Prevention of Venous Thromboembolism in Microvascular Surgery Patients Using Weight-Based Unfractionated Heparin Infusions

Abstract

Background Unfractionated heparin infusions are commonly used in microvascular surgery to prevent microvascular thrombosis. Previously, fixed-dose heparin infusions were believed to provide sufficient venous thromboembolism (VTE) prophylaxis; however, we now know that this practice is inadequate for the majority of patients. Anti-factor Xa (aFXa) level is a measure of unfractionated heparin efficacy and safety. This study evaluated the pharmacodynamics of weight-based dose heparin infusions and the impacts of real-time aFXa-guided heparin dose adjustments.

Methods This prospective clinical trial enrolled adult microvascular surgery patients who received a weight-based heparin dose following a microsurgical procedure. Steady-state aFXa levels were monitored, and patients with out-of-range levels received dose adjustments. The study outcomes assessed were aFXa levels at a dose of heparin 10 units/kg/hour, time to adequate aFXa level, number of dose adjustments required to reach in-range aFXa levels, and clinically relevant bleeding and VTE at 90 days.

Results Twenty-one patients were prospectively recruited, and usable data were available for twenty patients. Four of twenty patients (20%) had adequate prophylaxis at a heparin dose of 10 units/kg/hour. Among patients who received dose adjustments and achieved in-range aFXa levels, the median number of dose adjustments was 2 and the median weight-based dose was 11 units/kg/hour. The percentage of patients with in-range levels was significantly increased (65 vs. 15%, p = 0.0002) as a result of real-time dose adjustments. The rate of VTE at 90 days was 0%, and clinically relevant bleeding rate at 90 days was 15%.

Conclusion Weight-based heparin infusions at a rate of 10 units/kg/hour provide a detectable level of anticoagulation for some patients following microsurgical procedures, but most patients require dose adjustment to ensure adequate VTE prophylaxis.

Keywords

heparin - plastic surgery - microvascular surgery - venous thromboembolism - anti-factor Xa

