Heckathorn's disease: variable functional dificiency of antihemophilic
factor (factor VIII)
OD Ratnoff and JH Lewis
A family is described in which a syndrome resembling moderately severe
classic hemophilia was apparently inherited as an X chromosome-linked
trait. In two affected individuals, the titer of functional antihemophilic
factor varied dramatically from time to time, while the conversion of
prothrombin to thrombin was impaired in no apparent relationship to AHF
functional activity. A transfusion of 200 ml of fresh-frozen plasma did not
correct the serum prothrombin times in either patient. In vitro, the
additions of 10% of normal plasma or serum or washed plain or frozen
platelets also did not normalize the serum prothrombin times. No inhibitor
could be demonstrated in the blood of either patient. In one patient, RH,
dissipation of infused cryoprecipitated AHF was abnormally slow, and, after
an intensive course of transfusion of cryoprecipitate and whole blood, the
titer of functional AHF remained at normal levels for at least 1 wk. The
plasma of RH inhibited a human antibody against AHF in proportion to its
titer of functional AHF (i.e., the defect was CRM-) despite the presence of
relatively greater amounts of antigenic material recognized by heterologous
antiserum. No qualitative abnormality of the AHF-like material in RH's
plasma was identified. Inheritance of the abnormality appears superficially
to be X chromosome-linked; on this assumption, three of four obligate
carriers of the disorder were recognized by the presence of excess amounts
of AHF-like antigens relative to AHF functional activity. This coagulation
disorder has been designated Heckathorn's disease and may presage the
discovery of other examples of hemophilia-related syndromes.
Volume 46,
Issue 2,
pp. 161-173,
08/01/1975
Copyright © 1975 by The American Society of Hematology
