Acquired Factor XI Deficiency Associated with Chronic Hepatitis C in Patients with Inherited Bleeding Disorders.
Authors: Rangarajan Savita , Moore Gary , Sunner Tony , Boast Katie , Savidge Geoffrey 
Published: April 2020

Abstract
In the past many patients with inherited bleeding disorders contracted hepatitis C infection from the use of untreated plasma products leading to chronic liver disease. FVII, because of its short half-life has traditionally been used as a sensitive marker for subtle liver damage. In this study we measured Factors II, V, VII, X and XI in a cohort of 25 haemophilia patients who had longstanding hepatitis C infection in order to assess the effects of liver damage on these coagulation factors. The table below shows the number of patients with deficiencies of the measured factors together with the median levels in deficient patients. Also shown are the medians levels in cirrhotic and non cirrhotic patients.
Frequencies of acquired factor deficiencies and median values Factor (Ref Range) FII (78–117)iu/dl FV (66–114)u/dl FVII (82–179)iu/dl FX (87–145)iu/dl FXI (76–136)u/dl Total patients = 25 Number of patients with deficiency 5/25 3/25 8/25 9/25 16/25 Median value in deficient patients(range) 52.6iu/dl (25.3–86.6)) 50.2u/dl (39.9–51.7) 60.6iu/dl (18.1–65.5) 73.5iu/dl (33.2–82) 52.2u/dl (20.5–68.9) Median value for cirrhotics(range) 52.6iu/dl (25.3–86.6) 51.7u/dl (39.9–76.3) 60iu/dl (18.1–65.5) 61.7iu/dl (33.2–73.5) 36.1u/dl (20.5–63.3) Median value for non cirrhotics(range) 89.6iu/dl (74.6–118.27) 118.2u/dl (84.9–174.3) 100.4iu/dl (49.5–150.3) 99.1iu/dl (78–146.8) 66.7u/dl (30.8–127)
This data demonstrates that an acquired deficiency of FXI is much more common and severe than the other coagulation factors. 16 patients had low FXI levels compared to only 8 patients with low FVII. 5/25 patients had evidence of cirrhosis (median FVII-60iu/dl; median FXI-36.1u/dl). In the non-cirrhotic group, only 3 patients had low FVII compared to 11 patients with low FXI. 15/25 patients were non-cirrhotic with persistent hepatitis C viraemia (median FVII-100.4iu/dl; median FXI-66.7u/dl). 5/25 had cleared the hepatitis C virus after treatment with combination therapy with interferon and ribavarin with only one patient with persistently low FXI level (median FVII-112.9iu/dl; median XI-88.2u/dl). Our data suggests that low FXI levels have a greater discriminatory value for liver damage and possibly for liver regeneration after successful treatment for hepatitis C. This deficiency is a quantitative defect as the functional levels of FXI correlated with FXI antigen levels. Factor XI deficiency causes variable bleeding symptoms which are not predictable by the degree of deficiency. In contrast, deficiencies of Factors II, V, VII, X need to be severely reduced before bleeding symptoms are experienced. In the context of patients with inherited bleeding disorders the presence of an additional, acquired factor XI deficiency may have an impact on the severity of bleeding symptoms and patient management. This may be evidenced by breakthrough bleeding episodes on adequate prophylaxis or protracted resolution of a bleeding episode despite appropriate treatment with Factor VIII or IX concentrates. Increasing the dose of Factor VIII or IX concentrates may only partially resolve the bleeding episode but has significant impact on the cost of care for these patients. It is therefore crucial to be aware of the need to measure and monitor FXI levels in patients with haemophilia and hepatitis C. In these circumstances replacement of factor XI may need to be considered.