Immunoradiometric Assay of Factor VIII Related Antigen, with Observations in 32 Patients with von Willebrand's Disease

S ummary . A solid phase non‐competitive immunoradiometric assay (IRMA) has been developed which allows measurement of factor VIII related antigen (VIIIR: AG) levels in normal plasma as low as 2.5 × 10 −4 U/ml. The assay is based on the extraction of VIIIR: AG from test plasma by means of polystyrene tubes coated with a specific unlabelled anti‐VIIIR: AG rabbit antiserum and subsequent labelling of the extracted antigen with 125 I‐labelled anti‐VIIIR: AG rabbit IgG. The amount of radioactivity retained by the tubes (percentage bound) is proportional to VIIIR: AG concentration and a linear correlation is observed when logs of plasma dilutions (from 1 in 300 to 1 in 4000) are plotted against logits of percentage bound. The IRMA is technically simple, specific and reproducible. In 32 normal persons there was a highly significant correlation ( r = 0.94) between IRMA and rocket electro‐immunodiffusion assay (EIA) of VIIIR: AG plasma levels using the same antibody. IRMA has also been used to investigate 32 patients with von Willebrand's disease (vWd) in whom VIIIR: AG plasma levels were below the lowest measurable concentration using EIA (< 0.10 U/ml). In 17 patients with an autosomal recessive mode of inheritance and unusually severe symptoms, the markedly abnormal laboratory findings were consistent with the homozygous state. In 11 of these VIIIR: AG was < 2.5 × 10 −4 U/ml and was extremely low in the remaining 6 (1.3 × 10 −2 to 4 × 10 −3 U/ml). In 15 patients the disease was familial (being transmitted as an autosomal dominant trait) and of moderate clinical severity; the IRMA or VIIIR: AG ranged between 1.2 × 10 −1 and 4 × 10 −2 U/ml. The assay thus appears a useful tooi in the investigation of vWd and helps to identify two different types of the disease.