Four factor prothrombin complex concentrate for warfarin reversal in patients with left ventricular assist devices

Abstract

Continuous flow left ventricular assist devices (CF-LVAD) require therapeutic anticoagulation which is often interrupted for procedures or bleeding. Prior to the availability of four factor prothrombin complex concentrate (4F-PCC) in the United States, warfarin was held and its effects reversed by vitamin K or fresh frozen plasma. We evaluated the use of 4F-PCC for temporary warfarin reversal in patients with CF-LVADs and assessed outcomes. This analysis is a retrospective study of CF-LVAD patients who received 4F-PCC for warfarin reversal in the setting of bleeding or need for urgent or elective procedures. Primary outcome assessments included feasibility of administration in elective versus emergent situations, safety measured as incidence of thrombotic events, and change in INR after administration. In total, 37 CF-LVAD patients received 49 4F-PCC administrations. The average 4F-PCC dose was 1842 units (range 518-4292 units), or 22 units/kg (range 5.8-58 units/kg). 4F-PCC significantly decreased the mean INR from 2.9 to 1.7 (p < 0.0001) in 47 of 49 administrations; two patients did not have post infusion INR testing. No cases of new confirmed or suspected pump thrombosis, stroke, venous thromboembolism, arterial thrombosis, or myocardial infarction were observed within 30 days of administration of 4F-PCC. 4F-PCC administration for temporary warfarin reversal was demonstrated to be feasible, effective, and, safe in CF-LVAD patients and judged to be 96% effective in patients for whom data were available. We observed no thrombotic events attributed to use of 4F-PCC.

Prothrombin Complex Concentrate Use in Durable and Short-Term Left Ventricular Assist Device Implantation

“…Our study agrees with previous findings on PCC safety of use in cases where warfarin reversal was needed or use due to excessive post-OP bleeding (7)(8)(9). However, in our cohort the patient population that was supported by a short term LVAD was different, they were younger and usually supported due to an acute event thus making them an INTERMACS 1 profile type of patient; while age was not shown to be a risk factor for thrombosis in the literature, INTERMACS 1 patient profile was (10).…”

Clinical utilization of four-factor prothrombin complex concentrate: a retrospective single center study

“…7 Despite its rising popularity, few studies have reported indications and outcomes with use of 4F-PCC, and those that do focus on niche patient populations or specific dosing regimens. [9][10][11] In our study, we describe use of 4F-PCC in the emergency department at a large, suburban academic center to elucidate practice patterns.…”

Clinical protocols for oral anticoagulant reversal during high risk of bleeding for emergency surgical and nonsurgical settings: a narrative review

“… Rapid INR reduction in 55% of the PCC group vs 10% of the FFP group Kerebel, 2012 37 Prospective, randomized, open-label study 59 VKA-associated intracranial hemorrhage 4F-PCC 40 IU.kg -1 of 4F-PCC significantly decreased the INR compared to that of the 25 IU.kg -1 group ( p = 0.001). Demeyere, 2010 55 Prospective, randomized, open-label, clinical study 40 cardiac surgery patients 4F-PCC vs FFP Faster target INR with PCC ( p = 0.007), and less additional dose ( p < 0.001) Burburry 2011 33 Prospective single-arm clinical study 178 presurgical patients under warfarin Vitamin K 94% with INR levels 1.5 or less on the day of surgery Chausson, 2018 41 Pilot clinical study 26 acute ischemic stroke patients 4F-PCC and vitamin K No symptomatic ICH or thrombotic events Pautas, 2011 34 Prospective, observational study 239 elderly hospitalized patients with over-anticoagulation Vitamin K Decrease in INR levels, achieving 2.7 ± 1.3 on Day 1 ( p < .0001) Bhatia, 2010 32 Prospective, observational study 45 proximal hip fracture patients Vitamin K INR levels decreased to 1.5 or less in 2 days (mean, 38 h; range, 15–64 h Rimsans, 2018 42 Prospective, observational study 37 patients with continuous flow left ventricular assistive devices 4F-PCC Efficient reversal, no case of thromboembolism, mean INR from 2.9 to 1.7 (p < 0.0001) …”

“…Prospective, randomized clinical trials show the clinical efficacy of 4-factor PCC in the reversal of warfarin as being superior to that of FFP in patients presenting VKA-related ICH 40 and achieving faster homeostasis in patients needing reversal for surgical interventions. 30 A retrospective observational study demonstrated the efficacy and safety of warfarin reversal using 4-factor PCC and vitamin K in acute ischemic stroke patients before undergoing intravenous thrombolysis; 41 in patients with continuous flow left ventricular assistive devices presenting bleeding or the need for urgent surgery, with no thromboembolic event observed; 42 in patients with intracranial bleeding requiring urgent neurosurgical intervention; 43 and in patients undergoing early orthopedic surgery (within 24 hours) due to hip fractures. 44 In an observational study of 143 patients on warfarin, the use of 4-factor PCC was safe as a reversal agent mainly for bleeding and prior to surgery, with 5 cases of thromboembolic complications.…”