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 These are a heterogeneous
family of autoantibodies
that bind to negatively
charged phospholipids,
phopholipid binding proteins,
or a combination of the two
 More than 20 aPL antibodies have been described
 Most clinically significant
 Lupus Anticoagulant (LA) and
 Anticardiolipin antibodies (aCA)
 Recurrent pregnancy loss
 Intrauterine growth restriction (IUGR)
 Intrauterine fetal death (IUFD)
 Preterm brith
 Pre-eclampsia (early/ late onset)
 Abruptio placentae
 Thrombocytopaenia
 Deep vein thrombosis/ Pulmonary embolism
 Stroke
 Postpartum/ Catastrophic APS
 Some aPL positive women have
uncomplicated pregnancy outcomes
without treatment
 Variation in opinion on the rate of
detection of aPL antibodies in women
with adverse pregnancy outcomes
 Paucity of prospective studies on the
natural history of aPL in pregnant women and
identifying the subset of aPL positive mothers
who need medical therapy
 Disagreement regarding clinically relevant
levels, isotypes and specificities of aPL
antibodies
 Whether aPL antibodies other than LA & aCA
are relevant
We studied
 The prevalence of aPL antibodies in
selected at-risk obstetric cases
 The significance of these antibodies with
respect to pregnancy outcomes
 Comparison of the results with a cohort
of obstetric cases with past history of
uncomplicated pregnancy outcome
having similar demographic
characteristics
MATERIALS AND METHODSMATERIALS AND METHODS
 STUDY AREASTUDY AREA
 R G Kar Medical College and Hospital, Kolkata
 Medical College and Hospital, Kolkata
 STUDYSTUDY PERIODPERIOD
3 years (March 2006- February 2009)
 STUDY DESIGNSTUDY DESIGN
Prospective comparative study
 STUDY POPULATIONSTUDY POPULATION
Antenatal mothers who conform to inclusion criteria
 STUDY DESIGNSTUDY DESIGN
INCLUSION CRITERIA
I. Study group
120 Antenatal mothers attending OPD
1. Having past H/O-
 Pre-eclampsia
 Eclampsia
 Recurrent abortion
 Intrauterine growth restriction (IUGR)
 Intrauterine Fetal death (IUFD)
 Abruptio placentae
 Without any apparent aetiologyWithout any apparent aetiology
1. Registered into AN Clinic during 1st
trimester
II. Control Group
Cohort of 120 Antenatal mothers attending OPD
1. Of comparable age, gravidity, parity, Body Mass Index
(BMI)
2. Having past H/O uncomplicated pregnancy
3. Followed similar registration protocol
EXCLUSION CRITERIA
Presence of known medical disorders which might
adversely affect pregnancy outcome
 STUDY OBJECTIVESSTUDY OBJECTIVES
 Primary- Prevalence of aPL antibodies in both groups
 Secondary- Obstetric outcome in those women
 STUDY TOOLSTUDY TOOL
 Anti Cardiolipin antibody (aCA)-
IgG and IgM
by solid phase ELISA
 Lupus Anticoagulant (LA)-
by dilute Russle Viper venom test (dRVVT)
 Single referral laboratory tests were used
 Analysis of dataAnalysis of data
 Visually double checked by an
independent second
investigator
 Analysed using MedCalc
(version 10.0.0.0) statistical
software (
http://www.medcalc.be)
 P value less than 0.05 was
considered as statistically
significant
RESULTSRESULTS
DEMOGRAPHIC PROFILEDEMOGRAPHIC PROFILE
Characteristics Study group
(n = 112)
(mean ± SD)
Control group
(n = 112)
(mean ± SD)
p value
Age (years) 26.4 ± 2.28 25.8 ± 2.42 0.0608
Gravidity 2.90 ± 0.52 2.86 ± 0.24 0.4708
Parity 1.48 ± 0.34 1.76 ± 0.22 0.0001
BMI (Kg/M2
) 24.2 ± 1.8 23.8 ± 2.06 0.1278
Gestational age at
sampling (weeks)
15.08 ± 0.31 15.04 ± 0.34 0.3646
DISTRIBUTION OF CASES ACCORDING TODISTRIBUTION OF CASES ACCORDING TO
PAST OBSTETRICS IN STUDY GROUPPAST OBSTETRICS IN STUDY GROUP
