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Benha University Hospital Email: [email protected] Aboubakr Elnashar

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Obstetric antiphospholipid antibody syndrome


Page 1: Obstetric antiphospholipid  antibody syndrome

Benha University Hospital

Email: [email protected]

Aboubakr Elnashar

Page 2: Obstetric antiphospholipid  antibody syndrome

An acquired autoimmune disorder characterized by

-moderate to high levels of antiphospholipid


(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

Page 3: Obstetric antiphospholipid  antibody syndrome

Primary: 50% other features of connective tissue disease are


Secondary: 50% to connective tissue disease e.g. SLE

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Page 4: Obstetric antiphospholipid  antibody syndrome

Epidemiology General population:

2-4%. increases with age and chronic disease

Recurrent fetal loss:

15 %



aCL antibodies:

more common than LA

(aCL 5X more than LA)

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Page 5: Obstetric antiphospholipid  antibody syndrome

1. Recurrent pregnancy loss. 25%.

Majority: in 1st T after the establishment of FHR


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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Page 6: Obstetric antiphospholipid  antibody syndrome


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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Page 7: Obstetric antiphospholipid  antibody syndrome


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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Page 8: Obstetric antiphospholipid  antibody syndrome

Postpartum syndrome Rare


Pleuropulmonary disease


Cardiac manifestations



extensive Img and C3 deposition in myocardium

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Page 9: Obstetric antiphospholipid  antibody syndrome

Aboubakr Elnashar

Page 10: Obstetric antiphospholipid  antibody syndrome

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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Page 11: Obstetric antiphospholipid  antibody syndrome

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.

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Page 12: Obstetric antiphospholipid  antibody syndrome

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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Page 13: Obstetric antiphospholipid  antibody syndrome

2. Comparison of laboratory criteria of APS.

Test Sapporo criteria (1999) Sydney criteria (2006)


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




IgG and/or IgM

Titer >99th percentile

Two or more occasions at least

12 weeks apart

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Page 14: Obstetric antiphospholipid  antibody syndrome

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


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Page 15: Obstetric antiphospholipid  antibody syndrome


positive or negative

more specific.


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)


-no greater risk (Silver et al 1996).

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Page 16: Obstetric antiphospholipid  antibody syndrome

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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Page 17: Obstetric antiphospholipid  antibody syndrome

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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Page 18: Obstetric antiphospholipid  antibody syndrome

Obstetric indications:

1. Unexplained stillbirth

2. Recurrent pregnancy loss

3.Unexplained 2nd or 3rd T fetal death


5. Severe preeclampsia at less than 34 w.

6. Placental abruption (previous or current)

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Page 19: Obstetric antiphospholipid  antibody syndrome

.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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Page 20: Obstetric antiphospholipid  antibody syndrome

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Page 21: Obstetric antiphospholipid  antibody syndrome

A. Before pregnancy: Pre-conceptional


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

Page 22: Obstetric antiphospholipid  antibody syndrome

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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Page 23: Obstetric antiphospholipid  antibody syndrome

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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Page 24: Obstetric antiphospholipid  antibody syndrome

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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Page 25: Obstetric antiphospholipid  antibody syndrome




Thrombocytopenia: Rare


Loss in BMD of the lumbar spine is similar to

physiological osteopenia in untreated pregnancies

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Page 26: Obstetric antiphospholipid  antibody syndrome

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


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Page 27: Obstetric antiphospholipid  antibody syndrome

Dose: A. No history of thrombosis:

Standard heparin:

1st T: 5000-10000 U /12 h

2nd and 3rd T: 10000 U/12 hrs


Enoxaparin (clexan) 20 mg once daily

Dalteprin 5000 U once daily.

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Page 28: Obstetric antiphospholipid  antibody syndrome

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.


Enoxaparine: 0.5 mg/kg /12 h or 40 mg once daily.

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Page 29: Obstetric antiphospholipid  antibody syndrome

IV immunoglobulin:


No benefit relative to heparin & low dose aspirin.

Reserved for cases refractory to aspirin & heparin (Jivaraj & Rai,2003)

Corticosteroids (prednisone):


{do not improve the live birth

significant maternal & fetal morbidity} (Laskin et al,1997).


History of recurrent thrombosis or cerebral

thrombosis (Branch et al, 2003)

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Page 30: Obstetric antiphospholipid  antibody syndrome

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


estrogen-containing are contraindicated.

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Page 31: Obstetric antiphospholipid  antibody syndrome

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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Page 32: Obstetric antiphospholipid  antibody syndrome

• 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.

Aboubakr Elnashar

Page 33: Obstetric antiphospholipid  antibody syndrome

Aboubakr Elnashar