Lung transplant anticoagulation strategies

Anticoagulation strategies in the perioperative period for lung transplant

Barac YD, Klapper J, Pollack A, Poisson J, Welsby I, Hartwig M, Bottiger B. Ann Thorac Surg. 2020 Jul;110(1):e23-e25. doi: 10.1016/j.athoracsur.2019.11.056.

• Lung Transplant patients may require anticoagulation at the time of the procedure
• 4-FPCC warfarin reversal has been approved in the US for patients requiring urgent surgery
• Perioperative 4F-PCC anticoagulation reversal of warfarin may be feasible for LTx patients

When lung transplant (LTx) recipients require anticoagulation, increased bleeding can occur during surgery if anticoagulation is not rapidly reversed. Despite this, there is currently no best practice recommendations on which anticoagulant to use for patients requiring urgent transplantation.

Warfarin is considered a less desirable choice because of the worsened outcomes associated with the fresh frozen plasma (FFP) transfusion used for its reversal during LTx (Ong et al. 2014).

Four-factor prothrombin complex concentrates (4-FPCC) can however directly reverse warfarin’s effects without the administration of unnecessary volume. Warfarin reversal with 4F-PCC has also shown greater efficacy in cardiac transplant populations than FFP (Ghadimi et al. 2016).

In this US-based case report, the authors describe a perioperative anticoagulation strategy with warfarin that is reversed prior to incision using 4F-PCC for off-pump LTx patients.

Lung transplant case report

Electronic medical records for 451 adult LTx patients were included in the cohort. During LTx, 4F-PCC was administered upon OR arrival prior to incision, per recommended dose (Beriplex ™ Prescribing Information, 2013). Once the pulmonary artery is clamped, patients were heparinised to maintain an activated clotting time (ACT) of 200-250 for vascular anastomoses. After reperfusion, heparin was reversed with protamine prior to closure.

Figure 1: Inclusion and exclusion criteria with patients receiving off-pump LTx and 4F-PCC for warfarin reversal.

Of the entire cohort, four patients received 25 U/kg 4F-PCC for warfarin reversal prior to incision. Patient one was indicated anticoagulation for pulmonary embolism and all other patients for atrial fibrillation prophylaxis. 72-hr transfusion requirements were comparable to other off-pump lung transplants performed over the same period.

48-72 hours post-transplant, warfarin was restarted once there was no concern for bleeding. After thirty days, patient two had an upper extremity deep vein thrombosis (DVT). However, no other patients experienced thromboembolic events and all patients recovered and were discharged.

Previously, 4F-PCC has been used for warfarin reversal in patients needing urgent non-cardiac surgery with equal efficacy to FFP (Pabinger et al. 2008), for left ventricular assist device (LVAD) impant surgery and in cardiac transplant patients (Barac et al. 2020).

Unfractionated and low molecular weight heparins, warfarin, and direct acting oral anticoagulants are common for anticoagulation in LTx. However, historically these have been difficult to reverse without transfusion.

The 4F-PCC strategy could therefore be useful in LTx patients that are expecting:

• Pulmonary artery clamping
• Right ventricular dysfunction
• Primary graft dysfunction
• Endothelial disruption
• Lymphatic disruption

There is also an advantage to avoiding the unnecessary volume associated with FFP, ease of acquisition and storage, rapid INR correction, lack of need for ABO compatibility, and effective purification.

However, 4F-PCC reversal of warfarin has not been studied in patients who have known underlying risk for thromboembolism or in LTx patients requiring mechanical circulatory support (MCS). In a prospective, randomized controlled trial for PCC reversal of warfarin in acute major bleeding the rate of major thromboembolic events was 9.7% in the 4F-PCC treated group compared to 5% in the plasma treated group (Pabinger et al. 2008).

Barac et al. suggest that the use of 4F-PCC, for the reversal of systemic anticoagulation with warfarin, in the perioperative setting could be feasible for LTx patients. However further research will be needed to determine if benefits of this anticoagulation and reversal strategy outweigh the potential risks of the thromboembolic complications associated with PCC administration in LTx patients.

References

Barac YD, Nevo A, Jawitz O, Hashmi NK, Henkel P, Blue LJ, et al. Prothrombin complex concentrate use in durable and short-term left ventricular assist device implantation. ASAIO J. 2020;66(1):E8–E10.

Beriplex^® [package insert], CSL Behring LLC. 2013. Kankakee, IL www.fda.gov/medwatch. Accessed 13 October 2020.

Ghadimi K, Levy JH, Welsby IJ. Prothrombin Complex Concentrates for Bleeding in the Perioperative Setting. Anesth Analg. 2016;122(5):1287–1300.

Goldstein JN, Refaai MA, Milling TJ, Lewis B, Goldberg-Alberts R, Hug BA, et al. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: A phase 3b, open-label, non-inferiority, randomised trial. Lancet. 2015;385(9982):2077–2087.

Ong LP, Tristan Z, Muse H, Wallace K, Whitehead S, Parry G, et al. Blood transfusion after lung transplantation: impact on early function and survival. Interact Cardiovasc Thorac Surg. 2014;19(suppl 1):S74–S74.

Pabinger I, Brenner B, Kalina U, Knaub S, Nagy A, Ostermann H, et al. Prothrombin complex concentrate (Beriplex^® P/N) for emergency anticoagulation reversal: A prospective multinational clinical trial. J Thromb Haemost. 2008;6(4):622–631.