

Kaikita K, Hosokawa K, Dahlen JR, Tsujita K (2019) Total Thrombus-Formation Analysis System (T-TAS): clinical application of quantitative analysis of thrombus formation in cardiovascular disease. Thromb Haemost 119:1554–1562. https://doi.org/10.1055/s-0039-1693411CrossRefPubMed

13.

Sikora J, Karczmarska-Wódzka A, Bugieda J, Sobczak P (2021) The use of total thrombus formation analysis system as a tool to assess platelet function in bleeding and thrombosis risk-a systematic review. Int J Mol Sci 22:8605. https://doi.org/10.3390/ijms22168605CrossRefPubMedPubMedCentral

14.

Ito M, Kaikita K, Sueta D, Ishii M, Oimatsu Y, Arima Y, Iwashita S et al (2016) Total Thrombus-Formation Analysis System (T-TAS) can predict periprocedural bleeding events in patients undergoing catheter ablation for atrial fibrillation. J Am Heart Assoc 5:e002744. https://doi.org/10.1161/JAHA.115.002744CrossRefPubMedPubMedCentral

15.

Ishii M, Kaikita K, Ito M, Sueta D, Arima Y, Takashio S, Izumiya Y et al (2017) Direct oral anticoagulants form thrombus different from warfarin in a microchip flow chamber system. Sci Rep 7:7399. https://doi.org/10.1038/s41598-017-07939-6CrossRefPubMedPubMedCentral

16.

Kajimoto H, Nakazawa M, Murasaki K, Hagiwara N, Nakanishi T (2009) Increased P-selectin expression on platelets and decreased plasma thrombomodulin in Fontan patients. Circ J 73:1705–1710. https://doi.org/10.1253/circj.CJ-08-1087CrossRefPubMed

17.

Tomkiewicz-Pajak L, Hoffman P, Trojnarska O, Lipczyńska M, Podolec P, Undas A (2014) Abnormalities in blood coagulation, fibrinolysis, and platelet activation in adult patients after the Fontan procedure. J Thorac Cardiovasc Surg 147:1284–1290. https://doi.org/10.1016/j.jtcvs.2013.06.011CrossRefPubMed

18.

Hosokawa K, Ohnishi T, Sameshima H, Miura N, Ito T, Koide T, Maruyama I (2013) Analysing responses to aspirin and clopidogrel by measuring platelet thrombus formation under arterial flow conditions. Thromb Haemost 109:102–111. https://doi.org/10.1160/TH12-06-0441CrossRefPubMed

19.

Nakajima Y, Nogami K, Yada K, Kawamura T, Ogiwara K, Furukawa S, Shimonishi N et al (2020) Evaluation of clinical severity in patients with type 2N von Willebrand disease using microchip-based flow-chamber system. Int J Hematol 111:369–377. https://doi.org/10.1007/s12185-019-02782-zCrossRefPubMed

20.

Nakajima Y, Yada K, Ogiwara K, Furukawa S, Shimonishi N, Shima M, Nogami K (2021) A microchip flow-chamber assay screens congenital primary hemostasis disorders. Pediatr Int 63:160–167. https://doi.org/10.1111/ped.14378CrossRefPubMed

21.

Takashio S, Kaikita K, Nishi M, Morioka M, Higo T, Shiose A, Doman T et al (2020) Detection of acquired von Willebrand syndrome after ventricular assist device by total thrombus-formation analysis system. ESC Heart Fail 7:3235–3239. https://doi.org/10.1002/ehf2.12824CrossRefPubMedPubMedCentral

22.

Raffini L, Schwed A, Zheng XL, Tanzer M, Nicolson S, Gaynor JW, Jobes D (2009) Thromboelastography of patients after Fontan compared with healthy children. Pediatr Cardiol 30:771–776. https://doi.org/10.1007/s00246-009-9434-1CrossRefPubMedPubMedCentral

23.

Oda Y, Ito T, Yamada Y, Koga T, Nagasato T, Ohnishi-Wada T, Hosokawa K et al (2021) Cardiovascular risk factors are associated with augmented thrombogenicity in healthy individuals: analysis using the total thrombus-formation analysis system. Thromb J 19:88. https://doi.org/10.1186/s12959-021-00341-3CrossRefPubMedPubMedCentral

24.