Publication History

Received: 11 April 2021

Accepted: 22 June 2021

Article published online:
24 August 2021

• References

• 1 Keyes GR, Singer R, Iverson RE. et al. Analysis of outpatient surgery center safety using an internet-based quality improvement and peer review program. Plast Reconstr Surg 2004; 113 (06) 1760-1770
• 2 Keyes GR, Singer R, Iverson RE. et al. Mortality in outpatient surgery. Plast Reconstr Surg 2008; 122 (01) 245-250
• 3 Pannucci CJ, Bailey SH, Dreszer G. et al. Validation of the Caprini risk assessment model in plastic and reconstructive surgery patients. J Am Coll Surg 2011; 212 (01) 105-112
• 4 Pannucci CJ, Rockwell WB, Ghanem M, Fleming KI, Momeni A, Agarwal J. Inadequate enoxaparin dosing predicts 90-day venous thromboembolism risk among plastic surgery inpatients: an examination of enoxaparin pharmacodynamics. Plast Reconstr Surg 2017; 139 (04) 1009-1020
• 5 Ko A, Harada MY, Barmparas G. et al. Association between enoxaparin dosage adjusted by anti-factor Xa trough level and clinically evident venous thromboembolism after trauma. JAMA Surg 2016; 151 (11) 1006-1013
• 6 Malinoski D, Ewing T, Patel MS. et al. Risk factors for venous thromboembolism in critically ill trauma patients who cannot receive chemical prophylaxis. Injury 2013; 44 (01) 80-85
• 7 Hirsh J, Levine M. Prevention of venous thrombosis in patients undergoing major orthopaedic surgical procedures. Br J Clin Pract Suppl 1989; 65: 02-08
• 8 Swartz JE, Aarts MC, Swart KM. et al. The value of postoperative anticoagulants to improve flap survival in the free radial forearm flap: a systematic review and retrospective multicentre analysis. Clin Otolaryngol 2015; 40 (06) 600-609
• 9 Cigna E, Lo Torto F, Maruccia M. et al. Postoperative care in finger replantation: our case-load and review of the literature. Eur Rev Med Pharmacol Sci 2015; 19 (14) 2552-2561
• 10 Glicksman A, Ferder M, Casale P, Posner J, Kim R, Strauch B. 1457 years of microsurgical experience. Plast Reconstr Surg 1997; 100 (02) 355-363
• 11 Kroll SS, Schusterman MA, Reece GP. et al. Timing of pedicle thrombosis and flap loss after free-tissue transfer. Plast Reconstr Surg 1996; 98 (07) 1230-1233
• 12 Pršić A, Kiwanuka E, Caterson SA, Caterson EJ. Anticoagulants and statins as pharmacological agents in free flap surgery: current rationale. Eplasty 2015; 15: e51
• 13 Cannady SB, Hatten K, Wax MK. Postoperative controversies in the management of free flap surgery in the head and neck. Facial Plast Surg Clin North Am 2016; 24 (03) 309-314
• 14 Bertolaccini CM, Prazak AMB, Agarwal J, Goodwin IA, Rockwell WB, Pannucci CJ. Adequacy of fixed dose heparin infusions for venous thromboembolism prevention after microsurgical procedures. J Reconstr Microsurg 2018; 34 (09) 729-734
• 15 Ramanathan R, Gu Z, Limkemann AJ. et al. Association between interruptions in chemical prophylaxis and VTE formation. Am Surg 2015; 81 (07) 732-737
• 16 Sutzko DC, Georgoff PE, Obi AT, Healy MA, Osborne NH. The association of venous thromboembolism chemoprophylaxis timing on venous thromboembolism after major vascular surgery. J Vasc Surg 2018; 67 (01) 262-271.e1
• 17 Pannucci CJ, Prazak AM, Scheefer M. Utility of anti-factor Xa monitoring in surgical patients receiving prophylactic doses of enoxaparin for venous thromboembolism prophylaxis. Am J Surg 2017; 213 (06) 1143-1152
• 18 Lin H, Faraklas I, Cochran A, Saffle J. Enoxaparin and antifactor Xa levels in acute burn patients. J Burn Care Res 2011; 32 (01) 1-5
• 19 Wall V, Fleming KI, Tonna JE. et al. Anti-factor Xa measurements in acute care surgery patients to examine enoxaparin dose. Am J Surg 2018; 216 (02) 222-229
• 20 Clark NP, Delate T, Cleary SJ, Witt DM. Unfractionated heparin (UFH) dosing requirements and monitoring parameters to achieve target antifactor Xa concentration in pregnant women receiving intermediate-dose UFH therapy. Pharmacotherapy 2010; 30 (04) 369-374
• 21 Cheng SS, Nordenholz K, Matero D. et al. Standard subcutaneous dosing of unfractionated heparin for venous thromboembolism prophylaxis in surgical ICU patients leads to subtherapeutic factor Xa inhibition. Intensive Care Med 2012; 38 (04) 642-648
• 22 Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon 2005; 51 (2-3): 70-78
• 23 Chien W, Varvares MA, Hadlock T, Cheney M, Deschler DG. Effects of aspirin and low-dose heparin in head and neck reconstruction using microvascular free flaps. Laryngoscope 2005; 115 (06) 973-976
• 24 Kroll SS, Miller MJ, Reece GP. et al. Anticoagulants and hematomas in free flap surgery. Plast Reconstr Surg 1995; 96 (03) 643-647
• 25 Nikolis A, Tahiri Y, St-Supery V. et al. Intravenous heparin use in digital replantation and revascularization: The Quebec Provincial Replantation program experience. Microsurgery 2011; 31 (06) 421-427
• 26 Pannucci CJ, Fleming KI, Varghese Jr TK. et al. Low anti-Factor Xa level predicts 90-day symptomatic venous thromboembolism in surgical patients receiving enoxaparin prophylaxis: a pooled analysis of eight clinical trials. Ann Surg 2020; . Published online October 19, 2020. DOI: 10.1097/SLA.0000000000004589.
• 27 Shepherd MF, Rosborough TK, Schwartz ML. Unfractionated heparin prophylaxis in high risk gastric surgery patients. Obes Surg 2004; 14 (05) 601-605
• 28 Whitman-Purves E, Coons JC, Miller T. et al. Performance of anti-factor Xa versus activated partial thromboplastin time for heparin monitoring using multiple nomograms. Clin Appl Thromb Hemost 2018; 24 (02) 310-316
• 29 Nelson JA, Chung CU, Bauder AR, Wu LC. Prevention of thrombosis in hypercoagulable patients undergoing microsurgery: a novel anticoagulation protocol. J Plast Reconstr Aesthet Surg 2017; 70 (03) 307-312