PREVALENCE OF aPL ANTIBODIES INPREVALENCE OF aPL ANTIBODIES IN
STUDY AND CONTROL GROUPSTUDY AND CONTROL GROUP
Study group
(n = 112)
Control group
(n = 112)
Characteristics n (%) n (%) p value
LA activity 15 13.39 2 1.89 0.0036
IgG aCA >10 GPL units 17 15.18 3 2.83 0.0035
IgM aCA >10 MPL units 21 18.75 4 3.77 0.0011
Both IgG aCA > 10 and
IgM aCA >10
12 10.71 0 0 0.0015
Both LA and aCA +ve 11 9.82 2 1.89 0.0289
Total No. of aPL +ve
cases
41 36.61 9 8.49 <0.0001
INCIDENCE OFINCIDENCE OF
ANTI-PHOSPHOLIPID ANTIBODIESANTI-PHOSPHOLIPID ANTIBODIES
ACCORDING TOACCORDING TO
PAST OBSTETRIC HISTORYPAST OBSTETRIC HISTORY
aPL Positive
cases
Character
istics
Cases
(n)
Total
aPL
+ve
(%) LA
+ve
Only
IgG aCA
>10 GPL
Only IgM
aCA > 10
MPL
Both IgG &
IgM aCA
>10 units
Study
Group
Pre-
eclampsia
14 4 28.57 2 2
Eclampsia 10 1 10 1
Recurrent
abortion
32 15 46.87 6 2 3 4
IUGR 24 10 41.66 3 2 3 2
IUFD 22 8 36.36 3 2 3
Abruptio
placentae
10 3 30 1 1 1
TOTAL 112 41 15 5 9 12
Control Group 106 9 8.49 2 3 4 0
In SummaryIn Summary
aPL POSITIVEaPL POSITIVE aPL NEGATIVEaPL NEGATIVE
STUDY group 41 97
CONTROL Group 9 71
Total 50 168
Dropped out 2 14
Net Total 48 154
INCIDENCE OF OBSTETRICINCIDENCE OF OBSTETRIC
COMPLICATIONSCOMPLICATIONS
ObstetricObstetric
ComplicationsComplications
aPL Positive
mothers (n= 48)
aPL Negative
mothers (n= 154)
n (%) n (%) p value
Early
Abortion 12 25 11 07.14 0.0017
Pre-eclampsia <28 wk 7 14.58 2 01.3 0.0005
IUFD <28 wk 3 06.25 0 0 0.0146
Late
Pre-eclampsia 12 25 9 05.84 0.0004
Eclampsia 1 02.08 0 0 0.5382
IUGR 13 27.08 14 09.09 0.0031
Oligohydramnios 16 33.33 10 06.49 <0.0001
Abruptio placentae 9 18.75 6 03.9 0.0019
IUFD >28 wk 2 04.17 2 01.3 0.5104
OBSTETRIC COMPLICATIONSOBSTETRIC COMPLICATIONS
LIVE BIRTH RATESLIVE BIRTH RATES
aPL POSITIVE aPL NEGATIVE
Total cases 48 154
Live
birth
n 31 141
(%)
64.58 91.56
OUTCOMES OF LIVE BIRTHOUTCOMES OF LIVE BIRTH
aPL Positive
mothers
(n = 31)
aPL negative
mothers
(n = 141)
Characteristics n (%) n (%) p value 95% CI
No. of Vaginal
deliveries (VD)
17 54.84 120 85.11 0.0004 12.88- 48.04
No. of Caesarean
Section (SC)
14 45.16 21 14.89 0.0004 12.88-48.04
Gestational age at
VD (weeks)
(Mean ± SD)
35.9 ± 0.8 37.4 ± 0.8 <0.0001 1.19-1.81
Gestational age at
CS (weeks)
(Mean ± SD)
35.4 ± 0.5 37.8 ± 0.4 <0.0001 2.24-2.56
Early neonatal
death
3 9.68 3 2.13 0.1252 0.09-22.84
OUTCOMES OF LIVE BIRTHOUTCOMES OF LIVE BIRTH
DIFFERENCES IN WEIGHTDIFFERENCES IN WEIGHT
Placental
weight
Birth Weight
aPL
Negative
(Mean ±
SD)
488.7 ± 22.3 3024.3 ± 229.5
aPL
positive
(Mean ±
SD)
424.2 ± 9.5 2523.6 ± 216.3
p value <0.0001 <0.0001
95% CI 56.42- 72.58 411.72- 589.68
DISCUSSIONDISCUSSION
There is high prevalence of aPL
antibodies in complicated
pregnancy
Both lupus anticoagulant and
anticardiolipin antibodies
significantly affect pregnancy
outcome
In our study outcome was
worse in aPL positive mothers
despite heparin treatment
 Commencement of treatment after
repeat test result for aPL positivity,
which was not before 20-22 weeks’
gestation
 Poor patient compliance
(OPD based treatment)
CONCLUSIONCONCLUSION
Following women should be screened
for antiphospholipid antibodies-
 Whose previous pregnancies were
complicated by
Recurrent abortion
Pre-eclampsia (particularly early
onset)
Eclampsia
IUGR
IUFD
Abruption placentae
 With no apparent aetiology
THANK YOUTHANK YOU

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Prevalence And Significance Of Anti-Phospholipid Antibodies In Selected At-Risk Obstetric Cases: A Comparative Prospective Study

  • 1.