Yamaguchi Y, Moriki T, Igari A, Matsubara Y, Ohnishi T, Hosokawa K, Murata M (2013) Studies of a microchip flow-chamber system to characterize whole blood thrombogenicity in healthy individuals. Thromb Res 132:263–270. https://doi.org/10.1016/j.thromres.2013.05.026CrossRefPubMed

25.

Ohuchi H, Ono S, Tanabe Y, Fujimoto K, Yagi H, Sakaguchi H, Miyazaki A, Yamada O (2012) Long-term serial aerobic exercise capacity and hemodynamic properties in clinically and hemodynamically good, “excellent.” Fontan survivors Circ J 76:195–203. https://doi.org/10.1253/circj.CJ-11-0540CrossRefPubMed

26.

Tomkiewicz-Pajak L, Wojcik T, Chłopicki S, Olszowska M, Pajak J, Podolec J, Sitek B et al (2015) Aspirin resistance in adult patients after Fontan surgery. Int J Cardiol 181:19–26. https://doi.org/10.1016/j.ijcard.2014.11.219CrossRefPubMed

27.

Patregnani J, Klugman D, Zurakowski D, Sinha P, Freishtat R, Berger J, Diab Y (2016) High on aspirin platelet reactivity in pediatric patients undergoing the Fontan procedure. Circulation 134:1303–1305. https://doi.org/10.1161/CIRCULATIONAHA.116.023457CrossRefPubMedPubMedCentral

28.

Pina LM, Dong X, Zhang L, Samtani MN, Michelson AD, Justino H, Bonnet D et al (2019) Rivaroxaban, a direct Factor Xa inhibitor, versus acetylsalicylic acid as thromboprophylaxis in children post-Fontan procedure: rationale and design of a prospective, randomized trial (the UNIVERSE study). Am Heart J 213:97–104. https://doi.org/10.1016/j.ahj.2019.04.009CrossRefPubMed

29.

Rychik J, Dodds KM, Goldberg D, Glatz AC, Fogel M, Rossano J, Chen J et al (2020) Protein losing enteropathy after Fontan operation: glimpses of clarity through the lifting fog. World J Pediatr Congenit Heart Surg 11:92–96. https://doi.org/10.1177/2150135119890555CrossRefPubMed

30.

Coon PD, Rychik J, Novello RT, Ro PS, Gaynor JW, Spray TL (2001) Thrombus formation after the Fontan operation. Ann Thorac Surg 71:1990–1994. https://doi.org/10.1016/S0003-4975(01)02472-9CrossRefPubMed

31.

Emamaullee J, Zaidi AN, Schiano T, Kahn J, Valentino PL, Hofer RE, Taner T et al (2020) Fontan-associated liver disease: screening, management, and transplant considerations. Circulation 142:591–604. https://doi.org/10.1161/CIRCULATIONAHA.120.045597CrossRefPubMedPubMedCentral

Title: Utility of the Total Thrombus-Formation Analysis System as a Tool for Evaluating Thrombogenicity and Monitoring Antithrombotic Therapy in Pediatric Fontan Patients
Authors: Osamu Matsuo
Masanobu Ishii
Koichi Kaikita
Jun Morinaga
Fumiya Miyamura
Shiro Matsumoto
Kenichi Tsujita
Kimitoshi Nakamura
Publication date: 22-12-2022
Publisher: Springer US
Keyword: Warfarin
Published in: Pediatric Cardiology / Issue 5/2023
Print ISSN: 0172-0643
Electronic ISSN: 1432-1971
DOI: https://doi.org/10.1007/s00246-022-03076-8

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

At a glance: The STEP trials

Springer Medicine

Utility of the Total Thrombus-Formation Analysis System as a Tool for Evaluating Thrombogenicity and Monitoring Antithrombotic Therapy in Pediatric Fontan Patients

Abstract

Background

Methods and Results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods and Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 5/2023

Vortex Formation Time is a Novel Measure for Early Detection of Diastolic Abnormalities in Adolescents with Hypertension

Prenatal Congenital Heart Disease—It Takes a Multidisciplinary Village

Safety and Feasibility of Skin-to-Skin Contact in the Delivery Room for High-Risk Cardiac Neonates

Ventricular Functional Analysis in Congenital Complete Heart Block Using Speckle Tracking: Left Ventricular Epicardial Compared to Right Ventricular Septal Pacing

Initial Counseling Prior to Palliation for Hypoplastic Left Heart Syndrome: 2021 vs 2011

Implantable Loop Recorder with Long Sensing Vector: Safety, Acceptability, and Sensing Performance in Pediatric Patients

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page