Prothrombin Complex Concentrates for Coagulopathy in Liver Disease: Single‐Center, Clinical Experience in 105 Patients

Abstract

Patients with liver disease frequently develop coagulopathy, and fresh frozen plasma is traditionally used for correction of coagulopathy to manage and prevent bleeding. Prothrombin complex concentrates (PCCs) offer an attractive alternative because they are more readily available and avoid large‐volume transfusion. This retrospective, single‐center study reviewed clinical use of PCC in patients with acute/chronic liver disease. A total of 105 patients with 194 episodes of PCC administration were reviewed. Data pertaining to indication, dosing, effectiveness, and safety were collected. The effect of PCC on coagulation was analyzed in patients for whom coagulation results were available 7 hours before and after PCC. Data on thromboembolic events and mortality within 4 weeks of PCC administration were captured. Most patients (77%) had chronic liver disease; the remainder had acute liver failure. Indications for PCC were preprocedure prophylaxis and treatment for active/recent bleeding in 48% and 52% of 194 treatment episodes, respectively. The median dose of PCC administered was 22 IU/kg (interquartile range, 16‐29 IU/kg). Before PCC administration, 45% of patients had an international normalized ratio (INR) greater than 2.0, and 36% had fibrinogen levels of at least 1.5 g/L. PCC produced statistically significant reductions in prothrombin time and INR (coadministration with fibrinogen or cryoprecipitate: 3.1 versus 1.9; P < 0.001; no coadministration: 2.3 versus 1.8; P < 0.001). Three patients with multiple risk factors developed thrombotic events (hepatic artery thrombosis, incidental bilateral pulmonary embolism, nonocclusive portal vein thrombosis); there were no cardiovascular or cerebrovascular adverse events. Overall, 46 patients died of causes unrelated to PCC treatment. Conclusion: In patients with liver disease, PCC therapy was effective in improving coagulation test results without an excess of thrombotic events. Further assessment of PCC as hemostatic therapy in this setting is required.

Impaired platelet‐dependent thrombin generation associated with thrombocytopenia is improved by prothrombin complex concentrates in vitro

“…A study in liver transplant patients with prolonged INR confirmed that PCC can effectively restore thrombin generation, but noted that the required doses of PCC are lower than for warfarin reversal, likely as a result of slow thrombin inhibition . A recent study confirmed the efficacy of PCC in patients with liver disease, without an excess of thrombotic events, and also observed lower dosing with PCC compared to anticoagulant reversal . Additionally, this study did not evaluate interactions with other hemostatic modalities, such as desmopressin and antifibrinolytics, and therefore may not fully reflect the multifaceted treatments that patients with thrombocytopenia may receive in clinical practice …”

“…32 A recent study confirmed the efficacy of PCC in patients with liver disease, without an excess of thrombotic events, and also observed lower dosing with PCC compared to anticoagulant reversal. 33 Additionally, this study did not evaluate interactions with other hemostatic modalities, such as desmopressin and antifibrinolytics, and therefore may not fully reflect the multifaceted treatments that patients with thrombocytopenia may receive in clinical practice. 34 In contrast to our ex vivo studies of spiking with PCCs, the increases in the levels of clotting factors in patients, after administration of PCCs, are variable due to redistribution of the factors to extravascular compartments, which affect the recovery and half-life.…”

Coagulation abnormalities, bleeding, thrombosis, and management of patients with acute liver failure in Australia and New Zealand

“…PCC use was relatively uncommon in our study. In two small single center studies that evaluated a combined total of 33 ALF patients, PCC administration was shown to improve hemostatic parameters with a low incidence of thrombotic complications. Given the theoretical prothrombotic risks of PCC and the limited data on safety for use in ALF, further evaluation is warranted .…”

Prothrombin Complex Concentrate in Liver Transplant Surgery: Correction of Therapeutic Anticoagulation and the Coagulopathy of End-Stage Liver Disease: Case Series

“…Fresh frozen plasma (FFP) or prothrombin complex concentrates (PCC) as treatment for active bleeding or in preparation for invasive procedure have been described for patients with ESLD not receiving anticoagulation. However, the recommended correction of therapeutic anticoagulation in the ever-more-common anticoagulated patient with ESLD undergoing liver transplantation is not well-described in literature and is varied and physician-dependent in practice (Drebes et al, 2019) as is observed in this case series from our leading transplant center.…”

“…PCC is easily reconstituted from the lyophilized form and requires no blood group specificity (Cappabiana et al, 2016). PCC likely does not increase the risk of thromboses, and has lower risk of viral transmission and volume overload than FFP (Bezinover et al, 2018;Drebes et al, 2019). Dosing is typically based on INR, however fixed-dosing strategies have been investigated (Leissinger et al, 2008;Dane et al, 2019).…”