APS non criteria

1. Non-criteria
Obstetric
Antiphospholipid
Syndrome
Prof. Aboubakr
Elnashar
Benha university Hospital, Egypt
elnashar53@hotmail.com
ABOUBAKR ELNASHAR

2. CONTENTS
1.ANTIPHOSPHOLIPID ANTIBODIES
2.DIAGNOSTIC CRITERIA FOR APS
3.NON-CRITERIA OBSTETRIC APS
4.SERONEGATIVE APS
5.ASYMPTOMATIC APL CARRIERS
CONCLUSION
5
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3. 1. ANTIPHOSPHOLIPID ANTIBODIES
20
Heterogeneous group of autoantibodies
(Immune reaction against self)
Can be found in
1. Full blown APS
2. Thrombotic APS
3. Obstetric APS
4. Asymptomatic carriers.
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4. 2. DIAGNOSTIC CRITERIA
Accurate diagnosis of obstetric APS
Important
Firm, evidence based, diagnostic criteria
(Arachchillage et al, 2015)
1. Optimal clinical management
2. Prevention of long-term disability of the
offspring
{placenta-mediated obstetric morbidity}
1. IUGR
2. Early onset PET
3. Placental insufficiency
3. Prevention of RM
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5.  1983:
Described by Graham Hughes
 1999: Sapporo criteria (Japan)
 An acquired autoimmune disorder characterized by
1. Moderate to high levels of antiphospholipid antibodies:
LA or aCl &
2. Specific clinical features
arterial or venous thrombosis or
Pregnancy morbidity
At least 1 clinical and 1 laboratory criterion.
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6. 2006: Sydney criteria (Australia).
The international consensus (Revised Sapporo)
1. Moderate to high levels of antiphospholipid antibodies:
LA or aCl or a-ß2GPI &
2. Specific clinical features
arterial or venous thrombosis or
pregnancy morbidity
 At least 1 clinical and 1 laboratory criterion.
 Not if:
 <12 W or > 5 years between
+ve aPLab and
clinical manifestation
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7. ABOUBAKR ELNASHAR

8. 3. NON-CRITERIA OBSTETRIC APS
2012: European Registry on Obstetric
Antiphospholipid Syndrome (EURO APS)
Added obstetric manifestations to those in the
international consensus criteria
2 unexplained miscarriages
3 non-consecutive miscarriages
2 or more unexplained in vitro fertilisation failures.
 late pre-eclampsia
placental abruption
late premature birth
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9. 2014: Rio de Janeiro (Brazil)
14th International Congress on APS:
New consensus
2 different entities
Thrombotic APS
Obstetric APS
Clinical criteria
Laboratory criteria.
Evidence is accumulating on the potential clinical
significance of
Non-criteria
clinical and laboratory manifestations of
O APS
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10. Obs APS differs from thrombotic APS.
(Arachchillage et al, 2015)
Pathogenesis
Lab findings
I. Pathogenesis
1. Thrombosis
neither a universal nor a specific feature especially
in RM in O APS
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11.  Small percentage (≤5%) of women with obstetric APS
subsequently develop thrombosis.
(Cervera et al; 2009).
Multicentre prospective study of 1,000 patients,
during 5 year period.
Annual rate of complications of pure O APS
(Gris et al, 2012).
%Annual rate
1.4DVT
0.4P. embolism
0.4Superficial v thrombosis
0.3Cerebro V events
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12. 2. Complement activation by aPL:
major role in the pathogenesis of
RM
Thrombosis in APS
aPL bound to trophoblasts activate complement via the
classical pathway:
split products:
placental injury:
fetal loss and growth restriction.
Appropriate complement inhibition is an essential
requirement for normal pregnancy
2GPI/anti-2GPI complex formation may activate complement:
local inflammatory damage
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13. 3. Passive transfer of IgG from women with RM and
aPL:
significant increase in the frequency of fetal
resorption:
reduced average weight of the surviving fetuses
Heparin
prevents obstetric complications caused by aPL,
by blocking complement activation
rather than through its antithrombotic properties
(Girardi G, et al.2004).
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14. II. The laboratory findings:
1. aCL or a2GPI alone
rather than LA is more common in O APS
(Gardiner C, et al.2013).
2. Positivity for IgM aCL
an independent risk factor for placental-mediated
complications.
(NOH-APS observational study)
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15. 3. 50 % of women with obstetric APS
had low positive aCL and/or a2GPI in the absence of
LA.
(Gardiner et al.2013)
IgG/IgM aCL levels and IgM a2GPI levels
significantly lower in patients with a history of purely obstetric APS than
in women with a history of thrombosis (p< 0.05)
4. Rate of LA positivity
 significantly lower in obstetric APS compared with
those with thrombosis
(15 % Vs 50.5 %; p< 0.0002).
(Gardiner et al., 2013)
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16. 5. Low positive aCL
should be defined as those between the 95th and
99th centiles
Not the 99th centile as suggested by the
International consensus criteria.
(Boffa et al, 2009, European cohort ,2012)
6. An arbitrary interval 12 w
to establish persistence of aPL
challenging to achieve in women with obstetric
morbidity.
aPL testing may not be representative during
pregnancy
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17. Non-criteria (clinical and laboratory) obstetric APS.
Diagnosis:
a) Non-criteria clinical manifestations with
international consensus laboratory criteria OR
b) International consensus clinical criteria with
non-criteria laboratory manifestation.
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18. No statistically significant differences in pregnancy
outcome between O APS, as defined by
International consensus criteria, or
non criteria O APS.
LBR
79.4 % with O APS
93.7 % patients with non criteria O APS
(European Registry on O APS (EURO APS), 2012)
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19. Non-criteria O APS
clinically relevant
standard treatment
LMWH plus LDA
starting as soon as pregnancy is confirmed
continuing until 6 w post-partum.
(The European Registry on Obstetric Antiphospholipid Syndrome
(EUROAPS)2012; Gardiner et al, 2013)
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20. 3. SERONEGATIVE APS
(Arachchillag et al, 2015)
Clinical criteria
 Highly suggestive of APS
 Repetitive obstetric complications
Laboratory tests:
Persistently negative conventional aPLs
Follow up:
Rapidly develop the classical accelerated and
progressive multi organ damage of patients with APS
persistent negative conventional aPL tests.
(Hughes et al,2003; Nayfe et al, 2013; Arachchillag et al, 2015)
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21. Clinical relevance other aPL AB
zwitterionic phospholipid, namely
Phosphatidyl ethanol amine
Phospholipid-binding plasma proteins
Phospho lipidprotein complexes
Anionic phospholipids
still debatable
needs to be confirmed
aPl Ab
Traditional techniques (TLC immunostaining).
New antigenic targets (mainly vimentin/cardiolipin)
(Misasi et al, 2015)
Not a non criteria O APS
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22. 4. ASYMPTOMATIC APL CARRIERS
Clinical criteria:
Non
Lab tests:
Positive
Prophylactic treatment with aspirin
not superior to placebo to prevent pregnancy
complications
(Amengual et al, SR, 2015)
Not a non criteria O APS
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23. CONCLUSION
Obstetric APS:
Accurate diagnosis is important
Differs from thrombotic APS.
Non-criteria obstetric APS
standard treatment with LMWH plus LDA
good pregnancy outcomes.
ABOUBAKR ELNASHAR

24. You can get this lecture and 375
lecture from:
1.My scientific page on Face book:
Aboubakr Elnashar Lectures.
https://www.facebook.com/groups/2277
44884091351/
2.Slide share web site
3. elnashar53@hotmail.com
4.My clinic: Althwara st, Mansura, Egypt
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