A 'blind' study has been made to try to find out if it is possible to diagnose carriers of haemophilia. A group of 34 obligatory carriers of haemophilia were compared with 34 normal women. Levels of factor VIII activity, factor VIII-related antigen, factor V and ratio of factor VIII activity to factor VIII-related antigen were measured. In the carrier group the mean level of factor VIII activity and the mean level of the ratio of activity to antigen were each approximately half of those found in the normal women. The mean level of factor V was the same in both groups of women. By setting the lower limit of normal at the lowest level of the different factors found in the normal women, 12 out of 34 (35%) carriers could be distinguished on the basis of their factor VIII level alone; 24 out of 34 (71%) could be detected on the basis of the ratio of factor VIII activity to factor VIII related antigen and 25 out of 34 (73%) could be detected if both factor VIII activity and the ratio were taken into account. It is concluded that consideration of both the level of factor VIII activity and the ratio of factor VIII activity to factor VIII-related antigen is of some value in detecting carriers of haemophilia. The number of carriers detected (73%) in the present study is not as high as that found by other workers.

Detection of Carriers of Haemophilia: a ‘Blind’ Study

Asymptomatic relatives of a girl with an extremely severe form of von Willebrand's disease who had consanguineous parents were investigated to determine whether they carried the von Willeb...

Detection of heterozygotes for recessive von Willebrand's disease by the assay of antihemophilic-factor-like antigen.

Summary. A patient representing the family with autosomal haemophilia A described elsewhere (Hensen et al, 1965) shows ‘de novo synthesis’ of factor VIII after transfusion with normal and haemophilic cryoprecipitate. Several patients in the family have very low factor VIII-related antigen levels. These findings are consistent with a diagnosis of von Willebrand's disease but the normal or nearly normal bleeding times and the similarity in factor-VIII activity levels in all the members of this family are unusual in this condition.



Thus far, three loci involved in factor-VIII synthesis have been postulated. The locus most frequently occupied by a mutant gene is on the X chromosome and results in haemophilia A, a trait long known to be sex-linked (for instance in ancient Jewish and Arabian literature; see review by Ikkala, 1960). The effects of mutation in an autosomal locus were first described by von Willebrand (1926, 1931). A third locus involved in factor-VIII synthesis was postulated by Hensen et al (1965). The effects of this mutant gene have been particularly difficult to study because the features that led to postulate its existence have been reported in only one family. This report deals with the evidence that this condition, originally described as ‘autosomal haemophilia’, is only a variant of von Willebrand's disease.

'Autosomal haemophilia': a variant of von Willebrand's disease

RECENT immunological studies on the antihaemophilic factor (AHF, factor VIII) indicate that a nonfunctional AHF-like protein is synthesized in haemophilia A and that von Willebrand's disease is associated with reduced AHF synthesis1–3. These conclusions are based on the immunological measurement of proteins which have AHF antigenic determinants using methods that detect secondary properties of the interaction of AHF with the rabbit antibody such as immunoprecipitation1, haemagglutination inhibition2, radioimmunoassay3 and antibody neutralization assays1.

Specificity of precipitating antibodies in immunological identification of antihaemophilic factor.

Factor VIII and factor-VIII-related antigen (FVIIIRA) were estimated in 19 patients with paraproteinaemia. The FVIIIRA levels were above the normal range in 12 cases with II of these showing an abnormal FVIII/FVIIIRA ratio. The patients could be subdivied into three groups according to their FVIIIRA levels: normal levels, levels greater than normal but less than 200%, greater than 200%. This subdivision correlated with the degree of bone involvement as assessed by radiological skeletal survey.

G.I.C. Ingram

Papers

Antigen/biological-activity ratio for factor VIII.