  • 2.  These are a heterogeneous family of autoantibodies that bind to negatively charged phospholipids, phopholipid binding proteins, or a combination of the two  More than 20 aPL antibodies have been described  Most clinically significant  Lupus Anticoagulant (LA) and  Anticardiolipin antibodies (aCA)
  • 3.  Recurrent pregnancy loss  Intrauterine growth restriction (IUGR)  Intrauterine fetal death (IUFD)  Preterm brith  Pre-eclampsia (early/ late onset)  Abruptio placentae  Thrombocytopaenia  Deep vein thrombosis/ Pulmonary embolism  Stroke  Postpartum/ Catastrophic APS
  • 4.
  • 5.  Some aPL positive women have uncomplicated pregnancy outcomes without treatment  Variation in opinion on the rate of detection of aPL antibodies in women with adverse pregnancy outcomes  Paucity of prospective studies on the natural history of aPL in pregnant women and identifying the subset of aPL positive mothers who need medical therapy  Disagreement regarding clinically relevant levels, isotypes and specificities of aPL antibodies  Whether aPL antibodies other than LA & aCA are relevant
  • 6. We studied  The prevalence of aPL antibodies in selected at-risk obstetric cases  The significance of these antibodies with respect to pregnancy outcomes  Comparison of the results with a cohort of obstetric cases with past history of uncomplicated pregnancy outcome having similar demographic characteristics
  • 8.  STUDY AREASTUDY AREA  R G Kar Medical College and Hospital, Kolkata  Medical College and Hospital, Kolkata  STUDYSTUDY PERIODPERIOD 3 years (March 2006- February 2009)  STUDY DESIGNSTUDY DESIGN Prospective comparative study  STUDY POPULATIONSTUDY POPULATION Antenatal mothers who conform to inclusion criteria
  • 9.  STUDY DESIGNSTUDY DESIGN INCLUSION CRITERIA I. Study group 120 Antenatal mothers attending OPD 1. Having past H/O-  Pre-eclampsia  Eclampsia  Recurrent abortion  Intrauterine growth restriction (IUGR)  Intrauterine Fetal death (IUFD)  Abruptio placentae  Without any apparent aetiologyWithout any apparent aetiology 1. Registered into AN Clinic during 1st trimester
  • 10. II. Control Group Cohort of 120 Antenatal mothers attending OPD 1. Of comparable age, gravidity, parity, Body Mass Index (BMI) 2. Having past H/O uncomplicated pregnancy 3. Followed similar registration protocol EXCLUSION CRITERIA Presence of known medical disorders which might adversely affect pregnancy outcome
  • 11.  STUDY OBJECTIVESSTUDY OBJECTIVES  Primary- Prevalence of aPL antibodies in both groups  Secondary- Obstetric outcome in those women  STUDY TOOLSTUDY TOOL  Anti Cardiolipin antibody (aCA)- IgG and IgM by solid phase ELISA  Lupus Anticoagulant (LA)- by dilute Russle Viper venom test (dRVVT)  Single referral laboratory tests were used
  • 12.
  • 13.
  • 14.
  • 15.  Analysis of dataAnalysis of data  Visually double checked by an independent second investigator  Analysed using MedCalc (version 10.0.0.0) statistical software ( http://www.medcalc.be)  P value less than 0.05 was considered as statistically significant
  • 17. DEMOGRAPHIC PROFILEDEMOGRAPHIC PROFILE Characteristics Study group (n = 112) (mean ± SD) Control group (n = 112) (mean ± SD) p value Age (years) 26.4 ± 2.28 25.8 ± 2.42 0.0608 Gravidity 2.90 ± 0.52 2.86 ± 0.24 0.4708 Parity 1.48 ± 0.34 1.76 ± 0.22 0.0001 BMI (Kg/M2 ) 24.2 ± 1.8 23.8 ± 2.06 0.1278 Gestational age at sampling (weeks) 15.08 ± 0.31 15.04 ± 0.34 0.3646
  • 18.
  • 19. DISTRIBUTION OF CASES ACCORDING TODISTRIBUTION OF CASES ACCORDING TO PAST OBSTETRICS IN STUDY GROUPPAST OBSTETRICS IN STUDY GROUP
  • 20. PREVALENCE OF aPL ANTIBODIES INPREVALENCE OF aPL ANTIBODIES IN STUDY AND CONTROL GROUPSTUDY AND CONTROL GROUP Study group (n = 112) Control group (n = 112) Characteristics n (%) n (%) p value LA activity 15 13.39 2 1.89 0.0036 IgG aCA >10 GPL units 17 15.18 3 2.83 0.0035 IgM aCA >10 MPL units 21 18.75 4 3.77 0.0011 Both IgG aCA > 10 and IgM aCA >10 12 10.71 0 0 0.0015 Both LA and aCA +ve 11 9.82 2 1.89 0.0289 Total No. of aPL +ve cases 41 36.61 9 8.49 <0.0001
  • 21.
