Thrombophile Genmutationen bei Patientinnen mit rezidivierenden Spontanaborten unklarer Genese

BACKGROUND: Successful pregnancies require fine tuning of
fibrinolytic activities in order to secure fibrin polymerization
and stabilization of the placental basal plate as well as to
prevent excess fibrin deposition in placental vessels and
intervillous spaces. Fibrinolysis is tightly regulated by
plasminogen activator inhibitor-1 (PAI-1). Endothelial PAI-1
synthesis is induced by angiotensin II, which is generated by
angiotensin I-converting enzyme (ACE). METHODS: We studied the ACE
deletion (D)/insertion (I) polymorphism and the PAI-1 4G/5G
polymorphism in women with recurrent spontaneous miscarriages (RM).
Both polymorphisms have been shown to be associated with ACE and
PAI-1 expression levels respectively. A study group of 184 patients
with a history of two or more consecutive unexplained spontaneous
miscarriages was compared with a control group of 127 patients with
uneventful term deliveries and no history of miscarriages. RESULTS:
Our findings show: (i) homozygosity for the D allele of the ACE
gene, which results in elevated PAI-1 concentrations and
hypofibrinolysis, is associated with an elevated risk of RM; (ii)
the combination of the D/D genotype with two 4G alleles of the
PAI-1 promoter, which further increases PAI-1 plasma levels, is
significantly more frequent in RM patients compared with controls.
CONCLUSIONS: Based on these results, we recommend the incorporation
of these two polymorphisms into the spectrum of thrombophilic
mutations which should be analysed in individuals with recurrent
spontaneous miscarriages. Patients homozygous for both the ACE D
and PAI-1 4G alleles may benefit from the application of low
molecular weight heparin as early as possible in the pregnancy in
order to prevent uteroplacental microthromboses.