Obstetric antiphospholipid antibody syndrome

1. Benha University Hospital
Email: elnashar53@hotmail.com
Aboubakr Elnashar

2.  An acquired autoimmune disorder characterized by
-moderate to high levels of antiphospholipid
antibodies
(LA or aCl or a-ß2GPI) &
-specific clinical features
(arterial or venous thrombosis or pregnancy morbidity)
(Miyakis et al, 2006)
 20 antibodies
 First description:
1983 (Graham Hughes)
Aboubakr Elnashar

3. Primary: 50%
other features of connective tissue disease are
absent
Secondary: 50%
to connective tissue disease e.g. SLE
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4. Epidemiology
 General population:
2-4%. increases with age and chronic disease
 Recurrent fetal loss:
15 %
 SLE:
30%
 aCL antibodies:
more common than LA
(aCL 5X more than LA)
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5. 1. Recurrent pregnancy loss. 25%.
Majority: in 1st T after the establishment of FHR
activity.
15% of RPL
2. Preeclampsia: 15-50%.
15% of severe PET before 34 w have APL Ab
3. IUGR: 30%
4. Preterm labor
5. Maternal thrombosis (including strokes)
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6. Mechanisms
1. Inhibition of trophoblastic function& differentiation
(Bose et al, 2005)
2. Activation of complement pathways at the
maternal–fetal interface: local inflammatory
response
(Salmon et al, 2003)
3. In later pregnancy, thrombosis of the
uteroplacental vasculature
(Peaceman et al, 1993).
neither universal nor specific
(Jivraj & Rai, 2003)
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7. Controversy.
 aPl is responsible for implantation failure.
aPL is 23% in females referred for IVF Vs 2% in
fertile females
(Chilcott et al,2000)
 Routine screening for aPL among women
undergoing IVF-ET is not warranted
(Branch et al,2003)
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8. Postpartum syndrome
Rare
Manifestations
Pleuropulmonary disease
Fever
Cardiac manifestations
Mechanism
Unknown
extensive Img and C3 deposition in myocardium
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9. Aboubakr Elnashar

10. Sydney clinical criteria for APS (2006)
 At least 1 clinical and 1 laboratory criterion.
 Not if there is <12 W or > 5 years between
+ve aPLab and the clinical manifestation
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11. I. Clinical
1. Vascular thrombosis
One or more clinical episodes of
arterial, venous, or small-vessel
thrombosis in any tissue or organ
confirmed by imaging, Doppler
studies, or histopathology, with
the exception of superficial
venous thrombosis.
For histopathologic confirmation,
thrombosis should be present
without significant evidence of
inflammation of the vessel wall.
Aboubakr Elnashar

12. 2. Pregnancy morbidity
(a) One or more unexplained deaths of a
morphologically normal fetus at or beyond the 10th w,
with normal fetal morphology documented by US or by
direct examination of the fetus, or
(b) One or more premature births of a morphologically
normal neonate at or before the 34th w because of
severe preeclampsia or eclampsia or severe placental
insufficiency, or
(c) Three or more unexplained consecutive
spontaneous abortions before the 10th w, with
maternal anatomic or hormonal abnormalities and
paternal and maternal chromosomal causes excluded.
N.B: in practice evaluation after 2 early miscarriage
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13. 2. Comparison of laboratory criteria of APS.
Test Sapporo criteria (1999) Sydney criteria (2006)
LACs Screening, mixing, and
confirmation tests
Two or more occasions at least 6
w Apart
Screening, mixing, and
confirmation tests
Two or more occasions at least
12 w Apart
aCL Ab Detected by standardized ELISA
IgG and/or IgM
Medium or high titer
Two or more occasions at least 6
w apart
Detected by standardized ELISA
IgG and/or IgM
Medium or high titer (>40 units
titer or >99th percentile)
Two or more occasions at least
12 w apart
Anti-
ß2GPI
Ab
IgG and/or IgM
Titer >99th percentile
Two or more occasions at least
12 weeks apart
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14. Interpretation:
•A repeat tests at least 6 (12) W apart.
{Individuals may have transiently positive test
because a low to mid positive level can be due to viral
illness and revert to normal& those with an initial
negative test may be in the transient negative phase
of their aPL cycle.}
•LA, aCL and aβ2GPI testing are all required for the
accurate diagnosis
•Once APS is diagnosed, serial aPL testing is not
useful
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15. •LA:
positive or negative
more specific.
aCL:
international units.
more sensitive
Titer is related to risk of fetal loss
(Rai et al,1995)
•IgG Ab
more specific than IgM.
better predictors of fetal outcome
(Lockwood et al,1986)
-IgA
-no greater risk
(Silver et al 1996). Aboubakr Elnashar