  • 22. INCIDENCE OFINCIDENCE OF ANTI-PHOSPHOLIPID ANTIBODIESANTI-PHOSPHOLIPID ANTIBODIES ACCORDING TOACCORDING TO PAST OBSTETRIC HISTORYPAST OBSTETRIC HISTORY
  • 23. aPL Positive cases Character istics Cases (n) Total aPL +ve (%) LA +ve Only IgG aCA >10 GPL Only IgM aCA > 10 MPL Both IgG & IgM aCA >10 units Study Group Pre- eclampsia 14 4 28.57 2 2 Eclampsia 10 1 10 1 Recurrent abortion 32 15 46.87 6 2 3 4 IUGR 24 10 41.66 3 2 3 2 IUFD 22 8 36.36 3 2 3 Abruptio placentae 10 3 30 1 1 1 TOTAL 112 41 15 5 9 12 Control Group 106 9 8.49 2 3 4 0
  • 24.
  • 25. In SummaryIn Summary aPL POSITIVEaPL POSITIVE aPL NEGATIVEaPL NEGATIVE STUDY group 41 97 CONTROL Group 9 71 Total 50 168 Dropped out 2 14 Net Total 48 154
  • 26. INCIDENCE OF OBSTETRICINCIDENCE OF OBSTETRIC COMPLICATIONSCOMPLICATIONS
  • 27. ObstetricObstetric ComplicationsComplications aPL Positive mothers (n= 48) aPL Negative mothers (n= 154) n (%) n (%) p value Early Abortion 12 25 11 07.14 0.0017 Pre-eclampsia <28 wk 7 14.58 2 01.3 0.0005 IUFD <28 wk 3 06.25 0 0 0.0146 Late Pre-eclampsia 12 25 9 05.84 0.0004 Eclampsia 1 02.08 0 0 0.5382 IUGR 13 27.08 14 09.09 0.0031 Oligohydramnios 16 33.33 10 06.49 <0.0001 Abruptio placentae 9 18.75 6 03.9 0.0019 IUFD >28 wk 2 04.17 2 01.3 0.5104
  • 29. LIVE BIRTH RATESLIVE BIRTH RATES aPL POSITIVE aPL NEGATIVE Total cases 48 154 Live birth n 31 141 (%) 64.58 91.56
  • 30. OUTCOMES OF LIVE BIRTHOUTCOMES OF LIVE BIRTH aPL Positive mothers (n = 31) aPL negative mothers (n = 141) Characteristics n (%) n (%) p value 95% CI No. of Vaginal deliveries (VD) 17 54.84 120 85.11 0.0004 12.88- 48.04 No. of Caesarean Section (SC) 14 45.16 21 14.89 0.0004 12.88-48.04 Gestational age at VD (weeks) (Mean ± SD) 35.9 ± 0.8 37.4 ± 0.8 <0.0001 1.19-1.81 Gestational age at CS (weeks) (Mean ± SD) 35.4 ± 0.5 37.8 ± 0.4 <0.0001 2.24-2.56 Early neonatal death 3 9.68 3 2.13 0.1252 0.09-22.84
  • 31. OUTCOMES OF LIVE BIRTHOUTCOMES OF LIVE BIRTH
  • 32. DIFFERENCES IN WEIGHTDIFFERENCES IN WEIGHT Placental weight Birth Weight aPL Negative (Mean ± SD) 488.7 ± 22.3 3024.3 ± 229.5 aPL positive (Mean ± SD) 424.2 ± 9.5 2523.6 ± 216.3 p value <0.0001 <0.0001 95% CI 56.42- 72.58 411.72- 589.68
  • 34. There is high prevalence of aPL antibodies in complicated pregnancy Both lupus anticoagulant and anticardiolipin antibodies significantly affect pregnancy outcome
  • 35. In our study outcome was worse in aPL positive mothers despite heparin treatment  Commencement of treatment after repeat test result for aPL positivity, which was not before 20-22 weeks’ gestation  Poor patient compliance (OPD based treatment)
  • 37. Following women should be screened for antiphospholipid antibodies-  Whose previous pregnancies were complicated by Recurrent abortion Pre-eclampsia (particularly early onset) Eclampsia IUGR IUFD Abruption placentae  With no apparent aetiology