Impact of antithrombin III and enoxaparin dosage adjustment on prophylactic anti-Xa concentrations in trauma patients at high risk for venous thromboembolism: a randomized pilot trial

Journal of Thrombosis and Thrombolysis - Tập 52 - Trang 1117-1128 - 2021
Molly Elizabeth Droege1,2, Christopher Allen Droege1,2, Carolyn Dosen Philpott1,2, Megan Leslie Webb1,3, Neil Edward Ernst1,2, Krishna Athota4, Devin Wakefield4, Joseph Richard Dowd4, Dina Gomaa4, Bryce H. R. Robinson4,5, Dennis Hanseman4, Joel Elterman4,6, Eric William Mueller1,2
1UC Health - University of Cincinnati Medical Center, Cincinnati, USA
2University of Cincinnati James L. Winkle College of Pharmacy, Cincinnati, USA
3Baptist Health Louisville, Louisville, USA
4Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, USA
5Department of Surgery, Harborview Medical Center, School of Medicine, University of Washington, Seattle, Washington, USA
6UCHealth - University of Colorado, Loveland, USA

Tóm tắt

The impact of antithrombin III activity (AT-III) on prophylactic enoxaparin anti-factor Xa concentration (anti-Xa) is unknown in high-risk trauma patients. So too is the optimal anti-Xa-adjusted enoxaparin dosage. This prospective, randomized, pilot study sought to explore the association between AT-III and anti-Xa goal attainment and to preliminarily evaluate two enoxaparin dosage adjustment strategies in patients with subprophylactic anti-Xa. Adult trauma patients with Risk Assessment Profile (RAP) ≥ 5 prescribed enoxaparin 30 mg subcutaneously every 12 h were eligible. AT-III and anti-Xa were drawn 8 h after the third enoxaparin dose and compared between patients with anti-Xa ≥ 0.1 IU/mL (goal; control group) or anti-Xa < 0.1 IU/mL (subprophylactic; intervention group). The primary outcome was difference in baseline AT-III. Subsequently, intervention group patients underwent 1:1 randomization to either enoxaparin 40 mg every 12 h (up to 50 mg every 12 h if repeat anti-Xa < 0.1 IU/mL) (enox12) or enoxaparin 30 mg every 8 h (enox8) with repeat anti-Xa assessments. The proportion of patients achieving goal anti-Xa after dosage adjustment were compared. A total of 103 patients were included. Anti-Xa was subprophylactic in 50.5%. Baseline AT-III (median [IQR]) was 87% [80–98%] in control patients versus 82% [71–96%] in intervention patients (p = 0.092). Goal trough anti-Xa was achieved on first assessment in 38.1% enox12 versus 50% enox8 patients (p = 0.67), 84.6% versus 53.3% on second assessment (p = 0.11), and 100% vs. 54.5% on third trough assessment (p = 0.045). AT-III activity did not differ between high-risk trauma patients with goal and subprophylactic enoxaparin anti-Xa concentrations, although future investigation is warranted. Enoxaparin dose adjustment rather than frequency adjustment may be associated with a higher proportion of patients achieving goal anti-Xa over time.

