Factors XI and XII are Low in Subjects with Liver Disease IRWIN R. WALKER, MBBS, FRCP(C), FRACP, RUTH A. MILNER, BSc, MIS, MARILYN A. JOHNSTON, ART, CAROL A. RAND, BSc, PETER B. NEAME, MD, FRCP(C), and JACK HIRSH, MD, FRACP, FRCP(C) We prospectively measured levels of factors XI and XII in parallel with other coagulation factors in 39 unselected patients with liver disease and in 20 control subjects. Mean levels of factors XI and XII in subject s with liver disease were significantly reduced, being 58% and 61%,'respectively, compared with 100% and 94% in controls. Reductionsin levels of factors X1 and XII were most pronounced in those subjects with low serum albumin. The partial thromboplastin time (APTT) reflected low levels of either factor XI or XII and was most prolonged when both were low, but 'cause and effect was not demonstrated. Low levels ofthese factors may explain previous reports of poor response of APTT to infusions of prothrombin complex concentrates. Finally, these low levels strongly suggest that factors XI and XII are produced in the liver. The Small amount of information in the literature regarding the levels of factors XI and XII in patients with liver disease is in contrast to the abundant and recent information on other coagulation factors (1). This lack Of information has led to uncertain state- ments regarding the levels of these factors in sub- jects with liver disease and the role of the liver in their production (2, 3). Factor XII was found by Jergens (4) tobe low in Subjects with liVer disease, but this finding has not been confirmed (5). The data regarding factor XI levels in subjects with liver disease is more consistent in showing that some subjects do have low levels (6-8); however, the number of subjects studied is Small and results derived from current methods have not been report- ed. It has also been observed that a prolonged Manuscript received January 4, 1983; revised manuscript received April 29, 1983; accepted June 2,1983. From the Departments of Medicine, Pathology and Clinical Epidemiology and Biostatistics, McMaster University, Hamil- ton, Ontario, Canada. Supported in part by the Department of Laboratories, McMas- ter University Medical Centre. Address for reprint requests: Dr. I. Walker, McMaster Uni- versity Medical Centre, 1200 Main St. West, Hamilton, Ontario, Canada, L8N 3Z5. activated partial thromboplastin time (APTT) in subject s with liver disease respond's poorly to infu- sions of prothrombin complex concentrates (2, 9). This is perhaps due to reduced levels of factors XI and XII in these subjects and the absence of factors XI and XI! in prothrombin complex concentrates. We decided to measure, factors XI and XII system- atically in subjects with liver disease after noting that prolonged APTT in these subjects were some- times not explained by the levels of the other coagulation factors. MATERIALS AND METHODS Subjects. Subjects were drawn from the clinical ser- vice. Patients were not selected as a result of having abnormal Coagulations tests. Liver disease had been documented either by biopsy or by gross clinical features (usually liver failure and/or encephalopathy) and/or clini cal and biochemical features associated with esophogeal varices. Altered liver biochemist?y alone was insufficient for inclusion. All subjects with abnormalities of PT and/or APTT were given parenteral vitamin K for at least 3 days prior to testing. Control subjects were hospitalized pa- tients who had no evidence of liver impairment, inflam- mation, infection, and malignancy. Most of them had been admitted for elective orthopedic surgery for nonin- flammatory conditions and blood was taken from these Digestive Diseases and Sciences, Vol. 28, No. 11 (Novembe r 1983) 0163-2116/83/1100-0967503.00/0 9 1983 PlenumPublishingCorporation 967