MOLECULAR HETEROGENEITY IN FAMILIAL HEPARIN COFACTOR II DEFICIENCY
In our normal material of 379 blood donors,3 indivi-uals had values below mean −2.5 SD (below 56%).Further studies revealed hereditary deficiency in two of these individuals. In the family study,5 out of 7 individuals had heparin cofactor II (HC II) values below 56%. In only one of these 5 a history of DVT was obtained. In deceased members of her family, however, frequent episodes of thromboembolic disease had occurred.Crossed immunoelectrophoresis (CIE) was performed in plasma from deficiency individuals from both families. Heparin in the first dimension gave a pattern similar to that observed with normal pooled plasma. The inactivation of thrombin by HC II is preferentially accelerated by dermatan sulfate (DS).HC II consumption in in vitro coagulation is increased by DS rather than by heparin. This prompted the addition ofTBS to the first dimension, which makes the antigen move faster, but produced no alteration in the antigenic pattern or size, neither in pooled plasma nor in a family member with normal activity. In family members with low HC II activity, DS in the first dimension, resulted in an abnormal CIE pattern with two distinct precipitation arcs with identity pattern. Molecular heterogeneity of HC II has previously not been reported.Screening 70 individuals who had sustained thrombosis before the age of 50,no values suggesting congenital deficiency were encountered.Conclusion. The CIE findings suggest that plasma of affected family members contain two types of HC II molecules of immunological identity. One type shows the normal accelerated mobility in the presence of DS and the other lacks this effect. The abnormal electrophoretic pattern becomes, however, first apparent when DS is added to the first dimension. When looking for molecular defects in congenital HC II deficiency, it is important that the first dimension is run with DS.