Tài liệu tham khảo

Byrne JP, Geerts W, Mason SA et al (2017) Effectiveness of low-molecular-weight heparin versus unfractionated heparin to prevent pulmonary embolism following major trauma: a propensity-matched analysis. J Trauma Acute Care Surg 82:252–262 Jacobs BN, Cain-Neilson AH, Jakubus JL et al (2017) Unfractionated heparin versus low-molecular-weight heparin for venous thromboembolism prophylaxis in trauma. J Trauma Acute Care Surg 83:151–158 Geerts WH, Jay RM, Code KI et al (1996) A comparison of low-dose heparin with low-molecular-weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med 335:701–707 Knudson MM, Morabito D, Paiement GD, Shakleford S (1996) Use of low molecular weight heparin in preventing thromboembolism in trauma patients. J Trauma 41:446–459 Velhamos GC, Nigro J, Tatevossiam R et al (1998) Inability of an aggressive policy of thromboprophylaxis to prevent deep venous thrombosis (DVT) in critically injured patients: are current methods of DVT prophylaxis insufficient? J Am Coll Surg 187:529–533 Cothren CC, Smith WR, Moore EE, Morgan SJ (2007) Utility of once-daily dose of low-molecular-weight heparin to prevent venous thromboembolism in multisystem trauma patients. World J Surg 31:98–104 Arnold JD, Dart BW, Barker DE et al (2010) Unfractionated heparin three times a day versus enoxaparin in the prevention of deep venous thrombosis in trauma patients. Am Surg. 76(6):563–70 Falck-Ytter Y, Francis CW, Johanson NA et al (2012) Prevention of VTE in Orthopedic Surgery Patients Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 141(2):e278S-325S Gould MK, Garcia DA, Wren SM et al (2012) Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141(2 (Suppl)):e227S – e277 Rogers FB, Cipolle MD, Velmahos G, Rozycki G, Luchette FA (2002) Practice management guidelines for the prevention of venous thromboembolism in trauma patients: The EAST practice management guidelines work group. J Trauma 53(1):142–164 Bush S, LeClaire A, Hampp C, Lottenberg L (2011) Once- versus twice-daily enoxaparin for venous thromboembolism prophylaxis in high-risk trauma patients. J Intensive Care Med 26(2):111–115 Norwood SH, McAuley CE, Berne JD et al (2001) A potentially expanded role for enoxaparin in preventing venous thromboembolism in high risk blunt trauma patients. J Am Coll Surg 192:161–167 Devlin JW, Tyburski JG, Moed B (2001) Implementation and evaluation of guidelines for use of enoxaparin as deep vein thrombosis prophylaxis after major trauma. Pharmacotherapy 21(6):740–747 Om SP, Oswanski MF, Joseph RJ et al (2007) Venous thromboembolism in trauma patients. Am Surg 73:1173–1180 Knudson MM, Ikossi DG, Khaw L, Morabito D, Speetzen LS (2004) Thromboembolism after trauma: an analysis of 1602 episodes from the American College of Surgeons National Trauma Data Bank. Ann Surg 240(3):490–498 Malinoski D, Jafari F, Ewing T et al (2010) Standard prophylactic enoxaparin dosing leads to inadequate anti-Xa levels and increased deep venous thrombosis rates in critically ill trauma and surgical patients. J Trauma 68(4):874–880 Constantini TW, Min E, Box K et al (2013) Dose adjusting enoxaparin is necessary to achieve adequate venous thromboembolism prophylaxis in trauma patients. J Trauma Acute Care Surg 74(1):128–133 Kopelman TR, O’Neill PJ, Pieri PG et al (2013) Alternative dosing of prophylactic enoxaparin in the trauma patient: is more the answer? Am Journal Surg 206:911–916 Nunez JM, Becher RD, Rebo GJ et al (2015) Prospective evaluation of weight-based prophylactic enoxaparin dosing in critically ill trauma patients: adequacy of antiXa levels is improved. Am Surg 81:605–609 Rostas JW, Brevard SB, Ahmed N et al (2015) Standard dosing of enoxaparin for venous thromboembolism prophylaxis is not sufficient for most patients within a trauma intensive care unit. Am Surg 81:889–892 Berndtson AE, Constantini TW, Lane J, Box K, Coimbra R (2016) If some is good, more is better: an enoxaparin dosing strategy to improve pharmacologic venous thromboembolism prophylaxis. J Trauma Acute Care Surg 81:1095–1100 Ko A, Harada MY, Barmpara G et al (2016) Association between enoxaparin dosage adjusted by anti-factor Xa through level and clinically evident venous thromboembolism after trauma. JAMA Surg 151(11):1006–1013 Chapman SA, Irwin ED, Reicks P, Beilman GJ (2016) Non-weight-based enoxaparin dosing subtherapeutic in trauma