Resonant Acoustic Rheometry to Measure Coagulation Kinetics in Hemophilia A and Healthy Plasma: A Novel Viscoelastic Method

Abstract

Compared with conventional coagulation tests and factor-specific assays, viscoelastic hemostatic assays (VHAs) can provide a more thorough evaluation of clot formation and lysis but have several limitations including clot deformation. In this proof-of-concept study, we test a noncontact technique, termed resonant acoustic rheometry (RAR), for measuring the kinetics of human plasma coagulation. Specifically, RAR utilizes a dual-mode ultrasound technique to induce and detect surface oscillation of blood samples without direct physical contact and measures the resonant frequency of the surface oscillation over time, which is reflective of the viscoelasticity of the sample. Analysis of RAR results of normal plasma allowed defining a set of parameters for quantifying coagulation. RAR detected a flat-line tracing of resonant frequency in hemophilia A plasma that was corrected with the addition of tissue factor. Our RAR results captured the kinetics of plasma coagulation and the newly defined RAR parameters correlated with increasing tissue factor concentration in both healthy and hemophilia A plasma. These findings demonstrate the feasibility of RAR as a novel approach for VHA, providing the foundation for future studies to compare RAR parameters to conventional coagulation tests, factor-specific assays, and VHA parameters.

Keywords

hemophilia A - hemostatic - point of care - thromboelastography - ultrasonic

Publikationsverlauf

Artikel online veröffentlicht:
01. November 2022

• References

• 1 Ramiz S, Hartmann J, Young G, Escobar MA, Chitlur M. Clinical utility of viscoelastic testing (TEG and ROTEM analyzers) in the management of old and new therapies for hemophilia. Am J Hematol 2019; 94 (02) 249-256
• 2 Sørensen B, Ingerslev J. Whole blood clot formation phenotypes in hemophilia A and rare coagulation disorders. Patterns of response to recombinant factor VIIa. J Thromb Haemost 2004; 2 (01) 102-110
• 3 Bolton-Maggs PH. The rare inherited coagulation disorders. Pediatr Blood Cancer 2013; 60 (Suppl 1): S37-S40
• 4 Aghighi S, Riddell A, Lee CA, Brown SA, Tuddenham E, Chowdary P. Global coagulation assays in hemophilia A: a comparison to conventional assays. Res Pract Thromb Haemost 2019; 4 (02) 298-308
• 5 Nogami K. The utility of thromboelastography in inherited and acquired bleeding disorders. Br J Haematol 2016; 174 (04) 503-514
• 6 Yada K, Nogami K, Wakabayashi H, Fay PJ, Shima M. The mild phenotype in severe hemophilia A with Arg1781His mutation is associated with enhanced binding affinity of factor VIII for factor X. Thromb Haemost 2013; 109 (06) 1007-1015
• 7 Dunkley SM, Yang K. The use of combination FEIBA and rFVIIa bypassing therapy, with TEG profiling, in uncontrollable bleeding associated with acquired haemophilia A. Haemophilia 2009; 15 (03) 828-830
• 8 Young G, Blain R, Nakagawa P, Nugent DJ. Individualization of bypassing agent treatment for haemophilic patients with inhibitors utilizing thromboelastography. Haemophilia 2006; 12 (06) 598-604
• 9 Shima M, Matsumoto T, Ogiwara K. New assays for monitoring haemophilia treatment. Haemophilia 2008; 14 (Suppl 3): 83-92
• 10 Fisher C, Mo A, Warrillow S, Smith C, Jones D. Utility of thromboelastography in managing acquired Factor VIII inhibitor associated massive haemorrhage. Anaesth Intensive Care 2013; 41 (06) 799-803
• 11 Qi X, Zhao Y, Li K, Fan L, Hua B. Evaluating and monitoring the efficacy of recombinant activated factor VIIa in patients with haemophilia and inhibitors. Blood Coagul Fibrinolysis 2014; 25 (07) 754-760
• 12 Schneiderman J, Rubin E, Nugent DJ, Young G. Sequential therapy with activated prothrombin complex concentrates and recombinant FVIIa in patients with severe haemophilia and inhibitors: update of our previous experience. Haemophilia 2007; 13 (03) 244-248
• 13 Furukawa S, Nogami K, Ogiwara K, Yada K, Minami H, Shima M. Systematic monitoring of hemostatic management in hemophilia A patients with inhibitor in the perioperative period using rotational thromboelastometry. J Thromb Haemost 2015; 13 (07) 1279-1284
• 14 Pivalizza EG, Escobar MA. Thrombelastography-guided factor VIIa therapy in a surgical patient with severe hemophilia and factor VIII inhibitor. Anesth Analg 2008; 107 (02) 398-401
