Failure to detect variant (CRM+) plasma thromboplastin antecedent (factor XI) molecules in hereditary plasma thromboplastin antecedent deficiency: a study of 125 patients of several ethnic backgrounds.

Plasma samples of 125 patients from 80 kindreds with hereditary plasma thromboplastin antecedent (PTA, factor XI) deficiency were tested by factor XI radioimmunoassay (RIA) and electroimmunoassay (EIA) in an attempt to detect variant molecules. Ninety-six patients (70 kindreds) were Jewish, and 29 (10 kindreds) were of other ethnic backgrounds, namely, Japanese, black American, Korean, Arab, Indian, and English. Seventy-eight patients were homozygotes, and 47 were heterozygotes. Both non-Jewish homozygotes and heterozygotes had lower factor XI activity than respective Jewish subjects. Twenty-eight homozygotes whose factor XI clotting activities (XI:C) were 1.5% to 13% had factor XI-related antigen (XI:RAG) levels less than 10% by EIA. In 72 homozygotes, including 22 patients who were also tested with EIA, XI:C was 2.9% +/- 3.0% (mean +/- SD) and XI:RAG tested by RIA, 2.9% +/- 3.0%. In 47 heterozygotes, XI:C and XI:RAG tested by RIA were 51.9% +/- 16.6% and 51.0% +/- 16.2%, respectively. Similar results were obtained when only unrelated patients (62 homozygotes and 27 heterozygotes) were analyzed. There was a highly significant correlation between XI:C and XI:RAG (RIA) in 38 homozygotes and 47 heterozygotes (r = 0.94, n = 85, P less than 0.001). Thus, we failed to identify functionally abnormal factor XI molecules (CRM+ variant) in these patients with hereditary factor XI deficiency.