Use Of Prothrombin Complex Concentrates In Patients With Hepatic Coagulopathy: A Single Center Retrospective

The National Advisory Committee on Blood and Blood Products (NAC) of Canada (Canadian Blood Services) do not recommend the use of prothrombin complex concentrates (PCC) in patients with liver disease except in selected circumstances. There is a concern about their potential association with thromboembolic events in this patients’ population. The Centre Hospitalier de l’Université de Montréal (CHUM) is a major reference center in hepatology and liver transplantation in Quebec, Canada. PCC have been used in selected patients with liver disease in this center. This study aims to analyze the efficacy and security of this use.

A retrospective study was conducted by reviewing the medical records of all patients with liver disease who received PCC at the CHUM between January 1^st 2009 and December 31^st 2012. During this time period, only 2 four-factor PCCs (Octaplex, Octapharma AG, Switzerland and Beriplex, CSL Behring, USA) were available for use. Adequate dose of PCC was based on NAC recommendations according to the INR (1000 UI for INR <3; 2000 UI for INR 3-5; 3000 UI for INR >5). We collected the INR before and after the administration of PCC and searched for adverse events. Bleeding control was defined by: cessation of bleeding, absence of rebleeding, absence of surgical intervention for hemostasis, and absence of decrease in hemoglobin level 24h post PCC (more than 1g/dL).

A total of 51 patients were included. Median age was 57 (range; 19-90) and 63% were male (32/51). Forty-one patients (80%) had cirrhosis and nine (18%) had acute liver failure. The status of liver disease could not be determined for one patient. Among patients with cirrhosis, 10 were classified as Child-Pugh A (24%), 13 as Child-Pugh B (32%), and 18 as Child-Pugh C (44%). Ten patients were taking warfarin. Twenty-eight patients (55%) received PCC for bleeding and 20 patients (39%) received PCC before an invasive procedure. Adequate dose of PCC was used in 28 patients (55%). Thirty-one patients (61%) had an INR done within 6 hours of PCC administration. Seventeen patients (33%) had an INR done at 30 minutes and 40 patients (78%) at six hours after PCC administration. The INR was corrected to ≤1.3 in 5 patients (10%) and to ≤1.8 in 30 patients (61%). Eight of ten patients (80%) corrected their INR in the Child-Pugh A group, compared to 10 of 13 (77%) in the Child-Pugh B group, 10 of 17 (59%) in the Child-Pugh C group and 2 of 9 (22%) in the acute liver failure group. Significantly less patients with Child-Pugh C cirrhosis and acute hepatic failure corrected their INR to ≤1.8 when compared to patients with Child-Pugh A and B cirrhosis (p=0.02; chi-square test). Control of bleeding was achieved in 32% of patients (9/28) who received PCC for this indication. Of those patients, the bleeding was controlled in 22% of patients (4/18) when the INR was corrected to ≤1.8 and 44% of patients (4/9) when the INR was not corrected to ≤1.8. Three patients (6%) had thromboembolic events after receiving PCC. One had infectious mitral endocarditis and multiple systemic embolisms, one had a portal vein thrombosis three days after splenectomy, and one had a hepatic artery and portal vein thrombosis after liver transplantation but was know to have a mutation of JAK2. Four patients (8%) died within 24 hours of PCC administration but all the deaths were related to an underlying condition.

Our study showed that in patients with hepatic coagulopathy only a minority of bleeding events were controlled by the administration of PCC. This study did not show an association between the correction of INR and the efficacy of PCC to control bleeding. PCC is less effective in patients with Child-Pugh C cirrhosis and acute liver failure. This might be due to deficit in coagulation factors such as factor V and fibrinogen that are not supplemented by PCC. Bleeding associated with hepatic coagulopathy is complex and the role of PCC requires further evaluation in regards to other blood products utilization and interventions. Some thromboembolic events and deaths occurred after PCC administration warranting further studies of these agents in different disorders of hemostasis.

Blais:Leo: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy.