Less is More: Low-dose Prothrombin Complex Concentrate Effective in Acute Care Surgery Patients

Abstract

Optimal dosing of prothrombin complex concentrate (PCC) has yet to be defined and varies widely due to concerns of efficacy and thrombosis. We hypothesized a dose of 15 IU/kg actual body weight of a three-factor PCC would effectively correct coagulopathy in acute care surgery patients. Retrospective review of 41 acute care surgery patients who received 15 IU/kg (610%) actual body weight PCC for correction of coagulopathy. Demographics, laboratory results, PCC dose, blood and plasma transfusions, and thrombotic complications were analyzed. We performed subset analyses of trauma patients and those taking warfarin. Mean age was 69 years (18–94 years). Thirty (73%) trauma patients, 8 (20%) emergency surgery patients, 2 (5%) burns, and 1 (2%) non-trauma neurosurgical patient were included. Mean PCC dose was 1305.4 IU (14.2 IU/kg actual body weight). Mean change in INR was 2.52 to 1.42 (p 0.00004). Successful correction (INR <1.5) was seen in 78 per cent. Treatment failures had a higher initial INR (4.3 vs 2.03, p 0.01). Mean plasma transfusion was 1.46 units. Mean blood transfusion was 1.61 units. Patients taking pre-hospital warfarin (n = 29, 71%) had higher initial INR (2.78 vs 1.92, p 0.05) and received more units of plasma (1.93 vs 0.33, p 0.01) than those not taking warfarin. No statistical differences were seen between trauma and nontrauma patients. One thrombotic event occurred. Administration of low-dose PCC, 15 IU/kg actual body weight, effectively corrects coagulopathy in acute care surgery patients regardless of warfarin use, diagnosis or plasma transfusion.

Reversal of Warfarin-Associated Life-Threatening Bleed With an Attenuated Dose of 4-Factor Prothrombin Complex Concentrate

“…Clinical studies evaluating the role of 4F-PCC did not include patient populations at high risk of thromboembolic events. [1][2][3][4][5] It remains unclear if these patients should receive full-dose 4F-PCC on presentation with a life-threatening bleed or need for emergent surgical procedure. This case adds to the literature by demonstrating that an attenuated dose may be effective for the reversal of life-threatening bleeding while minimizing potential for thromboembolic complications in this patient population.…”

“…[1][2][3] Although dosing of 4F-PCC for warfarinassociated bleeding is typically based on international normalized ratio (INR), there are limited reports of using an attenuated dose to achieve hemostasis, which can potentially decrease the incidence of thromboembolic events. [3][4][5]…”

Recent advances in use of fresh frozen plasma, cryoprecipitate, immunoglobulins, and clotting factors for transfusion support in patients with hematologic disease

“…Prothrombin is available in the form of a concentrate of multiple factors, referred to as prothrombin complex concentrate, and it exists in 2 forms: 3-factor PCC (3F-PCC) consisting of Factors II (prothrombin), IX, and X, as well as Protein C and S, and 4-factor PCC (4F-PCC) that also contains Factor VII [115] . Its indication is currently only for urgent reversal of the VKA warfarin in adults with acute major bleeding; however, multiple off-label uses exist including reversal of direct oral anticoagulants in major bleeding or surgery [116 , 117] , treatment of bleeding in congenital deficiencies of any of the coagulation factors found in PCC (the vitamin K-dependent factors), prophylactic usage to reduce perioperative bleeding and reduce transfusion requirements [118] , [119] , [120] , and in traumatic bleeding alongside FFP to correct coagulopathy [121] , [122] , [123] . Clinicaltrials.gov lists multiple ongoing studies investigating PCC for usage in reducing perioperative bleeding [NCT02740335, NCT04244981, NCT03341156] as well as treatment of coagulopathy and bleeding including the prehospital setting [NCT03981484, NCT04019015].…”

Efficacy and safety of four-factor prothrombin complex concentrate fixed, weight-based dosing for reversal of warfarin anticoagulation

“…4F-PCC has the advantage of being infused in lower volumes than FFP and has a better safety profile due to viral inactivation [3]. However, optimal dosing guidelines have yet to be defined [4,5] and currently, there are varying doses (25 or 50 IU/kg) that have been used both in clinical trials and in practice [6][7][8][9]. The generally accepted strategy is the use of a variable dose based on pre-treatment INR and patient body weight; however, recent evidence suggests that a fixed dosing strategy may provide superior hemostatic control [10].…”