Two Variants of Canine von Willebrand’s Disease

Previous studies in our laboratory have characterized von Willebrand’s disease (VWD) in three families of dogs: German shepherds, miniature Schnauzers, and golden retrievers (Blood, 45, 221, 1975; Thromb. Res., 7, 383, 1975). In each family the disease follows a classical pattern of autosomal inheritance; reduced factor VIII activity, factor VIII-related antigen (FVIII-RA), platelet retention and ristocetin-induced platelet aggregation; and long bleeding times; although the severity of expression varies between the breeds. Two new families currently being studied (Doberman pinschers and Scottish terriers) deviate significantly from this expected pattern. Several severely affected dogs, presumed homozygous by virtue of having two affected parents and undetectable FVIII-RA, have factor VIII activity between 20–50% of normal. Even more unusual is that mildly affected or clinically normal close relatives of these dogs have low-normal or normal factor VIII activity but very low FVIII-RA (5–25%) . However, there are also severely affected dogs from both families with classic VWD including very low factor VIII activity (<10%>) and undetectable FVIII-RA. The same monospecific rabbit anticanine factor VIII was used to quantitate and compare the FVIII-RA levels of affected and normal members of all five dog families. The explanation for finding low antigen levels in conjunction with normal biologic activity in families where complete expression of the disease coexists remains obscure.