16. laboratory data-based classification system
International Consensus Guidelines, 2006
Category Criteria
I More than 1 laboratory criterion present
in any combination
IIa LA present, only
IIb aCL present, only
IIc anti-β2GPI present, only
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17. Controversial points in interpreting
-Low positive IgG AcL Ab:
No greater risk for APA related events
(Silver et al, 1996).
should be regarded as of questionable clinical
significance (Branch et al,2003)
should be included in the diagnosis of obstetric
APS.
(Gardiner et al, 2013)
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18. Obstetric indications:
1. Unexplained stillbirth
2. Recurrent pregnancy loss
3.Unexplained 2nd or 3rd T fetal death
4. IUGR
5. Severe preeclampsia at less than 34 w.
6. Placental abruption (previous or current)
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19. .Non-obstetric indication
1.False positive serologic test for syphilis
2.Autoimmune diseases: SLE, thrombocytopenia
3.Unexplained thrombosis
4.Haemolytic anaemia
5.Stroke, especially between 25-50 yr
6.Livedo reticularis
Livedo reticularis
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20. Aboubakr Elnashar

21. A. Before pregnancy: Pre-conceptional
counseling
1. Clinical: review med and obs history, asses other
risk factors, obesity, age
2. Lab:
Confirm persistent aPLab
Assess R function
CBC: anaemia thrompocytopenia
3. Treatment
Postpone pregnancy if thrombotic event <6 month
Initial low dose aspirin [increase success]Aboubakr Elnashar

22. B. During pregnancy
 Objectives:
Improve maternal & fetal-neonatal outcome by
preventing complications
Reduce or eliminate the maternal thrombotic risk
1. TVS: confirm live embryo at 5.5-6.5 W
2. Continue low dose aspirin
3. Initial heparin treatment
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23. Clinical care
ANV/4 W until 20W
then /1-2 W
Monitor for fetal
death, PET, IUGR
Diagnostic tests
U/S:/4W beginning at 20 W.
Assess fetal growth & AFV
Fetal surveillance: weekly from
30W. CTG,
Uterine a Doppler: at 20 for
prediction of PET
If early diastolic notch seen: do
2 weekly growth scans due to
high risk of IUGR
Platelet count
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24. Medications:
Low dose aspirin (75 mg) in combination with
heparin is the first line treatment
(MRCOG, 2011)
Start with the positive pregnancy test till 34 w.
-Success: 70%
(Rai et al,1997)
-Reduces the miscarriage rate by 54%
(Empson et al, Cochrane Database Syst Rev, 2005)
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25. Heparin:
Complications:
Hemorrhage
Thrombocytopenia: Rare
Osteopenia:
Loss in BMD of the lumbar spine is similar to
physiological osteopenia in untreated pregnancies
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26. Un-fractionated heparin Vs LMWH:
•LMWH is widely used in Europe, whereas cost
considerations limit its use in other countries.
•No significant difference in
BMD or live birth rate
(Farquharson,2000)
LMWH advantages
once daily
less thrombocytopenia
osteopenia
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27. Dose:
A. No history of thrombosis:
Standard heparin:
1st T: 5000-10000 U /12 h
2nd and 3rd T: 10000 U/12 hrs
LMWH:
Enoxaparin (clexan) 20 mg once daily
Dalteprin 5000 U once daily.
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28. B. History of thrombosis
Standard heparin:
/8-12 hrs {maintain the midinterval heparin levels in
the therapeutic range}.
(Heparin level = anti-factorXa levels.)
Women without a LA in whom APTT is normal can
be observed using APTT.
LMWH
Enoxaparine: 0.5 mg/kg /12 h or 40 mg once daily.
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29. IV immunoglobulin:
Expensive
No benefit relative to heparin & low dose aspirin.
Reserved for cases refractory to aspirin & heparin
(Jivaraj & Rai,2003)
Corticosteroids (prednisone):
abandoned
{do not improve the live birth
significant maternal & fetal morbidity}
(Laskin et al,1997).
Warfarin:
History of recurrent thrombosis or cerebral
thrombosis
(Branch et al, 2003)
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30. C. Postpartum
 History of thrombosis:
Warfarin thromboprophylaxis as soon as the patient
is clinically stable after delivery
(International normalized ratio (INR) of 3 is
desirable).
No history of thrombosis:
UK: Heparin for 5 d
USA: anticoagulant for 6 w.
Breast feeding:
Heparin & warfarin: safe
Contraception
estrogen-containing are contraindicated.
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31. Women refractory to aspirin & heparin
(Branch et al,2003).
Full anticoagulation in the next pregnancy
if failed:
IV immunoglobulin:
{antiidiotypic down-regulation of auto-antibody
production}
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32. • For diagnosis: 2
1 of 2 clinical criteria (thrombosis or pregnancy
morbidity) &
1 of 3 laboratory criteria (medium to high titer of aCL
or positive LA or Anti-ß2GPI Ab)
• For treatment: 2
low dose aspirin & heparin starting with positive
pregnancy test till 34 w.
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33. Aboubakr Elnashar