Detection of Carriers of Haemophilia: a ‘Blind’ Study

Abstract

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.

Inactivation of human factor VIII by activated protein C. Cofactor activity of protein S and protective effect of von Willebrand factor.

“…Similarly, Zucker et al (52) have shown that von Willebrand factor in plasma can be loaded with at least 12 times the amount of Factor VIII that is normally present. In spite of this excess of apparent binding sites on von Willebrand factor for Factor VIII, there exists a close correlation between the concentrations of the two proteins in normals and in many disease states (53,54). The study ofWeiss et al (26) demonstrated an increased lability ofFactor VIII especially in those plasmas which expressed a Factor VIII/von Willebrand factor ratio of more than one.…”

Bleeding in carriers of hemophilia

“…Previously, pedigree analysis and clotting factor VIII or IX levels were used to diagnose carriership for hemophilia. 1 In the early 1980s, it became possible to ascertain the carrier status by means of DNA analysis, which has evolved from haplotyping to mutation analysis offering certainty about the carrier status. 2 During the last 3 decades, genetic counseling, carrier testing, and prenatal diagnosis of hemophilia have become an integrated part of the comprehensive care for hemophilia.…”

Hemophilia Carrier Status and Counseling the Symptomatic and Asymptomatic Adolescent

“…A wide range of clotting factor levels (22e116 IU/dL) has been reported. 1 This is the result of the random inactivation of one of the two X chromosomes, a phenomenon known as lyonization. 2 If a carrier has a son, there is a 50% chance he will have hemophilia and a daughter has a 50% chance of being a carrier.…”