Follow-up of the FRUIT-RCT; aspirin resistance and cardiovascular risk factors in women after recurrent hypertensive disorders in pregnancy

The multicenter FRUIT-RCT demonstrated that adding low-molecular-weight heparin
(LMWH) to the standard care aspirin, is beneficial in preventing early-onset
hypertensive disorders of pregnancy (HD) in women with inheritable
thrombophilia. Bujold et al suggested in a letter to the editor, responding to
the FRUIT-RCT1 that the effect of LMWH could have been mainly beneficial in the
subgroup of women who are resistant to aspirin. To evaluate this potential
relationship we perform a two stage experiment: firstly evaluation of aspirin
resistance in the non-pregnant FRUIT-RCT, and secondly the evaluation of
aspirin resistance during pregnancy and post-puerperium.
Furthermore, we want to assess the prevalence of cardiovascular risk factors in
women with inheritable thrombophilia and a history of recurrent HD. We want to
examine if women with a history of recurrent hypertensive disorder of pregnancy
develop cardiovascular risk factors more frequently than women with a history
of single HD.

1a. Determine whether the effect of low-molecular-weight heparin can be
explained by aspirin resistance.
1b. Assess the consistency of aspirin resistance during and after pregnancy
measured with several complementary devices.
2. Determine cardiovascular risk factors in the FRUIT-RCT; women with and
without recurrent HD.

To answer question 1a and 2, we will perform a follow-up study of the
FRUIT-RCT1 cohort. To answer question 1b (which we need for question 1a), we
will perform a longitudinal cohort study in women who have an indication for
aspirin usage during pregnancy to reduce the change for (recurrent) HD.

not applicable

Women will be visited 3 times in their regional hospital, of in VUmc. We'll ask
them to fill in a questionnairre, perform physical examination and collect
blood samples three times. These methods of research are safe and hardly
invasive. The venous blood sampling can result in a hematoma, infection or
vasovagal reaction.

Knowledge about aspirin resistance probably makes it possible in the future to
individualize dose administration for patient with an indication for aspirin
usage. If women have cardiovascular risk factors, they will be sent to their
general practitioner for further treatment.
We will inform patients about the presence or absence of aspirin resistance,
although it has no further implications in their pregnancy.
Few studies examined the potential influence of aspirin resistance and the
effect on recurrent HD. This makes these studies of additional value to the
current literature. Moreover, no prospective study has been performed to see
whether recurrent HD is associated with a change in the incidence of
cardiovascular risk factors compared to single HD.