This document discusses non-criteria obstetric antiphospholipid syndrome (APS). It begins by defining antiphospholipid antibodies and the diagnostic criteria for APS. It then examines non-criteria obstetric APS, which includes additional clinical manifestations like recurrent miscarriages or preeclampsia. While these do not meet international diagnostic criteria, treatment with low molecular weight heparin and low-dose aspirin can still yield good pregnancy outcomes. The document also reviews seronegative APS, asymptomatic APL carriers, and concludes that accurate diagnosis of obstetric APS is important and treatment should still be given for non-criteria cases.

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
ABOUBAKR ELNASHAR

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.
ABOUBAKR ELNASHAR

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
ABOUBAKR ELNASHAR

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.
ABOUBAKR ELNASHAR

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
ABOUBAKR ELNASHAR

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
ABOUBAKR ELNASHAR

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
ABOUBAKR ELNASHAR

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
ABOUBAKR ELNASHAR

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
ABOUBAKR ELNASHAR

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
ABOUBAKR ELNASHAR

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).
ABOUBAKR ELNASHAR

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)
ABOUBAKR ELNASHAR

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)
ABOUBAKR ELNASHAR

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
ABOUBAKR ELNASHAR

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.
ABOUBAKR ELNASHAR

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)
ABOUBAKR ELNASHAR

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)
ABOUBAKR ELNASHAR

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)
ABOUBAKR ELNASHAR

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
ABOUBAKR ELNASHAR

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
ABOUBAKR ELNASHAR

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
ABOUBAKR ELNASHAR