• 15 Misgav M, Mandelbaum T, Kassif Y, Berkenstadt H, Tamarin I, Kenet G. Thromboelastography during coronary artery bypass grafting surgery of severe hemophilia A patient - the effect of heparin and protamine on factor VIII activity. Blood Coagul Fibrinolysis 2017; 28 (04) 329-333
• 16 Fogarty PF, Mancuso ME, Kasthuri R. et al; Global Emerging Hemophilia Panel (GEHEP). Presentation and management of acute coronary syndromes among adult persons with haemophilia: results of an international, retrospective, 10-year survey. Haemophilia 2015; 21 (05) 589-597
• 17 Moore EE, Moore HB, Kornblith LZ. et al. Trauma-induced coagulopathy. Nat Rev Dis Primers 2021; 7 (01) 30
• 18 Görlinger K, Pérez-Ferrer A, Dirkmann D. et al. The role of evidence-based algorithms for rotational thromboelastometry-guided bleeding management. Korean J Anesthesiol 2019; 72 (04) 297-322
• 19 Hartmann J, Walsh M, Grisoli A. et al. Diagnosis and treatment of trauma-induced coagulopathy by viscoelastography. Semin Thromb Hemost 2020; 46 (02) 134-146
• 20 Görlinger K, Dirkmann D, Hanke AA. Rotational thromboelastometry (ROTEM®). In: Moore HB, Moore EE, Neal MD, eds. Trauma Induced Coagulopathy. 2nd ed. Cham: Springer International Publishing; 2021: 279-312
• 21 Walsh M, Thomas S, Kwaan H. et al. Modern methods for monitoring hemorrhagic resuscitation in the United States: why the delay?. J Trauma Acute Care Surg 2020; 89 (06) 1018-1022
• 22 Hartmann J, Murphy M, Dias JD. Viscoelastic hemostatic assays: moving from the laboratory to the site of care-a review of established and emerging technologies. Diagnostics (Basel) 2020; 10 (02) E118
• 23 Volod O, Bunch CM, Zackariya N. et al. Viscoelastic hemostatic assays: a primer on legacy and new generation devices. J Clin Med 2022; 11 (03) 860
• 24 Speybroeck J, Marsee M, Shariff F. et al. Viscoelastic testing in benign hematologic disorders: clinical perspectives and future implications of point-of-care testing to assess hemostatic competence. Transfusion 2020; 60 (Suppl 6): S101-S121
• 25 Allen TW, Winegar D, Viola F. The Quantra® system and SEER sonorheometry. In: Moore HB, Neal MD, Moore EE, eds. Trauma Induced Coagulopathy. Cham: Springer International Publishing; 2021: 693-704
• 26 Hobson EC, Li W, Juliar BA, Putnam AJ, Stegemann JP, Deng CX. Resonant acoustic rheometry for non-contact characterization of viscoelastic biomaterials. Biomaterials 2021; 269: 120676
• 27 Ranucci M, Laddomada T, Ranucci M, Baryshnikova E. Blood viscosity during coagulation at different shear rates. Physiol Rep 2014; 2 (07) e12065
• 28 Walsh M, Moore EE, Moore HB. et al. Whole Blood, fixed ratio, or goal-directed blood component therapy for the initial resuscitation of severely hemorrhaging trauma patients: a narrative review. J Clin Med 2021; 10 (02) 320
• 29 Mengoli C, Franchini M, Marano G. et al. The use of fibrinogen concentrate for the management of trauma-related bleeding: a systematic review and meta-analysis. Blood Transfus 2017; 15 (04) 318-324
• 30 Ziegler B, Bachler M, Haberfellner H. et al; FIinTIC study group. Efficacy of prehospital administration of fibrinogen concentrate in trauma patients bleeding or presumed to bleed (FIinTIC): a multicentre, double-blind, placebo-controlled, randomised pilot study. Eur J Anaesthesiol 2021; 38 (04) 348-357
• 31 Curry N, Foley C, Wong H. et al. Early fibrinogen concentrate therapy for major haemorrhage in trauma (E-FIT 1): results from a UK multi-centre, randomised, double blind, placebo-controlled pilot trial. Crit Care 2018; 22 (01) 164
• 32 Nascimento B, Callum J, Tien H. et al. Fibrinogen in the initial resuscitation of severe trauma (FiiRST): a randomized feasibility trial. Br J Anaesth 2016; 117 (06) 775-782
• 33 Yamamoto K, Yamaguchi A, Sawano M. et al. Pre-emptive administration of fibrinogen concentrate contributes to improved prognosis in patients with severe trauma. Trauma Surg Acute Care Open 2016; 1 (01) e000037
• 34 Innerhofer P, Fries D, Mittermayr M. et al. Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial. Lancet Haematol 2017; 4 (06) e258-e271
• 35 Winearls J, Wullschleger M, Wake E. et al. Fibrinogen Early In Severe Trauma studY (FEISTY): study protocol for a randomised controlled trial. Trials 2017; 18 (01) 241