low dose Aspirin in obstetrics

1. low dose
Aspirin
in obstetrics
Aboubakr
Elnashar
Benha University
Hospital, Egypt
Aboubakr Elnashar

2. Contents
I. SAFETY
II. Mechanism of action
III.USES:
1.Prevention of
1.PET
2. IUGR
3.PTL
4.hypertension in multiple pregnancy
5.repeated miscarriage
6.DVT
2.Treatment of antiphysolipid syndrome
Aboubakr Elnashar

3. I. SAFETY
Fetal and neonatal complications
stillbirths, neonatal death, birth defects:
Similar
(Ahren et al, 2016).
No increased risk of hemorrhage
either before or after delivery
(HR: .57, 95% CI: .25-1.33; p = .194).
(Ayal et al, 2013)
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4. SCH
LDA: 40.2%
Control: 10.9%
LDA may be associated with an increased risk of
developing a SCH during the first trimester.
(Truong et al, 2016)
Vaginal bleeding:
LDA: 22%
Control: 17%, P=0.02
(Ahren et al, 2016).
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5. Placental abruption
LDA increases the incidence of placental
abruption
(OR, 1.35; 95% CI, 1.05-1.73)
not other major complications
LDA is effective in preventing:
PET
PTL
IUGR
in high-risk pregnancies without posing a
major safety risk to mothers or fetuses.
(XU et al, 2015)
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6. No adverse effects on infants
Decrease behavioral difficulties
(Vinod et al, 2009)
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7. Aboubakr Elnashar

8. II. MECHANISM OF ACTION
diminishes platelet thromboxane A2 synthesis
maintaining vascular wall prostacyclin synthesis:
altering the balance in favor of prostacyclin
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9. Aboubakr Elnashar