patients. J Surg Res 201:181–187 Singer GA, Riggi G, Karcutskie CA et al (2016) Anti-Xa-guided enoxaparin thromboprophylaxis reduces rate of deep venous thromboembolism in high-risk trauma patients. J Trauma Acute Care Surg 81:1101–1108 Karcutskie CA, Dharmaraja A, Patel J et al (2017) Relation of antifactor-Xa peak levels and venous thromboembolism after trauma. J Trauma Acute Care Surg 83:1102–1107 Karcutskie CA, Dharmaraja A, Patel J et al (2018) Association of anti-factor Xa-guided dosing of enoxaparin with venous thromboembolism after trauma. JAMA Surg 153(2):144–149 Kopelman TR, Walters JW, Bogert JN et al (2017) Goal directed enoxaparin dosing provides superior chemoprophylaxis against deep vein thrombosis. Injury 48:1088–1092 Dhillon NK, Smith EJT, Gillette E et al (2018) Trauma patients with lower extremity and pelvic fractures: should anti-factor Xa trough level guide prophylactic enoxaparin dose? Int J Surg 51:128–132 Kay AB, Majercik S, Sorensen J et al (2018) Weight-based enoxaparin dosing and deep vein thrombosis in hospitalized trauma patients: a double-blind, randomized, pilot study. Surgery 164(1):144–149 Imran JB, Madni TD, Clark AT et al (2018) Inability to predict subprophylactic anti-factor Xa levels in trauma patients receiving early low-molecular-weight heparin. J Trauma Acute Care Surg 85:867–872 Bethea A, Adams E, Lucente FC, Samanta D, Chumbe JT (2018) Improving pharmacologic prevention of VTE in trauma: IMPACT-IT QI project. Am Surg 84:1097–1104 Rutherford EJ, Schooler WG, Sredzienski E, Abrams JE, Skeete DA (2005) Optimal dose of enoxaparin in critically ill trauma and surgical patients. J Trauma 58:1167–1170 Droege ME, Mueller EW, Besl KM et al (2014) Effect of a dalteparin prophylaxis protocol using anti-factor Xa concentrations on venous thromboembolism in high-risk trauma patients. J Trauma Acute Care Surg 76:450–456 Haas CE, Nelsen JL, Raghavendran K et al (2005) Pharmacokinetics and pharmacodynamics of enoxaparin in multiple trauma patients. J Trauma 59(6):1336–1343 Liener UC, Bruckner UB, Strecker W et al (2001) Trauma severity-dependent changes in AT-III activity. Shock 15(5):344–347 Miller RS, Weatherford DA, Stein D, Crane MM, Stein M (1994) Antithrombin III and trauma patients: factors that determine low levels. J Trauma 37(3):442–445 Owings JT, Bagley M, Gosselin R, Romac D, Disbrow E (1996) Effect of critical injury on plasma antithrombin activity: low antithrombin levels are associated with thromboembolic complications. J Trauma 41(3):396–405 Floccard B, Rugeri L, Faure A et al (2012) Early coagulopathy in trauma patients: an on-scene and hospital admission study. Injury 43:26–32 Scherer R, Spangenberg P (1998) Procoagulant activity in patients with isolated severe head trauma. Crit Care Med 26(1):149–156 Waydhas C, Nast-Kolb D, Gippner-Steppert C et al (1998) High-dose antithrombin III treatment of severely injured patients: results of a prospective study. J Trauma 45(5):931–940 Wilson RF, Mammen EF, Tyburski JG, Warsow KM, Kubinec SM (1996) Antithrombin levels related to infections and outcome. J Trauma 40(3):384–387 Connelly CR, Van PY, Hart KD et al (2016) Thromboelastograpy-based dosing of enoxaparin for thromboprophylaxis in trauma and surgical patients: a randomized clinical trial. JAMA Surg 151(10):1–8 Louis SG, Van PY, Riha GM et al (2014) Thromboelasogram-guided enoxaparin dosing dose not confer protection from deep venous thrombosis: a randomized controlled pilot trial. J Trauma Acute Care Surg 76(4):937–942 Robinson S, Zincuk A, Larsen UL et al (2013) A comparative study of varying doses of enoxaparin for thromboprophylaxis in critically ill patients: a double-blinded, randomized controlled trial. Crit Care 17:1–8 Greenfield LJ, Proctor MC, Rodriguez JL et al (1997) Posttrauma thromboembolism prophylaxis. J Trauma 42:100–103 Baker JE, Niziolek GM, Elson NC et al (2019) Optimizing lower extremity duplex ultrasound screening after traumatic injuries. J Surg Res 243:143–150 Baker SP, O’Neill B, Haddon W, Long WB (1974) The injury severity score: a method for describing patients with multiple injuries and evaluating emergency care. J Trauma 14(3):187–196 Ley EJ, Brown CV, Moore EE et al (2020) Updated guidelines to reduce venous thromboembolism in trauma patients: a Western Trauma Association Critical Decisions Algorithm. J Trauma Acute Care Surg. 89(5):971