Inheritance and bleeding in factor XI deficiency

A study of 20 Jewish and four non-Jewish kindreds transmitting factor XI deficiency (164 individuals) confirmed inheritance to be autosomal with severe deficiency in homozygotes (mean factor XI level 3.8 u/dl, SD 2.91) and partial deficiency in heterozygotes (mean factor XI level 57 u/dl, SD 10.42; normal mean factor XI level 96 u/dl, SD 11.6). The probability of an individual being heterozygous can be predicted from the factor XI level using a graph derived from this data. The accuracy is increased by including the prior probability derived from the pedigree. A high frequency of heterozygote to heterozygote mating was observed in the Jewish families consistent with an estimated gene frequency of 13.4% in this racial group. The relationship between factor XI level and bleeding tendency is poor; a third of heterozygotes had bled excessively after surgery, including six with factor XI levels above 50 u/dl, showing this condition to have clear signs of expression in heterozygotes. The lower limit of the normal range (2 SDs from the mean) was found to be 72 u/dl.