Factor IX Complex Linked to Disseminated Intravascular Coagulation in Patients with Cirrhosis: A Single Center Experience

Background: Decompensated cirrhosis is associated with both bleeding and thrombotic complications. These patients, especially those undergoing liver transplant evaluations, often receive multiple blood products for correction of coagulopathy prior to invasive procedures or in the setting of acute bleeding. Profilnine SD, a non-activated purified Factor IX Complex containing Factor IX, Factor II, Factor X, and low levels of Factor VII is often used off-label in these patients to promote hemostasis. However, its safety in this clinical setting is not well known.

Aim: To evaluate safety of Factor IX complex use in patients with decompensated liver cirrhosis.

Methods: This is a retrospective study that included all patients who were hospitalized in a tertiary care liver transplant center and received Factor IX complex (Profilnine SD) between November 2011 and October 2013. Demographic, clinical, laboratory, procedural and outcome data were collected from manual review of electronic medical records. The primary endpoint of our study was to determine the safety of Factor IX complex in decompensated cirrhotic patients. Disseminated Intravascular Coagulation (DIC) was diagnosed based upon ISTH criteria and included a constellation of laboratory markers in the appropriate clinical setting. SPSS software was used for data analysis.

Results: 69 doses of Factor IX complex were given to 41 patients with decompensated liver cirrhosis on 43 occasions. Mean age was 53.5 +/- 13.5 years (54% females, 76% Caucasians), weight was 88 +/- 25 kg and mean BMI was 29.8 +/- 7.7. Mean MELD score was 32 +/- 9 and 95% patients had Child Pugh Class C cirrhosis. Median follow up was 43 days (IQR 8, 150). Mean dose of Factor IX complex was 3269 Units +/- 3055 Units. Most common etiologies of liver cirrhosis included alcoholic liver disease (19.5%), Hepatitis C (17%), non-alcoholic fatty liver disease (17%), combined Hepatitis C and alcohol liver disease (24.4%) and others (21.6%). Five patients (12.2%) had Hepatocellular cancer. Common indications for the use of Profilnine included bleeding (33.8%), prior to catheter placement (dialysis or cardiac catheterization, 20.6% ), paracentesis or thoracentesis (13.2%), and others including endoscopic procedures (26.5%). Mean prothrombin time (PT) was 33.4+/- 15.2 s before Factor IX complex infusion as compared 34.9 +/- 32.4 s after Factor IX complex infusion, (p=0.001). Mean pre dose partial thromboplastin time (PTT) was 68.7 +/-33s and mean post dose PTT was 62.7+/- 56.5, (p=0.002). Mean pre dose hemoglobin (Hgb) was 8.2+/- 1.4 gm/dL and post dose Hgb was 7.1+/- 1.3 gm/dL, (p=0.001).

Eight patients (18.6%) developed DIC related complications likely related to Factor IX complex use, based upon clinical and laboratory data. Patients developing DIC complications had received significantly higher doses of Factor IX complex (mean 6601 +/- 4591 units vs. 2507 +/- 1995 units, p= 0.04), had higher MELD score (mean MELD 37 +/- 5.7 vs. 30 +/- 8.2, p = 0.03). Development of complication did not depend upon age, gender, presence of HCC, indication of the procedure, or pre procedure laboratory variables including platelet count, Hemoglobin, PT, PTT or INR. Patients who developed DIC also required more transfusions of platelets (4.4 vs. 1.8, p=0.014), cryoprecipitate (9.6 vs. 2.4, p=0.008) and fresh frozen plasma (12.5 vs. 4.5, p=0.008). Seven out of eight patients who developed DIC died and five of them (62.5%) died within 10 days of Factor IX complex administration. In contrast, out of the 33 patients who did not develop DIC, 7 (21.2%) died within 10 days of receiving Factor IX complex (p=0.02).

Conclusions: DIC is a serious but under-recognized complication of Factor IX complex use in patients with decompensated liver cirrhosis, affecting 18% of patients. Risk increases with higher doses of the Factor IX complex. Thus its use in decompensated liver cirrhosis can lead to serious outcomes, as compared to Factor IX complex use to reverse warfarin overdose in patients with intracranial hemorrhage where it has a better safety profile. Awareness regarding the use of this product in patients with liver failure and its potential for serious side effects should be evaluated further.