10. III. USES
1. Prevention of PET
Rationale
PE:
increased platelet turnover
increased platelet derived thromboxane levels
LDA:
diminishes platelet thromboxane A2
synthesis while
maintaining vascular wall prostacyclin
synthesis: altering the balance in favor of
prostacyclin
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11. I. Studies on moderate and high risk women
low dose aspirin: effective
modest reduction in risk of
PE (0-3% in treated vs 12-35% in controls)
other adverse pregnancy outcome:
PTL, IUGR (by 10-20%).
[Dekker et al, 2001].level 2 evidence (Cochrane SR, 2007 )
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12.  When to start?
≤16 w, at 12 w
significant reduction in:
PE
(RR 0.47, 95% CI 0.360.62; 7.6 vs 17.9%)
 severe PE
(RR 0.18, 95% CI 0.080.41; 1.5 vs 12.3%)
IUGR (RR 0.46; 8.0 vs 17.6%)
PTL
(RR 0.35, 95% CI 0.220.57; 4.8 vs 13.4%)
[Roberge et al, 2013; Meher et al, 2013; XU et al, 2015; Roberge et al,
2016}
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13. Dose:
75-80 mg seems to be the right dosage for about
two thirds of the women
[Rey et al, 2011]
1/3: need higher dosages up to 160 mg
Aspirin resistance test:
woman is resistant to 75-80 mg: increase the
dose.
(Bujold, 2013)
100 mg/d should be the minimum dose for
prevention of complications in pregnancy
(Ayal et al, 2013)
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14. Aspirin non-responsiveness= Aspirin
resistance= Aspirin treatment failure
Significant proportion of aspirin-treated
individuals exhibit suboptimal platelet response
inability of aspirin to reduce platelet
production of thromboxane A2 and thereby
platelet activation and aggregation.
Determination:
Measurements of
whole blood TXA2 formation
urinary excretion of TXA2 metabolites
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15. Causes
inadequate dose
drug interactions
genetic polymorphisms of COX-1 and other
genes involved in thromboxane biosynthesis
upregulation of non-platelet sources of
thromboxane biosynthesis
increased platelet turnover.
can be overcome by
treating the cause or causes
 minimising thromboxane production and activity
blocking other pathways of platelet activation.
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16.  At bed time:
 Not upon awakening
 significantly regulates ambulatory BP
 reduces the incidence of
 Preeclampsia
 gestational hypertension
 preterm delivery, and
 IUGR.
(Ayal et al, 2013)
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17. II. Unselected nulliparous women
little or no benefit
[Sibai et al, 1993]
no effect on incidence of FGR, or length of
gestation
[Subtil et al, 2003].
1. Although nulliparity is a risk factor for PE,
prevalence rates are relatively low (4%)
compared with moderate to high risk groups
(8-30%)
[Henderson et al, 2014].
2. Pathogenesis of PE in nulliparous is
different from that in women with previous
PE or preexisting vascular disease
[Sibai et al, 2005].
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18. III. Studies on women with abnormal uterine artery
Doppler (UAD)
Abnormal UAD: identified women who are likely
to develop PE and IUGR
[Subtil et al, 2003].
PE: 6 vs 1%
IUGR: 18 vs 8%
LDA of abnormal UAD:
Did not reduce the incidence of PE
PE occurred in 2% of patients in each group.
Did not reduce the incidence of IUGR.
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19. Guidelines
ACOG, 2013
LDA:
not recommended for women at low risk for
PE.
Recommend in high risk women: women
with history of :
early onset PE
superimposed PE plus delivery at <34 w
or
PE in >1 pregnancy.
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20. NICE, 2010
low dose (75 mg) aspirin for
 1 high risk factor for PE
chronic hypertension
kidney disease
diabetes
autoimmune disease
hypertension in previous pregnancy OR
2 moderate risk factors for PE
age ≥40 y
first pregnancy
multiple gestation
>10 y between pregnancies,
BMI≥35 kg/m at presentation
family history of PE
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21. US Preventive Services Task Force (USPSTF)
2014
LDA:
≥1 high risk factors
absolute risk for PE ≥ 8%.
{No validated methods (biomarkers, clinical
diagnostic tests, medical history) for identifying
women at high risk for PE}
81 mg/d
at 12 w
Discontinue
5 to 10 days before expected delivery
{diminish the risk of bleeding during delivery}
[Hirsh et al, 2008}
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22. 2. Prevention of IUGR
LDA:
effective in preventing SGA birth in women at
high risk of PET although the effect size is small
(RR 0.51, 95% CI 0.28–0.92)
number needed to treat = 10 (95%CI 5–50).
should be commenced at, or before, 16 w of
pregnancy.
(NICE, 2011)
It is not possible to determine to what extent the
effect of LDA is due to the reduction of pre-
eclampsia in these women.
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23. LDA:
Started
early pregnancy
reduces the risk of placenta-mediated
complications such as IUGR and perinatal
death
after 20 ws:
not effective in reducing the risk of a SGA
infant.
Efficacy has been demonstrated in:
abnormal first-trimester uterine artery Doppler
Prior history of chronic hypertension or PET
(Roberge et al, 2016)
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24. 3. Prevention of PTL
LDA
started early in pregnancy in high-risk women:
prevent more than half of PET and IUGR
significant decrease of PTL
(relative risk 0.22, 95% confidence interval: 0.10-0.49).
(Bujol et al, 2011)
could become an additional weapon in the
prevention of PTL
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25. LDA:
Started at 15 and 18 w
In singleton pregnant women, who had
unexplained AFP >2.5 MOM
reduces
adverse pregnancy outcome
delivery before 34 w
(Khazardoos et al, RCT, 2014)
Preconception LDA:
not significantly associated with the overall rate
of PTL
(Silver et al, 2015)
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26. 4. Prevention of adverse pregnancy outcome In
multiple pregnancy
LDA:
75 mg daily from 12 w until the birth of the babies
if they have one or more of the following risk factors
for hypertension:
1. first pregnancy
2. age 40 years or older
3. pregnancy interval of more than 10 y
4. BMI of 35 kg/m2 or more at first visit
5. family history of PET.
(NICE, 2011)
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27. 5. Prevention of RM
Preconception initiated LDA:
1-2 previous losses:
no significantly associated with live birth or
pregnancy loss
Single documented loss at less than 20 ws during
the previous year:
higher live birth rates
Not recommended for the prevention of pregnancy
loss
(Schisterma et al, 2014; Mumfor et al, 2016)
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28. Preconception-initiated LDA
history of 1-2 pregnancy losses:
non significant increase in fecundability of
14%
history of only one pregnancy loss of <20 w in
the preceding year:
significant increase of 28%
Preconception-initiated LDA may increase
fecundability in certain women with a recent
early pregnancy loss
(Schisterma et al, 2015)
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29. LDA+ LMWH:
No reduction in pregnancy loss rate in pregnant
women with 2 or more consecutive previous
pregnancy losses.
(SPIN (Scottish Pregnancy Intervention) multicenter, RCT; Clar
et al, 2010)
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30. 6. Prevention of thrombosis
Not recommended in:
Any patient group
(American College of Physicians)
Obstetric patient:
(RCOG, 2015)
Postoperative
(NICE,2013)
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31. 7. Treatment of APAS
Improvement of fetal outcomes in APAS
LDA
in combination with heparin is the first line
treatment
(MRCOG, 2011)
-Success:
70%
(Rai et al,1997)
-Reduces the miscarriage rate by
54%
(Empson et al, Cochrane Database Syst Rev, 2005)
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32.  Baseline nonpregnant studies of aPLs:
 CBC with platelets
 PT, PTT
 LA, aCL and aβ2GP
LDA:
75-81 mg:
initiated before conception
discontinued 4 ws before EDD
resumed postpartum
continued for life unless otherwise contraindicated
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33. Thanks
Aboubakr Elnashar