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Activated protein C resistance as an additional risk factor for thrombosis
in protein C-deficient families
BP Koeleman, PH Reitsma, CF Allaart and RM Bertina
Department of Hematology, University Hospital Leiden, The Netherlands.
Heterozygous protein C deficiency is associated with an increased risk for
thrombosis. This association is restricted to a minority of protein
C-deficient families, which have been defined as clinically dominant
protein C-deficient. In contrast, in the clinically recessive protein C-
deficient families, only the homozygous family members are (severely)
affected. One possible explanation for this difference in thrombotic risk
between families may be the presence of a second hereditary risk factor. A
good candidate for this second risk factor is the recently identified
resistance to activated protein C (APC). APC resistance, which is
associated with a mutation in the FV gene (FV Leiden), is a common and
strong risk factor for thrombosis. We show here that the prevalence of the
FV Leiden mutation is high among symptomatic protein C-deficient probands
(19%). In 6 clinically dominant protein C- deficient families, the
segregation of the FV Leiden mutation and the protein C gene mutation was
studied. A thrombotic episode had been experienced by 73% of the family
members having both the protein C gene mutation and the FV Leiden mutation.
In contrast, respectively, 31% and 13% of the family members having either
the protein C gene mutation or the FV Leiden mutation had experienced a
thrombotic episode. Moreover, the result of a two locus linkage analysis
support the assumption that the FV gene and the protein C gene are the two
trait loci responsible for the thrombophilia. These results indicate that
carriers of both gene defects have an increased risk for thrombosis
compared with related carriers of the single defect.
Volume 84,
Issue 4,
pp. 1031-1035,
08/15/1994
Copyright © 1994 by The American Society of Hematology
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